Measurement of Heavy Ion Irradiation Induced In-Plane Strain in Patterned Face-Centered-Cubic Metal Films: An in Situ Study.

Nanocrystalline Ag, Cu, and Ni thin films and their coarse grained counterparts are patterned using focused ion beam and then irradiated by Kr ions within an electron microscope at room temperature. Irradiation induced in-plane strain of the films is measured by tracking the location of nanosized holes. The magnitude of the strain in all specimens is linearly dose-dependent and the strain rates of nanocrystalline metals are significantly greater as compared to that of the coarse grained metals. Real-time microscopic observation suggests that substantial grain boundary migration and grain rotation are responsible for the significant in-plane strain.

Damage-tolerant nanotwinned metals with nanovoids under radiation environments.

Material performance in extreme radiation environments is central to the design of future nuclear reactors. Radiation induces significant damage in the form of dislocation loops and voids in irradiated materials, and continuous radiation often leads to void growth and subsequent void swelling in metals with low stacking fault energy. Here we show that by using in situ heavy ion irradiation in a transmission electron microscope, pre-introduced nanovoids in nanotwinned Cu efficiently absorb radiation-induced defects accompanied by gradual elimination of nanovoids, enhancing radiation tolerance of Cu. In situ studies and atomistic simulations reveal that such remarkable self-healing capability stems from high density of coherent and incoherent twin boundaries that rapidly capture and transport point defects and dislocation loops to nanovoids, which act as storage bins for interstitial loops. This study describes a counterintuitive yet significant concept: deliberate introduction of nanovoids in conjunction with nanotwins enables unprecedented damage tolerance in metallic materials.

In situ study of defect migration kinetics and self-healing of twin boundaries in heavy ion irradiated nanotwinned metals.

High energy particles introduce severe radiation damage in metallic materials, such as Ag. Here we report on the study on twin boundary (TB) affected zone in irradiated nanotwinned Ag wherein time accumulative defect density and defect diffusivity are substantially different from those in twin interior. In situ studies also reveal surprising resilience and self-healing of TBs in response to radiation. This study provides further support for the design of radiation-tolerant nanotwinned metallic materials.

Elastic trapping of dislocation loops in cascades in ion-irradiated tungsten foils.

Using in situ transmission electron microscopy (TEM), we have observed nanometre scale dislocation loops formed when an ultra-high-purity tungsten foil is irradiated with a very low fluence of self-ions. Analysis of the TEM images has revealed the largest loops to be predominantly of prismatic 1/2〈111〉 type and of vacancy character. The formation of such dislocation loops is surprising since isolated loops are expected to be highly mobile, and should escape from the foil. In this work we show that the observed size and number density of loops can be explained by the fact that the loops are not isolated-the loops formed in close proximity in the cascades interact with each other and with vacancy clusters, also formed in cascades, through long-range elastic fields, which prevent the escape of loops from the foil. We find that experimental observations are well reproduced by object Kinetic Monte Carlo simulations of evolution of cascades only if elastic interaction between the loops is taken into account. Our analysis highlights the profound effect of elastic interaction between defects on the microstructural evolution of irradiated materials.

In situ study of defect migration kinetics in nanoporous Ag with enhanced radiation tolerance.

Defect sinks, such as grain boundaries and phase boundaries, have been widely accepted to improve the irradiation resistance of metallic materials. However, free surface, an ideal defect sink, has received little attention in bulk materials as surface-to-volume ratio is typically low. Here by using in situ Kr ion irradiation technique in a transmission electron microscope, we show that nanoporous (NP) Ag has enhanced radiation tolerance. Besides direct evidence of free surface induced frequent removal of various types of defect clusters, we determined, for the first time, the global and instantaneous diffusivity of defect clusters in both coarse-grained (CG) and NP Ag. Opposite to conventional wisdom, both types of diffusivities are lower in NP Ag. Such a surprise is largely related to the reduced interaction energy between isolated defect clusters in NP Ag. Determination of kinetics of defect clusters is essential to understand and model their migration and clustering in irradiated materials.

Removal of stacking-fault tetrahedra by twin boundaries in nanotwinned metals.

Stacking-fault tetrahedra are detrimental defects in neutron- or proton-irradiated structural metals with face-centered cubic structures. Their removal is very challenging and typically requires annealing at very high temperatures, incorporation of interstitials or interaction with mobile dislocations. Here we present an alternative solution to remove stacking-fault tetrahedra discovered during room temperature, in situ Kr ion irradiation of epitaxial nanotwinned Ag with an average twin spacing of ~8 nm. A large number of stacking-fault tetrahedra were removed during their interactions with abundant coherent twin boundaries. Consequently the density of stacking-fault tetrahedra in irradiated nanotwinned Ag was much lower than that in its bulk counterpart. Two fundamental interaction mechanisms were identified, and compared with predictions by molecular dynamics simulations. In situ studies also revealed a new phenomenon: radiation-induced frequent migration of coherent and incoherent twin boundaries. Potential migration mechanisms are discussed.

Reactive skin decontamination lotion (RSDL) for the decontamination of chemical warfare agent (CWA) dermal exposure.

Rapid decontamination of the skin is the single most important action to prevent dermal absorption of chemical contaminants in persons exposed to chemical warfare agents (CWA) and toxic industrial chemicals (TICs) as a result of accidental or intentional release. Chemicals on the skin may be removed by mechanical means through the use of dry sorbents or water. Recent interest in decontamination systems which both partition contaminants away from the skin and actively neutralize the chemical has led to the development of several reactive decontamination solutions. This article will review the recently FDA-approved Reactive Skin Decontamination Lotion (RSDL) and will summarize the toxicity and efficacy studies conducted to date. Evidence of RSDL's superior performance against vesicant and organophosphorus chemical warfare agents compared to water, bleach, and dry sorbents, suggests that RSDL may have a role in mass human exposure chemical decontamination in both the military and civilian arenas.

Preparation of TEM samples of ferritic alloys.

We describe techniques for electropolishing irradiated ferritic specimens for examination under the TEM in situations where the foil quality is of utmost importance. First, we describe some modifications to the standard technique for making plan-view specimens aimed at optimizing the foil quality. Second, we describe a technique for making plan-view specimens from a region of buried damage in a specimen irradiated with 2 MeV Fe(+) ions.

A pilot study to assess the safety of dobutamine stress echocardiography in the emergency department evaluation of cocaine-associated chest pain.

STUDY OBJECTIVE: Chest pain in the setting of cocaine use poses a diagnostic dilemma. Dobutamine stress echocardiography (DSE) is a widely available and sensitive test for evaluating cardiac ischemia. Because of the theoretical concern regarding administration of dobutamine in the setting of cocaine use, we conducted a pilot study to assess the safety of DSE in emergency department patients with cocaine-associated chest pain. METHODS: A prospective case series was conducted in the intensive diagnostic and treatment unit in the ED of an urban tertiary-care teaching hospital. Patients were eligible for DSE if they had used cocaine within 24 hours preceding the onset of chest pain and had a normal ECG and tropinin I level. Patients exhibiting signs of continuing cocaine toxicity were excluded from the study. All patients were admitted to the hospital for serial testing after the DSE testing in the intensive diagnostic and treatment unit. RESULTS: Twenty-four patients were enrolled. Two patients had inadequate resting images, one DSE was terminated because of inferior hypokinesis, another DSE was terminated because of a rate-related atrial conduction deficit, and 1 patient did not reach the target heart rate. Thus, 19 patients completed a DSE and reached their target heart rates. None of the patients experienced signs of exaggerated adrenergic response, which was defined as a systolic blood pressure of greater than 200 mm Hg or the occurrence of tachydysrhythmias (excluding sinus tachycardia). Further suggesting lack of exaggerated adrenergic response, 13 (65%) of 20 patients required supplemental atropine to reach their target heart rates. CONCLUSION: No exaggerated adrenergic response was detected when dobutamine was administered to patients with cocaine-related chest pain.

Organ procurement and successful transplantation after malathion poisoning.

BACKGROUND: One of the major limitations to organ procurement and donation is the lack of suitable donors. As the demand for suitable organs exceeds the supply, identification of potential donors continues to evolve. Due to perceived risks of transmittable toxins and insufficient understanding of toxicological fate, poisoned patients are often overlooked as organ donors. CASE REPORT: A 17-year-old white male was found by his mother having a seizure in bed. A strong odor of pesticides was noted and an empty container of malathion was found. He was transported to an outlying hospital and underwent prolonged cardiopulmonary resuscitation. The patient exhibited symptoms consistent with cholinergic poisoning and received a total of 12 mg of atropine and a pralidoxime bolus of 1 g followed by an infusion at 500 mg/h. Initial plasma cholinesterase was 1433 IU/L (normal 7500-14,600). The patient developed aspiration pneumonia and remained comatose. No further treatment for cholinergic toxicity was needed 5 days after admission and a cerebral blood flow scan confirmed brain death. After review of the available literature on the disposition andfate of malathion in human tissues, the patient's liver and kidneys were harvested for transplantation. The recipients were all doing well 1 year posttransplantation. CONCLUSIONS: This case of successful transplantation after organophosphate exposure underscores the fact that poisoned patients should not be overlooked as transplant candidates. Decisions should be based on the clinical presentation and knowledge of the properties of the toxin.

A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results.

BACKGROUND: A phase III randomized comparison of radiotherapy alone versus combination chemotherapy and concurrent continuous-course radiotherapy was performed at the Cleveland Clinic Foundation. METHODS: Between March 1990 and June 1995, 100 patients with resectable stage III and IV squamous cell head and neck cancer were randomized to either Arm A: radiotherapy alone, 68-72 Gy at 1.8-2.0 Gy per day; or to Arm B: the identical radiotherapy with concurrent chemotherapy. Chemotherapy consisted of 5-fluorouracil, 1000 mg/m2/day, and cisplatin 20 mg/m2/ day, both given as continuous intravenous infusions over 4 days beginning on day 1 and day 22 of the radiotherapy. At 50-55 Gy, patients were clinically reassessed. If a response was evident, radiotherapy was completed. In non-responding patients, however, radiotherapy was terminated and surgery recommended. After completion of all treatment, salvage surgery was performed, if possible, for any residual primary or nodal disease or for any subsequent locoregional recurrence. RESULTS: Except for an overrepresentation of T1 patients on Arm A, the treatment arms were equivalent. Toxicity was greater in the patients on Arm B with a higher incidence of grade III and IV neutropenia, thrombocytopenia, cutaneous reaction, and mucositis. Feeding tubes were also required more often, and weight loss was greater on the chemotherapy arm. No toxic deaths occurred. With a median follow-up of 36 months, the Kaplan-Meier 3-year projections of relapse-free survival are 52% for Arm A and 67% for Arm B (p = .03), and the likelihood of developing hematogenous metastases is 21% for Arm A and 10% for Arm B (p = .04). Although overall survival is not significantly different, overall survival with successful primary site preservation was 35% for Arm A and 57% for Arm B (p = .02). This difference remains statistically significant in the subsets of patients with laryngeal and hypopharyngeal primaries but not in patients with oropharyngeal primaries. CONCLUSIONS: Continuous-course radiotherapy and concurrent combination chemotherapy is an intensive, toxic but tolerable treatment regimen, which, when compared with radio therapy alone, can produce an improvement in relapse-free survival, a decrease in distant metastases, and an improvement in overall survival with successful primary site preservation.

Squamous cell head and neck cancer in nonsmokers.

Tobacco and alcohol abuse are the major known risk factors for the development of squamous cell head and neck cancer (SCHNC). Information about this disease in nonsmokers, however, is limited. We retrospectively studied a group of 59 tobacco nonusers with SCHNC, diagnosed since 1986 at the Cleveland Clinic Foundation (CCF). Two objectives were defined: (a) to characterize this nonsmoking population of patients and identify any significant differences compared with a control population consisting of all patients diagnosed with SCHNC at the CCF between 1986 and 1993 and (b) to determine the prevalence of exposure to environmental tobacco smoke in this nonsmoking group of patients with SCHNC and compare it with the environmental tobacco-smoke exposure in a second, control population of non-SCHNC, nonsmoking patients matched for age, race, sex, and alcohol use. The group of nonsmoking patients with SCHNC was notable for only rare alcohol abuse, a preponderance of whites, and relatively fewer laryngeal primary tumors. There were significantly more women and more tongue primaries. When compared with the control population without cancer, the nonsmoking patients had a significantly higher risk of exposure to environmental tobacco smoke both in the home and in the workplace. We conclude that the tobacco nonuser who develops SCHNC is likely to be female and white and to have a primary tongue cancer. A significant association with environmental tobacco smoke exposure is suggested by our data.

Sodium bicarbonate to correct widened QRS in a case of flecainide overdose.

A 16-yr-old male attempted suicide by ingesting approximately 4000 mg of flecainide. He developed coma, hypotension, and ventricular tachycardia. In addition to supportive care and antidysrhythmics, he received intravenous sodium bicarbonate for the wide complex dysrhythmia. Animal studies and anecdotal human experience have suggested that increasing the extracellular sodium improves cardiac conduction in flecainide toxicity. The patient's QRS narrowed immediately following sodium bicarbonate infusion. Sodium bicarbonate may be useful in the treatment of widened QRS and ventricular ectopy resulting from flecainide toxicity.

Concurrent chemoradiotherapy for salvage in relapsed squamous cell head and neck cancer.

The results in 9 patients with unresectable recurrent squamous cell cancer of the head and neck who were treated with aggressive concurrent chemoradiotherapy are reported. Treatment consisted of one or two courses of chemotherapy with 5-fluorouracil 1000 mg/m2/day and cisplatin 20 mg/m2/day, both given as 4-day continuous intravenous infusions, concurrent with radiation therapy. Salvage radiation doses between 30 and 70 Gy were administered. Seven patients had previously undergone an attempt at curative surgery, and 7 had been treated with radiation doses between 52 and 72 Gy. The recurrent disease was locally confined in 3, locoregional in 5, and locoregional with metastases in 1 of the 9 patients. Treatment toxicity was significant and included mucositis, nausea/vomiting, and granulocytopenia, but there were no toxic deaths. Complete tumor clearance was possible in 6 of these 9 patients, and 5 patients remain disease-free at 41+, 43+, 45+, 47+, and 50+ months. Of these 5 patients, 4 had previously been treated with both surgery and radiation, while 1 had only undergone surgery. We conclude that aggressive chemotherapy and concurrent (re)irradiation can be given to patients with unresectable, recurrent, squamous cell cancer of the head and neck. Treatment is tolerable, and disease-free long-term survival is possible. Careful patient selection, however, is required.

Accelerated induction therapy and resection for poor prognosis stage III non-small cell lung cancer.

BACKGROUND: Induction therapy and resection may improve the survival of patients with poor prognosis stage III non-small cell lung cancer, at the cost of significant treatment prolongation. The purpose of this study was to assess toxicity, response, and survival of an accelerated induction regimen and resection in poor prognosis stage III non-small cell lung cancer. METHODS: Forty-two surgically staged patients with poor prognosis stage III non-small cell lung cancer received 11 days of induction treatment consisting of 96 hours of continuous chemotherapy infusions of cisplatin (20 mg.m-2.day-2), 5 fluorouracil (1,000 mg.m-2.day-2), and etoposide (75 mg.m-2.day-2) concurrent with accelerated fractionation radiation therapy (1.5 Gy twice a day, to a dose of 27 Gy). Induction was followed in 4 weeks by resection. Postoperatively, a second course of continuous chemotherapy and concurrent accelerated fractionation radiation therapy (postoperative dose 13 to 36 Gy) was given. RESULTS: Despite some degree of induction toxicity in all patients there was only one induction death (2.4%). A clinical partial response was seen in 24 patients (57%). Thirty-six patients (86%) underwent thoracotomy, and resection was possible in 33 (79%). Pathologic downstaging was seen in 17 patients (40%), and 2 patients (5%) had no residual carcinoma at operation. There were 11 postoperative complications (31%) and 4 postoperative deaths (11%). Thirteen patients (31%) are alive and disease-free, 24 (57%) have persistent disease or have recurred (15 distant, 5 locoregional, 4 both), and 9 patients are alive with disease. The median survival is 21 months and the 2-year Kaplan-Meier survival is 43%, with no differences identified between stages IIIA and IIIB patients (p = 0.63). CONCLUSIONS: We conclude that accelerated induction therapy and resection in poor prognosis stage III non-small cell lung cancer (1) is toxic, with a 12% treatment mortality; (2) is effective with a 79% resection rate and 40% pathologic downstaging rate; (3) provides excellent local control; (4) may prolong survival; and (5) is of value in stage IIIB as well as stage IIIA patients.

Continuous course radiation therapy and concurrent combination chemotherapy for squamous cell head and neck cancer.

Concurrent radiation therapy and chemotherapy is a promising approach to the treatment of squamous cell head and neck cancer. Toxicity, however, has required either scheduled breaks in radiation therapy administration or compromise in chemotherapy dose intensity. We describe the toxicity and results in 19 patients treated at diagnosis with a continuous course of radiation therapy and intensive concurrent combination chemotherapy using 5-fluorouracil and cisplatin. Toxicity among these 19 patients was significant, including mucositis, myelosuppression, and weight loss, and aggressive supportive efforts were required. No toxic deaths occurred, however. At the end of treatment, all patients had achieved complete control of their primary-site tumor. Primary-site resection was not required in any patient for tumor control, but neck dissections were performed in selected individuals with involved nodes at diagnosis. No patient recurred at the primary site and only a single patient recurred in the neck. We conclude that this chemoradiotherapy schedule is very effective, albeit toxic. Toxicity, however, can be managed with appropriate aggressive supportive measures. Confirmation of these encouraging treatment results will require performance of a randomized clinical trial.

Aggressive concurrent chemoradiotherapy and surgical resection for proximal esophageal squamous cell carcinoma.

BACKGROUND: Proximal esophageal cancer has been a disease associated with relatively poor treatment success, partly due to advanced disease at presentation and the morbidity of the surgery required. Therefore, most patients receive palliative radiation therapy, and disease control is poor. METHODS: Between July 1990 and December 1992, nine consecutive patients with proximal esophageal squamous cell carcinoma were treated with aggressive concurrent chemoradiotherapy followed by surgical resection. Treatment consisted of cisplatin (20 mg/m2/day) and 5-fluorouracil (1000 mg/m2/day), both given as continuous intravenous infusions over 4 days concurrent with accelerated fractionation external beam radiation therapy (150 cGy twice a day to a dose of 2400 cGy). Three weeks after beginning treatment, a second course of chemotherapy and accelerated fractionation radiation therapy was administered to a total preoperative radiation therapy dose of 4500 cGy. After restaging of their disease, patients next underwent surgical resection. A single postoperative course of chemotherapy and 2400 cGy of concurrent accelerated fractionation radiation therapy was administered to those patients with residual tumor in the resection specimen. Two of these nine patients also were given 4-day etoposide infusions (75 mg/m2/day) as part of their chemotherapy and received lower induction radiation therapy doses. RESULTS: Although significant toxicity was experienced, there were no deaths attributable to the chemoradiotherapy and only one perioperative death. All nine patients underwent surgery; five required pharyngolaryngoesophagectomy. No residual tumor was found in the resection specimen in three of the nine patients. Continuous locoregional tumor control was achieved in all patients. Only two developed distant metastases. CONCLUSIONS: These results, using aggressive multimodality treatment, suggest that excellent locoregional control and long term, disease free survival can be achieved in selected patients with proximal esophageal cancer.

Comparison of topical magnesium and calcium treatment for dermal hydrofluoric acid burns.

STUDY OBJECTIVE: To compare topical preparations of magnesium and calcium in the treatment of dermal hydrofluoric acid burns. DESIGN: A randomized, blinded, controlled animal model study. SETTING: Animal care facility. TYPE OF PARTICIPANTS: New Zealand rabbits. INTERVENTIONS: Each rabbit was burned with hydrofluoric acid at four sites along the thoracolumbar spine. Equimolar amounts of calcium gluconate, magnesium gluconate, and a magnesium hydroxide antacid were added into a lubricating jelly. The jelly alone was a control preparation. After a water rinse, the burns were massaged with the gels for 1 minute five times; at 4 and 20 minutes and at 1, 4, and 24 hours. Each rabbit served as its own control by receiving all four treatments. MEASUREMENTS AND MAIN RESULTS: Burn diameter and burn surface area diminished over time, but there were no statistically significantly differences among the treatments. Burn ranking and burn rating of severity also did not demonstrate differences. The histologic analysis of the burns, however, demonstrated that calcium gluconate-treated burns were less severe and more superficial than the control and magnesium gluconate-treated burns; the magnesium hydroxide antacid-treated burns were not statistically different compared to the calcium gluconate-treated burns. CONCLUSION: Topical calcium gluconate is an efficacious treatment for dermal hydrofluoric acid burns. Further research is needed to determine the role of magnesium-containing antacids in the treatment of hydrofluoric acid burns.

Aggressive multimodality therapy for malignant pleural mesothelioma.

Nineteen patients with clinical stage I malignant pleural mesothelioma were treated with aggressive multimodality therapy. Nine patients underwent pleurectomy and decortication followed by immediate intrapleural chemotherapy with cisplatin and mitomycin C. Ten patients required pleuropneumonectomy followed within 1 week to 2 weeks by intrapleural administration of cisplatin (100 mg). Four to 8 weeks after operation, 15 patients underwent postoperative adjuvant cisplatin-based systemic chemotherapy. There were three postoperative complications (16%) requiring reoperation and one postoperative death (5%). Intrapleural chemotherapy was well tolerated with no complications. Systemic chemotherapy was poorly tolerated, and there was one chemotherapy-related death. Sixteen patients (84%) experienced good to excellent palliation. Three patients are currently alive with no evidence of recurrent disease at 10, 35, and 43 months. The median overall survival was 13 months and the median disease-free survival, 11 months. Overall and disease-free 3-year survivals were 17% and 22%, respectively. Patients with epithelial malignant pleural mesothelioma had significantly better overall survival (p = 0.037) and disease-free survival (p = 0.02) than patients with sarcomatous or biphasic malignant pleural mesothelioma. We conclude that despite major toxicity, in select patients with clinical stage I malignant pleural mesothelioma, aggressive multimodality therapy offers effective palliation and occasional long-term disease-free survival.

Emergency department response to hazardous materials incidents.

Emergency physicians must stay alert to situations that involve toxic chemical exposures. An appropriate response to victims of chemical contamination is important for the victim's outcome and the safety of hospital personnel. Successful management of such a situation requires managing information, resources, and patients with complex medical conditions. Chemical contamination may affect one or hundreds of victims. Community planning is essential for an effective response to toxic chemical accidents (Haz-Mat).