Surgical management of mycosis fungoides.

Mycosis fungoides (MF) is a type of cutaneous hyperproliferative T-cell disorder that may be localized. Although there is considerable controversy regarding whether MF may originate as a non-neoplastic condition, or even whether MF is a neoplastic condition until late in its course, we have seen a few cases undergo what appeared to us to be a clear progression from an inflammatory disorder to MF. We now report a 32-year-old man with MF most prominent on his right flank and buttock who developed his patches several weeks following, and in the precise locations in which he had experienced, exposure to toxic chemicals in an industrial accident. Because of this history, and because all lesions were transient except for these sites, these permanent lesions were treated with local surgical excision. There was no recurrence of disease at the treated sites, and the progression of MF markedly slowed following surgery, although he has continued to experience multi-focal transient recurrent disease, controlled by a combination of topical and systemic treatments, until the present time. Destructive methods such as excisional surgery or carbon dioxide laser may be considered a therapeutic option for localized MF.

Immunization for prevention and treatment of cocaine abuse: legal and ethical implications.

A cocaine vaccine, currently under investigation by several laboratories, would be an innovative and exciting means of treating and preventing cocaine addiction. However, an approved vaccine will raise at least two major areas of concern. (1) Loss of privacy: cocaine antibodies might be used as a marker to identify, penalize, and stigmatize vaccinated individuals. (2) Selection for vaccination: should immunization be voluntary or compelled: should immunization be restricted to addicts, to those at risk of addiction, or should it be universal; should immunization be used in children? I propose to analogize cocaine addiction to an infectious disease which poses a major public health problem. This approach can provide an ethical and legal foundation on which we may begin to formulate a societal approach to the use of the cocaine vaccine.

The quantification and distribution of nasal sebaceous glands using image analysis.

The distribution of sebaceous glands in nasal skin is of interest because the presence of these adnexal structures significantly influences the outcome of healing. Using whole nasal skins dissected from cadavers, we prepared tissue sections from the nasal bridge to the nasal tip, both from the midline and lateral aspects. The sebaceous glands in these sections were analyzed for the following parameters: (1) size of the glands, (2) width of luminal cross-sections, and (3) depth of the glands. These parameters were studied using a Leitz Quantimet 500 Plus image analyzer and software to quantify the results. We found that the superior or proximal nasal skin contains fewer, smaller, more superficially located sebaceous glands. The inferior or distal nasal skin contains increased numbers of sebaceous glands which are markedly larger in size. The glands in the distal nose have larger lumina, are situated both superficially and deep in the dermis, and also occupy a greater percentage of the dermis. We identified an anatomical breakpoint on the nasal skin, marking the transition from superficial, small sebaceous glands to superficial-and-deep, enlarged glands. The columella was found to be similar to the proximal nasal skin.

Murine epidermal Langerhans cells and splenic dendritic cells present tumor-associated antigens to primed T cells.

We examined the ability of epidermal Langerhans cells and splenic dendritic cells to present tumor-associated antigens (Ag) to immune T cells. Methylcholanthrene (MCA)-induced subcutaneous fibrosarcomas derived from C57BL/6 mice were used as tumor models. Our data demonstrate that both murine Langerhans cells and splenic dendritic cells have the capacity to present tumor-associated Ag to primed T cells. We found that variously treated tumor preparations (irradiated viable tumor cells, irradiated frozen-stored tumor cells, mitomycin C-treated viable tumor cells, and snap freeze-thawed tumor cell lysates) can be utilized for tumor Ag-pulsing. Primed CD4+ T cells demonstrated in vitro specificity towards their respective tumors and did not cross-react to other syngeneic MCA-induced or non-MCA-induced tumors. The T cell proliferative response critically depended on the presence of immune CD4+ T cells. We discuss the implications of these findings for the adoptive immunotherapy of cancer using immune CD4+ T cells.

CD4+ T-cells from mice immunized to syngeneic sarcomas recognize distinct, non-shared tumor antigens.

We have utilized a newly developed culture system to study the properties of antitumor CD4+ T-cells relevant to the rejection of syngeneic methylcholanthrene sarcomas. Fresh syngeneic dendritic cells prepared from spleen, then pulsed with crude lysates of methylcholanthrene sarcomas, evoke antigen-specific proliferation by CD4+ but not by CD8+ T-cells from tumor-immune mice. Unfractionated splenocytes display similar antigen presenting capacity if they are not irradiated before the pulse with tumor lysate. CD4+ T-cells from mice immunized to individual methylcholanthrene sarcomas proliferate cross-reactively to dendritic cells pulsed with fresh tumor digests, but not to dendritic cells pulsed with cultured tumor cells. This apparent shared recognition of sarcoma lysates was demonstrated to be a result of sensitization to bacterial collagenase during the immunization procedure. Therefore, the murine CD4+ T-cell response to tumor immunization is similar to the CD8+ response in that sensitization occurs predominantly to tumor specific transplantation antigens rather than to shared tumor antigens. Strategies to avoid artefactual tumor cross-recognition by CD4+ T-cells are discussed.

Keloidal Kaposi's sarcoma: report of three patients.

Kaposi's sarcoma is a unique neoplasm which has emerged as an important element of AIDS in homosexuals but not in others at high risk for AIDS. The biology of this important tumor may be related to cytokines secreted by HIV-infected cells and/or by Kaposi's sarcoma cells themselves. We report 3 patients with multiple keloid-like tumors. These lesions proved to be Kaposi's sarcoma histologically, yet with a unique keloidal component. This variant has not been described previously. It is possible that cytokines that stimulate Kaposi's sarcoma cell growth may also stimulate proliferation of local fibroblasts to produce this variant.

Administration of pentosan polysulfate to patients with human immunodeficiency virus-associated Kaposi's sarcoma.

BACKGROUND: Neovascularization induced by basic fibroblast growth factor (basic FGF) or FGF-like cytokines is thought to play a substantial role in the pathogenesis of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma. Pentosan polysulfate has been shown to inhibit basic FGF and FGF-like dependent tumor growth both in vitro and in vivo. Moreover, it has been found to inhibit the growth of Kaposi's sarcoma-derived spindle cells in vitro. These observations suggested that pentosan polysulfate might be worth exploring as a potential agent for the treatment of Kaposi's sarcoma. PURPOSE: The purpose of this phase 1 clinical trial was to determine the maximum tolerated dose of pentosan polysulfate in patients with HIV-associated Kaposi's sarcoma and whether or not this compound had activity against this neoplasm. METHODS: Sixteen HIV-seropositive patients with Kaposi's sarcoma received pentosan polysulfate via continuous venous infusion for 3-6 weeks and then received a subcutaneous dose three times per week. Three different doses of pentosan polysulfate were administered: 2 mg/kg per day by infusion followed by 2 mg/kg per dose given subcutaneously (six patients), 3 mg/kg per day by infusion followed by 3 mg/kg per dose given subcutaneously (five patients), and 4 mg/kg per day by infusion followed by 4 mg/kg per dose given subcutaneously (five patients). Five of the 16 patients in the study also received injections of 1 mg of pentosan polysulfate into two different lesions two times a week for 3 weeks, followed by intralesional therapy once weekly. After receiving pentosan polysulfate for 6 weeks, patients were administered 100 mg zidovudine (AZT) orally every 4 hours in conjunction with pentosan polysulfate. RESULTS: The maximally tolerated dose of pentosan polysulfate given by continuous venous infusion was found to be 3 mg/kg per day. No patient had an objective clinical antitumor response to either systemic or intralesional pentosan polysulfate administration; however, three patients had stable Kaposi's sarcoma for 3-27 weeks. No statistically significant effect on CD4 cells or serum HIV p24 antigen was noted during pentosan polysulfate administration. Dose-limiting toxic effects were characterized by anticoagulation and thrombocytopenia and were reversible. CONCLUSION: Pentosan polysulfate was well tolerated in this patient population. However, no objective tumor response or evidence of anti-HIV activity was noted; therefore, no claim of activity can be made in this trial. IMPLICATION: Continued investigation into the use of angiogenesis inhibitors with improved activity and toxicity profiles or different mechanisms of action is warranted.

Allopurinol administered prior to hepatic ischaemia in the rat prevents chemiluminescence following restoration of circulation.

Oxygen-derived free radicals produced during reperfusion may be responsible for the disturbed pathology which follows prolonged ischaemia. Measurement of hepatic chemiluminescence (low level light emission resulting from the energy released during chemical reactions of free radicals) allowed determination of whether allopurinol could prevent formation of oxygen-derived free radicals during reperfusion of the ischaemic liver. While control animals demonstrated a burst of light emission shortly after reperfusion, the rats pretreated with allupurinol showed no evidence of chemiluminescence during either ischaemia or reperfusion. It is concluded that allopurinol may modify reperfusion-induced free radical formation and possibly ameliorate the organ damage which can follow ischaemia.

Phorbol myristate acetate-induced lung injury: involvement of reactive oxygen species.

Using lucigenin-enhanced chemiluminescence, isolated rat lungs perfused with physiological salt-Ficoll solution were studied to test whether phorbol myristate acetate (PMA)-induced lung injury was mediated by reactive oxygen species (ROS). PMA (0.03 micrograms ml-1) caused small but significant increases in lung ROS levels and pulmonary arterial perfusion pressure (Ppa) but did not induce lung oedema. PMA (0.15 micrograms ml-1) induced lung oedema with large increases in ROS production and Ppa. Superoxide dismutase (SOD) inhibited the increases in ROS, Ppa, and lung oedema. Catalase and dimethylthiourea inhibited lung oedema but did not attenuate the increases in ROS and Ppa entirely. Indomethacin attenuated lung oedema partially but did not inhibit the increases in ROS and Ppa. These data indicate that PMA-induced lung injury is dependent on PMA concentration and ROS are responsible for such lung injury. Thromboxane plays a minor role for PMA-induced lung injury. The different effects of oxygen radical scavengers suggest that different radical species contribute to the increased pulmonary vascular response and lung injury.