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PubMed2002

CD30-positive T-cell-rich pseudolymphoma induced by gold acupuncture.

Cases of pseudolymphoma induced by intradermal gold injection or gold piercing have previously been described. Most of these cases showed the histopathological finding of B-lymphocyte predominant lymphocytoma cutis. We describe a patient with gold acupuncture-induced T-cell-rich pseudolymphoma. Some T cells showed positive staining with CD30. The lesions responded to an intralesional injection of triamcinolone acetonide.

Acupuncture Therapy↗
PubMed1977

Effect of corticosteroids on collagen synthesis.

Contraction and epithelization are two phenomena of "wound healing" retarded by corticosteroids. It is unclear how these agents affect collagen synthesis and wound remodeling. The methods used by several authors to conclude that steroids inhibit collagen synthesis are questioned. Therefore, collagen synthesis was measured in cultured steroid-treated chick embryo calvaria, 5 day open wounds in treated rats, and intralesionally injected human keloids. Collagen synthesis was suppressed only by long-term administration of massive systemic doses of a sustained release form of methylprednisolone (Depo-Medrol). Large, intermittent doses of corticosteroids (triamcinolone and Solu-Medrol) did not alter collagen synthesis. Because human keloids become softer and smaller following intralesional administration of triamcinolone without lowering the normally high rate of collagen synthesis, we hypothesize that corticosteroids enhance collagen degradation.

Animals↗
PubMed2003

Persistent replication of the modified chimeric adenovirus ONYX-015 in both tumor and stromal cells from a patient with gall bladder carcinoma implants.

PURPOSE: ONYX-015 is a chimeric, E1B-deleted adenovirus designed to replicate preferentially in p53-deficient tumor cells; however, little is understood about its actual replication potential in human tumors. We hypothesized that replication of a late viral gene, hexon, would demonstrate replication of virus in human tissues. EXPERIMENTAL DESIGN: In the course of a clinical trial, a patient with paired abdominal wall implants from a primary gall bladder carcinoma was injected with ONYX-015, 1 x 10(10) viral particles/lesion, followed by sequential excision of the lesions at 37 h and 7 days. Tissue sections were analyzed for evidence of viral replication. RESULTS: In situ Reverse transcription-PCR was used to measure expression of hexon. Strong signals were obtained in gland-forming tumor cells both at 37 h and at 7 days. Signal was predominantly observed in the cytoplasm. The signal was also observed in adjacent normal stromal cells. Analysis of p53 status of the tumor by immunohistochemistry and Affymetrix Genechip demonstrated an inactivating mutation in p53. Routine H&E staining of the tumor sections revealed no evidence of necrosis at 37 h or 7 days after injection of virus. Presence of viral protein at both 37 h and 7 days was confirmed by immunohistochemistry using antibodies directed against hexon, penton, and fiber proteins. CONCLUSIONS: Evidence for replication of hexon confirms that ONYX-015 is not only present but capable of replicating in tumor cells up to 1 week after intralesional injection and that replication is not confined to p53-mutated tumor cells.

Adenoviridae↗
PubMed1984

The clinical application of fibroblast interferon--an overview.

Preclinical as well as clinical studies with fibroblast interferon (IFN) are still lagging behind on those with leukocyte interferon. Its side-effects seem to be less pronounced than those of human IFN-alpha, yet it may be slightly pyrogenic after intravenous injection. Pyrogenicity of current impure preparations might for the larger part be due to impurities. Higher doses of HuIFN-beta than of HuIFN-alpha are required to obtain measurable blood titers by intramuscular injections. Since there is concern about this being due to destruction of the interferon before it has reached its target organ(s), most current clinical studies use either local (e.g. intratumoral) treatment or intravenous infusions. A study of topical treatment for acute rhinovirus infection has indicated that there is very little if any chance for fibroblast interferon to be a clinically useful substance to prevent or cure common cold. In herpetic dendritic keratitis eye drops of fibroblast interferon may be useful as such or in combination with debridement. Topical treatment of warts (multiple intralesional injections) has been shown to yield a high success rate, especially in the case of verrucae vulgares, but less so in the case of verrucae planae juveniles. Studies on condyloma accuminatum are not so far advanced as to permit a documented conclusion. Topical (intralesional) treatment of neoplastic diseases has been investigated, especially in Japan, to demonstrate that fibroblast interferon does have an antineoplastic effect in vivo. While there seems to be little doubt that local delivery does indeed cause tumor nodules to regress, the question is whether this procedure can offer a true clinical benefit to the patient. Systemic (intravenous) administration for chronic hepatitis B has been investigated further: given alone or in combination with adenine-arabinoside, fibroblast interferon seems to be able to reduce the level of viral activity. Whether this will lead to a generally accepted treatment of chronic active hepatitis is difficult to say at this moment. In treating herpes zoster in cancer patients, results have been obtained which are comparable to those found for leukocyte interferon. The practical significance of this finding must be seen in the perspective of recent developments in the chemotherapy of herpes zoster. In breast cancer patients given intramuscular injections, metastases in the skin, but not in other organs, showed alterations suggestive of an effect on tumor progression. Yet there was no true clinical benefit for the patient. In other tumors, e.g. head and neck epithelioma, no effect was seen.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Topical↗
PubMed1976

Phosphonoacetic acid treatment of shope fibroma and vaccinia virus skin infections in rabbits.

The antiviral efficacy of phosphonoacetic acid (PAA) was studied in localized skin lesions of rabbits produced by the intradermal inoculation of vaccinia virus (VV) and of Shope fibroma virus (SFV). Systemic administration of PAA by intraperitoneal injections had no significant effect on the pustular lesions induced by VV or on the benign skin tumors caused by SFV. A complete suppression of the appearance of VV-induced pustular lesions was achieved by 2% PAA ointment applied twice daily for 4 days, starting 24 hr after virus inoculation. A significant effect against SFV-induced tumors was obtained by PAA ointment applied beginning either 24 or 72 hr after virus inoculation. A complete suppression of SFV-induced tumors was observed when a dose of 10 mg PAA was injected intralesionally once daily for 5 days, beginning treatment 24 hr after virus inoculation. A significant reduction of the intensity of the tumors was seen following the same treatment schedule but with a delay of 72 hr after virus inoculation or by reducing the length of treatment to 3 days or with a dose of 1 mg injected intradermally daily for 5 days. After the healing of the lesions, PAA-treated rabbits were resistant to reinfections to the same extent as those in which spontaneous healing had occurred.

Acetates↗
PubMed1995

Treatment of olecranon bursitis in horses: 10 cases (1986-1993).

Medical records of 10 horses with olecranon bursitis were reviewed to examine treatments, evaluate a technique for en bloc resection of the bursa in standing horses, and determine outcome of the horses after treatment. Before admission, 6 horses had been treated by needle aspiration of fluid from the mass, followed by injection of corticosteroids. Subsequent treatment for 2 of these 6 horses included open drainage and packing of the cavity with gauze soaked in 7% iodine solution. None resolved after these treatments. After admission to the hospital, 5 horses were treated medically and 5 were treated by en bloc resection of the bursa. One horse that had received intralesional injection of a radionuclide was lost to follow-up evaluation. One horse treated conservatively by open drainage and packing and 1 treated by injection of a radionuclide had resolution of the olecranon bursitis. Only 1 of these 2 horses had a cosmetic result. The acquired bursae decreased in size in 2 horses (1 treated with a corticosteroid and 1 with orgotein), but were still visible 7 and 46 months after treatment, respectively. The surgery site of 4 horses that were treated by en bloc resection healed by primary intention, and the owners of these horses were pleased with the cosmetic results. The suture line of 1 horse dehisced 5 days after surgery. Proliferative granulation tissue was removed on 2 occasions, and the site healed by second intention after 2 months. A small knot and some white hair remained at the surgery site.

Adrenal Cortex Hormones↗
PubMed1975

Nonspecific Immunotherapy of Murine Solid Tumors With Corynebacterium granulosum.

A single intraperitoneal (ip) or intravenous (iv) injection of Corynebacterium granulosum into C3Hf/Bu mice shortly after subcutaneous (sc) injection of cells from a strongly antigenic syngeneic fibrosarcoma induced by 3-methylcholanthrene caused complete and lasting regressions of 100 and 70% of resulting tumors, respectively. Treatment with this bacterium sc only slightly inhibited the growth of some tumors. C. granulosum given iv to mice 3 days after the sc injection of fibrosarcoma cells caused complete regressions of 39 of 45 tumors; two iv injections with this immunostimulant given 1 month apart were no more effective than a single injection. Intralesional treatment of fibrosarcomas 8 mm in diameter induced complete regressions of tumors in 30% of the animals, whereas sc treatment contralateral to the growing tumor only slightly reduced tumor growth. Intraperitoneal growth of a fibrosarcoma was efficiently controlled (58-80% survival of mice) if C. granulosum was given ip, but not iv, 3 days after inoculation with tumor cells. Again, two injections of C. granulosum (given ip 4 days apart) were only as effective as a single injection. Treatment with C. granulosum iv at 3, 7, 14, or 21 days after sc inoculation of a weakly antigenic, spontaneously arising mammary carcinoma (MC-1) strongly inhibited tumor growth. Three complete but temporary tumor regressions were observed. The subcutaneous growth of another spontaneous mammary carcinoma (MC-2), which contained fairly strong tumor-specific antigen(s), was also significantly inhibited if C. granulosum was given 3,7, or 14 days after, but not 7 days before, tumor cell inoculation. However, pretreatment of mice with the immunostimulant significantly protected the mice against artifically induced pulmonary metastases of this tumor.

Animals↗
PubMed1976

Discussion paper: effect of supernatants from long-term lymphoid cell lines on metastatic cutaneous tumors following local injection.

A fraction with lymphokine properties was isolated from supernatant medium of the continuous cultured human lymphoblast cell line, 1788. Culture medium containing 2% human serum was used for cell growth in order to minimize antigenicity of supernatant fractions isolated from the medium. The culture medium was passed through an Amicon XM-100 membrane, concentrated over a PM-10 membrane, lyophilized, and reconstituted to a final concentration of approximately 40:1. Studies in vivo and in vitro showed that the active fraction contained skin reactive factor (when injected intradermally into guinea pigs and humans), lymphotoxin, migration inhibition factor, chemotactic factor, and macrophage activation factor. This same preparation, when injected intralesionally into cutaneous tumors, induced an inflammatory reaction followed by tumor regression. The fraction confined between membranes of pore size 10,000-100,000 daltons was active in promoting tumor regression, while the fraction less than 10,000 daltons was inactive. Patients with skin lesions from metastatic carcinoma of the breast and other malignancies were studied, and 16 out of 30 treated lesions were judged to have undergone either complete or greater than 50% regression. Of these, 8 were biopsied before and after lymphokine injection, and 6 out of 9 were negative for tumor cells. Additional studies in vitro with material fractionated on Sephadex G-200 indicated that the macrophage-activating component binds to alpha-2 macroglobulin in the culture medium.

Acid Phosphatase↗
PubMed2006

Treatment of cystic lymphatic vascular malformations with OK-432 sclerotherapy.

BACKGROUND: Cystic lymphatic vascular malformations are benign lesions that can cause disfigurement and functional impairment. Complete surgical resection is often difficult, and clinical recurrence is common. Sclerotherapy has been used as an alternative to excision. OK-432 is a lyophilized mixture of Streptococcus pyogenes and benzylpenicillin which, when injected into a lesion, has shown significant ability to reduce its size or obliterate it completely. METHODS: The authors report a series of 12 patients treated in this fashion at the Vascular Anomalies Clinic, British Columbia Children's Hospital, between 1999 and 2004. All patients underwent imaging of the lesion: 10 had magnetic resonance imaging, one had a computed tomographic scan, and one had ultrasound examination. Six patients had macrocystic malformations (cysts > or = 2 cm) and six had microcystic or combined lymphaticovenous malformations. Patients were treated with intralesional injection of OK-432. The position of the injection was confirmed by angiography and/or ultrasound in 10 cases. Response to treatment was assessed clinically. RESULTS: All patients with macrocystic malformations had complete resolution or good response to treatment. None required any additional treatment. In contrast, those with microcystic or combined malformations responded poorly. All of these patients underwent subsequent excision without adverse consequences. The size and location of the lesion did not correlate with response to treatment. Seventy-five percent of patients experienced pyrexia. Local swelling is an expected phenomenon and must be anticipated, particularly for lesions near the airway. CONCLUSIONS: OK-432 is an excellent treatment for patients with macrocystic lymphatic malformations. However, it is ineffective for microcystic lesions.

Child↗
PubMed2004

Efficacy of cidofovir injection for the treatment of recurrent respiratory papillomatosis.

To evaluate the efficacy of intralesional cidofovir injection for the treatment of recurrent respiratory papillomatosis (RRP). It is a prospective, open-label study design. This prospective study included 16 RRP patients, ages 9 to 68 years, who were treated with intralesional injections of cidofovir combined with surgical excision of RRP. The disease states of the patients pretreatment and posttreatment were assessed by assigning RRP severity scores, examining the need for any surgical excision of RRP, and evaluating the presence of RRP upon long-term follow-up. Sixteen patients were treated with cidofovir; however, three were lost to follow-up. Thirteen patients are the subjects of this report. This study group included three pediatric patients. Ten of thirteen patients (76.9%) responded to the treatment and are presently in remission. One patient did not respond, and two patients relapsed after initial success or had a partial response. The responders consisted of eight adults and two children. The mean number of injections the responders received was 3.5, and the average follow-up period of the responders was 25.4 months. No immediate complication of cidofovir treatment was evident. However, three patients were found to have significant vocal fold scarring after long-term follow-up. Cidofovir has been found to be efficacious in treating RRP. Further study regarding long-term follow-up and the assessment of possible side effects after cidofovir intralesional injection for RRP is required.

Adolescent↗
PubMed1979

Influence of oil concentration on the efficacy of tumor regression by emulsified components of mycobacteria.

The influence of mineral oil content on the antitumor activity of emulsified Bacillus Calmette-Guérin cell walls (CW) was studied in mice each with an established transplant of a syngeneic fibrosarcoma. Animals received intratumoral injections of CW (0.02 to 0.6 mg/mouse) emulsified in 1 to 9% oil. The number of animals in which tumor regressed completely depended on the concentration of oil in the emulsion. The methanol extraction residue (MER) of Bacillus Calmette-Guérin administered intratumorally in oil in water emulsion was also immunotherapeutically active. Neither CW nor MER was active when given as aqueous suspensions without oil. Guinea pigs with transplanted hepatomas growing in their skin and with tumor cells in the draining lymph node could be cured of malignant disease by a single intralesional injection of CW or MER (1 mg per guinea pig) if these agents were emulsified in oil (3.3%) and water. Aqueous suspensions of CW and MER were not therapeutically active in the guinea pig.

Animals↗
PubMed1979

Safety and efficacy of living BCG or BCG cell walls (CW) in the treatment of guinea pig hepatoma.

Guinea pigs with established intradermal tumors and microscopic lymph node metastases were treated by intralesional injection of graded doses of living BCG or BCG CW. The lowest dose of living BCG used produced a significant cure rate and no grossly evident toxicity. An intermediate and the highest dose of living BCG used cured some animals but others lost weight and a significant number died as a result of the treatment. Histologic examination of animals with significant weight loss showed fatty degeneration of the liver, granulomatous hepatitis and histiocytic infiltration of the spleen. None of the doses of BCG CW used was toxic and they were at least as effective as living BCG in intralesional treatment. In some experiments in which treatment was delayed it was found that the extent of disease required to render treatment ineffective was about the same for living BCG and for BCG CW.

Animals↗
PubMed2000

In vivo anti-papillomavirus activity of nucleoside analogues including cidofovir on CRPV-induced rabbit papillomas.

A series of nucleoside analogues were tested for in vivo anti-papillomavirus activity using the cottontail rabbit papillomavirus (CRPV) domestic rabbit model. Compounds were delivered either topically, injected into growing papillomas, or delivered subcutaneously at a site remote from the papillomas. Compounds tested included cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] (HPMPC); cyclic HPMPC (cHPMPC); cyclopentenylcytosine (CPE-C); lobucavir [1R(1alpha,2beta,3alpha)]-9-[2, 3-bis(hydroxymethyl)cyclobutyl]guanine; 9-((2-phosphonylmethoxy)propyl)adenine (PMPA); adefovir 9-((2-phosphonylmethoxy)ethyl)adenine(PMEA) and cyclopropyl 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (cyclopropylPMEDAP). Dose response curves and time-course treatments were included for most compounds tested. Strong anti-viral activity was detected using cidofovir and cHPMPC when delivered either topically or by the intralesional route. Complete cures were obtained using 1% (w/v) topical cidofovir at dosing schedules of twice daily for 8 weeks beginning at 4 weeks after CRPV infection, which represents a time when papillomas were clearly visible. Complete cures of large established papillomas were obtained by intralesional injection of 1% cidofovir three times per week for 8 weeks. Topical treatments with adefovir had strong anti-viral activity, cyclopropyl PMEDAP had moderate anti-viral activity, and CPE-C, PMPA and lobucavir showed no effects. These data indicate that certain nucleoside analogues have strong in vivo anti-papillomavirus activity and that the CRPV/rabbit model is a good model for assessing clinical responses of anti-viral treatments for patients with HPV disease.

Animals↗
PubMed1992

Trace amounts of murine immunoglobulin in affinity purified leukocyte interferon alpha are not immunogenic.

Human leukocyte-derived interferon alfa-n3 (Alferon N Injection) is purified to very high specific activity over a murine immunoaffinity column specific for human interferon alpha. Trace amounts of murine immunoglobulin copurify with the interferon alfa-n3. Three populations of individuals were studied for the development of human anto-murine antibodies (HAMA), that is, normal donors, Condylomata acuminata patients receiving interferon alfa-n3, and Condylomata acuminata patients receiving placebo. High and variable endogenous levels of HAMA were observed in all three populations. The same relative increase in HAMA was seen in the placebo as in the interferon alfa-n3 treatment groups. The data demonstrate that intralesional injection of the interferon alfa-n3 did not induce the development of HAMA.

Animals↗
PubMed1981

Effect of Nocardia rubra cell wall skeleton on T-cell-mediated cytotoxicity in mice bearing syngeneic sarcoma.

Cell-mediated cytotoxicity against syngeneic MC104 fibrosarcoma cells was detected in C57BL/6N mice 7 days after tumor inoculation in the hind foot. This cytotoxicity was undetectable by Day 14 in the Winn test using spleen and draining popliteal lymph node (DPLN) cells. Similar results were obtained with the 51Cr release assay following in vitro activation of these lymphoid cells with mitomycin C-treated tumor cells. The antitumor cytotoxicity was shown to be mediated by T-cells. Spleen but not DPLN cells from 14-day tumor bearers enhanced tumor growth in the Winn test, suggesting the presence of immunosuppressor cells in the spleen. Two intralesional injections of 50 microgram of cell wall skeleton (CWS) of Nocardia rubra on Days 2 and 7 resulted in apparent tumor growth inhibition and prolongation of the survival period of tumor bearers. DPLN cells from tumor bearers treated with N. rubra CWS exhibited significant recovery in the cytotoxicity tested on Day 14, whereas the recovery in that of spleen cells was not apparent. The cytotoxicity augmented by N. rubra CWS was specific to MC104 tumor cells and was shown to be mediated by T-cells. These cytotoxic T-cells were shown to be able to localize not only in DPLN but also in the spleen and tumor in mice receiving the intralesional immunotherapy with N. rubra CWS. These results suggest that T-cell-mediated cytotoxicity against syngeneic tumor can be augmented by N. rubra CWS and might play an important role in the systemic development of its antitumor effect, although the effector cell increase in the spleen might be suppressed by splenic suppressor cells during tumor growth.

Animals↗
PubMed1986

Humoral immune responses in Peyronie's disease patients receiving clostridial collagenase therapy.

Human IgG and IgE antibody responses to clostridial collagenase (Nucleolysin) were monitored in 150 untreated healthy blood donors and 44 patients receiving intrapenile injections of collagenase for treatment of Peyronie's disease. Pre, 1 and/or 2 month post treatment sera were analyzed in radioimmunoassays for human IgG and IgE antibodies using solid phase purified Cl. histolyticum collagenase to extract antibodies from serum and 125I-Protein A or rabbit anti-human IgE to detect bound IgG and IgE, respectively. IgG and IgE antibody levels greater than 2.5 Units and 0.2 per cent Bmax, respectively, were considered positive if the binding was greater than 80 per cent inhibitable with soluble collagenase. IgG anti-collagenase was detected in 34 per cent of the 150 healthy controls and 58 per cent (24/41) of untreated Peyronie's disease patients. Intralesional injection of 3,000 to 12,650 Units of collagenase induced an increase of two- to 10-fold in the IgG levels at one to two months in 88 per cent of patients. Of the 186 individuals tested, only one (0.5 per cent) had detectable collagenase-specific IgE antibody in his serum as defined by positive threshold and antigen inhibition criteria.

Adult↗
PubMed1976

Topically applied thiabendazole in the treatment of scabies.

Forty patients were treated for scabies with a 10% suspension of thiabendazole applied externally. Thirty-two patients (80%) had a satisfactory response to one course of therapy, while a second course was necessary in six (15%). Two patients (5%) required intralesional injections of triamcinolone diacetate because of persistent scabious nodules.

Administration, Topical↗