Biochemical requirements for singlet oxygen production by purified human myeloperoxidase.

The myeloperoxidase (MPO)-hydrogen peroxide (H2O2)-halide systems were found to produce chemiluminescence at 1,268 nm, a characteristic emission band for singlet oxygen (1O2). The emission was enhanced by a factor of 29 +/- 5 in deuterium oxide and was inhibited by the 1O2 quenchers, histidine and azide ion. Inactivation of MPO with heat or with cyanide ion prevented light production. The combined weight of all data strongly supported the production of 1O2 by these enzyme systems. The amount of 1O2 produced was sensitive to the conditions employed. Under optimal conditions at pH 5, the MPO-H2O2-bromide (Br-) system produced 0.42 +/- 0.03 mol 1O2/mol H2O2 consumed, close to the theoretical value of 0.5 that was predicted by the reaction stoichiometry. In contrast, the MPO-H2O2-chloride (Cl-) system was much less efficient. The maximum yield of 1O2 was 0.09 +/- 0.02 mol/mol H2O2 consumed and required pH 4 and 5 mM H2O2. At higher pH, the 1O2 production rapidly decreased. The yield at pH 7 was 0.0004 +/- 0.0002 mol/mol H2O2 consumed. Enzyme inactivation was a major factor limiting the yield of 1O2 with both Cl- and Br-. While the MPO-H2O2-halide systems can efficiently produce 1O2, the conditions required are not physiologic, which suggests that the chemiluminescence of the stimulated neutrophil does not derive from 1O2 generated by a MPO mechanism.

Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics.

BACKGROUND: Analyses of phase III trials showed that denosumab was superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) irrespective of age, history of SREs, or baseline pain status. This analysis assessed the risk of SREs across additional baseline characteristics. PATIENTS AND METHODS: Patients (N = 5543) from three phase III trials who had breast cancer, prostate cancer, or other solid tumours and one or more bone metastasis were included. Superiority of denosumab versus ZA in reducing risk of first SRE and first and subsequent SREs was assessed in subgroups defined by the Eastern Cooperative Oncology Group performance status (ECOG PS), bone metastasis location, bone metastasis number, visceral metastasis presence/absence, and urinary N-telopeptide (uNTx) level using Cox proportional hazards and Anderson-Gill models. Subgroups except bone metastasis location were also assessed for each solid tumour type. RESULTS: Compared with ZA, denosumab significantly reduced the risk of first SRE across all subgroups (hazard ratio [HR] ranges: ECOG PS, 0.79-0.84; bone metastasis location, 0.78-0.83; bone metastasis number, 0.78-0.84; visceral metastasis presence/absence, 0.80-0.82; uNTx level, 0.73-0.86) and reduced the risk of first and subsequent SREs in all subgroups (HR ranges: ECOG PS, 0.76-0.83; bone metastasis location, 0.78-0.84; bone metastasis number, 0.79-0.81; visceral metastasis presence/absence, 0.79-0.81; uNTx level, 0.74-0.83). Similar results were observed in subgroups across tumour types. CONCLUSION: Denosumab was superior to ZA in preventing SREs in patients with bone metastases from advanced cancer, regardless of ECOG PS, bone metastasis number, baseline visceral metastasis presence/absence, and uNTx level.

Risk of second aerodigestive cancers increases in patients who survive free of small-cell lung cancer for more than 2 years.

PURPOSE: Patients who survived small-cell lung cancer (SCLC) for more than 2 years were evaluated to determine the frequency and anatomic pattern of redevelopment of small-cell cancer and development of non-small-cell lung cancer (NSCLC) and aerodigestive cancers with the passage of time. PATIENTS AND METHODS: From April 1973 through December 1991, 578 patients with previously untreated SCLC were entered onto prospective therapeutic trials at the National Cancer Institute (NCI), Bethesda, MD. Sixty-two (11%) were cancer-free 2 years after initiation of therapy and were assessable for redevelopment of SCLC and development of NSCLC, and aerodigestive cancers. RESULTS: Twenty patients redeveloped SCLC 2.0 to 12.2 years after initiation of chemotherapy, of whom two patients were deemed to have a second primary small-cell cancer that involved the aerodigestive tract. Fifteen patients developed 16 cancers in the lung other than SCLC 3.4 to 14.9 years after initiation of therapy. Two developed other aerodigestive cancers that involved the larynx and lip. The risk of a NSCLC and aerodigestive cancer in these patients increased more than sixfold from 2% per patient per year during years 2 to 4 to 12.6% and 14.4%, respectively, after more than 10 years. The cumulative actuarial risk of a second primary NSCLC or aerodigestive cancer at 16 years is 69% and 72%, respectively. CONCLUSION: The increasing risk of second aerodigestive cancers with the passage of time is a mounting problem for patients cured of SCLC. Chemoprevention trials for these patients should be considered.

Application of an algorithm for staging small-cell lung cancer can save one third of the initial evaluation costs.

OBJECTIVE: Design of a cost-effective algorithm for staging disease in patients with small-cell lung cancer. DESIGN: An algorithm was constructed by analyzing all permutations of a sequence of procedures required to stage disease in patients with small-cell lung cancer. Procedural costs were determined, and the model was applied to the small-cell lung cancer patient population treated at the National Cancer Institute, Bethesda, Md, from 1973 to 1989. The final algorithm was derived from the permutation with the lowest cost per accurately staged patient. SETTING: A single government institute, the National Cancer Institute. PATIENTS: Four hundred fifty-one patients with previously untreated, consecutive histologically documented small-cell lung cancer entered into therapeutic protocols at the National Cancer Institute from April 1973 through July 1989. Data were obtained from small-cell lung cancer protocol databases and patients' medical records. MAIN OUTCOME MEASURE: The cost per patient of each sequence of staging procedures when applied to the patient population. RESULTS: The least expensive sequence of procedures saved $1418 per patient when compared with application of a standard set of staging procedures to all patients. The major factor in reducing costs was the concept of stopping the staging procedures after a site of distant metastatic disease had been identified. CONCLUSIONS: An algorithm consisting of a set of sequential staging procedures can accurately stage disease in patients with small-cell lung cancer and save more than one third of the costs of an inclusive standard set of staging procedures.

Initial clinical results of LINAC-based stereotactic radiosurgery and stereotactic radiotherapy for pituitary adenomas.

PURPOSE: To retrospectively evaluate the initial clinical results of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) for pituitary adenomas with regard to tumor and hormonal control and adverse effects of the treatment. SUBJECTS AND METHODS: Forty-eight patients with pituitary adenoma who underwent SRS or SRT between September 1989 and September 1995 were analyzed. Of these, 18 received SRS and 30 received SRT. The median tumor volumes were 1.9 cm3 for SRS and 5.7 cm3 for SRT. Eleven of the SRS and 18 of the SRT patients were hormonally active at the time of the initial diagnosis. Four of the SRS and none of the SRT patients had a history of prior radiation therapy. Both SRS and SRT were performed using a dedicated stereotactic 6-MV linear accelerator (LINAC). The dose and normalization used for the SRS varied from 1000 cGy at 85% of the isodose line to 1500 cGy at 65% of the isodose line. For SRT patients, a total dose of 4500 cGy at 90% or 95% of the isodose line was delivered in 25 fractions of 180 cGy daily doses. RESULTS: Disease control-The three year tumor control rate was 91.1% (100% for SRS and 85.3% for SRT). Normalization of the hormonal abnormality was achieved in 47% of the 48 patients (33% for SRS and 54% for SRT). The average time required for normalization was 8.5 months for SRS and 18 months for SRT. Adverse effects-The 3-year rate of freedom from central nervous system adverse effects was 89.7% (72.2% for SRS and 100% for SRT). Three patients who received SRS for a tumor in the cavernous sinus developed a ring enhancement in the temporal lobe as shown by follow-up magnetic resonance imaging. Two of these cases were irreversible and were considered to be radiation necrosis. None of the 48 patients developed new neurocognitive or visual disorders attributable to the irradiation. The incidence of endocrinological adverse effects were similar in the two groups, resulting in 3-year rates of freedom from newly initiated hormonal replacement of 78.4% (77.1% for SRS and 79.9% for SRT). CONCLUSION: Considering the relatively high incidence of morbidity observed in the SRS group, we recommend SRT as the primary method of radiation therapy for pituitary tumors. When treating a lesion in the cavernous sinus with SRS, special attention should be paid to dose distribution in the adjacent brain parenchyma. Longer follow-up is necessary before drawing any conclusions about the advantages of these techniques over conventional external beam radiation therapy.

Is IgD Myeloma a Separate Clinical Entity? Report of Six Cases Investigated by Isoelectric Focusing.

Six IgD myeloma patients whose monoclonal components were identified by isoelectric focusing are presented. They represented 4% of all patients with myeloma seen at our institute between 1982 and 1986. The patients did not display many of the features described as typical for IgD myeloma: in particular younger age group, decreased survival and increased incidence of lymphadenopathy, hepatosplenomegaly, extraosseous disease, anemia, renal failure and hypercalcemia. However males predominated, the concentrations of circulating monoclonal IgD were low and concentrations of serum and urinary monoclonal free light chains were high, findings previously reported in IgD myeloma. The concentrations of circulating IgD were at the lower end of ranges reported previously. The hypothesis that our patients represent the malignant equivalent of the normal "low secretory phenotype", possibly associated with improved survival, is discussed. The belief that IgD myeloma is a separate clinical entity is questioned. The sensitive, high-resolution technique of isoelectric focusing is recommended as the investigation of choice for the detection of monoclonal gammopathies in body fluids.

The life-after-death phenomenon.

The life-after-death phenomenon has created student interest and is often a topic initiated by students by students in death education courses. The article summarizes some popular publications about the life-after-death phenomenon and extracts commonalities that potentially affect other topic areas in a death education course or unit. Topic areas such as coping with death, suicide and stages of dying are then examined to note the effect the phenomenon can have on the topical discussions. The article concludes with a section on precautions in teaching the phenomenon.

Exercise science and health enhancement: a curriculum imperative in professional preparation.

Exercise as a strategy to maintain and promote health continues to gain prominence because of increasing public participation in exercise programs and a growing body of literature supporting its efficacy. This paper addresses the need for including exercise science in the formal training of the health educator by 1) summarizing research concerning the effectiveness of exercise in health maintenance and enhancement, 2) presenting a rationale for including exercise science in the health educator's professional preparation curriculum, and 3) providing an outline for the course.

Development of a tool to assess suicide risk factors in urban adolescents.

Dramatic increases in the adolescent suicide rate over the past three decades have underscored the need for risk-assessment tools. The tools that do exist are oriented to older populations and their application to adolescents is questionable. A project was initiated at the University of Utah's Health Education Department to develop a pilot instrument to examine the differences between adolescents who have attempted suicide and other teenagers. Eighty-two subjects between the ages of 14 and 19 participated in the test of this instrument. Twenty-five subjects were identified by a physician or psychologist as having failed in a sincere suicide attempt within the previous 18 months. Fifty-seven nonsuicide attempters with similar demographic profiles served as a comparison group. An 86-item questionnaire was administered to both groups. Questions were generated from a review of the literature of the past three decades for problems associated with suicide in this population. Questions were sorted into three domains (family environment, social environment, and self-perceptions), with each domain having several subdomains. Statistical analysis revealed significant differences for each of the three domains and on 55 of 86 questions. The results were used to create a streamlined instrument for assessing suicide risk that can be administered in 20 minutes.

Educational imagery and the allied health educator.

Educational imagery is a classroom teaching methodology that allows students to mentally isolate themselves and to use their natural abilities to daydream or fantasize in ways that accomplish educational objectives. Educational imagery is used to facilitate decision making, clarify values, memorize, incorporate behavioral outcomes of teaching, and reinforce cognitive concepts. The technique can help allied health students prepare for the clinical setting. The behavioral components, ethical concerns, and decision making that will occur in the clinical setting can be rehearsed in the classroom before the actual experience by guiding students' imagination. This article describes the nature of imagery and its sources, describes how to implement the strategy in the classroom, and gives examples of educational imagery strategies for the allied health disciplines.

Contraception-abortion lifeline.

PIP: The contraception abortion lifeline is a technique that deals with the sensitive issues of abortion and contraception and yet integrates both teaching and valuing. The technique can be adapted to a 20 minute period or continued for several hours of discussion, depending on age group, objectives of the unit, and the skills of the facilitator. On the chalk board or on a large piece of paper, the instructor initially draws a lifeline with some key points labeled. A values questions is then asked, "When does life begin?" Students respond independently until all who want to respond do so. An "L" for life is placed on the continuum for each voluntary response. After the students have privately or openly contemplated where life begins, a cognitive discussion of contraception and abortion methods can ensue. For each method of contraception that is discussed, the instructor puts a mark on the continuum above the lifeline. The decision of where to place the contraceptive method depends on the action of the contraceptive method. Following the discussion of contraceptive techniques, abortion techniques can be discussed and the periods of most appropriate use placed on the lifeline. Once the cognitive portion of the technique is completed, then the valuing questions begin. The final question in the technique is one that will reinforce personal values or promote the examination of personal values in a way that personal affective and cognitive value dissonance will be avoided or clarified. The question is, "Is the mark where you believe life begins on the right or left of your personally accepted contraceptive or abortion methods?" This final question can lead to a discussion of how to find peace of mind when using contraceptive methods, i.e., using appropriate methods (if any) which conform to one's own values. If students are uncertain as to when life begins, the technique will most likely stimulate some thinking. It can also lead to a discussion of the ease of modifying behaviors versus the facility of changing values. Other questions can be developed to relate the lifeline to other values. The abortion contraception lifeline places a traditional discussion of contraception and abortion method within a valuing framework.^ieng

Treating the spiritual dimension through educational imagery.

Recently, health educators have shown an interest in the spiritual dimension of health. Despite this interest, most health educators have taken the "safe" approach and avoided the discussion of spiritual issues in the classroom. The problem with this avoidance position is that sensitive issues such as sexuality, drug use, and death and dying are laden with spiritual implications, particularly when students are asked to make personal decisions regarding these issues. The present article suggests the use of Educational Imagery as a method for incorporating the spiritual dimension into the health lesson. When certain simple precautions are taken, the educational imagery technique applied to the spiritual dimension can be both useful in meeting educational objectives and in making the classroom exciting and interesting for the students. The reader is provided with a definition of the spiritual dimension, along with a complete description of Educational Imagery. In addition, specific strategies for incorporating spiritual health in the classroom are given. The final section of the article includes implications and precautions for the teacher.

Paraneoplastic syndromes in thoracic malignancies.

Paraneoplastic syndromes are caused by factors produced by cancer cells that often act at a distance from both the primary site and its metastases. The most extensively characterized syndromes caused by cancer are those produced by polypeptide hormones, such as adrenocorticotropic hormone, and those produced by antibodies directed against tumor antigens that cross-react with neural tissue, such as in the Eaton-Lambert myasthenic syndrome. These syndromes develop in a minority of cancer patients, and are diagnoses of exclusion. Lung cancer, particularly small cell lung cancer, is the most common malignancy causing paraneoplastic syndromes. A large number of paraneoplastic syndromes have been described. This review focuses on the increased understanding of some of the well-documented syndromes that has occurred through recent advances principally in molecular biology and immunology.

Paraneoplastic syndromes in lung cancer.

Paraneoplastic syndromes are caused by factors produced by cancer cells that often act at a site distant from both the primary site and its metastases. These syndromes are estimated to occur in only 7% to 15% of patients with cancer and are diagnoses of exclusion. If the definition of paraneoplastic syndrome is broadened to include indirect effects of the tumor such as cachexia or the anemia of chronic disease, the incidence is much higher. Lung cancer, particularly small cell lung cancer, is the most common malignancy causing paraneoplastic syndromes. This review focuses on recently published literature on paraneoplastic syndromes associated with lung cancer, including humoral hypercalcemia of malignancy, autoimmune paraneoplastic neurologic syndromes, neuromuscular disorders, and cancer cachexia. It includes advances in both molecular biology and immunology, and in clinical investigation.

Multiple cavitating pulmonary nodules in Hodgkin's disease.

Although pulmonary involvement in Hodgkin's disease is common, the presentation with multiple cavitating lung lesions is exceedingly rare, having been described in only five patients. The authors present a case report of a 27-year-old woman with nodular sclerosing Hodgkin's disease treated with conventional chemotherapy and autologous bone marrow transplantation. The patient relapsed with multiple cavitating lung lesions requiring open-lung biopsy for diagnosis.