Biomedical subjects
Publications and source records attributed to D Lew.
Six patients who presented with unusual symptoms or uncommon ailments after a trip to a Third World country, and who were seen during the last ten years by a member of the Infectious Diseases Division, Cantonal University Hospital of Geneva, are reviewed and discussed.
We review our clinical experience with infectious sphenoid sinusitis in an effort to characterize the clinical presentation, bacteriology and associated severe complications of this frequently misdiagnosed infection.
We studied 30 patients with infectious sphenoid sinusitis (15 acute cases and 15 chronic cases) in an effort to characterize the clinical presentation, bacteriology, and associated complications of this frequently misdiagnosed infection. Severe frontal, temporal, or retro-orbital headache that radiated to the occipital regions or pain in the trigeminal (V1 to V3) distribution or both were the most prominent presenting symptoms. In acute cases, purulent exudate was frequently seen in the middle and superior nasal turbinates. Computerized axial tomography or sinus tomography and cannulation of the sphenoid sinus proved to be the most useful diagnostic studies. Organisms detected in acute cases included streptococci other than Streptococcus pneumoniae (41 per cent), Staphylococcus aureus (29 per cent), and Str. pneumoniae (17 per cent). In chronic infections, gram-negative bacilli (43 per cent) and staphylococcal species (24 per cent) were the predominant organisms. In acute disease, early diagnosis and aggressive therapy, including surgical drainage, were important. Delay in treatment was always associated with serious morbidity or mortality. Fatal complications included cavernous sinus thrombosis and bacterial meningitis.
Amydopyrine is known to cause agranulocytosis by an immunological mechanism [2]. However, pancytopenia due to amydopyrine is extremely rare and usually mild and transient [3]. This report describes a patient with severe pancytopenia presumably due to amydopyrine sensitivity. Granulocytotoxic and lymphocytotoxic antibodies were detected in the patient's serum using a 51Cr-release test.
Occurrence of immune complexes in malignant pleural effusions has been investigated by the 125I-c1q binding test. 55% of the pleural effusions had C1q binding activity levels higher than those found in transudates used as controls. The levels of C1q binding activity in effusions were significantly higher than those found in the serum of the same cancer patients. High levels of C1q binding activity were found in malignant effusion independently of type or differentiation of the tumors involved. The C1q binding material had properties of immune complexes. The levels of CH50 and C3d, i.e. the degradation product of C3, in malignant effusion were similar to those of transudates. These observations show a high incidence of immune complexes in malignant effusions and a slight activation of complement inadequate for its local consumption. The persistence in major quantity of immune complexes in malignant effusion suggests local formation or decreased clearance.
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Up to 30% of patients with advanced germ cell tumors will fail induction chemotherapy or will relapse. New agents with activity in this still potentially curable subgroup of patients are needed. Edatrexate (10-ethyl, 10-deaza-aminopterin) is a methotrexate analogue that has preclinical and clinical activity in breast, lung, and head and neck cancers, as well as in non-Hodgkin's lymphomas. A phase II trial of edatrexate in relapsed or refractory malignant germ cell tumors was conducted by the Southwest Oncology Group (SWOG). Twenty-five patients were enrolled in the trial. Edatrexate was administered intravenously at a dose of 80 mg/m2 weekly for four weeks followed by a one-week rest period. The treatment course was repeated every five weeks. Among the 23 patients evaluable for response, there were no objective responses with all patients developing progressive disease. Thirteen patients (56%) developed Grade 3-4 toxicities, predominantly stomatitis and malaise/fatigue/lethargy. One patient developed Grade 4 anemia while another developed grade 4 anemia and thrombocytopenia. No patients discontinued treatment due to toxicity nor were there any toxic deaths. Edatrexate administered in this dose and schedule has no antitumor activity and has substantial toxicity in patients with relapsed or refractory germ cell tumors.
A phase II trial of Tomudex (raltitrexed, ZD 1694), a new thymidylate synthase inhibitor, was performed in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. This trial demonstrated that Tomudex was well tolerated in this patient population. Nausea and vomiting were minimal, and hematologic toxicities were relatively infrequent. Only one patient was withdrawn from the study due to toxicity (grade 4 diarrhea). One patient exsanguinated from a rent in the carotid artery in an area of tumor involvement, and was categorized as a grade 5 toxicity. Thus 25/27 patients were able to complete at least 2 cycles of treatment. Tomudex demonstrated a 3.7% response rate (95% CI 0.1-19%), with a median survival of 6 months in this highly resistant disease population. Tomudex is not considered active enough as monotherapy for further evaluation in this disease population.
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The plasmid DNA vector pVCL-1102 containing the coding sequence for the human IL-2 gene was evaluated for expression in tumor cells in vitro and in vivo. In vitro transfection of murine B16 tumor cells with pVCL-1102 resulted in the expression of 36,000 IU (5.7 micrograms) of biologically active IL-2/10(6) cells/48 h. In vitro transfection of human tumor lines and primary cultures from human biopsies with pVCL-1102 resulted in the expression of 1,289 to 9345 IU of IL-2/10(6) cells/48 h and 30 to 794 IU of IL-2/10(6) cells/48 h, respectively. In vivo, direct intratumor injection of pVCL-1102 resulted in retention of intact plasmid DNA in the tumor tissue and IL-2 secretion by cell cultures derived from the injected tumors. Formulation of pVCL-1102 with the cationic lipid DMRIE/DOPE inhibited DNA degradation and enhanced in vivo transfection efficiency over plasmid DNA alone. Antitumor activity of the pVCL-1102/DMRIE/DOPE complex was evaluated in a B16 melanoma model in mice. An IL-2-specific effect could not be demonstrated in a subcutaneous model because the intratumor injection of plasmid DNA lacking the IL-2 coding sequence also resulted in a significant reduction in tumor volume. However, an IL-2-specific effect was observed when B16 cells were transfected in vitro prior to implantation into the mouse. Transient transfection of B16 cells with pVCL-1102 rendered the cells less tumorigenic in vivo and produced a significant reduction in tumor volume. These data demonstrate that a plasmid DNA expression vector can be used to deliver the IL-2 gene to tumor cells in vitro and in vivo, resulting in the expression of significant levels of IL-2 protein. These data also illustrate the need for the use of appropriate controls when evaluating the in vivo biological activity of plasmid DNA in murine tumor models.