Fish muscle mercury concentration and bioaccumulation fluctuate year-round - Insights from cyprinid and percid fishes in a humic boreal lake.

Boreal lakes demonstrate pronounced seasonality, where the warm open-water season and subsequent cold and ice-covered season dominate natural cycles. While fish muscle total mercury concentration (mg/kg) [THg] is well documented in open-water summer months, there is limited knowledge on the ice-covered winter and spring mercury dynamics in fish from various foraging and thermal guilds. This year-round study tested how seasonality influences [THg] and its bioaccumulation in three percids, perch (Perca fluviatilis), pikeperch (Sander lucioperca), ruffe (Gymnocephalus cernua), and three cyprinids, roach (Rutilus rutilus), bleak (Alburnus alburnus), and bream (Abramis brama) in deep boreal mesotrophic Lake Pääjärvi, southern Finland. Fish were sampled and [THg] was quantified in the dorsal muscle during four seasons in this humic lake. Bioaccumulation regression slopes (mean ± STD, 0.039 ± 0.030, range 0.013-0.114) between [THg] and fish length were steepest during and after spawning and shallowest during autumn and winter for all species. Fish [THg] was significantly higher in the winter-spring than summer-autumn in all percids, however, not in cyprinids. The lowest [THg] was observed in summer and autumn, likely due to recovery from spring spawning, somatic growth and lipid accumulation. Fish [THg] was best described by multiple regression models (R2adj: 52-76%) which included total length and varying combinations of seasonally changing environmental (water temperature, total carbon, total nitrogen, and oxygen saturation) and biotic factors (gonadosomatic index, and sex) in all species. The seasonal variation in [THg] and bioaccumulation slopes across multiple species suggests a need for standardized sampling seasons in long-term monitoring to avoid any seasonality bias. From the fisheries and fish consumption perspective in seasonally ice-covered lakes, monitoring of both winter-spring and summer-autumn would improve knowledge of [THg] variation in fish muscle.

The value of "routine tests" in the staging evaluation of gynecologic malignancies: a cost effectiveness analysis.

The value of tests employed in the clinical staging of patients with carcinomas of the cervix and endometrium has been examined in a retrospective review of 739 consecutive patients seen at Tufts-New England Medical Center. The yield of positive results of the barium enema (0%) and proctosigmoidoscopy (0.8%) in carcinoma of the cervix suggests that some of these studies may be omitted in asymptomatic patients with early disease on pelvic examinations. Similarly, for carcinoma of the endometrium, the yields from barium enema (0.9%) cytoscopy (0.9%) and proctosigmoidoscopy (0.6) are low. It is concluded that optimal patient care (with respect to morbidity and costs) may be provided without routinely performing these studies in staging asymptomatic patients with cervical and endometrial carcinomas.

Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes.

To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600-800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800-400-400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients.

Lack of selective killing by steroids in normal and malignant cells.

Using a colony formation assay, the cytotoxic effects of steroids and an anti-steroid on an established human breast tumor line and two human diploid fibroblast strains were studied. Experiments involving 17 a-estradiol, 17 beta-estradiol, dexamethasone, cortisone, dihydrotestosterone, and the anti-estrogen Tamoxifen showed no killing at concentrations below 10(-7)M following a 24-hour exposure to these agents. A maximum of 80% killing was observed at 10(-5)M with dexamethasone in one fibroblast strain and at the same dose of 17 beta-estradiol in the breast tumor line. The extent of killing observed is insufficient to account for many of the clinical remissions observed with steroid therapy. The data also suggest that at therapeutic doses, there is no selective killing of malignant cells by these agents.

Interaction between radiation and drug damage in mammalian cells. III. The effect of adriamycin and actinomycin-D on the repair of potentially lethal radiation damage.

We have studied the effects of actinomycin-D (AMD) and Adriamycin (ADRM) on the repair of radiation damage in Chinese hamster cells (V79) in plateau phase growth. Suppression of potentially lethal damage repair (PLDR) was observed in the presence of non-toxic levels of AMD and minimally toxic levels of ADRM. The suppression of PLDR by AMD persisted as long as the drug was present. Removal of AMD was followed by prompt repair of potentially lethal injury suggesting that suppression of PLDR by AMD was not accompanied by fixation of injury to a non-repairable state. On the other hand, irradiated cells exposed to ADRM eventually repair potentially lethal injury in the presence of drug after an initial delay. AMD, but not ADRM, inhibited repair of sublethal radiation damage.

An evaluation of total nodal irradiation as treatment for stage III A Hodgkin's disease.

Between April 1969 and December 1974, 37 patients with surgically staged III A Hodgkin's disease were treated with total nodal irradiation (TNI). Their probability of relapse-free survival at 7 years is 51% and overall survival 82% with the majority of patients remaining disease free after retreatment with MOPP (10 of 16). In contrast, 21 stage III B patients treated with TNI and MOPP chemotherapy over the same time period have a relapse-free survival of 74% and overall survival of 91%. Because of superior results in treating stage III B patients with combined modality treatment, we fell that a relapse-free survival of 51% may not justify continuation of TNI as the only modality of treatment for patients with stage III A disease, and we have initiated a trial of combined radiation therapy and MOPP chemotherapy in these patients. The most effective treatment of stage III A Hodgkin's disease, however, remains uncertain and depends both on the ultimate risk of combined modality treatment and the success of retreatment following relapse after radiation.

Effect of primary treatment modality on the metastatic pattern of mammary carcinoma.

In animal tumor systems, all three major treatment modalities, surgery, radiotherapy, and chemotherapy, may increase the incidence of metastases in the presence of circulating viable tumor cells. In breast cancer patients, selected studies can be found which report an increased incidence of metastases after surgery, radiotherapy, or chemotherapy, but these effects appear to exert little influence on overall survival. Caution is advised in using systemic therapy prior to effective primary tumor cytoreductive treatment. Clinical trials in advanced local disease should be done to test this concern. Minimal surgery, loco-regional radiotherapy, and effective adjuvant systemic therapy may result in the improved survival of patients with breast cancer with minimal functional or cosmetic impairment.

Proliferation kinetics of a human breast cancer line in vitro following treatment with 17beta-estradiol and 1-beta-D-arabinofuranosylcytosine.

The effect of 17beta-estradiol on an estrogen receptor-positive human breast cancer cell line (MCF-7) was studied. Low concentrations (10(-9) M) of 17beta-estradiol enhanced the rate of cell proliferation; the overall cell cycle time was shortened; and the proportion of cells in the S phase increased. Higher concentrations (10(-7) M) suppressed proliferation and slightly decreased the proportion of the cells in DNA synthesis. When combined with 1-beta-D-arabinofuranosylcytosine, an S-phase-specific chemotherapeutic agent, 10(-9) M 17beta-estradiol enhanced cell killing. This enhancement was not observed with 10(-7) M 17beta-estradiol. Kinetic changes caused by hormones have profound implications in clinical therapy, since the efficacy of cycle active agents may be altered.

Value of computed tomography in radiotherapy of lung cancer.

The effectiveness of CT scanning in radiotherapeutic treatment planning was evaluated in 32 patients with bronchogenic carcinoma. CT of the chest in pretreatment evaluation of these patients supplemented conventional clinical and radiographic patients supplemented conventional clinical and radiographic studies, resulting in (1) more clear delineation of tumor extent in 24 patients (75%); (2) change in assessment of the size of lesions in 14 patients (43%); (3) change of disease stage in 13 (40%); (4) demonstration of inadequacy of treatment plan in nine (28%); and (5) changes in the volume of normal tissue irradiated in 14 (40%). CT scan data was judged essential for treatment planning in 17 patients studied (53%). Unsuspected areas of tumor involvement were seen in 21 patients (65%). Use of the CT scan as a patient contour for radiotherapy treatment planning of lung cancer and alternative techniques are discussed.

An aggressive approach to marginally resectable lung cancer.

Between July 1968 and December 1974, 53 patients with lung cancer were planned for preoperative irradiation and surgery. All patients were considered clinically marginally resectable because of advanced local disease, 4 Stage II patients, with limited pulmonary reserve and 49 Stage III patients. Most patients received 3000 to 4000 rad followed in two weeks by thoracotomy. Forty-six patients were explored and 38 were resectable. Twelve patients are alive with a median follow-up of 48 months. The cumulative 5-year survival of all resectable patients is 27%. The survival of patients with marginally resectable lung cancer treated by accelerated radiotherapy followed by aggressive surgery approaches the survival experience of patients with primary resectable lung cancer and is superior to such patients treated with radiation therapy alone.

Palliation of hepatic metastasis.

Between 1971 and 1975, 55 patients underwent palliative radiation therapy for symptomatic hepatic metastasis. Most patients received 2400 rad in 300 rad fractions to the entire liver. There were 31 patients who received concomitant chemotherapy, and 14 who were prior chemotherapy failures. Ninety percent of the patients with symptomatic pain and liver enlargement and significant palliation of their symptoms. The median survival of the entire group was 4.5 months, while those patients experiencing an excellent response (21) had a median survival of 9 months. The median survival of patients having an excellent response to radiation is comparable to that of patients having regional arterial chemotherapy while incuring fewer complications. The overall complication rate of those patients completing therapy (50) was 12%.

The interaction between radiation and adriamycin damage in mammalian cells.

Interaction between radiation and Adriamycin damage reduced the width of the shoulder of the X-ray survival curve. This effect was found to persist for at least 24 hr after Adriamycin treatment. Adriamycin did not affect radiation damage when cells were treated either before two-dose fractionation or with the drug present between X-ray exposures. Adriamycin is unique in that its major effect on radiation response is to reduce the survival curve shoulder without affecting two-dose recovery. It is suggested that Adriamycin and radiation produce independent classes of damage that are expressed mutually for killing, with regard to the registration of sublethal radiation damage, but that repair of the latter is unaffected by Adriamycin.