Controlled stimulation of magnetospheric electrons by radio waves: experimental model for lightning effects.

Magnetospheric electrons precipitated by ground-based coded very low frequency radio transmissions have been detected by rocket measurement of bremsstrahlung x-rays, caused by impact of the electrons with the upper atmosphere. The direct correlations obtained between the very low frequency signals and the x-rays demonstrate the limits of sensitivity required and indicate that this remote sensing technique would be useful for future study of very low frequency effects induced by single lightning strokes.

Evaluating feasibility of an automated 3-dimensional scanner using Raman spectroscopy for intraoperative breast margin assessment.

Breast conserving surgery is the preferred treatment for women diagnosed with early stage invasive breast cancer. To ensure successful breast conserving surgeries, efficient tumour margin resection is required for minimizing tumour recurrence. Currently surgeons rely on touch preparation cytology or frozen section analysis to assess tumour margin status intraoperatively. These techniques have suboptimal accuracy and are time-consuming. Tumour margin status is eventually confirmed using postoperative histopathology that takes several days. Thus, there is a need for a real-time, accurate, automated guidance tool that can be used during tumour resection intraoperatively to assure complete tumour removal in a single procedure. In this paper, we evaluate feasibility of a 3-dimensional scanner that relies on Raman Spectroscopy to assess the entire margins of a resected specimen within clinically feasible time. We initially tested this device on a phantom sample that simulated positive tumour margins. This device first scans the margins of the sample and then depicts the margin status in relation to an automatically reconstructed image of the phantom sample. The device was further investigated on breast tissues excised from prophylactic mastectomy specimens. Our findings demonstrate immense potential of this device for automated breast tumour margin assessment to minimise repeat invasive surgeries.

Ductal lavage for detection of cellular atypia in women at high risk for breast cancer.

BACKGROUND: Breast cancer originates in breast epithelium and is associated with progressive molecular and morphologic changes. Women with atypical breast ductal epithelial cells have an increased relative risk of breast cancer. In this study, ductal lavage, a new procedure for collecting ductal cells with a microcatheter, was compared with nipple aspiration with regard to safety, tolerability, and the ability to detect abnormal breast epithelial cells. METHODS: Women at high risk for breast cancer who had nonsuspicious mammograms and clinical breast examinations underwent nipple aspiration followed by lavage of fluid-yielding ducts. All statistical tests were two-sided. RESULTS: The 507 women enrolled included 291 (57%) with a history of breast cancer and 199 (39%) with a 5-year Gail risk for breast cancer of 1.7% or more. Nipple aspirate fluid (NAF) samples were evaluated cytologically for 417 women, and ductal lavage samples were evaluated for 383 women. Adequate samples for diagnosis were collected from 111 (27%) and 299 (78%) women, respectively. A median of 13,500 epithelial cells per duct (range, 43-492,000 cells) was collected by ductal lavage compared with a median of 120 epithelial cells per breast (range, 10-74,300) collected by nipple aspiration. For ductal lavage, 92 (24%) subjects had abnormal cells that were mildly (17%) or markedly (6%) atypical or malignant (<1%). For NAF, corresponding percentages were 6%, 3%, and fewer than 1%. Ductal lavage detected abnormal intraductal breast cells 3.2 times more often than nipple aspiration (79 versus 25 breasts; McNemar's test, P<.001). No serious procedure-related adverse events were reported. CONCLUSIONS: Large numbers of ductal cells can be collected by ductal lavage to detect atypical cellular changes within the breast. Ductal lavage is a safe and well-tolerated procedure and is a more sensitive method of detecting cellular atypia than nipple aspiration.

Tumor-associated antigen TA90 immune complex assay predicts recurrence and survival after surgical treatment of stage I-III melanoma.

PURPOSE: Immune complexes (IC) containing the tumor-associated antigen TA90 can be identified in the sera of melanoma patients. We have shown that an enzyme-linked immunosorbent assay for TA90-IC can detect subclinical metastasis before surgical treatment of early-stage melanoma. We assayed the TA90-IC levels of postoperative sera from patients with melanoma and evaluated their relationship to recurrence and survival. PATIENTS AND METHODS: Multiple archival serum samples prospectively collected during postoperative surveillance of 166 patients with American Joint Committee on Cancer stage I, II, or III melanoma were analyzed for TA90-IC in a blinded fashion. Results were correlated with disease recurrence and survival determined by database and chart review. RESULTS: TA90-IC status in the early postoperative period was strongly correlated with survival. Five-year overall survival rates were 84% for TA90-IC-negative patients and 36% for TA90-IC-positive patients (P =.0001). Respective 5-year disease-free survival rates were 74% and 24% (P =.0001). The TA90-IC assay was a significant predictor of survival for both stage II and III patients. Multivariate analysis identified TA90-IC status as the strongest independent prognostic factor for both overall and disease-free survival. The TA90-IC assay was elevated in 54 (77%) of 78 patients who developed recurrent disease, becoming positive 19 +/- 7 months before clinical evidence of recurrence. Overall, the assay detected recurrence with a sensitivity of 78% and specificity of 77%. Exclusion of patients receiving postoperative immunotherapy with a polyvalent melanoma cell vaccine increased sensitivity and specificity to 92% and 86%, respectively. CONCLUSION: The TA90-IC assay can accurately predict survival and detect the presence of subclinical disease after surgery for melanoma, which should be useful in selecting patients for adjuvant therapy. Because the TA90-IC assay detected recurrence on an average of 19 months sooner than did routine clinical and radiographic evaluation, it may allow more timely therapeutic interventions.

Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer.

PURPOSE: Immediate complete axillary lymphadenectomy (ALND) after sentinel lymphadenectomy (SLND) has confirmed that tumor-negative sentinel nodes accurately predict tumor-free axillary nodes in breast cancer. Therefore, we hypothesized that SLND alone in patients with tumor-negative sentinel nodes would achieve axillary control, with minimal complications. PATIENTS AND METHODS: Between October 1995 and July 1997, 133 consecutive women who had primary invasive breast tumors clinically

Pharmacological characterization of high affinity choline transporters in primary neuronal cultures in rat brain.

High affinity transport of choline was investigated kinetically and pharmacologically in primary neuronal cultures and synaptosomes of the brain of the rat. Both preparations took up and acetylated [3H]choline in a similar high affinity, sodium-dependent manner. However, monoethylcholine mustard aziridinium ion (AF64A) (an irreversible inhibitor and potential neurotoxin) and hemicholinium-3 (a reversible inhibitor) were much less potent in the neuronal cultures than in synaptosomes. Antibodies, highly selective for ubiquitin, and able to block synaptosomal synthesis of acetylcholine, coupled to high affinity transport of choline had no effect of the synthesis of acetylcholine in intact cultured neurons, suggesting differential post-translational modification of the transporters in these two preparations.

Ketorolac prevents postoperative small intestinal ileus in rats.

The effect of ketorolac, a parenterally administered, nonsteroidal anti-inflammatory drug, was examined in a rat model of postoperative ileus. Small intestinal transit was measured by calculating the geometric center (GC) of distribution of 51CrO4. Laparotomy significantly delayed transit (GC: 2.2 +/- 0.2 after laparotomy versus 5.6 +/- 0.5 for unoperated controls, p < 0.01). The administration of ketorolac (1 mg/kg) improved the GC to 5.2 +/- 0.2 (p < 0.01), indicating normal intestinal transit after surgery in ketorolac-treated animals. Small intestinal myoelectric activity was recorded in rats with implanted electrodes. Animals treated with saline 2 hours postoperatively did not show return of the migrating myoelectric complex (MMC) in 183 +/- 25 minutes. In contrast, rats receiving ketorolac postoperatively had return of MMC activity in 59 +/- 18 minutes (p < 0.01). Preoperative ketorolac treatment reduced the duration of MMC inhibition after surgery from 197 +/- 55 minutes to 13 +/- 5 minutes (p < 0.05) when compared with saline. In summary, ketorolac hastens the return of MMC activity when given postoperatively. When ketorolac is administered preoperatively, it completely prevents the delay in intestinal transit and the inhibition of myoelectric activity seen in postoperative ileus. We concluded that ketorolac may be of benefit in the prevention and treatment of postoperative ileus.

Sentinel lymph node detection and microstaging in vulvar carcinoma.

OBJECTIVE: To determine the efficacy of using complementary techniques for detecting sentinel lymph nodes (SLNs) in vulvar carcinoma and to evaluate the utility of microstaging techniques. STUDY DESIGN: Patients with invasive vulvar carcinoma underwent sentinel lymph node detection (SLND) using preoperative lymphoscintigraphy, intraoperative isosulfan blue dye injection and an intraoperative hand-held gamma-detecting probe. Eleven patients were included and a total of 16 groins evaluated. Sentinel nodes identified were excised, bisected and examined in surgical pathology using hematoxylin and eosin (H&E) staining. Pathologically negative SLNs were subjected to additional microstaging via serial sectioning and immunohistochemical staining for cytokeratin. Surgical management of the vulvar cancer and extent of inguinal-femoral lymphadenectomy were individualized based on clinicopathologic parameters, including depth of invasion, location of the tumor and patient performance status. RESULTS: Lymphoscintigraphy, dye and gamma-detector methods led to the total detection of 16, 19 and 17 SLNs, respectively. In two cases the isosulfan blue dye assisted in the isolation of an additional sentinel node over that of the gamma probe. Each method individually identified SLNs in 10/11 patients (91%). A total of 19 sentinel nodes were isolated. One SLN (5%) was positive for metastatic disease using H&E staining. Of the 18 negative SLNs, 2 (11%) had micrometastases (< 0.2 mm) upon serial sectioning and immunohistochemical staining. CONCLUSION: Combined-modality mapping enhances detection of SLNs in vulvar carcinoma. Histologic microstaging improves the detection of micrometastases within SLNs.

Use of hyperthermia and radiotherapy in treatment of a large mast cell sarcoma in a dog.

A large infiltrating mast cell sarcoma in a dog, which had been refractory before surgical excision, was controlled 2 months after completion of a combined radiotherapy and hyperthermia regimen. Treatment resulted in rapid tumor necrosis and resultant ulceration of adjacent skin. Ulceration was transient, resolving concurrently with tumor control. Radiation was administered as 3.5-Gy fractions 3 times/week, resulting in a total dose of 45.5 Gy in 13 treatments. Hyperthermia (44 C for 30 minutes) was given 4 to 5 hours after radiotherapy, once a week during the first 3 weeks of treatment.

Observation of radio-wave-induced red hydroxyl emission at low altitude in the ionosphere.

We report the discovery of radio-wave-induced red emission of OH Meinel rotation-vibrational bands at 629.79 nm. These are the first measurements of artificial aurora below 100 km. We believe that the 629.79-nm OH emission was due to radio-wave focusing by sporadic ionization clouds near 80-85 km altitude, thus giving a technique to visualize the low-altitude sporadic ionization and providing insight into ionospheric interactions at these low altitudes.

Lymphatic mapping and sentinel lymphadenectomy for melanoma.

Intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) for patients with clinical Stage I melanoma was developed to determine the tumor status of the regional lymphatic basin without elective regional node dissection. Only individuals with histologically confirmed sentinel node (SN) metastases undergo complete regional node dissection, sparing those with tumor-free SN the morbidity of this procedure. Studies worldwide have confirmed the validity of the SN concept and the accuracy of SLND as a staging procedure. The incidence of false-negative SN and the rate of recurrence in the regional node basin have been low. Routine preoperative lymphoscintigraphy and refinements in surgical technique have improved the accuracy of SLND for melanoma, making it the nodal staging procedure of choice when undertaken by an experienced nuclear medicine physician, surgical oncologist and pathologist. Ongoing studies are investigating the impact of SLND on survival as well as the prognostic significance of micrometastasis detected by histopathologic and molecular techniques.

Two-dimensional spectral analysis of mesospheric airglow image data.

A technique to analyze short-period (<1 hour) gravity wave structure in all-sky images of the airglow emissions is described. The technique involves spatial calibration, star removal, geographic projection, regridding, and flat fielding of the data prior to the determination of the horizontal wave parameters (wavelength, velocity, and period), by use of standard two-dimensional Fourier analysis techniques. The method was developed to exploit the information that is now available with wide-field solid state imaging systems. This technique permits interactive and quantitative investigations of large, complex data sets. Such studies are important for investigating gravity wave characteristics, their interaction with the airglow emissions, and their geographic and seasonal variability. We study one event of this type here and present possible evidence of a nonlinear wave-wave interaction in the upper atmosphere.

Update on active specific immunotherapy with melanoma vaccines.

Although a randomized clinical trial has yet to show a statistically significant improvement in the survival of patients receiving vaccine therapy for malignant melanoma, several studies have shown enhanced survival of patients developing an immune response to a melanoma vaccine. The knowledge and techniques of modern molecular biology and immunology suggest multiple strategies to augment this response. The challenge of immunotherapy research is to determine which combination of approaches leads to a favorable clinical response and how to monitor that response effectively. This review identifies components of a successful vaccine, discusses new ways to modulate and stimulate the immune system, and summarizes some of the more interesting clinical trials of melanoma vaccine immunotherapy.

Overview of melanoma vaccines: active specific immunotherapy for melanoma patients.

Although a phase III trial has yet to show a statistically significant improvement in the disease-free or overall survival of melanoma patients receiving vaccine therapy, several phase II trials have shown enhanced disease-free and overall survival of patients who develop a humoral and/or cellular response to a melanoma vaccine. The challenge of active specific immunotherapy research is to determine which combination of humoral and cellular immune responses optimizes clinical outcome and how to monitor the immune response effectively. This review identifies key components of a successful melanoma vaccine, discusses new ways to modulate and stimulate the immune system, and summarizes some of the important clinical trials of active specific immunotherapy for patients with melanoma.

Vasoactive intestinal peptide and substance P receptor antagonists improve postoperative ileus.

Octreotide, a somatostatin analogue that inhibits the release of most gut peptides, hastens the resolution of experimental postoperative ileus, suggesting that gut peptides mediate this process. We studied the role of two gut peptides involved in the control of normal gut motility, vasoactive intestinal peptide (VIP), and substance P (SP), in the initiation and maintenance of postoperative small bowel ileus in rats by preoperative administration of VIP and SP receptor antagonists, (VIP-ra and SP-ra). Thirty male Sprague-Dawley rats (300-350 g) underwent laparotomy. One half underwent placement of a duodenal catheter for transit studies while the other half had serosal electrodes placed on the proximal jejunum for myoelectric recordings. Six days later, animals were separated into three treatment groups of five each. Control animals were pretreated with ip saline, while the others received either VIP-ra or SP-ra prior to standardized laparotomy. Following abdominal closure, [Na51]CrO4 was injected into the duodenum and the animals were sacrificed 25 min later. The small bowel was then excised and divided into 10 equal segments. Small bowel transit was calculated as the geometric center of [Na51]CrO4 distribution. The interval until the return of migrating myoelectric complexes (MMCs) was determined in animals with intestinal electrodes. VIP-ra-treated rats demonstrated a 67% improvement in the geometric center of radiolabel relative to controls and SP-ra-treated rats had a 23% improvement (3.67 +/- 0.06 VIP-ra vs 2.69 +/- 0.09 SP-ra vs 2.20 +/- 0.09 control, P < 0.01). MMCs returned 180 +/- 17 min in controls vs 99 +/- 14 min in VIP-ra-treated rats (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection as a therapeutic procedure for early-stage melanoma.

BACKGROUND: Lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection (LM/SL/SCLND) is an increasingly popular alternative to elective lymphadenectomy (ELND) for patients with early-stage melanoma. Although several reports have demonstrated the accuracy of the LM/SL technique, there are no data on its therapeutic value. METHODS: We performed a matched-pair statistical analysis of 534 patients with clinical stage I melanoma; one half of the patients were treated with LM/SL and the other half were treated with ELND. Patients in the two treatment groups were matched for age (54% were < or =50 years of age), gender (63% were male patients), site of the primary melanoma (49% were on the extremities, 36% on the trunk, and 15% on the head and neck), and thickness of the primary melanoma (7% were < 0.75 mm, 42% between 0.75 and 1.5 mm, 43% between 1.51 and 4.0 mm, and 8% > 4 mm). Patients in the LM/SL group underwent complete regional lymphadenectomy (SCLND) only if the LM/SL specimen contained metastatic melanoma. RESULTS: The overall incidences of nodal metastases were no different (P = .18) between LM/SL (15.7%) and ELND (12%) groups, but the incidence of occult nodal disease was significantly (P = .025) higher among patients with intermediate-thickness (1.51-4.0-mm) primary tumors who underwent LM/SL (23.7%) instead of ELND (12.2%). Survival data were compared by the log-rank score test. LM/SL/SCLND and ELND resulted in equivalent 5-year rates of disease-free survival (79 +/- 3.3% and 84 +/- 2.2%, respectively; P = .25) and overall survival (88 +/- 3.0% and 86 +/- 2.1%, respectively; P = .98). The LM/SL and ELND groups also exhibited similar incidences of same-basin recurrences (4.8% vs. 2.1%, P = .10, respectively) and in-transit metastases (2.6% vs. 3.8%, P = .48) after tumor-negative dissections. Patients who underwent ELND showed a higher incidence of distant recurrences (8.9% vs. 4.0%, P = .03), but this may be related to the longer follow-up period for these patients (median, 169 months), compared with the LM/SL-treated patients (45 months). Among patients with tumor-positive nodal dissections, the 5-year overall survival rates were higher, and approached significance (P = .077) for patients treated by LM/SL/SCLND (64 +/- 12%) compared with ELND (45 +/- 10%). CONCLUSIONS: These findings suggest that LM/SL/SCLND is therapeutically equivalent to ELND but may be more effective for identifying nodal metastases in patients with intermediate-thickness primary tumors.

Tumor-associated antigen TA-90 immune complex assay predicts subclinical metastasis and survival for patients with early stage melanoma.

BACKGROUND: TA-90 is a tumor-associated antigen first identified in the urine and sera of patients with metastatic melanoma. In the early stages of disease, TA-90 is present in circulating immune complexes (ICs) that may be detected with an antigen specific enzyme-linked immunosorbent assay (ELISA). In this study, the authors evaluated the efficacy of the TA-90 IC assay in detecting subclinical metastasis of early stage melanoma and predicting the survival of patients with this disease. METHODS: Archival sera were collected preoperatively from 114 patients who underwent wide excision with or without regional lymphadenectomy in the treatment of clinical Stage I melanoma. Sera were analyzed for TA-90 IC in a blinded fashion, and results were correlated with the patient's clinical course as determined by database and chart review. Subclinical metastases were considered present at the time of surgery if the lymphadenectomy specimen was pathologically positive and/or the patient subsequently developed recurrence. RESULTS: The TA-90 IC assay predicted subclinical metastasis in 43 of 56 patients (P < 0.0001), with 14 false-positive and 13 false-negative results. Sensitivity and specificity for the detection of occult metastasis were 77% and 76%, respectively. Positive and negative predictive values were 75% and 77%, respectively. Fifteen of 18 tumor positive regional lymph node basins (83%) and 34 of 46 recurrences (74%) were accurately predicted when considered independently (P < 0.004). Preoperative TA-90 IC status was also highly correlated with survival: 5-year overall and disease free survival rates were 63% and 46%, respectively, for the TA-90 IC positive group, compared with 88% and 82%, respectively, for the TA-90 IC negative group (P=0.0001). A multivariate analysis with standard prognostic variables identified preoperative TA-90 IC status as a strong, independent prognostic factor for both overall and disease free survival. CONCLUSIONS: To the authors' knowledge, TA-90 is the first tumor marker that accurately predicts subclinical metastatic disease and survival for patients with early stage melanoma. For this reason, the TA-90 IC assay has the potential to improve dramatically the prognostic evaluation of patients with this disease. Its role in postoperative risk stratification and early detection of recurrence is being evaluated in a prospective study.

Validation of the Lidar In-Space Technology Experiment: stratospheric temperature and aerosol measurements.

The Lidar In-Space Technology Experiment (LITE) was flown on STS-64 in September 1994. The LITE employed a Nd:YAG laser operating at 1064, 532, and 355 nm to study the Earth's lower atmosphere. In this paper we investigate the nighttime stratospheric aerosol and temperature measurements derived from the 532- and 355-nm channels. The observations are compared with lidar observations obtained at Arecibo Observatory, Puerto Rico, and Starfire Optical Range, New Mexico, and with balloonsondes launched from the San Juan and Albuquerque airports. The backscatter ratios derived from the LITE and Arecibo data between 15 and 30 km differ by less than 5%. The Angstrom coefficients of the stratospheric aerosols derived from the 532- and 355-nm LITE channels exhibited only slight variation in altitude. The mean value between 15 and 30 km derived from three different orbital segments at approximately 20 degrees N and 35 degrees N was 1.7. The mean standard deviation was approximately 0.3. Temperature profiles were derived from the LITE data by correcting the 355-nm channel for aerosol scattering with the 532-nm signal and an assumed Angstrom coefficient. The rms differences between the corrected profiles and the balloonsonde data were as low as 2 K in the 15-30-km height range. The results were not particularly sensitive to the choice of the Angstrom coefficient and suggest that accurate temperature profiles can be derived from the LITE data in the upper troposphere and lower stratosphere provided that the aerosol loading is light.

Endothelial-selectin ligands sialyl Lewis(x) and sialyl Lewis(a) are differentiation antigens immunogenic in human melanoma.

BACKGROUND: Sialyl Lewis(x) (sLe(x)) and sialyl Lewis(a) (sLe(a)), the endothelial-selectin ligands involved in extravasation of neutrophils and carcinomas, have been identified in human melanoma. This study explored the following issue: If these ligands are immunogenic tumor-differentiation antigens, they would be potential targets for immunotherapy because of their putative roles in extravasation and metastasis. METHODS: Using a cell-suspension enzyme-linked immunosorbent assay (ELISA), the expression of sLe(x) and sLe(a) on the surface of normal melanocytes, melanoma cells from biopsies, and cell lines (M10-v, M24, and M101) constituting melanoma cell vaccine (MCV) were quantitated. Melanoma patients were immunized with the MCV expressing these antigens. Sera of normal individuals, sera of patients, and sera that adsorbed to sLe(x) and sLe(a) were titrated for anti-sLe antibodies by ELISA to verify the immunogenicity of the ligands. RESULTS: The normal melanocytes did not express sLe(x) and poorly expressed sLe(a). Melanoma cells from tumor biopsies and MCV lines expressed both sLe(x) and sLe(a). Sialyl Le(x) was associated with glycoprotein(s) in M10-v, and sLe(a) occurred as a glycolipid moiety in M24. MCV recipients developed high titers for immunoglobulin (Ig)M but not IgG to both ligands. IgM titers to these ligands were low in normal subjects. In some of the preimmune sera of patients, the titers were threefold above normal. Six of 13 MCV recipients developed at least a twofold increase in anti-sLe titers above preimmune level after the second or third immunization. Adsorption studies suggested that both ligands were immunogenic. CONCLUSIONS: The melanoma-associated sLe(x) and sLe(a) are immunogenic neoplasm-differentiation antigens and are therefore potential targets for passive and active specific immunotherapy in the treatment of melanoma.