Phase II study of combined levamisole with recombinant interleukin-2 in patients with advanced malignant melanoma

Adoptive immunotherapy (AI) with interleukin-2 (IL-2) and lymphokine-activated killer cells (LAK) is an antineoplastic modality in which immune-activated cells are administered to a host with advanced cancer in an attempt to mediate tumor regression. Levamisole (LEV), an immune stimulant, has been suggested to have therapeutic effectiveness in a variety of cancers. After a phase I trial of recombinant IL-2 plus LEV, a phase II trial of this combination was conducted in patients with advanced malignant melanoma. Nineteen patients were entered in the trial. They received IL-2 at 3 x 10(6) U/m2 subcutaneously daily x 5 plus LEV 50 mg/ m2 orally three times daily (p.o. t.i.d.) x 5. Patients were reevaluated at four-week intervals. None of the patients achieved a partial or complete regression (PR, CR). The median time to treatment failure (refusal, progression, or off study due to toxicity) was 56 days. Grade IV toxicities included vomiting (3 patients), lethargy (1 patient), and musculoskellar pain (1 patient). This regimen is not recommended for further testing in patients with advanced malignant melanoma.     

Graham's problem on shortest networks for points on a circle

Suppose a configurationX consists ofn points lying on a circle of radiusr. If at most one of the edges joining neighboring points has length strictly greater thanr, then the Steiner treeS consists of all these edges with a longest edge removed. In order to showS is, in fact, just the minimal spanning treeT, a variational approach is used to show the Steiner ratio for this configuration is at least one and equals one only ifS andT coincide. The variational approach greatly reduces the number of possible Steiner trees that need to be considered.     

Tunneled hemodialysis catheters: use of a silver-coated catheter for prevention of infection--a randomized study

OBJECTIVE: The purpose of this study was to determine the feasibility of high-resolution sonography for the detection of meniscal cysts and associated meniscal tears and for the differentiation of meniscal cysts from other masses at the knee joint. SUBJECTS AND METHODS: Fifty consecutive patients (51 knees) with a palpable mass at the knee joint were examined prospectively using a 7.5-MHz annular array transducer. Mass consistency and location and meniscal integrity were evaluated. Sonographic findings were correlated with surgery (46/51) and histopathology (15/51). Five patients did not undergo surgery. RESULTS: At surgery, 32 masses appeared to be meniscal cysts, whereas 19 were other types of masses. Sonographically, 31 of the 32 meniscal cysts were diagnosed correctly. Sonographic differentiation of the other types of masses from meniscal cysts could reliably be made in 17 of 19 cases; two masses were falsely interpreted as meniscal cysts. Sensitivity, specificity, and accuracy of sonography in the depiction of meniscal cysts were 97%, 86%, and 94%, respectively. The positive predictive value was 94% and the negative predictive value was 92%. Meniscal tears (31/46) and meniscal tears concomitant with meniscal cysts (26/32) were detected with an accuracy of 83% and 88%, respectively. CONCLUSION: Sonography is an accurate imaging technique for the detection of meniscal cysts and associated meniscal tears. Differentiation of meniscal cysts from other cystic and solid masses at the knee joint can be reliably made with sonography.     

Percutaneous radiologic, surgical endoscopic, and percutaneous endoscopic gastrostomy/gastrojejunostomy: comparative study and cost analysis

p27kip1 (p27) protein is an inhibitor of cyclin and cyclin-dependent kinase complexes and prevents progression of cells from G1 to the S phase of the cell cycle. p27 might have tumor suppressor activity, and decreased p27 expression is associated with aggressive tumor behavior in several human malignancies. The object of this study was to evaluate p27 expression in prostatic adenocarcinoma treated by radical prostatectomy and to assess its association with numerous morphologic and clinical features. One hundred thirty-eight prostatic adenocarcinomas were evaluated for p27 expression by quantifying nuclear immunohistochemical staining. p27 expression was tested for association with patient age, family history of prostate cancer, preoperative serum prostate-specific antigen level, Gleason score, extraprostatic extension, seminal vesicle involvement, lymph node metastases, tumor-node-metastasis stage, DNA ploidy by flow cytometric analysis, and subclinical biochemical failure. p27 expression was analyzed as a continuous variable, and we also classified the tumors as low expressors (< 50% of cells p27 positive) or high expressors (> 50% of cells p27 positive) for comparison. Patients with adenocarcinomas that exhibited low p27 expression had higher mean Gleason scores than did high expressors (7 vs. 6.2, respectively; P = .002). Low p27 expression correlated with positive surgical margins (P = .05), seminal vesicle involvement (P = .007), lymph node metastasis (P = .03), and aneuploid cancers (P = .003), but it did not correlate with subclinical biochemical failure. p27 expression correlated with a number of prognostic morphologic features in prostatic adenocarcinoma, and the evaluation of p27 expression might provide additional prognostic information.     

On relaxation algorithms in computation of noncooperativeequilibria

This paper considers a special class of numerical algorithms, the so-called relaxation algorithm, for Nash equilibrium points in noncooperative games. The relaxation algorithms have been studied by various authors for the deterministic case. Convergence conditions of this algorithm are based on fixed point theorems. For example, Basar (1987) and Li and Basar (1987) have proved its convergence for a two-player game via the contraction mapping theorem. For the quadratic case these conditions can be easily checked. For other nonlinear payoff functions it is sometimes difficult to check these convergence conditions. In this paper, the authors propose an alternative approach using the residual terms of the Nikaido-Isoda function. The convergence theorem is proved for nonsmooth weakly convex-concave Nikaido-Isoda functions. The family of weakly convex-concave functions is broad enough for applications, since if includes the family of smooth functions. When the payoff functions are twice continuously differentiable, the condition for the residual terms is reduced to strict positiveness of a matrix representing the difference of the Hessians of the Nikaido-Isoda function with respect to the first and second groups of variables. An analogous condition was used by Uryas'ev (1988) to prove convergence of the gradient-type algorithm for the Nash equilibrium problem. In this paper the authors discuss only the deterministic case; nevertheless this approach can be generalized for the stochastic Nash equilibrium problems with uncertainties in parameters     

Molecular and cellular mechanism of angiotensin II-mediated apoptosis

We hypothesized that the conventional ProMACE-CytaBOM regimen could be improved by administering all drugs on d1 with the S-phase agents first in the sequence, prednisone d2-6 only, increasing doxorubicin to 50 mg/m2, and adding G-CSF d2-13 to ameliorate neutropenia. This regimen was tested in a Phase I study of 20 patients (pt) with non-Hodgkin's lymphoma (NHL). The median age was 61 yrs (range, 29-79). Four pt had low grade and 16 intermediate/high NHL. The International Prognostic Index was low in 6 cases, low-intermediate in 12, and high-intermediate in 2. Twelve pt received > or =6 cycles; 4 had 5 cycles, 3 had 4 cycles, and 1 received only 1 cycle. Sixteen pt received subsequent cycles without delay. The response rate was 95% (19/20) with 12 CR and 7 PR; one pt progressed during treatment. After a median follow-up of 30 months, 85% (17/20) remain alive. This higher dose ProMACECytaBOM regimen can be given to older adult patients in an outpatient setting. Phase III studies would be required to determine if it produces a superior overall survival compared to other regimens.     

Effect of cholera toxin on intestinal elimination of ciprofloxacin in rabbits

The transepithelial intestinal elimination of ciprofloxacin (CPX) was studied in cholera toxin (CT)-challenged and control intestinal loops in the rabbit. CPX concentrations were similar in CT-challenged and control jejunal and ileal loops, while cecal elimination was negligible. The quantities of eliminated CPX per square centimeter of bowel wall were significantly higher in the small intestine CT-challenged loops. The mechanism of elimination of CPX in the small intestine is therefore mainly passive diffusion.