Establishment and molecular characterization of five cell lines derived from renal and extrarenal malignant rhabdoid tumors

Malignant rhabdoid tumor (MRT) is a rare, enigmatic childhood cancer characterized by extreme aggressiveness and resistance to chemotherapy. To understand better the origin of the tumor and the mechanisms by which it develops and resists treatment, five cell lines were established from patients presenting with MRT (two renal and three extrarenal tumors). All of the cell lines display the light microscopic and ultrastructural features, as well as the variable immunohistochemical profile, characteristic of MRT. All are capable of forming tumors in nude mice. Three of the cell lines have detectable abnormalities of chromosome 22: one a t(22, 22) unbalanced translocation and two others a loss of heterozygosity of polymerase chain reaction-based microsatellite markers. Northern blot analysis showed that overexpression of the c-myc message was a consistent characteristic of the five MRTs evaluated. Although mutations of the p53 gene were not detectable by sequence analysis, all of the cell lines showed nuclear accumulation of the p53 protein by an immunocytochemical analysis in a minority of the cells. This result suggests that dysfunction in a p53-dependent apoptotic pathway might play a role in the multiple drug resistance phenotype of these tumors.     

Acanthamoeba keratitis: multicentre survey in England 1992-6. National Acanthamoeba Keratitis Study Group

AIM: To investigate the frequency, outcomes, and risk factors for acanthamoeba keratitis (AK) in England during the past 4 years. METHODS: An ophthalmologist in 12 of the 14 regional health authorities (RHAs) coordinated identification of patients in their region presenting with AK between 1 October 1992 and 30 September 1996. Clinical and postal patient questionnaire data were analysed. RESULTS: 243 patients (259 eyes) with an AK diagnosis were identified, equating to an annualised incidence of 0.14 per 100,000 individuals. UK resident patients for each year numbered 50, 71, 73, and 32 respectively. Among patients with sufficient data 170/237 (72%) were diagnosed early (within 30 days of presentation), 197/218 (90%) were treated with polyhexamethyl biguanide and/or chlorhexidine, and 40/243 (16%) underwent surgery. Visual acuities of 6/12 or better were achieved by 222/259 (86%) eyes, including 84 eyes of patients under review or lost to follow up. Non-contact lens (CL) wearers were associated with delayed diagnosis, increased need for surgery and a poorer visual outcome (only 10/18 eyes, 56%, achieved 6/12 acuity). 225/243 (93%) patients were CL wearers, and 205/243 (84%) were soft CL (SCL) users. Among SCL user respondents, previously identified risk factors--swimming with CL (47/138, 34%), non-sterile CL rinsing (11/138, 8%), omitted disinfection (85/138, 62%), and chlorine release disinfection (65/138, 47%)--were identified for 125/138 (91%) patients. CONCLUSIONS: Earlier diagnosis and more effective medical therapy have improved the prognosis for most AK patients. The study demonstrates the highly preventable nature of the disease: 91% of the SCL wearers could have avoided the disease by refraining from inadvisable practices, and a marked fall in frequency was seen after intensive media attention to AK, possibly in conjunction with increasing penetrance of new CL products. Since the frequency of AK appears to be largely determined by the ever changing trends in CL use, continued monitoring is indicated.     

Differential responses to chemoimmunotherapy in patients with metastatic malignant melanoma

An open, multicentre non-randomised study was performed to evaluate the activity and toxicity of combination chemoimmunotherapy, consisting of cisplatin, interleukin-2 and interferon-alpha, in metastatic malignant melanoma. Between March 1992 and September 1993, 28 patients with pathologically proven metastatic malignant melanoma, bidimensionally measurable disease and an Eastern Co-operative Oncology Group score < or = 1 were treated with the combination chemoimmunotherapy. The regimen consisted of cisplatin (100 mg/m2 on day 0), interleukin-2 (Proleukin, Chiron, Middlesex, U.K.) 18 x 10(6)IU/m2/d continuous intravenous infusion on days 3-7 and 17-22, with interferon-alpha (Roferon-A, Roche, Hertfordshire, U.K.) 9 x 10(6) U/d subcutaneously on days 3, 5, 7, 17, 19, 21 during the interleukin-2 infusions. The treatment cycle lasted 28 days. Among 27 assessable patients, 5 patients achieved partial responses, for an overall response rate of 18% (95% CI 6-37%). Median progression-free survival was 44 days (range 8-279) and median overall survival was 264 days (range 41-1432). Differential responses were noted in 41% of patients and responses were more frequent in non-visceral disease (skin, lymph node and soft tissue disease) (P = 0.04). These results indicate that differential responses to chemoimmunotherapy are common in patients with metastatic melanoma. This may account for the broad range of response rates reported in the literature.     

Surgery for stage IIIa-N2 non-small cell lung cancer

BACKGROUND: The presence of ipsilateral mediastinal lymph node metastasis (N2 disease) in patients with non-small cell lung cancer presents a formidable challenge to the physician responsible for selecting therapy. The benefit of a surgical approach is controversial; however, it generally is agreed that only complete resection of all known tumor can provide a favorable outcome. This requires selecting patients for whom complete resection is a reasonable surgical objective. METHODS: Retrospective review of a collected data base comprising records for 2883 patients who underwent definitive surgical treatment was accomplished to emphasize the prognostic implications of regional lymph node metastasis. Patients making up the N2 subset (n = 307) were the focus of the investigation, and providing insight to the puzzle of appropriate patient selection was a major goal. RESULTS: Five-year cumulative survival rates for patients with N0, N1, and N2 disease were, respectively, 62%, 43% and 31%. Three factors significantly influenced the outcome: a complete lymph node dissection, the extent of mediastinal lymph node involvement, and apparent complete resection of all tumor. Important survival determinants were the number of nodes involved, the level of involvement (single or multiple levels), and a T1 primary tumor status. Criteria for unresectability and recommendations for patient selection were developed from (1) the end results of the study and (2) the contributions of imaging and invasive techniques to clinical staging and to the histologic verification of nodal disease.     

Identification/prediction algorithms for armax models with relaxed positive real conditions

Extended least squares (ELS) algorithms are proposed for ARMAX model identification with the objective of avoiding the positive real condition associated with standard equation error and output error algorithms. This is achieved by an overparametrization at the cost of additional richness requirements on excitation signals, but without introducing ill-conditioning or infinite-dimensional calculations as in earlier methods. Results for the case of D-step-ahead prediction ELS algorithms for ARMAX models are also explored in the paper. Some simulation studies are included to assess the relative performance characteristics of the proposed algorithms, and the nature of the relaxed positive real condition for different degrees of overparametrization N is investigated in detail for second-order noise models.     

Photographed impact of continuous fiber composites

Instrumented falling weight impact is conducted on eight different continuous carbon fiber composites. During impact, photography of the tension surface of the specimens enables crack propagation to be monitored. One photograph per specimen is taken. Measurements of integral crack length is related to corresponding absorbed energies during impact. These results enable an apparent value of G_c to be determined. These are tabulated for the eight advanced composite samples.