Differentiated dosage of microporous colestyramine and its double-blind comparison with a placebo in hypercholesterolaemic patients

A double-blind trial of microporous colestyramine (MPC) at different dosages was undertaken on 18 hypercholesterolaemic patients (Fredrickson classification Type II A) in three groups. During the attack phase of four weeks, three dosage regimens of MPC were used, 9 g, 12 g and 18 g for six patients in each group. During the maintenance phase of eight weeks, the patients were divided into two groups of nine each, one group receiving MPC 9 g/day and the other a placebo. The attack phase demonstrated the efficacy of the MPC therapy at all three dosage levels with minimal side-effects and the maintenance phase showed significant adverse variations in the total and HDL-cholesterol levels and in the intraratio in the placebo group, and in the physician's and patients judgement of the efficacy of the MPC therapy compared with the placebo. It is considered that MPC provides an excellent alternative therapy for prolonged treatment of hypercholesterolaemia, where a specific diet therapy is unacceptable.     

Differential tumorigenicity of growth factor-dependent versus -independent CCL39 lung fibroblast lines in nude mice

Several cell lines derived from CCL39 Chinese hamster fibroblasts were characterized so that comparison could be made of their tumorigenic potential and their ability to proliferate in vitro in response to growth factor stimulation. Tumor formation was assessed by implanting single-cell suspensions into the flanks (sc), peritoneal cavity (ip), or tail vein (iv) of BALB/c athymic nude mice, whose ages ranged from 8-10 days (neonatal), to 5-7 weeks (adult), to more than 5 months (old). Serum, insulin (INS), epidermal growth factor (EGF), and alpha-thrombin (THR) were tested for promoting short-term cell proliferation in serum-free medium. CCL39 fibroblasts arrestable in the Go phase required INS and EGF or THR to divide optimally. They formed sc tumors after a long latent period and only in the young and adult mice. Among such tumors, those composed of growth factor-independent variants became lethal ip and iv and grew sc earlier and rapidly in all age groups. These properties were shared by polyomavirus-transformed CCL39 fibroblasts and 1 mutant that divided without growth factors. Mutants that escaped only partially the growth factor requirements had been implanted ip but not iv. They grew at the sc site in newborn and adult mice, with kinetics comparable to that of CCL39 cells. Their expansion in old animals was variable, transient or slow. Neither CCL39 nor 39T10 tumor cells were susceptible to cytotoxic reactions mediated by activated macrophages or natural killer cells. These observations indicate that distinct anatomical regions in nude mice and factors related to their age contribute to present CCL39 heterotransplants with environments that are more or less permissive to their growth. These observations also suggest that cells that achieve growth factor autonomy are more malignant than cells in which growth factor controls of division are less stringent but not abrogated.     

Epirubicin, cisplatin and continuous-infusion 5-fluorouracil (ECF regimen) in the treatment of advanced colorectal cancer.

Thirty-one patients with advanced colorectal cancer were treated with a regimen of epirubicin, cisplatin and continuous-infusion (c.i.) 5-fluorouracil (5-FU) (ECF regimen). Twenty-seven patients were evaluable for response rate (RR), progression-free survival (PFS) and overall survival (OS). In this study, the ECF chemotherapy yielded a 51% RR with a PFS of more than 8 months, an OS of more than 11 months and tolerable toxicity. In spite of the perplexity concerning the use of anthracyclines in colorectal cancer, the ECF regimen seems to be a possible treatment even for this malignancy. Controlled studies with ECF versus standard treatments and versus 5-FU alone in c.i. are necessary.     

Sonographic measurement of the umbilical cord and fetal anthropometric parameters.

OBJECTIVE: To determine reference ranges for the diameter and the cross-sectional area of the umbilical cord during pregnancy and to determine if umbilical cord morphometry is related to fetal size. METHODS: A prospective cross-sectional study was designed to assess the sonographic cross-sectional diameter and area of the umbilical cord. The sonographic umbilical cord measurements were obtained in a plane adjacent to the insertion of the cord into the fetal abdomen. Nomograms for the umbilical cord diameter and area were computed. Fetal biometry included: biparietal diameter, abdominal circumference, and femur length. Polynomial regression analysis was conducted. RESULTS: Five hundred and fifty seven patients were included into the study. The regression equation for the umbilical cord diameter (y) according to gestational age (x) was y=-10.0563+1.4265x+0.0194x2 and for the umbilical cord area (y') was y'=91.6-3.3x+0.03x2-0.00007x3. A significant relationship was found between umbilical cord measurements and fetal anthropometric parameters. CONCLUSION: Reference ranges for umbilical cord diameter and area have been generated. The sonographic diameter and cross-sectional area of the umbilical cord increase as a function of gestational age and both diameter and area correlate with fetal size.     

Serous-papillary carcinoma of the endometrium. Usefulness and limitations of computerized tomography

The staging of endometrial carcinoma and the evaluation of tumor recurrences take advantage from Computerized Tomography (CT). The CT appearances are described of six new cases and two recurrences of uterine papillary serous carcinoma (UPSC), which is a particularly aggressive and rare form of endometrial carcinoma. CT has been scarcely useful in first clinical stages, while in advanced stage and when the tumor appears as a pelvic mass CT has allowed to recognize the uterine origin, to define the involvement of surrounding tissue and to depict the extrauterine spread patterns. CT has been extremely useful in the evaluation and in the search for tumor recurrences.     

Azidothymidine induces apoptosis and inhibits cell growth and telomerase activity of human parathyroid cancer cells in culture.

Telomerase activity has been correlated to parathyroid carcinoma. Because its role in acquisition of a malignant phenotype by parathyroid cells is unclear, we treated telomerase-positive cultured human parathyroid cancer cells with the telomerase inhibitor AZT, evaluating cell telomerase activity, cytotoxic effects, growth, and morphological changes. In vitro exposure of these cells to AZT correlated with inhibition of cell proliferation. INTRODUCTION: Parathyroid carcinoma represents an uncommon cause of primary hyperparathyroidism, whose spectrum of clinical presentation, degree of malignancy, and prognosis are difficult to be properly identified. Neck surgery, specifically an en bloc resection of primary tumor, is the only curative treatment. Alternatively, affected patients could undergo repetitive palliative surgical exeresis of metastatic nodules. It has been previously shown that telomerase activity is specifically present in parathyroid carcinoma cells, being absent in hyperplastic and adenomatous tissues. Thus, determination of telomerase activity could represent either a useful diagnostic molecular marker for human parathyroid carcinoma or a potential target for pharmacological intervention in a malignant neoplasia usually resistant to chemo- and radiotherapeutic interventions. MATERIALS AND METHODS: To further investigate the role of telomerase activity in acquisition of a malignant phenotype by parathyroid cells, we treated telomeric repeat amplification protocol-positive cultured human parathyroid cells with the telomerase inhibitor zidovudine, 3'-azido-3'deoxythymidine (AZT), evaluating cell telomerase activity, growth characteristics, potential cytotoxic effects, and morphological changes. RESULTS: Our findings indicate that in vitro exposure of human parathyroid cancer cells to AZT resulted in intracellular accumulation of AZT-monophosphate (AZT-MP) and inhibition of telomerase, which correlate with inhibition of human parathyroid cancer cell proliferation. Moreover, we also found that AZT induced an apoptotic rather than a necrotic type of cellular death. None of these effects were observed in human adenomatous parathyroid cells in culture. CONCLUSIONS: Altogether these results indicate that AZT may be a highly effective agent against cancer parathyroid cells proliferation, which is an extremely important observation for a neoplasia which shows lack of response to classical pharmacological and physical antiblastic treatments.     

Increased plasma free tryptophan levels in human cancer: a tumor related effect?

High free tryptophan (F-TRP) plasma levels are found in cancer patients (CP). F-TRP plasma concentrations are affected by the levels of its carrier, albumin (ALB), and free fatty acids (FFA) competing with TRP for ALB binding sites. The lack of correlation between F-TRP, ALB and FFA in CP suggests a tumor-dependent effect on the rise in F-TRP. To verify this hypothesis, F-TRP, ALB and FFA levels were assayed in 12 lung and 16 breast CP susceptible to radical surgery, before and 15 days after surgical removal of the tumor. F-TRP levels significantly decreased after tumor ablation. Since no correlation was found between F-TRP, ALB and FFA variations, it is conceivable that the tumor itself may be responsible for the high F-TRP levels in CP.