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PubMed1993

Oral traumatic granuloma. Characterization of the cellular infiltrate.

Oral traumatic granulomas are reactive mucosal lesions that are characterized by an intense mononuclear infiltrate (usually with eosinophils) that may mimic neoplasia. These pseudoneoplastic infiltrates were evaluated with the use of lineage-associated antibodies (CD3, OPD4, L26, KP1, XIIIa, S-100, HPCA-1, HHF-35). We determined that the large distinguishing mononuclear cells were either CD68-positive macrophages or factor XIIIa-positive dendrocytes (the oral counterparts to dermal dendrocytes). S-100-positive connective tissue cells occasionally contributed to this infiltrate. Also abundant in the infiltrate were smaller CD3-positive T-lymphocytes. Double-staining confirmed that there were separate populations of CD68-positive macrophages and XIIIa-positive dendrocytes. Because some XIIIa dendrocytes coexpressed CD68, phagocytosis may be one of the functions of dendrocytes.

Antibodies, Monoclonal↗

PubMed1990

Immunohistologic analysis of small lymphocytic infiltrates of the orbit and conjunctiva.

In a prior study we reported that monotypic immunoglobulin expression significantly correlated with an increased risk of dissemination by small lymphocytic infiltrates (SLIs) of the orbit and conjunctiva. However, less than half of all monotypic SLIs disseminated. In this study, we applied a large panel of monoclonal antibodies to cryostat sections of orbital and conjunctival SLIs to address two questions. First, might immunohistologic results other than immunoglobulin staining predict which patients with monotypic SLIs will develop disseminated lymphoma? Second, what is the usefulness of these findings in the diagnosis of orbital and conjunctival SLIs? We found that immunohistologic results did not significantly predict or correlate with disseminated lymphoma in patients with monotypic SLIs, either at time of presentation (ie, staging evaluation positive) and/or subsequently. However, three monotypic infiltrates (10%) had a proliferative rate (Ki-67-positive) of 20% or greater, and all three cases disseminated. Regarding the usefulness of the antibody panel, a B to T cell ratio of 4 or greater (76%), anomalous pan-T cell antigen expression by B cells (38%), and pan-B cell antigen loss (15%) were found exclusively in monotypic SLIs. Combining these results, 80% of monotypic SLIs had additional immunophenotypic criteria of lymphoma. Thus, these findings appear to be useful, although less helpful than immunoglobulin staining, and provide another means of immunophenotypic diagnosis when the results of immunoglobulin staining are technically unsatisfactory or difficult to interpret. We were unable to detect anomalous antigen expression or antigen loss in polytypic infiltrates, including one lesion which locally recurred 30 months later as a histologically indistinguishable, clearly monotypic SLI. We attribute the absence of these findings in polytypic SLIs to their relatively infrequent occurrence in monotypic infiltrates and/or to our inability to detect small clones of malignant cells (if present) by our immunohistologic methods.

Adult↗

PubMed1990

Infiltrating cribriform carcinoma of the breast: a distinctive clinicopathologic entity.

All cases of primary breast carcinoma seen at the George Washington University Medical Center between 1971 and 1975 and between 1981 and 1986 were reviewed, and examples of pure and mixed infiltrating cribriform carcinoma (ICC) were identified. The relative frequency of ICC did not change significantly from the earlier to the later study period. As previously reported by Page et al, there was a tendency for ICC to be associated with foci of tubular carcinoma and of intraductal carcinoma (often but not always of cribriform type). Pure ICC (defined as showing no other infiltrating carcinoma type), predominant ICC with lesser amounts of infiltrating carcinoma of any other type and any quantitative combination of ICC and tubular carcinoma metastasized to axillary lymph nodes frequently, but almost never to more than three nodes, in contradistinction to tumors composed of infiltrating duct carcinoma (IDC) not otherwise specified and less than 50% ICC, and a control group of IDC, which significantly more often involved four or more nodes. ICC cases were estrogen-receptor-positive in 100% and progesterone-receptor-positive in 69% of the cases. Five-year survival rates for eligible cases were 100% for pure and greater than or equal to 50% ICC, 88% for less than 50% ICC, and 78.3% for the IDC controls. ICC is a histologically and clinically distinctive type of mammary carcinoma that should be separated from IDC and other tumor types.

Adenocarcinoma↗

PubMed1983

Intense eosinophilic stromal infiltration in carcinoma of the uterine cervix: a clinicopathologic study of 14 cases.

Stromal responses to tumor, usually characterized by the intensity of the lymphoplasmacytic infiltration, have been felt to be of prognostic significance in a wide range of neoplasms. Little attention has been focused on stromal reactions composed primarily of infiltration by eosinophilic leukocytes. We describe here the clinical and histopathological findings in 14 patients with invasive carcinoma of the uterine cervix in whom pronounced eosinophilic infiltration was observed in the stroma in the initial diagnostic biopsy material. These patients tended to have early stage disease, had associated increased lymphoplasmacytic stromal response, and were somewhat younger than the patients lacking this intense eosinophilic infiltration. A suggestion of improved survival was noted in patients with intense stromal eosinophilia treated primarily with radiation therapy.

Adult↗

PubMed1994

Infiltrating gamma delta T-cells and selectin endothelial ligands in the cutaneous phytohaemagglutinin-induced inflammatory reaction.

The 24 h phytohaemagglutinin-induced skin inflammatory site (intradermal and subcutaneous) was studied in inbred MHC-homozygous (SLAb/b) pigs and it was found, by immunohistology, that the predominant lymphocytes in the infiltrate are CD2-CD4-CD8-sIg-T-cells, the Null/gamma delta T-cell family, identified using the monoclonal antibodies (mAbs) MAC320 and MAC319 (which recognises a subset of MAC320+ cells). A large percentage of the infiltrating cells expressed the gamma delta T-cell receptor phenotype identified by binding of the mAb 86D. Fewer CD2+, CD8+ and CD4+ cells were present and surface immunoglobulin positive (sIg+) cells were virtually absent in the infiltrate. Areas of lymphocytic infiltration were associated with endothelial activation as determined by expression of the E-selectin and a ligand for the L-selectin.

Animals↗

PubMed1991

Immunohistologic evaluation of the effect of cyclosporine treatment on the lichen planus immune infiltrate.

We have investigated immunohistologically the cutaneous immune infiltrate in the lesions of five patients with severe, extensive lichen planus of recent onset before and after 15 days of oral, low-dose cyclosporine therapy (3 mg/kg/day). Before therapy, we observed an abnormal bandlike cellular infiltrate localized in the papillary dermis, composed mostly of CD3+ cells, with a prevalence of CD4+ cells. Infiltrating lymphocytes showed markers of activation (HLA-DR antigens and interleukin 2 receptor), and there were many Langerhans (CD1+) cells in the dermal infiltrate. After 15 days of cyclosporine therapy, we observed a dramatic decrease in the total number of T cells and a corresponding decrease in interleukin 2 receptor-positive activated CD25+ cells and in antigen-presenting cells (CD1+ and CD14b+). These changes were concurrent with clinical improvement. Our results are compatible with the hypothesis that the inhibition of CD4 T cells by cyclosporine might explain the drug's therapeutic action and that the interaction between antigen-presenting cells and CD4 T cells is important in the pathogenesis of lichen planus.

Adult↗

PubMed1992

Differential expression of adhesion molecules on infiltrating cells in inflammatory dermatoses.

BACKGROUND: Adhesion molecules and their ligands are involved in coordination of the activities of the immune system. OBJECTIVE: To evaluate whether adhesion molecules are relevant in the pathogenesis of inflammatory dermatoses, we analyzed the expression pattern of many of these molecules. METHODS: The expression of 10 members of the integrin and immunoglobulin superfamilies was mapped by means of immunohistochemical techniques in biopsy specimens of psoriasis (n = 15), pityriasis lichenoides (n = 11), parapsoriasis en plaques (n = 11), contact dermatitis (n = 7), and lichen planus (n = 5). RESULTS: In all investigated skin diseases, almost every infiltrating cell expressed lymphocyte function-associated antigens 1 and 3 as well as very late activation (VLA) antigens 4 and 5. The subepidermal infiltrate differed with regard to the expression of VLA-1, VLA-3, and VLA-6, which was high in lichen planus and moderate or absent in the other dermatoses. The intraepidermal lymphocytes in psoriasis and pityriasis lichenoides were VLA-1 positive, whereas the subepidermal infiltrate lacked this marker. CONCLUSION: The differential upregulation of adhesion molecules in the mononuclear infiltrate and on keratinocytes demonstrates their importance in the pathogenesis of cutaneous inflammation.

Antigens, Differentiation↗

PubMed1992

Changes of host cell infiltration into Meth A fibrosarcoma tumor during the course of regression induced by injections of a BCG nucleic acid fraction.

MY-1, which consists of DNA and RNA extracted and purified from Mycobacterium bovis strain BCG, causes the regression of various experimental syngeneic tumors when injected intratumorally. In order to identify the host cells involved in the antitumor mechanism(s) of MY-1, we examined Meth A tumors inoculated intradermally to BALB/c mice, which were given multiple injections of MY-1 following tumor inoculation. Histological and immunohistochemical examinations were performed at several time points. On day 4 after inoculation, the MY-1-treated tumors were heavily infiltrated with a heterogeneous population of mononuclear cells with low density nuclei. The MY-1-injected tumors contained asialo-GM1-positive cells and Mac-1-positive cells, which indicated that the infiltrating mononuclear cells were natural killer cells and macrophages. On day 14 after inoculation, the tumors were infiltrated with a large number of L3T4-positive cells and fewer Lyt-2-positive cells, both of which were more abundant in the MY-1-treated tumors than in the control tumors. The observed sequence of host cell infiltration corresponded well with our previous studies which have indicated that the antitumor mechanism of MY-1 is divided into two phases, i.e. the early phase when natural killer cells and macrophages inhibit tumor growth, and the late phase when L3T4-positive cells act to induce tumor regression via a delayed-type hypersensitivity against tumor cells.

Animals↗

PubMed1989

Bone marrow infiltration in hairy cell leukemia after interferon therapy detected by magnetic resonance imaging.

Magnetic resonance imaging (MRI) can detect bone marrow infiltration by neoplastic cells in many hematological malignancies. We studied 10 patients affected by hairy cell leukemia (HCL) and treated with interferon (IFN) with both MRI and bone marrow biopsy. T1-weighted MR scans of femurs and pelvis proved to be effective to score hairy cell infiltration, while less information was obtained from the study of the lumbar vertebral column. A good correlation (less than 10% difference) was noted between biopsy and MRI in over 90% of cases. MR scans showed, in general, a higher grade of infiltration. MR scan, however, can be useful for monitoring the course of HCL and the response to the treatment. Moreover, MRI evaluating a large amount of tissue, can detect a nodular type of infiltration which can be missed in biopsy specimens.

Bone Marrow↗

PubMed1993

The effect of pre- versus postinjury infiltration with lidocaine on thermal and mechanical hyperalgesia after heat injury to the skin.

The aim of the study was to evaluate the effects of pre- and postinjury infiltration with lidocaine on alterations in mechanical and thermal sensitivity after heat injury to the skin. In the first part of the study, burn injuries (15 x 25 mm rectangular thermode, 50 degrees C, 7 min) were produced twice in each subject on the medial side of the left and right calves at least 24 h apart in 8 healthy, unmedicated male volunteers, in order to investigate the effects of the injury on sensitivity in untreated skin. In the second part of the study, burn injuries (15 x 25 mm rectangular thermode, 50 degrees C, 6 min) were produced twice in each subject on the medial side of the left and right calves at least 24 h apart (n = 10). This was preceded by subcutaneous (s.c.) infiltration with 5-6 ml of 1% plain lidocaine (pre-injury block) on one day, and the same block was performed 35 min after injury (postinjury block) on the other day. Warm detection thresholds (WDT) and heat pain detection thresholds (HPDT) were determined within and outside the injury before and at regular intervals after injury. Areas of hyperalgesia to pinprick and brush were determined at regular intervals after injury. In the first part of the study, it was observed that both WDT and HPDT were decreased within but not outside the injury, and areas of hyperalgesia to pinprick and brush were found in- and outside the injury in all subjects. These findings were relatively constant throughout the study period and reproducible between the 2 days of examination. In the second part of the study, it was observed that pre-injury infiltration with lidocaine reduced hyperalgesia to pinprick and brush outside the injury more effectively than postinjury block, but only for the first 70 min after injury, while no significant difference was observed 100-190 min after injury. Likewise, there was no difference in thermal thresholds inside the injury between pre- and postinjury treatment at the end of the study period. It is concluded, that a shortlasting 'preemptive' infiltration with lidocaine may postpone but not prevent the occurrence of hyperalgesia outside a thermal injury.

Adult↗

PubMed1991

The effect of pH buffering on reducing the pain associated with subcutaneous infiltration of bupivicaine.

The authors propose that pH buffering of bupivicaine with sodium bicarbonate reduces the pain associated with its local subcutaneous infiltration. In a double-blind, prospective study, 62 healthy adult volunteers received a 0.5 mL subcutaneous infiltration of 0.5% buffered bupivicaine into the dorsum of a randomly chosen hand. The pH was adjusted to 7.0 by adding 0.05 mL of sodium bicarbonate (1 mEq/L [corrected]) to 10 mL vials of commercially available bupivicaine (1:200 dilution). The control hand was injected with the same amount of unbuffered agent. Pain was scored after each infiltration using a nonsegmented visual analogue scale. Student's t-test for paired measurements was used to analyze intergroup pain score differences. Forty-three subjects (69%) reported less pain with buffered bupivicaine and only 17 (27%) noted a modest increase: two subjects (3%) reported no difference. The mean pain score for the buffered agent was 22 mm compared with 30 mm for the control. The mean difference (control-experimental) was 8 mm (t = 4.64, df = 61, P less than .001). The authors conclude that the addition of sodium bicarbonate to bupivicaine reduces the pain associated with its local infiltration.

Adult↗

PubMedDate not supplied

Minimizing the pain of local infiltration anesthesia for wounds by injection into the wound edges.

This study on low contamination wounds was conducted to compare the pain of local infiltration anaesthesia administered into the skin surrounding the wound with administration directly into the incised edges of the wound. Eighty-one adult patients were randomized by date of presentation to receive infiltration anesthesia by one of the two methods. Pain of anesthetic administration was rated on a visual analogue scale and recorded as a pain score in millimeters. The results demonstrated that the average pain score for infiltration into the wound was significantly lower than the average pain score for infiltration into skin surrounding the wound.

Adult↗

PubMed1988

Local anesthesia for radial artery cannulation: a comparison of a lidocaine-prilocaine emulsion and lidocaine infiltration.

A topical anesthetic emulsion consisting of a mixture of lidocaine and prilocaine (EMLA) was used in an attempt to reduce the pain associated with radial artery cannulation. Three groups were compared: (1) EMLA applied at least 90 minutes prior to cannulation (EMLA 90); (2) EMLA applied 60 minutes prior to cannulation (EMLA 60); and (3) lidocaine 2% infiltration performed immediately prior to the procedure (infiltration). Pain was registered using visual analog and verbal ranking scales by both the patient and an independent observer. The EMLA 90 group experienced significantly less pain (P < .001) than either the EMLA 60 or lidocaine infiltration groups. There was no statistically significant difference in pain scores between the EMLA 60 and infiltration groups. Local side-effects of EMLA were negligible.

Anesthesia, Local↗

PubMed1991

Phenotypic analysis of skin infiltrates in comparison with peripheral blood lymphocytes, spleen cells and thymocytes in early avian scleroderma.

University of California at Davis line 200 (UCD-200) chickens develop a hereditary connective tissue disease characterized by severe lymphocytic infiltration, vascular occlusion and fibrosis of skin and internal organs. To identify cellular immunological abnormalities in the acute inflammatory disease stage of this animal model for progressive systemic sclerosis (PSS) we investigated the phenotypic characteristics and function of peripheral blood lymphocytes (PBL), spleen cells and thymocytes in comparison with skin infiltrating cells. Immunofluorescence and immunohistochemical analysis using monoclonal antibodies revealed the overwhelming majority of skin infiltrating mononuclear cells in the deeper dermis and subcutaneous tissue to be T cell receptor alpha/beta (TcR2)+/CD3+/CD4+/class II+ cells, a small portion (5-10%) of which were interleukin 2 (IL-2) receptor positive. In contrast, the inflammatory infiltrate in perivascular areas of the papillary dermis was constituted of mainly TcR gamma/delta (TcR1)+/class II- lymphocytes. Only few B cells (T/B cell ratio greater than 5) were detected. These diseased chickens showed significantly reduced percentages and numbers of circulating peripheral T cells exhibiting TcR1, TcR2, CD3, CD4 or IL-2-receptor, probably owing to an increased influx into lymphoid organs and affected tissues. In contrast to healthy chickens, the thymi of UCD-200 animals revealed fewer cells expressing TcR1, TcR2 and class II antigen, suggesting an altered intrathymic maturation of the T cell lineage. Functional in vitro studies showed a significantly decreased T cell mitogen-induced proliferation rate associated with a decreased capacity to produce IL-2 and to express IL-2 receptors. In contrast to the deficient in vitro IL-2 production the sera of UCD-200 chickens contained significant levels of IL-2 bioactivity. The alteration of T lymphocyte physiology in UCD-200 chickens adds, at least in part, to the parallels between this animal model and its human counterpart. These data confirm our hypothesis that the PSS-like disease of UCD-200 chickens includes a numeric and/or functional alteration of peripheral T cell subsets, especially of TcR1 positive cells, in contrast to the pronounced accumulation in the afflicted tissues.

Animals↗

PubMed1993

A combined therapeutic modality with hyperthermia and locally administered rIFN-beta inhibited the growth of B16 melanoma in association with the modulation of cellular infiltrates.

Murine B16-F10 melanoma was treated with local microwave hyperthermia, local injection of murine recombinant interferon-beta (rIFN-beta) or a combination of both in order to investigate the augmentation of anti-proliferative effects with this combination treatment. Concerning the local modulation of immunological reactions of the host, local hyperthermia at 43 degrees C for 15 min on murine melanoma caused remarkable infiltration of natural killer cells and local injection of rIFN-beta led to considerable infiltration of T cells. When these two modalities were combined, the infiltration of NK cells completely disappeared and, instead, remarkable augmentation of T cell infiltration occurred. Synergistic suppressive effects on melanoma growth with occasional scar formation were seen with this combined modality. These results indicate that local hyperthermia with a combination of rIFN-beta modulates local immune reactions of the host, and probably this immune reaction is partly involved in the course of the suppression of tumor growth.

Animals↗

PubMed1995

Role of lipoxygenase metabolites in platelet-activating factor- and antigen-induced bronchial hyperresponsiveness and eosinophil infiltration.

The effect of a novel leuktriene B4 receptor antagonist N-[5[[8-(1-hydroxy-2- phenyl)ethyl]dibenzofuran-2yl]5-hydroxypentanoyl]pyrrolidine (PF 10042) has been evaluated in comparison with 2-[3(1-hydroxyhexyl)phenoxymethyl]quinoline hydrochloride (PF 5901), a specific inhibitor of the 5-lipoxygenase pathway of arachidonic acid metabolism, against platelet activating factor (PAF) and allergen induced bronchial hyperresponsiveness and pulmonary eosinophil infiltration in the guinea pig. PF 10042 significantly displaced radiolabelled [3H]leukotriene B4 from binding sites on human neutrophils with an EC50 of 3 muM. PF 10042 (100 mg/kg, i.p.) significantly inhibited PAF and allergen induced bronchial hyperresponsiveness without reducing the concomitant eosinophil infiltration, whereas PF 5901 (100 mg/kg, p.o.) significantly inhibited both PAF and allergen induced bronchial hyperresponsiveness and eosinophil infiltration. We suggest from these results that PAF and allergen induced bronchial hyperresponsiveness may be secondary to the release of leukotriene B4, but this lipoxygenase metabolite does not contribute significantly to the observed eosinophil infiltration.

Animals↗

PubMed1991

Effect of a novel 5-lipoxygenase inhibitor, E6080 on bronchospasm, airway cellular infiltration and leukotriene production in guinea pigs.

6-Hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le hydrochloride (E6080), an orally active and selective 5-lipoxygenase inhibitor, dose-dependently inhibited the bronchospasm induced by antigen (ovalbumin) inhalation in sensitized conscious guinea pigs. The inhibitory effect of E6080 was more potent than that of a typical 5-lipoxygenase inhibitor, AA861, but less than that of a leukotriene (LT) antagonist, LY171883. When airway infiltration of neutrophils and eosinophils was measured in bronchoalveolar lavage fluid (BALF) at 6 h after antigen inhalation by passively sensitized guinea pigs, the inhibitory effect of E6080 on neutrophil infiltration was more marked than that on eosinophil infiltration. The inhibitory effect of E6080 on bronchoalveolar cellular infiltration and bronchoepithelial damage was confirmed by examination of photomicrographs of the lung. In addition to the above pharmacological effects, E6080 inhibited the increase in BALF levels of both i-LTC4 and i-LTB4. These results suggest that E6080 may prove to be effective for the treatment of asthma, in which large amounts of leukotrienes (LTs) are elaborated.

Acetophenones↗

PubMedDate not supplied

Effects of alkalinization of lidocaine on the pain of skin infiltration and intravenous catheterization.

STUDY OBJECTIVE: To test the hypothesis that alkalinization of lidocaine decreases the pain of skin infiltration in surgical patients. DESIGN: Double-blind, randomized, prospective study. SETTING: Preoperative holding units, Brigham and Women's Hospital. PATIENTS: 184 adult surgical patients. INTERVENTIONS: We compared the efficacy of 1% lidocaine with and without 0.1 mEq/ml of sodium bicarbonate (NaHCO3) for relief of pain of (1) skin infiltration and (2) intravenous (i.v.) catheterization prior to surgery. MEASUREMENTS AND MAIN RESULTS: Patients evaluated the intensity of pain using a 100 mm visual analog scale (VAS). There were no differences between study groups (lidocaine with NaHCO3, n = 89; lidocaine alone, n = 95) with respect to site of catheterization or catheter gauge used. Lidocaine plus NaHCO3 caused significantly less pain on skin infiltration (median VAS = 4; range = 0 to 51) than did lidocaine alone (VAS = 8; range = 0 to 48; p < 0.008). Pain of i.v. catheterization also did not differ between groups. There was a weak correlation between catheter gauge and pain of i.v. catheterization (r = -0.19; p = 0.01). CONCLUSIONS: Pain resulting from skin infiltration of lidocaine solutions can be diminished by adding NaHCO3. However, catheter size is more important than the presence or absence of NaHCO3 in determining the pain of i.v. catheterization.

Adult↗