Ceruloplasmin level in women with breast disease. Preliminary results.

The average ceruloplasmin levels of 29 patients with active breast cancer and 22 patients in remission were 824 +/- 61 mg/l and 630 +/- 18 mg/l respectively. The average ceruloplasmin level of 17 patients with benign breast diseases was 555 +/- 29 mg/l and of 18 healthy women in a control group 584 +/- 17 mg/l. Breast cancer patients not in remission had ceruloplasmin levels which were significantly increased when compared to the other 3 groups. The CA 15-3 levels and ceruloplasmin levels were positively correlated. We propose that ceruloplasmin may be used as a tumour marker in the follow-up of patients with breast cancer.     

A review of adverse pregnancy outcomes and formaldehyde exposure in human and animal studies

We examine the potential for reproductive and developmental effects from formaldehyde exposure. Formaldehyde is unlikely to reach the reproductive system in humans in concentrations sufficient to cause damage since it is rapidly metabolized and detoxified upon contact with the respiratory tract. While there are effects seen in in vitro studies or after injection, there is little evidence of reproductive or developmental toxicity in animal studies under exposure levels and routes relevant to humans. Most of the epidemiology studies examined spontaneous abortion and showed some evidence of increased risk (meta-relative risk=1.4, 95% CI 0.9-2.1). We found evidence of reporting biases and publication biases among the epidemiology studies and when these biases were taken into account, we found no evidence of increased risk of spontaneous abortion among workers exposed to formaldehyde (meta-relative risk=0.7, 95% CI 0.5-1.0). The small number of studies on birth defects, low birth weight, and infertility among formaldehyde workers; the limitations in the design of these studies; and the inconsistent findings across these studies make it difficult to draw conclusions from the epidemiology data alone. However, information from experimental studies and studies of metabolism indicate reproductive impacts are unlikely at formaldehyde exposures levels observed in the epidemiology studies.     

Bioavailability of beryllium oxide particles: an in vitro study in the murine J774A.1 macrophage cell line model

Beryllium metal and its oxide and alloys are materials of industrial significance with recognized adverse effects on worker health. Currently, the degree of risk associated with exposure to these materials in the workplace is assessed through measurement of beryllium aerosol mass concentration. Compliance with the current mass-based occupational exposure limit has proven ineffective at eliminating the occurrence of chronic beryllium disease (CBD). The rationale for this research was to examine the mechanism of beryllium bioavailability, which may be pertinent to risk. The authors tested the hypothesis in vitro that dissolution of particles engulfed by macrophages is greater than dissolution in cellular medium alone. Physicochemical changes were evaluated in vitro for well-characterized high-purity beryllium oxide (BeO) particles in cell-free media alone and engulfed by and retained within murine J774A.1 monocyte-macrophage cells. The BeO particles were from a commercially available powder and consisted of diffuse clusters (aerodynamic diameter range 1.5 to 2.5 microm) of 200-nm diameter primary particles. Following incubation for 124 to 144 hours, particles were recovered and recharacterized. Recovered particles were similar in morphology, chemical composition, and size relative to the original material, confirming the relatively insoluble nature of the BeO particles. Measurable levels of dissolved beryllium, representing 0.3% to 4.8% of the estimated total beryllium mass added, were measured in the recovered intracellular fluid. Dissolved beryllium was not detected in the extracellular media. The BeO chemical dissolution rate constant in the J774A. 1 cells was 2.1 +/- 1.7 x 10(-8)g/(cm2 . day). In contrast, the BeO chemical dissolution rate constant in cell-free media was < 8.1 x 10(-9)g/(cm2 . day). In vivo, beryllium dissolved by macrophages may be released in the pulmonary alveolar environment, in the lymphatic system after transport of beryllium by macrophages, or in the alveolar interstitium after migration and dissolution of beryllium particles in tissue. These findings demonstrate a mechanism of bioavailability for beryllium, are consistent with previously observed results in canine alveolar macrophages, and provide insights into additional research needs to understand and prevent beryllium sensitization and CBD.     

Theoretical investigation of the interrelationships between stationary and personal sampling in exposure estimation

In exposure estimation, personal sampling is the method of choice as it is a nearby representative of the contaminant concentration in the breathing zone. Due to the versatility of the stationary sampling in obtaining much higher sensitivity, in its adaptability to telemetering observations, it may also be an attractive sampling method for many circumstances. However, the two sampling methods differ in many theoretically important ways that go beyond the obvious differences. The theoretical investigation of the stationary and personal sampling methods vis-à-vis sampling for exposure estimation shows that the area sampling can be used to represent personal sampling under restricted conditions. Under the restricted conditions, an area of concentration within specified bounds may be determined in relation to a reasonably well-defined source. The extension of the theory to multiple or ill-defined sources pose potential complications that may be intractable through a theoretical analysis. These limitations and restrictions are inherent to the underlying premises of the two methods; therefore they are not amenable to easy correction. Even though these restrictions may suggest only a limited role for area sampling in exposure assessment, the theory shown also suggests areas of further applied and theoretical research to extend the proper use of area sampling in exposure assessment.     

A field comparison of the IOM inhalable aerosol sampler and a modified 37-mm cassette

This research focused on comparing a modified 37-mm (Mod37) sampling cassette with an IOM inhalable dust sampler. Paired IOM and Mod37 breathing-zone air samples were collected for workers engaged in corrosion control maintenance operations on several types of aircraft at several U.S. Air Force bases in the United States. Sampled operations included hand and power sanding, blow-down and wipe-down to remove dust, and spray finishing. The cassettes' interior surfaces were swabbed and the swabs combined with the filters for chromium analysis by NIOSH Method 7300. This approach utilized total chromium as a sensitive surrogate indicator of total aspirated mass. The influences of work location, work type, sample duration, and sampler type on measured concentration were evaluated using analysis of variance techniques. Only work type (process) was found to be a statistically significant predictor of measured concentration. The relationship between IOM- and Mod37-measured values for paired samples was evaluated by work type using linear regression techniques. Linear regressions showed that the modified 37-mm cassette over-samples aerosol by 35 percent compared to the IOM when a wide range of aerosol concentrations and compositions for divergent work tasks in multiple field locations are sampled. Interpretation of these results in light of previous results involving filter-only Mod37 analyses suggests that while the Mod37 has a higher aspiration efficiency than the IOM, substantial Mod37 wall losses result in underestimation of exposure when only the 37-mm filter is analyzed rather than filters plus wall swabs.     

Neoadjuvant chemotherapy with taxotere-epirubicin-5-fluorouracil (TEF) in local-regionally advanced breast cancer: a preliminary report

AIMS AND BACKGROUND: Sixty-three patients with local-regionally advanced breast cancer were treated with neoadjuvant chemotherapy consisting of docetaxel (Taxotere), epirubicin, and 5-fluorouracil (TEF). METHODS AND STUDY DESIGN: Preoperatively, patients received four cycles of Taxotere (80 mg/m2), epirubicin (60 mg/m2), and 5-fluorouracil (500 mg/m2), repeated every 21 days. Following completion of four cycles of chemotherapy, appropriate surgery was performed. After the surgery, patients received one cycle of the TEF chemotherapy regimen; following chemotherapy, radiotherapy was applied, and at the end two more cycles of TEF chemotherapy regimen were given. RESULTS: Sixty-three patients with locally advanced breast cancer were treated. Three patients were excluded from the study before the evaluation of response. Median age of the patients was 50 years (range, 25-77). Twenty-seven and 33 patients were premenopausal and postmenopausal, respectively. Thirty-nine patients were in stage IIIA and 21 in stage IIIB. Complete and partial responses were observed in 15 (25%) and 42 (70%) of the patients following four cycles of preoperative TEF chemotherapy regimen, respectively. Overall response was 95%, and primary lesion progressed only in 3 (5%) patients. The mean disease-free survival was 15.9 +/- 6.8 (range, 3.5-28) months and the mean overall survival was 18.6 +/- 7.2 (range, 5-30) months. The most frequent side effects were nausea-vomiting, mucositis, alopecia and leukopenia. CONCLUSIONS: TEF therapy is a treatment with a high overall response rate and toxicities similar to other taxotere combinations. A longer follow-up of patients is necessary for the determination of disease-free survival and overall survival.     

VB-CHEP chemotherapy regimen for aggressive non-Hodgkin's lymphomas

Abstract: Despite intensive search for the optimal combination chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), the CHOP (cyclophosphamide, adriamycin, vincristine and prednisolone) regimen is still the standard therapy. We investigated the clinical efficacy of a new combination regimen consisting of vincristine, bleomycin–cyclophosphamide, adriamycin, etoposide and prednisolone (VB-CHEP) in patients with aggressive NHL. A total of 29 patients with aggressive NHL was enrolled into the protocol. Eight patients were consolidated with cisplatin and cytarabine and 5 patients received radiotherapy for bulky disease. Objective response was achieved in 82.8% of the patients. Complete remission (CR) and partial remission rates were 72.4%, and 10.3%, respectively. CR rate was significantly lower in patients with advanced stage, extranodal disease and bone marrow involvement. Median follow-up time is 34+ months; 17 patients are disease-free while 12 died and only 2 patients with CR have relapsed so far. Median response duration is 29+ months and the median survival is 48+ months. The survival rate is 69% in the first year and 66% in the second year. A total of 152 cycles were evaluated for toxicity. Major hematological toxicity was myelosuppression and neutropenia, detected in 50.65%, was mostly grades 1–2. Neutropenic fever occurred in only 11 cycles. The side effects of the consolidation therapy were also acceptable. We conclude that the VB-CHEP regimen with consolidation therapy for high-risk patients may be an effective treatment for advanced stage aggressive NHL.     

Method-induced misclassification for a respirable dust sampled using ISO/ACGIH/CEN criteria

The single cut measurement of exposure to respirable dust is the accepted method of exposure classification in occupational hygiene. We previously showed that actual pulmonary tissue dose may be substantially different from the dose expected, or the indicated dose, based on measurements using current single cut methodologies. We now examine exposure misclassification of workers based on any single cut respirable dust measurement using the internationally accepted ISO/ACGIH/CEN single cut respirable dust measurement criteria. Hypothetical aerosols with 12 generalized size distributions typical of the method of aerosol generation (condensation, aged condensation, mechanical low energy, mechanical high energy and mixtures thereof) were assumed. Using previously reported models for sampler penetration and pulmonary deposition, Monte Carlo simulations of actual mass dose to pulmonary tissues in comparison to the dose estimate from an ideal respirable aerosol sampler were carried out. Measurement-based indicated doses were used to classify exposures into five exposure categories and these classifications were compared with the 'true' classifications from the dose-based exposure estimates. Misclassification rates were generally severe and were greatest for aerosols with mass median aerodynamic diameter (MMAD) <1 microm (approximately 100%) and MMAD 5-15 microm (65-95%). Misclassification rates were moderate (<20%) only for extremely coarse aerosols of MMAD>15 microm. Misclassification rates for oral and nasal breathing at 750 and 1500 ml tidal volume and 15 breaths/min were similar for each aerosol examined.     

Comparison of alpha-stat and pH-stat cardiopulmonary bypass in relation to jugular venous oxygen saturation and cerebral glucose-oxygen utilization

Jugular venous oxygen saturation (SJVO(2)) reflects the balance between cerebral blood flow and metabolism. This study was designed to compare the effects of two different acid-base strategies on jugular venous desaturation (SJVO(2) <50%) and cerebral arteriovenous oxygen-glucose use. We performed a prospective, randomized study in 52 patients undergoing cardiopulmonary bypass (CPB) at 27 degrees C with either alpha-stat (n = 26) or pH-stat (n = 26) management. A retrograde internal jugular vein catheter was inserted, and blood samples were obtained at intervals during CPB. There were no differences in preoperative variables between the groups. SJVO(2) was significantly higher in the pH-stat group (at 30 min CPB: 86.2% +/- 6.1% versus 70.6% +/- 9.3%; P < 0.001). The differences in arteriovenous oxygen and glucose were smaller in the pH-stat group (at 30 min CPB: 1.9 +/- 0.82 mL/dL versus 3.98 +/- 1.12 mL/dL; P < 0.001; and 3.67 +/- 2.8 mL/dL versus 10.1 +/- 5.2 mL/dL; P < 0.001, respectively). All episodes of desaturation occurred during rewarming, and the difference in the incidence of desaturation between the two groups was not significant. All patients left the hospital in good condition. Compared with alpha-stat, the pH-stat strategy promotes an increase in SJVO(2) and a decrease in arteriovenous oxygen and arteriovenous glucose differences. These findings indicate an increased cerebral supply with pH-stat; however, this strategy does not eliminate jugular venous desaturation during CPB. IMPLICATIONS: A prospective, randomized study in 52 patients during cardiopulmonary bypass revealed that pH-stat increased jugular venous oxygen saturation and decreased arteriovenous oxygen-glucose differences. There was no difference in the incidence of jugular venous desaturation. These findings suggest an increased cerebral blood flow with no protection against jugular venous desaturation during pH-stat.     

The reliability of multiple regression and an alternative method for extracting task-specific exposure estimates from time-weighted average data

The reliability of multiple regression analysis as a method for determining task-specific exposures from multi-task time-weighted average data was evaluated in comparison with the alternative P-screen method. The performances of the two methods were tested using simulated sample data that were calculated as averages over six tasks, where task-specific concentrations drawn randomly from lognormal distributions were weighted by randomly generated task time-weights. Data sets consisted of 20 or 100 simulated samples. The simulated data sets conformed to requirements inherent in the P-screen method that at least one task be absent from each sample and each task be absent from at least one sample. In thousands of Monte Carlo trials under various conditions, the two methods were found to perform equally well when dichotomous task measures (occurrence/ nonoccurrence) were used. Combining the two methods did not improve reliability appreciably, suggesting that the methods are effectively equivalent when dichotomous task measures are used. When task durations were used as the regressors or time-weights, multiple regression was found to be more reliable than P-screen. It is well recognized that incidental or fundamental collinearities between regressors may undermine multiple regression analyses. The P-screen-related restrictions on the task structure of data sets reduces the potential for problems arising from such collinearities. However, the use of multivariate analysis of multiple-task samples will always be an imperfect substitute for single-task sampling.