Dynamics of secondary contamination from the interaction of high-power laser pulses with metal particles attached on the input surface of optical components.

We investigate the interaction of 355-nm and 1064-nm nanosecond laser pulses with nominally spherical metallic particles dispersed on the input surface of transparent substrates or high-reflectivity (HR) multilayer dielectric coatings, respectively. The objective is to elucidate the interaction mechanisms associated with contaminant-induced degradation and damage of transparent and reflective optical elements for high-power laser systems. The experiments involve time-resolved imaging capturing the dynamics of the interaction pathway, which includes plasma formation, particle ejection, and secondary contamination by droplets originating from the liquefied layer of the particle. The results suggest that HR coatings are more susceptible to secondary contamination by liquid droplets produced by the particles because of the different geometry of excitation and the location of plasma initiation. Modeling results focus on better understanding the melting of the particle surface, leading to ejections of liquid droplets and the pressure applied to the substrate, leading to mechanical damage.

Impact of laser-contaminant interaction on the performance of the protective capping layer of 1 ω high-reflection mirror coatings.

High dielectric constant multilayer coatings are commonly used on high-reflection mirrors for high-peak-power laser systems because of their high laser-damage resistance. However, surface contaminants often lead to damage upon laser exposure, thus limiting the mirror's lifetime and performance. One plausible approach to improve the overall mirror resistance against laser damage, including that induced by laser-contaminant coupling, is to coat the multilayers with a thin protective capping (absentee) layer on top of the multilayer coatings. An understanding of the underlying mechanism by which laser-particle interaction leads to capping layer damage is important for the rational design and selection of capping materials of high-reflection multilayer coatings. In this paper, we examine the responses of two candidate capping layer materials, made of SiO2 and Al2O3, over silica-hafnia multilayer coatings. These are exposed to a single oblique shot of a 1053 nm laser beam (fluence ∼10 J/cm2, pulse length 14 ns), in the presence of Ti particles on the surface. We find that the two capping layers show markedly different responses to the laser-particle interaction. The Al2O3 cap layer exhibits severe damage, with the capping layer becoming completely delaminated at the particle locations. The SiO2 capping layer, on the other hand, is only mildly modified by a shallow depression. Combining the observations with optical modeling and thermal/mechanical calculations, we argue that a high-temperature thermal field from plasma generated by the laser-particle interaction above a critical fluence is responsible for the surface modification of each capping layer. The great difference in damage behavior is mainly attributed to the large disparity in the thermal expansion coefficient of the two capping materials, with that of Al2O3 layer being about 15 times greater than that of SiO2.

NCI-Navy Medical Oncology Branch cell line data base.

The cell line data base described in this paper includes both clinical information about the patients from whom the cell lines were derived and information about the in vitro analyses performed of the cell lines. The cell line data base has evolved as a part of a systematic effort by a research group at the NCI since 1976 to generate human cell lines as biological tools to study cancer and other diseases. The cell lines were generated from clinical specimens obtained as part of a series of Institutional Review Board-approved clinical protocols. The preponderance of the data is on lung cancer cell lines, though a broad range of other cancers are represented. A bank of over 300 human cell lines including cancer cell and in some instances autologous B-lymphoblastoid cells from the NCI-VA and NCI-Navy Medical Oncology Branch are reposited at the American Type Culture Collection. The cell lines are available for the research community. The entire data base is available on the American Type Culture Collection Web Site (WWW:http:@www.atcc.org/).

Lymph node classification systems in cutaneous T-cell lymphoma. Evidence for the utility of the Working Formulation of Non-Hodgkin's Lymphomas for Clinical Usage.

BACKGROUND: This study was undertaken to compare three classification schemes used to evaluate lymph nodes (LN) obtained from patients with cutaneous T-cell lymphoma (CTCL): a modified Rappaport classification, the National Cancer Institute-Veterans Administration (NCI-VA) classification based on the relative numbers of cerebriform cells in the paracortical areas, and the Dutch classification based on the presence of cerebriform cells with large nuclei in mycosis fungoides (MF) and diffuse infiltration by cerebriform cells in Sézary syndrome. METHODS: A study set of 195 LN obtained from patients with CTCL (MF, Sézary syndrome, and nonepidermotropic T-cell lymphomas) and 14 LN from patients with benign dermatoses was reviewed independently by three groups of pathologists familiar with each classification system. RESULTS: Each classification system provided useful prognostic information. However, contrary to prior reports, no significant difference in survival was apparent in patients with uneffaced LN when classified according to the NCI-VA (LN0-2 versus LN3) or Dutch (Gr0-1 versus Gr2) ratings. In addition, all classification systems demonstrated a poor survival time associated with effaced LN. By combining results from the modified Rappaport and Dutch classifications, three prognostic groups could be identified based on cell morphology: a low-grade category with a small cell histologic subtype (median survival time, 40 months); a high-grade immunoblastic subtype (median survival time, 9 months) composed of cells with an oval nucleus containing a large, usually solitary central nucleolus; and an intermediate-grade category composed of all cases without the distinctive small cell and immunoblastic morphologies (median survival time, 26 months). CONCLUSIONS: The authors propose that clearly involved LN in CTCL can be categorized on the basis of cell morphology into prognostic groups analogous to what has been proposed for the Working Formulation for Non-Hodgkin's Lymphomas for Clinical Usage.

Effect of polysaccharide interactions on antibiotic susceptibility of Pseudomonas aeruginosa.

The relative viscosity of Pseudomonas aeruginosa alginate was shown to increase markedly when combined with mucin, Ca2+ ions and the exopolysaccharide from Pseudomonas cepacia. The presence of such a heterodisperse polysaccharide solution significantly reduced the diffusion and hence antimicrobial activity of tobramycin and to a lesser extent ciprofloxacin against Ps. aeruginosa by factors of 90 and 2.5-fold respectively over a 5 h incubation period. The clinical implications of these results are discussed in relation to cystic fibrosis.

Normal digital pressure changes following the postocclusive reactive hyperemia test.

The authors report digital pressure changes in normal subjects following the 5-min postocclusive reactive hyperemia test. This test increases the sensitivity of using toe pressures to assess the adequacy of blood flow.

Neuroendocrine differentiation in endocrine and nonendocrine lung carcinomas.

Bronchial carcinoids and small cell lung cancer (SCLC) are currently recognized as neuroendocrine (NE) neoplasms. However, non-SCLC (NSCLC) may also express NE properties. Paraffin-embedded sections of a comprehensive panel of 113 lung carcinomas were analyzed for the expression of three general markers common to all NE cells, namely, chromogranin A, Leu-7 and neuron-specific enolase (NSE), five specific NE secretory products, and four other tumor markers by immunohistochemistry using the sensitive avidin-biotinylated peroxidase technique. The authors were able to demonstrate the following: (1) most, but not all carcinoids and SCLCs expressed multiple NE markers in a high percentage of tumor cells; (2) up to a half of NSCLC cases contained small subpopulations of cells expressing NE in a high percentage of tumor cells; (2) up to half of NSCLC cases contained small subpopulations of cells expressing NE markers; and (3) occasional NSCLCs showed staining patterns indistinguishable from SCLC. Specifically, 7 of 77 NSCLCs expressed four or more NE markers. NE markers in NSCLCs were more commonly expressed in adenocarcinomas and large cell carcinomas and rarely in squamous cell carcinomas. For comparison, the mean number of NE markers expressed by all cases of NSCLC was 1.5, carcinoids 6.0, and SCLCs 3.8. Individual "marker counts" were not useful in categorizing lung tumors as carcinoids and SCLC versus NSCLC. Instead, 95% of the tumors were correctly classified, applying a statistical model created from staining indices of the three general NE markers (chromogranin A, Leu-7, NSE) and three other tumor markers (carcinoembryonic antigen, keratin, vimentin). Because NSCLCs with NE features might have different clinical characteristics than other NSCLCs, immunohistochemistry provides an effective manner to identify this biologically interesting subset of NSCLCs in routine paraffin sections.

Histopathologic classification of small cell lung cancer. Changing concepts and terminology.

Considerable attention has been devoted to the diagnosis of small cell lung carcinoma (SCLC) and its subtypes. In the literature contradictory opinions have been published concerning the clinical implications of subtyping, largely because of the different criteria used by different pathologists. This article is a consensus report by the Pathology Committee of the International Association for the Study of Lung Cancer. The following classification of SCLC is recommended: (1) Small cell carcinoma. This subtype includes most of the tumors previously included in the oat cell and intermediate subtypes. More than 90% of untreated SCLC fall into this category. (2) Mixed small cell/large cell carcinoma. This subtype, which may be associated with a poor prognosis and response to therapy, contains a spectrum of cell types ranging from typical SCLC to larger cells having prominent nucleoli and resembling large cell carcinoma. (3) Combined small cell carcinomas. Typical SCLC elements are intimately admixed with areas of differentiated squamous cell or adenocarcinoma. This simplified classification of SCLC will facilitate uniformity in the diagnosis and further our understanding of the clinical significance of the rarer SCLC with variant morphologies.

Differences between serum and urinary LH in hypergonadotropic states.

In an attempt to investigate the relationship between molecular configuration, immunoreactivity, radioligand binding, and biological activity, we compared the elution profiles of immunoreactive and radioligand receptor-active LH following gel filtration over Sephadex G-100 (1.6 X 100 cm column). Samples of sera and urinary acetone-insoluble material from normal cycling women during the LH surge (n = 4) and postmenopausal (n = 2) and castrate women (n = 2) were examined. One major peak of LH immunoreactivity was present in the sera and the urinary samples from all subjects. However, this peak of immunoreactive LH in the urinary precipitate consistently occurred 8-10 fractions later than the peak activity observed in the sera. Despite the differences in the profiles of immunoreactivity between sera and urinary precipitates, the major peak of radioligand receptor activity for LH was observed in the same fractions in all samples and corresponded to the major peak of immunoreactivity observed in the sera. Thus, binding activity was sometimes observed in urinary fractions containing little immunoreactivity for LH. Bioassay of selected fractions using the rat interstitial cell-testosterone assay revealed good agreement between receptor activity and bioactivity but not between immunoreactivity and bioactivity. The ratios of total radioreceptor-active to total immunoreactive LH were consistently higher in the sera than in the urinary precipitates. These data suggest alterations in molecular form during metabolism and/or excretion of LH. Whether these alterations represent differences in peptide structure or merely carbohydrate moieties remains to be determined.

Molecular forms of LH subunits in hypergonadotropic states.

To determine whether differences in subunits of LH exist in various hypergonadotropic states, we compared the elution profiles of immunoreactive alpha LH and beta LH following gel filtration over Sephadex G-100 (1.6 X 100 cm column) of sera and urinary acetone-insoluble precipitates from normal cycling women during the LH surge and untreated agonadal women and those receiving estrogen replacement. The elution profiles for the alpha subunit were similar in all subjects in both sera and urinary precipitates. In contrast, the elution profiles of beta LH varied between sera and urinary extracts among the 3 groups of subjects. Sera and urinary precipitates from the individual agonadal women eluted identically, but the profiles were distinct from those in samples from each of the cycling women. Exogenous estrogen therapy had no effect on the elution profiles of immunoreactive urinary beta LH in agonadal women but altered the ratios of beta LH/alpha LH excreted to those observed in normal cycling women. These data document the existence of immunoreactive subunits of LH in sera and urinary acetone-insoluble precipitates and confirm the existence of multiple forms of immunoreactive beta LH. The data further suggest that gonadal steroids may modulate the metabolism and/or excretion of beta LH in various hypergonadotropic states.

Chemotherapy alone or chemotherapy with chest radiation therapy in limited stage small cell lung cancer. A prospective, randomized trial.

STUDY OBJECTIVE: To determine the effect of concurrent chest radiation therapy on response rate, recurrence, and treatment toxicity among patients with limited stage small cell lung cancer who are receiving combination chemotherapy. DESIGN: Randomized trial with a median follow-up of 57 months. SETTING: A single government institution--the National Cancer Institute. PATIENTS: Consecutive sample of 96 patients with histologically confirmed small cell lung cancer that was confined to the hemithorax of origin or mediastinal and supraclavicular nodes, and which could be encompassed within a tolerable radiation portal ("limited stage"). All patients were followed until death or the end of the study period. INTERVENTIONS: Chemotherapy: Cyclophosphamide, methotrexate, and lomustine in 6-week cycles alternating with vincristine, adriamycin, and procarbazine in 6-week cycles, for a total of 48 weeks. Radiation therapy: Chest irradiation to 40 Gy in 15 fractions over 3 weeks, given simultaneously with the first chemotherapy cycle. MEASUREMENTS AND MAIN RESULTS: The combined therapy led to a significantly higher response rate (complete responses, 81%, compared with partial responses, 43%; 95% Cl for the difference, 20% to 56%), significantly improved local control of the chest tumor (p less than 0.001), and significantly longer survival (p less than 0.035) (median, 15.0 months, compared with 11.6 for chemotherapy alone). The combined therapy produced significantly more myelosuppression, weight loss, esophagitis, and pulmonary dysfunction. There were more infections and deaths from toxicity in the combined treatment group, but the differences between groups were not statistically significant. CONCLUSION: A regimen of combined chemotherapy and chest radiation therapy given concurrently is superior to chemotherapy given alone in inducing remission and prolonging survival in patients with limited stage small cell lung cancer, and the benefit of combined therapy is reduced by its greater toxicity.

Cytologic transformation in cutaneous T cell lymphoma: a clinicopathologic entity associated with poor prognosis.

The clinical course of cutaneous T cell lymphoma (mycosis fungoides and Sezary syndrome) is generally indolent, but in occasional patients becomes fulminant. We found that biopsies from patients with accelerating disease can reveal cytologic transformation from previously observed small, convoluted lymphocytes to large cells that are similar to cells seen in large-cell lymphoma. The cerebriform nuclei characteristic of malignant T cells can only rarely be identified. Of 150 cutaneous T cell lymphoma patients we treated from 1976 to 1984, cytologic transformation was identified in 12 after review of peripheral blood smears and biopsies from skin, lymph nodes, and visceral sites. Patients who developed cytologic transformation were initially characterized by advanced stage (11 of 12), with lymph node effacement (seven of 11) and erythroderma (five of 12). The tumor cell DNA content after transformation was aneuploid (four of four), and the ability to form rosettes with sheep erythrocytes was retained in transformed cells (three of three). The median time from diagnosis of cutaneous T cell lymphoma to cytologic transformation was 21.5 months (range, 4 to 64), and the median survival from transformation was only 2 months (range, 0 to 19+). We conclude that cytologic transformation in cutaneous T cell lymphoma represents a distinct clinicopathologic entity, characterized by an aggressive clinical course.

Non-small-cell lung cancer. Major cause of late mortality in patients with small cell lung cancer.

Among 360 patients with small cell lung cancer treated in National Cancer Institute therapeutic trials from 1973 to 1982, 40 were two-year cancer-free survivors. Of these 40 patients, six had later development of non-small-cell lung cancer at 3.5 to 8.0 years (median 5.1) after the diagnosis of small cell lung cancer. Three had the second malignant tumor in the contralateral lung, one in a different lobe, and two in the same lobe as the initial small cell lung cancer. Ten patients had relapses of small cell lung cancer at 2.1 to 6.2 years (median 3.2) from diagnosis. Three recurrences were in the same site or lobe as the initial lesion, four in the same lobe and in sites outside the thorax, and three solely in sites outside the thorax. It is concluded that these non-small-cell lung cancers usually represent second primary lung tumors and that most late small cell lung cancers represent relapses occurring up to 6.2 years from diagnosis. In this study, the risk of development of non-small-cell lung cancer after two years of disease-free survival following small cell lung cancer is 4.4 percent per person-year, approximately 10 times higher than the rate of 0.5 percent previously determined in screening studies of men at high risk for lung cancer. Non-small-cell lung cancer represents more than a third of lung cancer deaths in patients with small cell lung cancer surviving beyond two years from diagnosis and more than half of lung cancer deaths beyond three years. It is recommended that all patients treated for small cell lung cancer discontinue smoking.

Histologic assessment of lymph nodes in mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma): clinical correlations and prognostic import of a new classification system.

Mycosis fungoides and the Sézary syndrome share common cutaneous histopathologic features, and this spectrum of malignant disease is referred to here as cutaneous T-cell lymphoma (CTCL). A method (LN classification) for describing the histopathologic features of lymph nodes in CTCL is presented. In this system, lymph node biopsy specimens are scored according to the number of atypical lymphoid cells in T-cell-dependent paracortical zones and the preservation or distortion of the lymph node architecture. Lymph node architecture is preserved in lymph nodes scored LN1 to LN3, and these nodes may have coexistent dermatopathic change. LN1 nodes have single infrequent atypical lymphocytes in paracortical T-cell regions. LN2 nodes have small clusters of paracortical atypical cells. LN3 nodes have large clusters of atypical cells. LN4 nodes are partially or totally effaced by atypical cells. This system was used to classify 96 lymph node biopsy specimens obtained within six months of the initial diagnosis of CTCL; no LN1 nodes, 37 LN2, 44 LN3, and 15 LN4 nodes were found. The LN class was significantly correlated with the extent of skin, blood, and visceral involvement, as well as with survival. Patients with LN2 lymph nodes have an estimated five-year survival of 70 per cent, while patients with LN3 and LN4 nodes have estimated five-year survivals of 30 and 15 per cent, respectively. The survival differences between the LN subgroups were all significant (P less than 0.05). The LN classification system was clearly shown to be reproducible among experienced pathologists. The LN system for the histopathologic classification of lymph nodes in CTCL is of prognostic value and should be used to assess lymph node biopsies in patients with CTCL.

Patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. Data on potential cures, chronic toxicities, and late relapses after a five- to eleven-year follow-up.

We assessed the outcome in 252 patients with small-cell lung cancer 5 to 11 years after treatment with combination chemotherapy, with or without chest and cranial irradiation, in National Cancer Institute therapeutic trials from 1973 through 1978. Twenty-eight patients (11%) survived free of cancer for 30 months or more. Fourteen patients remain alive without evidence of cancer beyond 5 years (range, 6.4 to 11.3 years), and 7 patients have returned to a lifestyle similar to that before diagnosis. The other 14 patients who were cancer-free at 30 months have developed cancer or died; 6 patients had a relapse, 4 developed or died from non-small-cell lung cancer, and 4 died of unrelated causes. A few patients with small-cell lung cancer (5.6%) may be cured. Thirty-month, cancer-free survival is insufficient to show a cure. Although late toxicities are troublesome, they do not outweigh the benefits of prolonged survival and potential for cure with modern aggressive therapy in small-cell lung cancer.

Prognostic factors in patients with hepatocellular carcinoma receiving systemic chemotherapy. Identification of two groups of patients with prospects for prolonged survival.

Among 37 patients with hepatocellular carcinoma given systemic chemotherapy, 12 (32 percent) lived 14 to 37 months from initiation of treatment whereas the remainder died within five months. Individual factors associated with improved survival included fully ambulatory performance status, lack of jaundice, response to chemotherapy, the fibrolamellar carcinoma pathologic variant, absence of cirrhosis, and normal serum alpha-fetoprotein levels. Patients living longer than 12 months fell into two groups. Seven patients with fibrolamellar carcinoma lacked evidence of hepatitis B serum markers or cirrhosis and had normal alpha-fetoprotein levels and surprisingly frequent extrahepatic metastases. All but one were Caucasians aged 25 years or less. The other five "long-term" survivors were all fully ambulatory without jaundice, and the majority were older non-Caucasians with tumor confined to the liver at the time of diagnosis and with hepatitis B markers, elevated alpha-fetoprotein levels, or cirrhosis. All patients without fibrolamellar carcinoma who were less than fully ambulatory or who had jaundice died quickly. Patients with fibrolamellar carcinoma have homogeneous clinical features, and their disease follows a relatively indolent course. In other patients with hepatocellular carcinoma, assessment of ambulatory status and serum bilirubin determination can identify those with some prospect of prolonged survival.

Combination chemotherapy with doxorubicin and mitomycin C in non-small cell bronchogenic carcinoma. Severe pulmonary toxicity from q 3 weekly mitomycin C.

Forty-five patients with advanced, measurable, or evaluable non-small bronchogenic carcinoma (NSCBC) were treated with doxorubicin and mitomycin C combination chemotherapy. The first 27 patients received doxorubicin 50 mg/m2 I.V. every 3 weeks and mitomycin C 10 mg/m2 I.V. every 3 weeks. Because of severe cardiopulmonary toxicity in seven patients, with four otherwise unexplained deaths, the next 18 patients were treated with the mitomycin C dose reduced to 10 mg/m2 every 6 weeks. Overall, 11 patients (25%) responded, with one complete and 10 partial remissions. Eight responses (30%) were observed in the patients who received mitomycin C every 3 weeks and three responses (17%) were found in those given mitomycin C every 6 weeks (p less than 0.5), with no cardiopulmonary toxicity in the latter group. The median survival was 21 weeks for the entire group of patients, with the group receiving mitomycin C every 3 weeks living a median of 15.5 weeks and those given mitomycin C every 6 weeks surviving 35.5 weeks (p less than 0.025). We conclude that there is a higher tumor response rate but more cardiopulmonary toxicity and shorter survival among the group receiving mitomycin C every 3 weeks compared to those receiving mitomycin C every 6 weeks. Future studies should consider this toxicity of mitomycin C administered on an every-3-week schedule.

Diagnosis and significance of liver metastases in small cell carcinoma of the lung.

One hundred fifty-seven consecutive patients with small cell lung cancer seen at the National Cancer Institute over a four-year period underwent a series of pretherapy liver staging procedures to determine optimal means of detection and prognostic implications of hepatic metastases. Liver evaluation included physical examination, liver function tests, and liver scan (radionuclide or computerized tomography [CT]), as well as percutaneous and/or peritoneoscopy-directed liver biopsy when possible (74%). Liver metastases were detected in 26% of patients. Peritoneoscopy was the most sensitive method of liver evaluation and increased the detection of liver metastases when done in a sequential fashion after percutaneous liver biopsy from 18 to a total of 27 patients. Of the noninvasive procedures, radionuclide and CT liver scan were the most accurate concurring with liver biopsy in 87% of patients but permitting correct discrimination of stage in excess of 96% of patients. The accuracy of this noninvasive procedure was enhanced by an algorithm combining the results of radionuclide liver scan with liver function tests to detect patients with high or low likelihood of liver involvement. The survival and response of patients with liver metastases was significantly worse than those without such metastases with no three-year disease-free survivors among patients with liver metastases.