Distribution of epidermal growth-factor receptors in normal and neoplastic mammary tissues

Epidermal growth factor (EGF) is considered to be mitogenic for proliferation of mammary glands in animals. The action of EGF is mediated by specific EGF receptors (EFG-R). In the present study, we investigated distribution of EGF receptors during various physiological stages of mammary glands, N-methyl-N-nitrosourea (MNU)-induced mammary tumors in rats and human breast cancer samples. EGF receptor concentrations were determined by Scatchard analyses in the membrane fraction of the tissues. Results showed increased EGF receptor levels in the structurally differentiated mammary tissues from pregnant rats; whereas lower concentrations were observed in the functionally differentiated glands from lactating rats. EGF receptors were absent in the majority of the tumors induced by MNU. The loss of EGF receptor was not observed during the first 20 days post carcinogen treatment, but appeared to be correlated with the onset of the tumor. Consistent with the literature, the majority of the steroid receptor positive human breast cancer samples were EGF receptor negative, whereas steroid receptor negative samples contained EGF receptors. These results suggest that the loss of EGF receptors in ovarian hormone dependent mammary tumors does not occur gradually during carcinogenesis but appears to be a characteristic of hormone dependent mammary tumor cells.     

Linear Accelerator Configurations for Radiosurgery

The dramatic proliferation of radiosurgery in the 1980s and 1990s has resulted in the development of a plethora of hardware systems and an exponential increase in clinical use. This article summarizes the initial, now mostly historical, developments and emphasizes that most linear accelerator radiosurgery systems are based on three early prototypical systems from Buenos Aires, Heidelberg, and Montréal. These systems have more recently been tailored to permit fractionated radiosurgery, blurring the distinction between radiosurgery and radiotherapy. The commonly used fractionated systems are described. Clinical outcome data for arteriovenous are described. Clinical outcome data for arteriovenous malformations, acoustic neuroma, and meningioma, are mostly preliminary but substantial data are available for the radiosurgical management of metastases. With the recent emphasis on cost containment, cost-effectiveness issues have become significant and at least for metastases some preliminary data suggest a potential "cost benefit" with radiosurgery. The recent publication of data from a prospective randomized trial has established the superiority of boost therapy for malignant glioma and in this article, we present preliminary evidence supporting the use of radiosurgery. Finally, some of the new and exciting developments such as the robot-mounted linear accelerator, the use of shaped fields, and tomotherapy are described.     

Prevalence of the GABAA receptor assemblies containing alpha1-subunit in the rat cerebellum and cerebral cortex as determined by immunoprecipitation: lack of modulation by chronic ethanol administration

The anti-alpha1 antibody elicited higher immunoprecipitation (%) values of the [3H]flunitrazepam and [3H]muscimol binding activity in the rat cerebellum vs. cerebral cortex, whereas immunoprecipitation values for [3H]Ro 15-4513 and [3H]zolpidem were comparable in these brain regions. Chronic ethanol administration neither changed the radioligand binding to the immunoprecipitated pellet nor the percentage immunoprecip-itation values, thereby indicating that chronic ethanol did not result in down-regulation of the GABAA receptor assemblies containing alpha1-subunit.     

Polyglactin sutures versus nylon sutures for scleral flap suturing in trabeculectomy

BACKGROUND AND OBJECTIVES: To note the effect on filtration function of using polyglactin sutures for scleral flap suturing in trabeculectomy. PATIENTS AND METHODS: Polyglactin sutures were compared with nylon sutures to secure the scleral flap of trabeculectomy in 30 consecutive eyes. Parameters studied were intraocular pressure, central anterior chamber depth, and bleb score in this randomized prospective study. RESULTS: Observations regarding intraocular pressure, central anterior chamber depth and bleb score in the early postoperative period were comparable in the 2 groups. The results at 12 months follow-up reveal a lower mean IOP (P < 0.05) and a higher mean bleb score (P < 0.05) in the group with polyglactin sutures. Success rate (defined as IOP < 21 mm Hg) at 12 months was 100% with use of polyglactin sutures compared to 80% with nylon sutures. CONCLUSIONS: Polyglactin sutures can be used as an alternative to nylon sutures for scleral flap suturing in trabeculectomy, with the possible additional benefit of better long-term filtration function.     

Chronic diarrhea: Causes,presentation, and mangement

Important inroads are being made into understanding the pathophysiology of diarrhea. Clear understanding of key mechanisms should suggest new approaches to combat disease. Exciting developments are occurring in terms of super-ORS solutions, particularly with the promise of short chained glucose polymers and glutamine. Perhaps the most important development is the prospect of a good rotavirus vaccine being available before the end of the decade. Chronic diarrhea seems to be on the increase globally, probably because of the success of ORS. The mechanisms that lead to mucosal injury are elusive, and therapy still largely supportive and empiric. Celiac disease continues to be a puzzle, because of the uncomfortable feeling that a majority of cases may be missed because of atypical presentations. The successful use of long term parenteral nutrition has allowed survival and better charaterization of cases that otherwise would have perished as ‘lethal protracted diarrhea’. Microvillus inclusion disease may be the commonest congenital secretory diarrhea. The role of the recently reported high prevalence of glucoamlase deficiency may be important. Lastly, attention to micronutrients, particularly low vitamin A and probably zinc may prove to be important in prevention and amelioration of diarrhea and growth failure.     

Altered metabolism of all-trans-retinoic acid in liposome-encapsulated form

Treatment with all-trans-retinoic acid (ATRA) induces complete remission in many acute promyelocytic leukemia patients. However, plasma drug levels progressively decrease following prolonged treatment with oral ATRA. This decrease is due, at least in part, to the induced cytochrome P-450-dependent metabolism of ATRA. To investigate if incorporation of ATRA in liposomes could alter its metabolism, we compared the cellular metabolism of liposomal-ATRA (L-ATRA) with free drug. Microsomes isolated from the rat liver metabolized L-ATRA to a significantly lower extent than they did free-ATRA. Similarly, in F9 cells, L-ATRA was metabolized at a slower rate than the free drug. These results suggest that L-ATRA may have important clinical implications in terms of slowing down the rate of ATRA metabolism and producing long-term remission in APL patients.     

Pharmacokinetics and pharmacodynamics of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione in patients with postmenopausal breast cancer

Summary The pyridylglutarimide 3-ethyl-3-(4-pyridyl)-piperidine-2,6-dione (PyG) is a novel inhibitor of aromatase that was shown to cause effective suppression of plasma oestradiol levels in postmenopausal patients. In four patients receiving oral doses of PyG (500 mg) twice daily for 3–4 days, oestradiol levels fell to 31.1%±6.3% of baseline values within 48 h and remained suppressed during treatment. Of a further six patients who received oral PyG (1 g) as a single dose, five had quantifiable oestradiol levels. Oestradiol suppression was sustained for 36 h and recovery correlated with a fall of PyG concentrations below a threshold value of ca. 2 g/ml. The pharmacokinetics of PyG were non-linear and, when fitted to the integrated Michaelis-Menten equation, yielded good parameter estimates forC _o (21.7±1.82 g/ml),K _m (2.66±0.68 g/ml) and V_max (0.86±0.06 g ml^–1 h^–1). On subsequent repeated dosing with PyG, both theK _m (4.31±0.48 g/ml) and the V_max (1.83±0.13 g ml^–1 h^–1) values increased and recovery from oestradiol suppression was more rapid, indicating that PyG induces its own metabolism.Abbreviations PyG 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione - AG aminoglutethimide - CSCC cholesterol side-chain cleavage - HPLC high-performance liquid chromatography - AUC area under the concentration versus time curve This study was supported in part by grants to the Institute of Cancer Research (Royal Cancer Hospital) from the Cancer Research Campaign and Medical Research Council