Antiestrogenic effects of Z-1, 1-dichloro-2,3 diphenyl-2-(4-methoxyphenyl)cyclopropane(5a) on human breast cancer cells in culture.

Compound 5a ([Z]-1, 1-Dichloro-2,3 diphenyl-2-(4-methoxyphenyl)cyclopropane) is a novel cyclopropyl compound which was shown to be a pure antiestrogen. In the present study, the antiproliferative activity of 5a was examined on estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells and A-549 human lung cancer cells using the hemocytometric trypan blue exclusion method. Compound 5a inhibited the growth of MCF-7 cells in a dose-related manner over a concentration range of 10(-9) to 10(-5) M, but did not alter the growth of MDA-MB-231 or A-549 cells. Co-administration of estradiol (10(-8) M) reversed the antiproliferative activity of 5a (10(-7) M) on MCF-7 cells. Further, an ER-dependent mechanism of action is supported by the specific ER binding of 5a in MCF-7 cells observed in this study. The influence of 5a on the cell surface morphology of MCF-7 and MDA-MB-231 cells was studied using scanning electron microscopy (SEM). Compound 5a at 10(-6) M reduced the length and density of microvilli (MV) on MCF-7 cells, which was reversed by co-administration of estradiol (10(-8) M). This compound did not alter the cell surface morphology of ER-negative MDA-MB-231 cells. In conclusion, 5a and tamoxifen inhibited the growth of ER-prositive MCF-7 cells in an estradiol-reversible manner, and had no effect on ER-negative MDA-MB-231 cells. The results of this study with human breast cancer cells suggest that 5a may be highly effective in the treatment of estrogen-dependent breast cancer and/or in the prophylactic treatment of women with a high risk of breast cancer development.     

CT demonstration of complex dorsal spinal dysraphism.

An unusual case of dorsal spinal dysraphism in a four year old child is presented. Various abnormalities including diastematomyelia, an extradural arachnoid cyst arising from one of the two dural tubes, and lipomeningomyelocele with a related rib-like bony structure were demonstrated with Iohexol CT and subsequently confirmed at surgery.     

Effect of titanium surface texture on the cell-biomaterial interface.

To improve the in vivo performance of engineered implants, this study examines the independent effects of surface chemistry and topography on fibroblast morphology and density in vitro. Titanium (Ti) was sputter-coated onto smooth and microtextured polyethylene terephthalate (PET). Test specimens were evaluated in 24-h, fibroblast cultures and assessed with scanning electron microscopy (SEM) for cellular morphology and density. Fibroblast density increased, as the Ti film thickness increased. The fibroblasts exhibited contact guidance on the textured test specimens. The greatest cellular density was found on the Ti-coated, textured test specimens. In conclusion, Ti and surface texture appeared to strongly influence fibroblast density and morphology as compared to PET and smooth surfaces.     

Geometric Resistance and Microvascular Network Architecture of Human Colorectal Carcinoma

Objective : To measure the geometric resistance to blood flow in human colorectal carcinoma. Although tumor blood flow is of central importance in both the detection and the treatment of cancer, the determinants of blood flow through the neoplastic circulation are poorly understood. Methods : Human colorectal carcinomas (tissue weight = 272 g ± 43 g (SD), n = 6) were perfused ex vivo with a buffered physiological salt solution of known viscosity at flow rates ranging from 2.5 to 40 ml/min and perfusion pressures from 8 to 100 mm Hg. The geometric resistance was determined from the slope of the pressure-flow curve. For examination of the principal determinant of geometric resistance, the vascular architecture, one of the tumors was perfused with Batson's No. 17 polymer and macerated in KOH to produce a positive vascular cast that was used for measurement of vascular branching patterns and dimensions. Results : The pressure-flow relationship was linear at perfusion pressures above 40 mm Hg, and the geometric resistance, z₀, was constant at approximately 6.5 ± 10⁹g/cm³. Below 40 mm Hg, z₀ increased rapidly. The architecture of the arteriolar and capillary networks of human colorectal carcinoma is similar to those of experimental rodent tumors. Capillaries in planar and nonplanar mesh-works had mean segment diameters of 11 ± 2 and 9.6 ± 2 μm, lengths of 46 ± 24 and 107 ± 40 μm, and intercapillary distances of 46 ± 13 and 74 ± 24 μm, respectively. Conclusions : The geometric flow resistance in neoplastic tissue is 1–2 orders of magnitude higher than that observed in normal tissues. A decrease in functional vascular cross-sectional area may explain the additional increase in resistance at small perfusion pressures. The observed flow resistance may be due to the specialized arteriolar and capillary network architecture, pressures exerted by proliferating cancer cells, and/or coupling between vascular and extravascular flow. These observations demonstrate that tumor vascularity alone may not be indicative of flow resistance or tumor susceptibility to blood-borne therapeutic agents.     

The role of selective beta 1-blocker in the preoperative preparation of thyrotoxicosis: a comparative study with propranolol

Subtotal thyroidectomy was performed for hyperthyroidism on 130 patients; 95 treated before surgery with propranolol (Group I) and 35 given only metoprolol before surgery (Group II). These patient groups were compared with reference to preoperative medication, operative and immediate postoperative course, and late results with follow-up for one to five years. Clinical response was 100% in group II and 94.7% in group I. The median length of preoperative treatment was 7.96 +/- 1.84 days in group I and 6.25 +/- 1.73 days in group II (P less than 0.05). There were no serious adverse effects of the drugs in either treatment group. No anaesthesiologic or cardiovascular complication occurred during operation in either group. Ten patients in group I (10.5%) and six patients in group II (11.4%) observed hyperthyroid manifestations in the immediate postoperative period, eliminated by the administration of the propranolol/metoprolol, and no case of thyroid storm occurred. One patient in group II developed clinical hypocalcaemia. Two patients, one in each group, presented temporary unilateral recurrent laryngeal nerve paralysis. There were two recurrences of toxicity in group I (2.1%) and none in group II. Hypothyroidism occurred in 3 patients (2.3%) two of them were from group I and one was from group II. The postoperative hospital stay was 4.62 +/- 1.61 days in group I and 2.81 +/- 1.32 days in group II (P less than 0.05). One patient from group I died on the third postoperative day due to pulmonary oedema. The results suggest that metoprolol can be safely used and offers the advantages of desired clinical response, shorter preoperative preparation time, simplicity of dosage and shorter postoperative hospital stay in comparison to propranolol for preoperative treatment of hyperthyroidism.     

Hepatitis induced by traditional Chinese herbs; possible toxic components.

Traditional Chinese herbal remedies are widely available in the United Kingdom for the treatment of chronic skin disorders. Their benefits are considerable, but their use is completely unregulated. Two patients are described here who suffered an acute hepatitic illness related to taking traditional Chinese herbs. Both recovered fully. The mixtures that they took included two plant components also contained within the mixture taken by a previously reported patient who suffered fatal hepatic necrosis. These cases high-light the need for greater awareness of both the therapeutic and toxic potential of herbal remedies, as well as greater control of their use.     

Covered exstrophy: a rare variant

A case of covered exstrophy without sequestration of a bowel segment is reported. A 4-year-old female presented with dribbling of urine. Treatment to date has been simple excision of the covered membrane with functional closure of the bladder and bilateral posterior iliac osteotomies, with reconstruction of the bladder neck and genitalia to be performed at a later date. The embryogenesis of this rare variant, a review of the reported cases, and management options are discussed. Accepted: 6 November 1997     

Selecting a physical medicine and rehabilitation residency.

A 35-item questionnaire, designed to assess the relative importance of various factors to medical students when ranking physical medicine and rehabilitation (PM&R) residency training programs during the Match, was sent to all members of the 1991 senior class after Match Day. This mailing was coordinated with the National Resident Matching Program. The questionnaire was also sent to all PM&R residency training program directors and all physiatrist faculty members at the University of Medicine and Dentistry of New Jersey--New Jersey Medical School (UMDNJ-NJMS). Recipients were asked to grade selection factors based on a numerical scale: 1, extremely important; 2, very important; 3, important; 4, minimally important; 5, not important. A response rate of 41% (73/179) for medical students, 87% (62/71) for residency training directors and 71% (22/31) for UMDNJ-NJMS faculty members was attained. Analysis of the results indicates that, overall, there is no significant difference in ranking of the factors by each of the three groups surveyed. The intergroup responses for one-third of the factors were significantly different. Diversity of the training experience, current house officer satisfaction, it "feels" right and house officer quality were the four most important selection factors to the medical students.