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.     

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     

Profuse variceal hemorrhage as a presenting feature of pancreatic adenocarcinoma in a young non-icteric patient

Pancreatic adenocarcinoma can present with a vast spectrum of rare manifestations. It usually occurs after the age of 50 years, the peak incidence being in sixth and seventh decades. We report a previously asymptomatic subject of pancreatic adenocarcinoma who presented for the first time with massive upper gastrointestinal hemorrhage. Endoscopy revealed ruptured esophageal varices which were secondary to tumour-induced thrombosis of the portal vein. Besides the uncommon mode of presentation, the patient was unusual because of his young age. Further, he was non-icteric at the time of presentation and remained so throughout the clinical course despite having a large lesion in the head of the pancreas.     

The effect of carbon dioxide in the airways and alveoli on ventilation; a vagal reflex studied in the dog

1. The inhalation of CO(2) produces a tachypnoea only in the presence of intact vagus nerves; the present study was designed to examine the mechanism of this phenomenon in the dog.2. Closed-chest cardiopulmonary bypass was established in dogs weighing 16-24 kg, anaesthetized with chloralose. When the ;bypass' was established pulmonary blood flow ceased, P(A, CO2) was reduced and the respiratory rate slowed. 3-10% CO(2) in O(2) could then be inhaled without change in the level of P(a, CO2) set at the oxygenator.3. The addition of CO(2) in these concentrations to the inspired oxygen resulted in an increase in respiratory frequency, maximal at the first breath and sustained for the 1 min period of exposure. The increase in respiratory frequency was due to a shortening of expiratory duration. Inspiratory duration did not change. The response was absent after vagotomy.4. Inert gases in O(2), given as a control, had no effect on breathing.5. The effect of raising P(a, CO2) (by increasing the concentration of CO(2) in the gas equilibrating the blood in the oxygenator), was primarily to increase tidal volume.6. The ventilatory effect of inspiring CO(2)/O(2) mixtures was shown to be additive to the effect of raising P(a, CO2).7. These experiments show that an afferent vagal reflex originating from the lungs causes tachypnoea, when a dog, on ;bypass', inhales low concentrations of CO(2) in O(2).     

Aspiration cytology of ameloblastic fibroma: a diagnostic challenge

Ameloblastic fibroma of the jaw is a rare, benign mixed odontogenic tumor, having little tendency for local invasion and a low recurrence rate. Cytologic distinction from ameloblastoma, ameloblastic fibrosarcoma, and intraosseous adenoid cystic carcinoma is necessary, in view of the different biologic behavior. A painful, slow-growing swelling of the jaw in a 5-yr-old child clinicoradiologically considered as a benign cystic lesion was aspirated. Sheets of small monomorphic epithelial cells with peripheral palisading by columnar cells were seen on cytology smears. The striking feature was central hyaline globules in some tubules. A cytologic possibility of adenomatoid odontogenic tumor was suggested. Histopathology, however, confirmed it to be an ameloblastic fibroma.