Incidence and prevalence of eye cancer

A three and one half-year-old female with Melnick-Needles osteodysplasia is presented. In addition to the characteristic bone roengenograms and obstructive uropathy, the patient had inadequate formation of bone marrow elements and pulmonary arter hypertension.     

Multiple cellular and subcellular actions of general anaesthetics on cultured molluscan neurones

The pond snail Lymnaea stagnalis has been used as a model system to study the cellular and subcellular actions of general anaesthetics. Here we describe the actions of general anaesthetics mainly on cultured, identified neurones, maintained in isolation to prevent the actions of synaptic inputs upon them. Using the whole-cell patchclamp technique, we have found that application of clinical concentrations of inhalational anaesthetics (halothane and isoflurane) and barbiturates depresses whole-cell calcium currents and potassium currents in a concentration-dependent manner. After loading cultured neurones with the ratiofluorescent dye fura-2AM, we find that halothane raises intracellular calcium concentration in a concentration-dependent manner, both in the presence and absence of extracellular calcium. Thus anaesthetics have multiple cellular and subcellular actions, some of which we have described, but most of which are yet to be discovered.     

Adsorption of botulinum toxin to activated charcoal with a mouse bioassay

STUDY OBJECTIVE: We evaluated the effectiveness of activated charcoal (AC) in adsorbing Clostridium botulinum type A toxin using a mouse bioassay. DESIGN: Prospective, blinded, randomized, controlled animal study. SETTING: Animal care facility. PARTICIPANTS: One hundred forty Swiss/Webster ND-4 strain mice. INTERVENTION: Food contaminated with type A botulinum toxin was homogenized in a phosphate/gel buffer (pH 6.2). The concentrate was diluted by factors of 1:10, 1:50, and 1:100. AC was added to aliquots of the dilutions to a 20% final concentration. The samples were centrifuged, supernatant was removed, and separate groups of mice were injected intraperitoneally with .5 mL of each dilution (those treated with AC and controls untreated with AC). The animals were then observed over 5 days for signs of botulism. RESULTS: None of the 60 animals injected intraperitoneally with dilutions treated with AC was observed to have any signs of botulism. In contrast, deaths were observed in 10 of 20, 9 of 20 and 4 of 20 mice injected with untreated dilutions of 1:100, 1:50, and 1:10, respectively (P < .004). CONCLUSION: In this model, treatment of botulinum toxin with AC before administration resulted in greatly reduced morbidity and mortality.     

All-trans-retinoic acid interacts synergistically with basic fibroblast growth factor and epidermal growth factor to stimulate the production of tissue inhibitor of metalloproteinases from fibroblasts

This report examines the effect of all-trans-retinoic acid in combination with basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF) on collagenase and tissue inhibitor of metalloproteinases (TIMP) production from human foreskin and synovial fibroblasts. When 10(-5) M retinoic acid is applied in combination with 1, 10, and 100 ng/ml of either FGF or EGF to foreskin or synovial fibroblasts, this results in a dose-dependent synergistic increase in TIMP protein production which is greater than the additive effect of the agents by up to fourfold. These responses can be inhibited by the presence of specific neutralizing antibodies to bFGF and EGF, demonstrating that they result from the presence of the growth factors and not from an experimental artifact such as bacterial endotoxin. We have also found that retinoic acid potently inhibits bFGF- and EGF-stimulated collagenase protein production in both skin and synovial fibroblasts.     

Bovine ketosis and somatotrophin: risk factors for ketosis and effects of ketosis on health and production

Aspects of the metabolism and health of 63 cows which had been treated with different amounts of bovine somatotrophin (BST) daily in the preceding lactation and 25 control cows were studied. The aims of the study were first, to identify cows with ketotic conditions, either by measurements of blood metabolite concentrations or by clinical observations, secondly, to evaluate the risk of such conditions in cows treated with BST in the preceding lactation, and thirdly, to examine the metabolic and production consequences of the ketotic conditions in an environment in which the cows' health, body condition and nutrition were closely observed. The cows were categorised objectively by the use of cluster analysis into non-ketotic cows and ketonaemic cows, on the basis of their plasma metabolite concentrations. Twelve of the control cows and none of the cows previously treated with BST were classified as ketonaemic. Similarly, nine of the control cows but only two of the cows previously treated with BST had clinical ketosis. Some, but not all, of the decrease in the risk of clinical ketosis was attributable to the lower body condition score of the cows previously treated with BST. The clinically ketotic cows had a greater risk of other illness in the first 10 days post partum than their herdmates, but the ketonaemic cows had a significantly lower risk of other disease in the first 10 days post partum. The ketonaemic control cows were significantly heavier than the non-ketotic control cows, but they maintained a higher dry matter intake than the latter cows, probably a key factor in reducing the risk of clinical ketosis.     

Clinical and research issues in breast cancer genetics

Breast cancer is the most common form of cancer in women in the U.S. The risk factors for developing breast cancer include increasing age, a family history of breast cancer, and the lack of a child by age 30. A substantial fraction of breast cancer, however, occurs in women who have no identifiable risk factors. The diagnosis, pathology, treatment, and presymptomatic testing of cancer susceptibility genes are reviewed. Syndromes with an associated risk of breast cancer are described, such as hereditary breast-ovarian cancer syndrome, Li-Fraumeni syndrome, ataxia telangiectasia, and Cowden's disease. With the localization of the BRCA1 gene to chromosome 17q21 and the BRCA2 gene to chromosome 13q12, issues surrounding breast cancer susceptibility genetic testing are assuming an ever greater measure of importance. The sensitivity and specificity for molecular testing of cancer susceptibility genes, however, have not been well defined. The progress in presymptomatic genetic testing is further hampered by various factors such as the technical difficulty in distinguishing mutations from polymorphisms, the number of different mutations identified thus far and the possibility of false positive and false negative results. Laboratory quality assurance/quality control issues are of paramount importance to avoid misleading interpretations. Many issues surrounding genetic screening and testing, such as insurance and employment discrimination, privacy, and informed consent, are under active debate, and guidelines and standards are under active development. It is therefore important to proceed with caution, so that irreversible harm resulting from data misinterpretation can be avoided.     

CO2 laser treatment; an effective and minimally disruptive endoscopic therapy for small glottic laryngeal carcinomas

OBJECTIVE: To evaluate endoscopic CO2 laser vaporization as a treatment of small glottic laryngeal carcinomas selected by means of video laryngo-stroboscopy. DESIGN: Prospective. SETTING: ENT department, University hospital, Free University Amsterdam. METHODS: Patients with a small glottic laryngeal carcinoma (stage Tis or T1a), were selected by means of video-laryngo-stroboscopy for a single stage endoscopic CO2 laser vaporization treatment as an alternative for radiotherapy. They were followed up for at least 24 months. RESULTS: Three of the 46 patients (6%) developed a local recurrence within 2 years; one of these could be treated once more with the CO2 laser, the other two were irradiated. None of these patients developed metastases in cervical lymph nodes or distant metastases. Most patients (41, 89%) assessed their voices after CO2 laser vaporization as normal or almost normal. Slight dysphonia was reported by five patients (11%). No serious dysphonia or aphonia occurred. CONCLUSION: Endoscopic CO2 laser vaporization, compared with radiotherapy or more extensive surgery, constitutes an adequate treatment for selected patients with small glottic laryngeal carcinomas. As a result of this treatment, it will be possible to preserve the larynx in more patients.     

Expression of rat bone sialoprotein promoter in transgenic mice

Bone sialoprotein (BSP) is a major protein of the mineralized bone extracellular matrix that has been implicated in the nucleation of hydroxyapatite crystals. Our previous studies have demonstrated that BSP mRNA is expressed by differentiated osteoblasts, odontoblasts, and cementoblasts involved in de novo mineralized tissue formation in a tissue-specific and developmentally regulated manner. To determine the basis of the selective expression of the BSP gene, we have generated four transgenic mouse lines in which 2.7 kb of the rat BSP promoter ligated to a luciferase reporter gene has been stably integrated into the mouse genome. Assays of luciferase activities in 5-day-old animals has revealed consistently high levels in bone tissues with negligible activities in various other organs including kidney, liver, stomach, intestine, and spleen. In some animals, variable expression was observed in brain and skin. Temporal analyses revealed the highest luciferase expression in neonatal bones, with expression decreasing markedly with subsequent growth and development, as observed previously for the endogenous gene in rats. Immunohistochemical analysis of luciferase activity and in situ hybridization of luciferase mRNA in bone tissues show that differentiated osteoblasts express the highest levels of luciferase, consistent with the induction of endogenous gene expression. These studies demonstrate that the regulation of the BSP gene during osteoblastic differentiation, together with its tissue-specific, developmentally regulated expression, is primarily mediated within the 2.7 kb region of the promoter.