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PubMed2004

Grey scale and power Doppler sonographic changes induced by intra-articular steroid injection treatment.

OBJECTIVE: To investigate the ability of high resolution grey scale sonography (GSS) and power Doppler sonography (PDS) to assess short term soft tissue changes induced by intra-articular steroid injection in the small joints of patients with chronic synovitis. METHODS: 20 patients with clinically active synovitis of a small joint unresponsive to systemic drug treatment underwent a sonographic guided intralesional injection with triamcinolone acetonide. Clinical examinations were carried out by a trained rheumatologist. GSS and PDS examinations were performed independently by two examiners unaware of the results of the clinical examination. Joint cavity widening and power Doppler signal were evaluated and graded on a semiquantitative scale ranging from 1 to 4. Clinical and sonographic follow up examinations were carried out 2 weeks after the injection with triamcinolone acetonide. RESULTS: All intra-articular injections were successfully carried out and documented under sonographic guidance. In 19/20 patients, baseline sonographic examinations clearly detected morphological and perfusional signs of synovitis. At follow up examinations, clinical and sonographic scores had improved significantly. CONCLUSION: GSS and PDS appear to be a useful adjunctive tool for assessing short term soft tissue changes induced by intra-articular injection treatment with triamcinolone acetonide in small joints of patients with chronic arthritis.

Adult↗
PubMed1992

Incidence of alopecia areata in lupus erythematosus.

BACKGROUND: A small percentage of patients with alopecia areata have connective diseases such as systemic lupus erythematosus, discoid lupus erythematosus, rheumatoid arthritis, and scleroderma. Lupus erythematosus is associated with a number of different types of alopecia, but the incidence of alopecia areata in lupus erythematosus has not been examined. OBSERVATIONS: Of our cohort of 39 patients with lupus erythematosus, alopecia areata developed in 10% (four patients), in contrast to 0.42% of general dermatologic patients. Biopsy specimens of alopecia areata lesions in each of our patients showed continuous granular deposition of IgG at the dermoepidermal junction, a finding usually found in only a minority of alopecia areata cases. Intralesional injections of corticosteroids were effective treatment. CONCLUSIONS: The incidence of alopecia areata in patients with lupus erythematosus is increased. Recognition of this form of alopecia allows for specific therapy with intralesional corticosteroids.

Adult↗
PubMed1994

Induced regression of bovine papillomas by intralesional immunotherapy.

It has long been assumed that papilloma regression is mediated by immunological mechanisms which are probably cellular in nature. The potentiation of these responses may alter the course of papilloma progression. Certain strains of the bacterium Corynebacterium parvum (Propionibacterium acnes) have been shown to augment cellular immune mechanisms by increasing both macrophage and natural killer cell activity. This study involves the use of naturally occurring bovine papillomas to investigate the immune mechanisms involved in induced papilloma regression. Papillomas were treated by intralesional injection of a C. parvum suspension. Treated papillomas were biopsied at various stages of regression. Tissue samples were subjected to immunohistochemical staining to identify specific infiltrating cells. Results showed that intralesional administration of C. parvum was capable of inducing regression of bovine papillomas in 8-15 weeks. Immunological staining revealed that regression was associated with an increased number of CD8+ and gamma delta+ cells in the dermis, as well as a marked infiltration of neutrophils.

Adjuvants, Immunologic↗
PubMed1983

Immunoprophylaxis of an ocular solid malignant tumor in cattle.

Individual Hereford cows bearing benign precursor lesions of ocular squamous cell carcinoma were treated by intralesional injection of mycobacterial cell walls in an oil-in-water emulsion in an attempt to interrupt neoplastic progression. Thirty-one months after treatment, statistical analysis of data indicated that intralesional BCG cell wall vaccine can interrupt this process and provides effective immunoprophylactic prevention of malignant disease.

Animals↗
PubMed1981

Multiple cutaneous malignant melanomas with features of primary melanoma.

A case report and review of the literature regarding multiple primary melanomas, and a discussion of the histologic differentiation between cutaneous primary melanomas and dermal metastases are presented. This report concerns a patient who, following wide surgical resection of a 1.3 mm thick primary melanoma with satellite lesions, developed eight additional primary lesions and more than 50 dermal metastases. The primary nature of the lesions was confirmed by detailed pathologic study. The patient was rendered free of disease over a two-year period of intralesional injection of Bacillus Calmette-Guerin (BCG) and purified tuberculin protein. This was accompanied by substantial improvement in immune function tests. Although this patient represents an uncommon clinical entity, treatment results suggest that aggressive intralesional immunotherapy may complement surgical resection in achieving successful palliation of patients with multiple primary melanomas.

BCG Vaccine↗
PubMedDate not supplied

Lack of toxicity of EGFR antisense gene therapy.

PURPOSE: EGFR is overexpressed in many human cancer cells, including head and neck squamous cell carcinoma (HNSCC). We have previously shown that elevated EGFR levels in the primary HNSCC tumor are associated with decreased survival. Reduction of EGFR tumor expression levels using an antisense EGFR sequence under the control of the U6 small nuclear RNA promoter abrogates tumor growth in a head and neck xenograft model. In support of a phase I clinical trial of an EGFR antisense gene-liposome complex administered to HNSCC patients, we conducted a series of studies to evaluate the safety of intralesional injections of EGFR liposomal antisense gene therapy in normal mice. METHODS: Three dose tiers were examined including the starting DNA-lipid dose for the clinical trial. RESULTS: Tissues and blood were harvested from mice treated with the liposome-mediated gene therapy and control mice at several time points for analysis. In this dosing range, administration of the antisense EGFR DNA-liposome complex had no apparent adverse effect on renal, hepatic and hematologic parameters studied. No major organ pathologic changes were observed. CONCLUSIONS: These results suggest that the toxicity of intralesional EGFR antisense DNA plus liposomes is restricted to a self-limited inflammation at the injection site, and may be well-tolerated in the clinical setting. EGFR antisense gene therapy was reviewed by the Recombinant DNA Advisory Committee and the Food and Drug Administration, and a phase I clinical trial is currently underway in patients with advanced HNSCC.

Animals↗
PubMed2003

Intratumoral delivery of dendritic cells engineered to secrete both interleukin (IL)-12 and IL-18 effectively treats local and distant disease in association with broadly reactive Tc1-type immunity.

Dendritic cells (DCs) were adenovirally engineered to constitutively and durably secrete the potent Th1-biasing cytokines interleukin (IL)-12 (AdIL12DC) and/or IL-18 (AdIL18DC) and evaluated for their ability to promote therapeutic antitumor immunity in murine sarcoma models. Injection of either AdIL12DC or AdIL18DC into day 7 CMS4 or MethA tumors resulted in tumor rejection or slowed tumor growth when compared with control cohorts. Importantly, intratumoral injection with DCs engineered to secrete both IL-12 and IL-18 (AdIL12/IL18DC) resulted in complete and the most acute rejection of any treatment group analyzed. This strategy was also effective in promoting the regression of contralateral, untreated tumors. Both CD4+ and CD8+ T cells were required for tumor rejection. CD8+ splenic T cells from mice treated with AdIL12/IL18DC produced the highest levels of IFN-gamma in response to tumor rechallenge in vitro and displayed the broadest repertoire of Tc1-type reactivity to acid-eluted, tumor-derived peptides among all treatment cohorts. This apparent enhancement in cross-presentation of tumor-associated epitopes in vivo may result from the increased capacity of engineered DCs to kill tumor cells, survive tumor-induced apoptosis, and present immunogenic MHC/tumor peptide complexes to T cells after intratumoral injection. In support of this hypothesis, cytokine gene-engineered DCs expressed higher levels of MHC and costimulatory molecules, as well as Fas ligand and membrane-bound tumor necrosis factor alpha, with the latter markers associated with elevated tumoricidal activity in vitro. Cytokine gene-engineered DCs appeared to have a survival advantage in situ when injected into tumor lesions, to be found in approximation with regions of tumor apoptosis, and to have the capacity to ingest apoptotic tumor bodies. These results support the ability of combined cytokine gene transfer to enhance multiple effector functions mediated by intralesionally injected DCs that may concertedly promote cross-priming and the accelerated immune-mediated rejection of tumors.

Adenoviridae↗
PubMed2006

Localized Kaposi's sarcoma in a patient with pemphigus vulgaris.

We report the case of a patient with a 13-year history of pemphigus vulgaris (PV) treated with immunosuppressive agents, prednisone and mycophenolate mofetil who had developed lesions of Kaposi's sarcoma (KS) on a sole plaque of PV that had been previously treated with intralesional injections of steroids. The lesions were surgically removed and polymerase chain reaction (PCR) demonstrated human herpesvirus-8 (HHV-8) DNA. There were neither recurrences nor later dissemination of KS following gradual decrease of the immunosuppressive therapy. We suggest that the treatment with intralesional steroids may have influenced the local reactivation of a latent infection of the virus, determining the appearance of this localized KS.

Aged↗
PubMed1997

Genetically regulated response to intravesical bacillus Calmette Guerin immunotherapy of orthotopic murine bladder tumor.

PURPOSE: Genetically regulated host response to intravesical Bacillus Calmette Guerin (BCG) immunotherapy was assessed using the murine bladder tumor MM45T in Bcgr and Bcgs inbred congenic strains of mice. MATERIALS AND METHODS: Tumor detection and monitoring of treatment response to BCG was carried out using magnetic resonance imaging (MRI) of BALB/c (Bcgs allele) and BALB/c. CD2 (CD2) (Bcgr allele) mice implanted orthotopically with MM45T tumor cells. Intravesical BCG instillation (3 doses per week for 3 weeks) was used as prophylaxis against tumor implantation in both Bcgr and Bcgs strains and as definitive treatment against MRI-confirmed established tumors. Tumors implanted in both strains of untreated mice served as controls. Intravesical injection of BCG was also performed in established heterotopic subcutaneous tumors in both strains. Immunologic response in all groups was assessed by flow cytometric analysis of the bladder irrigation fluid cell composition, measuring CD4+ (helper/inducer) and CD8+ (cytotoxic/ suppressor) cell subsets. RESULTS: Intralesional injection of BCG into established heterotopic tumors showed growth inhibition in the Bcgs strain but not in the Bcgr strain. Intravesical BCG treatment against established orthotopic tumors showed significant tumor regression in the Bcgs strain compared to control but there was no effect in the Bcgr strain. CONCLUSION: The differential anti-tumor activity of BCG in the Bcgs and Bcgr congenic murine strains supports the notion that Bcg gene-controlled responsiveness to BCG innoculation determines, at least partially, the host response to immunotherapy. These results have potential clinical significance in patient selection for intravesical therapy for bladder cancer.

Adjuvants, Immunologic↗
PubMed2003

Late-onset granulomatous reaction to Artecoll.

BACKGROUND: Artecoll is permanent filler that is used for the correction of facial wrinkles. It has been used mainly in Europe in the last 9 years. It is a suspension of 25% polymethylmethacrylate microspheres of 30 to 40 microns in diameter and 75% athecollagen. OBJECTIVE: To report a side effect of a late-onset granulomatous reaction to Artecoll. METHODS: We report the case of a 54-year-old woman who presented with longitudinal hard nodules with slight overlying erythema in the glabella and nasolabial folds 14 months after she was treated with Artecoll injections to her glabellar and nasolabial wrinkles. An excisional biopsy of a glabellar nodule was performed. RESULTS: Microscopic examination of hematoxylin and eosin-stained specimen revealed histiocytic granulomas with giant cells and vacuoles, a picture of Artecoll granulomas. Treatment with topical steroids showed no improvement. Intralesional injections of Kenalog caused temporary disappearance of the granulomas. A few months later the nodules reappeared. No further treatment was done. CONCLUSION: Artecoll injection to wrinkles of the face can cause delayed granulomatous reaction. This side effect is not reversible and should be addressed in the informed consent.

Collagen↗
PubMed2003

Antineoplastic activity of honey in an experimental bladder cancer implantation model: in vivo and in vitro studies.

OBJECTIVES: The antitumor effect of bee honey against bladder cancer was examined in vitro and in vivo. METHODS: Three human bladder cancer cell lines (T24, 253J and RT4) and one murine bladder cancer cell line (MBT-2) were used in these experiments. In an in vitro study, the antitumor activity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay, 5-Bromodeoxyuridine (BrdU) labeling index and flowcytometry (FCM). In the in vivo study, cancer cells were implanted subcutaneously in the abdomens of mice, and the effects were assessed by the tumor growth. RESULTS: In vitro studies revealed significant inhibition of the proliferation of T24 and MBT-2 cell lines by 1-25% honey and of RT4 and 253J cell lines by 6-25% honey. BrdU labeling index was significantly lower. FCM showed lower S-phase fraction, as well as absence of aneuploidy compared with control cells. In the in vivo studies, intralesional injection of 6 and 12% honey as well as oral ingestion of honey significantly inhibited tumor growth. CONCLUSION: Bee honey is an effective agent for inhibiting the growth of T24, RT4, 253J and MBT-2 bladder cancer cell lines in vitro. It is also effective when administered intralesionally or orally in the MBT-2 bladder cancer implantation models. Our results are promising, and further research is needed to clarify the mechanisms of the antitumor activity of honey.

Administration, Intravesical↗
PubMed1978

Severe complications of intralesional BCG therapy in an unsensitized patient. Case report and clinical implications.

Since the introduction of BCG intralesional immunotherapy for melanoma, severe complications, including death, have been reported after treatment in hypersensitized individuals. This is a case report of BCG dissemination with ulceration, skin necrosis, lymphadenitis, and abscess formation following the first intralesional injection of a minimal dose of BCG in a PPD-negative patient. The case demonstrates that severe complications can occur in patients who are not hypersensitized, anergic, or debilitated or who have been treated multiple times. This patient's complication further suggests that migration of BCG after intralesional therapy may play a role in the regression of uninjected nodules seen in some patients.

BCG Vaccine↗
PubMed1975

Epilesional scarification. Preliminary report of a new approach to local immunotherapy with BCG.

Because of the serious toxicity of intralesionally injected BCG, including high fever, local ulceration, chronic drainage, and disseminated BCG disease, 13 patients received local BCG immunotherapy by the new approach of epilesional scarification. Three patients had complete responses, four had partial responses, and six had no response. Toxic reactions were minimal compared to those reported for intralesionally given BCG.

Adult↗
PubMed1978

Decreases in histamine forming enzyme activity of non-metastasizing fibrosarcomas in hamsters with progressive tumor growth.

A marked and progressive decrease in the activity of the histamine forming enzyme, histidine decarboxylase (HDC), of tumors was found to be associated with the progressive growth of SV-40 virus induced and transplanted syngeneic non-metastasizing fibrosarcomas in inbred LSH Syrian hamsters. Histamine forming enzyme activity was highest in the smallest tumors (p < .005) and in the tumors with the slowest growth rate (p < .005, r - 0.84). Tumor histamine forming enzyme activity was highest for each interval of animal exposure to inoculated tumor cells in those animals which had limited their tumor growth to the smallest tumor size. These findings suggested a local anti-inflammatory effect of progressive tumor growth. Induced local inflammation by repeated intratumor injections of bradykinin markedly elevated tumor histamine forming enzyme activity above expected levels for tumors of the same size in a small group of individual animals which were sampled at random from a larger group of animals which were being studied for the tumor growth kinetics effects of repeated intralesional injections of bradykinin. Tumor histamine forming enzyme activity was highest in those animals which were managed by the frequency of injection and dose schedules which were found in the tumor growth kinetics study to be most effective in limiting tumor growth. These findings suggested that the observed anti-inflammatory effects of progressive tumor growth may be reversed by locally induced inflammation at the tumor site with beneficial effects on tumor growth.

Animals↗
PubMed1987

Anti-tumor activity of recombinant mouse tumor necrosis factor (TNF) on colon cancer in rats is promoted by recombinant rat interferon gamma; toxicity is reduced by indomethacin.

The activity and toxicity of rMuTNF, alone or combined with rat recombinant interferon gamma (rRIFN gamma), was tested in inbred WAG rats bearing a weakly immunogenic colon adenocarcinoma (CC531). The tumor was implanted s.c. or under the renal capsule. A single i.v. injection of 10 micrograms of rMuTNF in non-tumor bearers was lethal in 3 to 5 hr, whereas 2 micrograms was not. Doses of 1 microgram rMuTNF were well tolerated when given daily for one week. The most prominent toxic feature was hemorrhagic colitis which could be alleviated when rMuTNF was preceded by i.p. administration of 10 mg/kg indomethacin. Three intralesional injections of 10 micrograms rMuTNF on days 0, 10 and 15 into s.c. tumors (diameter 1-1.5 cm) led to a moderate retardation of growth in 20% of the cases. Combined with 10(5) units of rRIFN gamma, which on its own had no effect, the overall response rate (arrest of tumor growth or regression) was 50%. Two out of 20 tumors treated intralesionally with rMuTNF and rRIFN gamma regressed. The subrenal capsule assay was used to study the possible interference of indomethacin with the anti-tumor activity of rMuTNF. Tumor cubes of 6-8 mg were implanted under the renal capsule; the test was evaluated by weighing. Treatment with 10 mg indomethacin alone on days 0, 2 and 4 had no effect (40 +/- 8 mg vs. 48 +/- 13 mg in controls) whereas 2 micrograms of rMuTNF on the same days resulted in significant tumor inhibition (24 +/- 7 mg, p less than 0.001). The combined administration of 2 micrograms of rMuTNF and indomethacin had an effect similar to that of rMuTNF alone (25 +/- 9 mg). Under protection of indomethacin the rMuTNF dose was increased from 2 micrograms to 10 micrograms. However, this did not lead to further improvement of the results.

Adenocarcinoma↗
PubMed1979

The effect of methanol extraction residue of BCG on the cellular immune response in patients with malignant melanoma.

Twenty-one patients with malignant melanoma stage III and IV were treated by intradermal injections of MER--methanol extraction residue of Baccillus Calmette-Guérin (BCG). Twelve of the patients, all with active disease, received chemotherapy in addition. Tests of skin reactivity to recall antigens and in vitro lymphocyte transformation by phytohemagglutinin (PHA), purified protein derivative (PPD), Canadidine, and Varidase were performed in 19 of the patients before and after the MER therapy. The skin reactivity improved in 8 patients, 5 patients maintained their cutaneous competence, 3 remained incompetent, and in 3 other patients a decrease in reactivity occurred. Improvement or maintenance of cutaneous response was more common in stage III than in stage IV patients. The in vitro lymphocyte stimulation tests have shown that reactivity increased or remained at a high level in 9 of 11 patients in stage III. It dropped or remained low in 2 patients in respect to all antigens used in spite of repeated MER injections. In most patients with stage IV disease no improvement could be detected. MER seems to be a potent immunostimulator in patients in stage III. The side effects were tolerable in all patients and consisted of local reactions and influenza-like symptoms. In 4 patients treated with MER by intralesional injections, transient flattening of nodules occurred but no complete regression was observed.

Adult↗
PubMed2002

Adrenaline plus cyanoacrylate injection for treatment of bleeding peptic ulcers after failure of conventional endoscopic haemostasis.

BACKGROUND: Endoscopic therapy is a safe and effective method for treating non-variceal upper gastrointestinal bleeding. However failure of therapy, in terms of continuing bleeding or rebleeding, is seen in up to 20%. Cyanoacrylate is a tissue glue used for variceal bleeding that has occasionally been reported as an alternative haemostatic technique in non-variceal haemorrhage. AIM: To retrospectively describe personal experience using cyanoacrylate injection in the management of bleeding ulcers after failure of first-line endoscopic modalities. PATIENTS AND METHODS: Between January 1995 and March 1998, 18 [12 M/6 F, mean age 68.1 years) out of 176 patients, referred to our Unit for non-variceal upper gastrointestinal bleeding, were treated with intralesional injection of adrenaline plus undiluted cyanoacrylate. Persistent bleeding after endoscopic haemostasis or early rebleeding were the indications for cyanoacrylate treatment. RESULTS: Definitive haemostasis was achieved in 17 out of 18 patients treated with cyanoacrylate. One patient needed surgery. No early or late rebleeding occurred during the follow-up. No complications or instrument lesions related to cyanoacrylate were recorded. CONCLUSIONS: In our retrospective series, cyanoacrylate plus adrenaline injection was found to be a potentially safe and effective alternative to endoscopic haemostasis when conventional treatment modalities fail in controlling bleeding from gastroduodenal ulcers.

Aged↗