Successful management of hepatic abscesses by percutaneous catheter drainage in chronic granulomatous disease

Chronic granulomatous disease (CGD) is a disorder of polymorphonuclear leukocytes that can cause multiple recurrent hepatic abscesses in 40% of those patients with the disorder. The mortality rate from this complication of CGD is estimated at 27%. Treatment has consisted of extensive surgical debridement and drainage and prolonged antibiotic therapy; however, this approach is accompanied by high morbidity and the frequent need for reoperation. Successful percutaneous drainage of multiple hepatic abscesses in a patient who had previously undergone 10 operative procedures to manage hepatic abscesses is reported. With the development of imaging and percutaneous drainage techniques, as well as the recurrent nature of this problem, percutaneous management should be given consideration in appropriate patients with CGD with hepatic abscesses.     

Dermatologic changes associated with interleukin 2 administration

We have prospectively evaluated the skin changes that occurred in ten patients who were undergoing immunotherapy with interleukin 2 (IL-2) and autologous lymphokine-activated killer cells to treat cancer. Serial skin biopsy specimens were obtained before therapy (baseline), during IL-2 administration, and during IL-2/lymphokine-activated killer cell infusion. All patients developed an eruption that was characterized by macular erythema, with burning and pruritus of the skin. It began after two or three days of IL-2 infusion and was usually localized to the head and neck; it occasionally became generalized (ie, erythroderma). The eruption resolved with desquamation within 48 to 72 hours after cessation of infusion of IL-2. Histologically, the changes were not specific. The only consistent immunohistological finding noted was the presence of DR+/Leu-4+ lymphoid cells surrounding blood vessels in the papillary dermis, with fewer of these cells in the epidermis. There was no difference between the clinical or histological features of the eruption that occurred with IL-2 alone and that which occurred with IL-2 and lymphokine-activated killer cell infusion, suggesting that the cutaneous effects were mediated by IL-2 alone.     

Influence of complement on sperm motility

Isolated sperm from normo-, oligo- and astheno-spermic men were incubated for 20 h in medium supplemented with 8% heat-inactivated or untreated human serum, and in medium with heated or untreated serum deficient in complement factor C3. Before and after incubation, sperm motility was assessed by means of a computer-assisted semen analyser. The results did not show significant differences between the motility of sperm incubated in heated or untreated serum. It is concluded that heating of homologous serum is not necessary for preserving sperm motility and in some cases may even be disadvantageous.     

A new approach to the therapy of cancer based on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2

A new approach to cancer therapy has been developed based on the adoptive transfer of autologous lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (IL-2). Forty-one patients with advanced cancer who have failed all standard treatments were treated in this experimental protocol. Fourteen patients experienced an objective regression of cancer, including one patient with metastatic melanoma who underwent a complete regression. Objective responses were seen in patients with colorectal cancer, renal cell cancer, melanoma, and lung adenocarcinoma. The sites of tumor regression included subcutaneous tissue, lung, and liver. The major side effect of therapy resulted from the administration of high-dose IL-2 and was manifested primarily as fluid retention, resulting in a generalized capillary permeability leak syndrome. This approach to adoptive immunotherapy represents a promising approach to the therapy of patients with metastatic cancer. Attempts to increase the potency and decrease the toxicity of therapy and extend this treatment to patients with smaller tumor burdens are in progress.     

Image-directed percutaneous biopsies with a biopsy gun

Core tissue for histologic study is believed by many pathologists to be more diagnostic than material from needle aspiration. Recently, a biopsy "gun" has been introduced, which simplifies core biopsies. With this device, 182 biopsies of multiple anatomic sites were performed with ultrasonic, computed tomographic, and fluoroscopic guidance and 18-gauge needles. High-quality histopathologic specimens were obtained in 177 of the biopsies, and diagnostic target tissue was obtained in 167. Only three significant complications occurred: one bleeding complication that required transfusion and two cases of pneumothorax that necessitated placement of chest tubes. The biopsy gun eliminated the disjointed movements of conventional "skinny" needle biopsies, and none of the samples demonstrated significant "crush" artifact or obscuring blood, problems that are commonly associated with manual biopsy techniques. Patient discomfort was decreased with this system compared with that of manual biopsies, and the total procedure time was reduced. Because of these distinct advantages, the authors now use the biopsy gun exclusively for all percutaneous biopsies and recommend that other institutions consider the use of this biopsy method.     

Gene-based strategies for the immunotherapy of cancer

 T lymphocytes play a crucial role in the host’s immune response to cancer. Although there is ample evidence for the presence of tumor-associated antigens on a variety of tumors, they are seemingly unable to elicit an adequate antitumor immune response. Modern cancer immunotherapies are therefore designed to induce or enhance T cell reactivity against tumor antigens. Vaccines consisting of tumor cells transduced with cytokine genes in order to enhance their immunogenicity have been intensely investigated in the past decade and are currently being tested in clinical trials. With the development of novel gene transfer technologies it has now become possible to transfer cytokine genes directly into tumors in vivo. The identification of genes encoding tumor-associated antigens and their peptide products which are recognized by cytotoxic T lymphocytes in the context of major histocompatibility complex class I molecules has allowed development of DNA-based vaccines against defined tumor antigens. Recombinant viral vectors expressing model tumor antigens have shown promising results in experimental models. This has led to clinical trials with replication-defective adenoviruses encoding melanoma-associated antigens for the treatment of patients with melanoma. An attractive alternative concept is the use of plasmid DNA, which can elicit both humoral and cellular immune responses following injection into muscle or skin. New insights into the molecular biology of antigen processing and presentation have revealed the importance of dendritic cells for the induction of primary antigen-specific T cell responses. Considerable clinical interest has arisen to employ dendritic cells as a vehicle to induce tumor antigen-specific immunity. Advances in culture techniques have allowed the generation of large numbers of immunostimulatory dendritic cells in vitro from precursor populations derived from blood or bone marrow. Experimental immunotherapies which now transfer genes encoding tumor-associated antigens or cytokines directly into professional antigen-presenting cells such as dendritic cells are under evaluation in preclinical studies at many centers. Gene therapy strategies such as in vivo cytokine gene transfer directly into tumors as well as the introduction of genes encoding tumor-associated antigens into antigen-presenting cells hold considerable promise for the treatment of patients with cancer. Received: 20 January 1997 / Accepted: 17 February 1997     

A biologic assay for IL-4. Rapid fluorescence assay for IL-4 detection in supernatants and serum

Interleukin-4 (IL-4) is a lymphokine produced by activated T helper cells with effects on T cells, B cells, monocytes and mast cells. The conventional tonsillar B cell assay used for quantification of IL-4 activity is sensitive to the presence of other cytokines and requires the acquisition of fresh cells on a regular basis. We have evaluated the ability of IL-4 in the presence of antibody to IgM to induce CD23 on a cultured B cell line (Ramos) The requirements of measuring hundreds of samples at a single time precluded ready use of a conventional flow cytometer. We therefore developed a rapid fluorescence assay which allows the detection of IL-4 in supernatants and serum. The use of a particle fluorescence immunoassay reproducibly allows detection of IL-4 to 6 U in supernatants and serum. This assay is specific for IL-4 and is not sensitive to other recombinant cytokines including IL-1, IL-2, IL-3, IL-6; interferon-alpha, -beta or -gamma, tumor necrosis factor (TNF) or GM-CSF. Finally, in cancer patients receiving IL-4 its detection in serum using this assay reveals an alpha distribution phase of approximately 8 min and a beta clearance phase of approximately 48 min.     

Recent advances in cellular immunology: implications for immunity to cancer

Basic immunologists, animal experimenters and clinicians came together earlier this year to discuss insights into, and applications of, cellular immunity to cancer. Major questions critical to the further evaluation and exploitation of the cellular immune response to cancer were explored. It was clear from this conference that there has been a move beyond phenomenology to reductionistic approaches to understanding immune events, raising hopes that the specificity of the T-cell response might be applied to the problem of human cancer.