Changes in blood and urinary cadmium levels and bone mineral density according to osteoporosis medication in individuals with an increased cadmium body burden.

The aim of this study was to assess changes in bone mineral density (BMD) and cadmium (Cd) levels in blood and urine in individuals living in a Cd-contaminated area according to the type of osteoporosis medication over a three-year period. This follow-up study included 204 residents living in the vicinity of a closed copper refinery, who had been found to have elevated urinary or blood Cd levels. Cd levels in the blood and urine, as well as BMD, were measured every 6 months. After the first BMD measurement, individuals were prescribed antiresorptives such as alendronate or vitamin D and calcium, according to their BMD. Subjects were classified according to the type of medicine provided over the previous 6 months. General linear models controlling for other factors were used to evaluate the effects of each type of medication on the participants' Cd levels and BMD. Spinal BMD showed a significant increase in the antiresorptive group compared to the nontreatment group. Significant decreases in blood Cd levels were found in the vitamin D and calcium group, in comparison to the nontreatment group, as well as a marginally significant decrease in the antiresorptive group. The vitamin D and calcium group showed a significantly greater decrease in urinary Cd levels than the nontreatment group. In contrast, antiresorptive medication was found to have a negative effect on urinary Cd excretion. These results suggest that vitamin D and calcium treatment for osteoporosis lowers blood Cd levels more effectively and improves urinary Cd excretion.

Plant regeneration from hairy-root cultures transformed by infection with Agrobacterium rhizogenes in Catharanthus roseus.

Hypocotyl explants of Catharanthus roseus produced hairy roots when cultured on Murashige and Skoog (MS) basal medium after infection by Agrobacterium rhizogenes. Explants gave rise to adventitious shoots at a frequency of up to 80% when cultured on MS medium supplemented with 31.1 microM 6-benzyladenine and 5.4 microM alpha-naphthaleneacetic acid. There was a significant difference in the frequency of adventitious shoot formation for each hairy-root line derived from a different cultivar. Plants derived from hairy roots exhibited prolific rooting and had shortened internodes. Approximately half of the plants had wrinkled leaves and an abundant root mass with extensive lateral branching, but otherwise appeared morphologically normal. Plants with hairy roots that were derived from the cultivar Cooler Apricot developed flowers with petals that were white in the proximal region, whereas the wild-type flower petals are red. PCR and Southern blot analyses revealed that plants derived from hairy roots retained the Ri TL-DNA.

Clinical and anatomical factors associated with thalamic dyskinesias.

To define the clinical and anatomical factors associated with dyskinesias following thalamic infarction, we performed neurological examination and three-dimensional brain magnetic resonance imaging for 23 patients with thalamic infarction. We measured the total volumes and the largest diameters of the lesions on axial and coronal images. Using the atlas of human thalamus, we investigated the damaged thalamic nuclei. We compared the means of the volumes and the largest diameters of the lesions, and the frequencies of damaged thalamic nuclei between patients with and without thalamic dyskinesias. Seven (two pseudochoreoathetosis and five dystonia) of the 23 patients with thalamic infarction developed dyskinesias. No specific neurological deficits at the onset of stroke predicted the development of dyskinesias. The mean volume of the lesions of patients with dyskinesias (739 mm(3)) was significantly larger than that of those without dyskiensias (92.9 mm(3)). The means of the largest axial (11.6 mm) and coronal (10.8 mm) diameters were significantly larger in patients with dyskinesias, compared to those (axial, 7.1 mm; coronal, 6.4 mm) of patients without dyskinesias. Patients with dyskinesias had damage in the centromedian (CM) thalamic nucleus more frequently compared to those without dyskinesias. Patients with a large thalamic infarction involving the CM nucleus are more likely to develop dyskinesias.

P16INK4a protein expression is associated with poor survival of the breast cancer patients after CMF chemotherapy.

Immunohistochemical assay for p16 protein expession was performed in 192 breast carcinoma patients treated with adjuvant chemotherapy. p16 expression was observed in 78 cases (40.6%). The frequency of p16 expression significantly decreased in moderately differentiated (histologic grade II) cancers, 20 (19.6%) of 102. In poorly differentiated cancers (histologic grade III), p16 expression was not observed in all 16 cases. p16 expression was significantly associated with histologic grade of the breast carcinomas (p < 0.001). The proliferative index (PI: S + G2/M) of individual tumors was measured by DNA flow cytometry. In 114 tumors with PI less than 20%, p16 expression was observed in 59 tumors (49.1%). In the tumors with PI equal or more than 20%, p16 expression was observed in 22 (28.2%) of 78 cases. p16 expression was significantly decreased in the tumor with higher PI (p =0.003). For the other clinicopathologic variables, no significant association was found with p16 expression status. Immunohistochemical assay for p53 protein expression was performed on the same breast carcinomas. There was no significant association between p16 and p53 expression in breast carcinomas. During median follow-up period of 52 months (range: 40-72 months), 46 patients (25.8%) had recurrent disease and 32 patients (18.91%) died of recurrent disease. p16 expression was observed in 20 (43.5%) of 46 patients with recurrent disease, while its expression was observed in 58 patients (39.7%) of 146 patients who were free of recurrence during the study period. p16 expression had no significant impact on predicting recurrence of breast carcinoma. Fourteen patients (12.2%) of 114 patients whose tumors did not show p16 expression died of recurrent breast carcinoma, whereas 18 patients (23.1%) of 78 patients with p16 expressing tumor died during the follow-up period. There was a significant difference of patient survival according to p16 expression status (p = 0.039). These results indicate that p16 expression is useful in predicting response to chemotherapy in breast cancer patients. p16 protein seems to have a role in tumor growth and differentiation of the breast carcinoma.

Reduced expression of p27Kip1 protein is associated with poor clinical outcome of breast cancer patients treated with systemic chemotherapy and is linked to cell proliferation and differentiation.

The cyclin-dependent kinase inhibitor p27Kip1 is a negative regulator of cell proliferation. Its expression is known to be altered in a proteasome-dependent manner without changes in DNA level. Reduced expression of p27Kip1 is associated with aggressive behavior in a variety of human cancers. We investigated expression of p27Kip1 protein in human breast cancer using immunohistochemistry to assess its biologic implication along with cell-cycle analysis by flow cytometry. A total of 68 patients with invasive ductal cancer received adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-FU every 3 weeks for six cycles. In epithelial cells of normal and benign breast disease, expression of p27Kip1 was well preserved while its expression markedly decreased in breast cancer (45 of 68). Expression of p27Kip1 is significantly reduced in poorly differentiated cancers and in the advanced stage of the disease. Levels of p27Kip1 expression correlated with cell populations in G0/G1 phase of the cell cycle. In survival analysis, p27Kip1 was useful to predict disease free survival but not overall survival of the patients after adjuvant chemotherapy. In summary, p27Kip1 seems to have a role in the cell proliferation and differentiation process during carcinogenesis of breast cancer. The results of the present study suggest that p27Kip1 can be used in predicting response to systemic chemotherapy in a subset of patients with breast cancer.

Noninvasive determination of core temperature during anesthesia.

A noninvasive, zero heat flux method of determining core (intracardiac blood) temperature was studied in ten anesthetized patients having whole body hyperthermia for the treatment of cancer. True intracardiac blood temperature was determined by a calibrated pulmonary artery thermistor. Accuracy, precision, and responsivity for the noninvasive system were comparable to conventional esophageal thermometry in reflecting intracardiac blood temperatures. This method of contact thermometry is convenient and independent of environmental influence, and it rapidly reflects the small changes in arterial blood temperature which evoke vasomotor responses.

Hemodynamic and plasma catecholamine responses to hyperthermic cancer therapy in humans.

Cancer patients, treated with hyperthermia (to 41.5 degrees C) under thiopental and fentanyl anesthesia, had smaller increases in heart rate and cardiac index and lesser decreases in mean arterial pressure than those reported in normal volunteers. At basal body temperature anesthesia did not alter catecholamine levels. Increasing body temperature to 39.5 degrees C and 41.5 degrees C resulted in parallel increases in heart rate and cardiac index that were directly related to the increases in plasma norepinephrine levels. At basal temperature cutaneous venous plasma norepinephrine levels exceeded those of arterial; mixed-venous plasma levels were intermediate. At 39.5 degrees C and 41.5 degrees C there were sequential increases in plasma norepinephrine. The increases in mixed-venous and arterial norepinephrine were significantly greater than in cutaneous venous blood. The differential increases in norepinephrine levels in cutaneous venous, mixed-venous, and arterial blood indicate that during hyperthermia sympathetic nerve activity in skin is decreased while that in other areas is increased, suggesting that alterations in sympathetic activity modulate the hemodynamic changes that attend hyperthermia in man.

Systemic thermotherapy (whole body hyperthermia).

This is an article reviewing the literature and our experience to date (six months) in the treatment of cancer using whole body hyperthermia in the first 60 patients. WBHT is an effective method of treating cancer. Patients were treated for a total of eight hours, 180 degrees F for two hours. WBHT was induced by means of two high-flow water filled blankets. Toxicity included fatigue, nausea, diarrhea and first degree burns. There was no evidence of visceral damage. There were no mortalities during the procedure. Objective responses were 50%, subjective responses were 65%. The literature demonstrates and our study confirms that under closely monitored conditions, WBHT is a feasible, safe and active anti-cancer therapy. WBHT may be safely used as an adjunct to other active cancer therapies including X-ray therapy and chemotherapy.

Hyperthermia potentiates doxorubicin-related cardiotoxic effects.

The intercurrent administration of doxorubicin hydrochloride to a patient undergoing whole-body hyperthermia for the treatment of metastatic cancer repeatedly produced ventricular irritability and cardiac dysfunction. Individually, doxorubicin and hyperthermia were tolerated by the patient without incident. Catecholamine determinations showed that the administration of doxorubicin under hyperthermic conditions increased the liberation of both epinephrine and norepinephrine. The acute synergistic cardiotoxic effects occurred with doxorubicin dosages that were severalfold less than those associated with only mild and transient ECG disturbances under normothermic conditions.