Recurrence and mortality after breast-conserving surgery without radiation.

Background: Breast-conserving surgery (bcs) and radiation therapy (rt) are the standard of care for early breast cancer; studies have demonstrated that adjuvant rt confers a protective effect with respect to recurrence, although no randomized trials have shown a survival benefit. Methods: This retrospective cohort study used Ontario data linked through ices to examine patients treated for breast cancer between 1 April 2007 and 31 March 2014. The primary outcome was death or recurrence. Outcomes were compared between patients who did and did not receive rt. Results: The total cohort size was 26,279. The hazard ratios (hrs) for various outcomes were significantly higher for patients who did not receive rt than for patients who did: recurrence or death combined [hr: 2.49; 95% confidence interval (ci): 2.25 to 2.75], recurrence (hr: 2.33; 95% ci: 1.91 to 2.84), and death (hr: 2.28; 95% ci: 2.03 to 2.56). The hr for death was 1.81 (95% ci: 1.65 to 1.99) for patients having stage ii cancer compared with those having stage i disease. The hr for death was 1.97 (95% ci: 1.74 to 2.22) for patients having high comorbidity compared with those having little comorbidity. Conclusions: Adjuvant rt carries a protective effect with respect to recurrence and survival in patients with early-stage breast cancer. That survival benefit has not been appreciated in previous randomized trials and underscores the importance of rt as a component of breast cancer treatment.

Appropriate treatment receipt after breast-conserving surgery.

Background: Breast-conserving surgery (bcs) and radiation therapy (rt) are the standard of care for early breast cancer, although some women receive ipsilateral mastectomy or adjuvant tamoxifen, both of which can be appropriate alternatives to rt. Objectives of the present study were to determine the proportion of women who are treated appropriately after bcs and to identify factors associated with non-receipt of rt. Methods: This retrospective cohort study used Ontario data linked at the Institute for Clinical and Evaluative Sciences to examine 33,718 patients who received bcs during 2004-2010. Primary outcome was rt receipt. The ipsilateral mastectomy rate and patient, surgeon, and setting variables were measured. Results: Of the study patients, 86.1% received either rt or completion mastectomy; in the cohort less than 70 years of age, 90.8% received rt or completion mastectomy. Among patients less than 70 years of age, 3 risk factors for non-receipt of rt were identified: age less than 46 years, treatment in a non-academic institution, and earlier year of initial bcs. Additionally, in the overall cohort, rt non-receipt was associated with high comorbidity, more than 40 km to the cancer centre, income quintile, and breast care specialization. Conclusions: In Ontario, 90.8% of patients less than 70 years of age are appropriately treated for early breast cancer; approximately 1 in 10 do not receive rt or completion mastectomy. Based on those findings, women less than 46 years of age might be at increased risk of recurrence and death because of incomplete treatment. It also appears that academic centres more effectively treat breast cancer; however, breast cancer care appears to be improving over time in Ontario.

Phosphorylation-associated conformation shift of anti-oncogene phosphoprotein p53 in concanavalin-A activated human T lymphocytes.

A new radioimmunoassay for p53, employing an anti-peptide antibody directed against conserved Domain V, exhibited specificity for a relatively dephosphorylated form of p53. This form, correlated with the monoclonal antibody PAB421+ conformation, appeared transiently in the cytosol of cycloheximide-treated T cells undergoing activation by concanavalin-A/serum. Concurrently, there were decreased levels of p53 in the nucleus that correlated with increased phosphorylation of p53. After 90 min nuclear levels of p53 increased steadily above levels of unstimulated cells. Anti-p53 antibodies introduced into cells prior to stimulation enhanced cell proliferation in response to mitogens.

Posterior semicircular canal occlusion in the normal hearing ear.

This report outlines our experience with posterior semicircular canal occlusion, a new operative procedure for intractable benign paroxysmal positional vertigo (BPPV). We postulate that the resulting solid canal "plug" prevents endolymph movement within the posterior canal, which effectively fixes the cupula. This selectively abolishes the receptivity of the posterior canal to both angular acceleration and gravity without influencing the other inner ear receptors. We previously reported the success of this procedure in two patients with BPPV and a co-existing profound sensorineural hearing loss in the affected ear. Since that report, a slightly modified technique has been used to occlude six more posterior canals--five in normal hearing ears. While our follow-up times range from only 3 to 18 months, all eight patients continue to be relieved of their BPPV. Temporary mixed hearing losses occurred in three of the five ears with normal preoperative hearing. Hearing in all five patients ultimately returned to the preoperative state. We believe this procedure is a simpler and safer alternative to singular neurectomy for the treatment of intractable benign paroxysmal positional vertigo.

Orbital Burkitt's lymphoma in a homosexual man with acquired immune deficiency.

A 22-year-old homosexual man had persistent systemic lymphadenopathy and a three-week history of rapid swelling and induration of his right upper eyelid. Acquired immune deficiency leading to the development of lymphoma was suspected. A biopsy specimen of the mass revealed Burkitt's lymphoma and treatment with systemic chemotherapy and radiation therapy resulted in remission. A significant number of patients with acquired immune deficiency are developing Burkitt's lymphoma. The three separate syndromes of acquired immune deficiency and their associated ophthalmic manifestations are discussed.

Purification of a protein phosphatase from Acanthamoeba that dephosphorylates and activates myosin II.

The actin-activated ATPase activity of myosin II from Acanthamoeba castellanii is inhibited by phosphorylation of 3 serine residues near the carboxyl end of the heavy chain of the molecule. We have purified a protein phosphatase from Acanthamoeba using myosin II as a substrate. This phosphatase has a molecular weight of 39,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an isoelectric point in urea of 5.2. The enzyme also is active against other phosphoserine protein substrates such as turkey gizzard smooth muscle myosin light chain, but not against a synthetic phosphotyrosine protein substrate. It does not hydrolyze ATP or p-nitrophenol phosphate. No effector has been found to increase substantially the activity of the enzyme as isolated, but it is inhibited by ATP, pyrophosphate, and NaF. This inhibition is reduced in the presence of MnCl2. The Mg2+-dependent actin-activated ATPase of myosin II is activated by dephosphorylation of phosphorylated myosin II by the phosphatase. Its broad substrate specificity, molecular weight, and response to protein phosphatase inhibitors suggest that the Acanthamoeba protein phosphatase is a type 2A phosphatase (Cohen, P. (1982) Nature (Lond.) 206, 613-620).

Recovery nystagmus in Ménière's disease.

Spontaneous nystagmus occurs during a Meniere's attack although the literature indicates that the direction can be variable. Previous observations made during the acute and recovery stages of a Meniere's attack suggested that the direction of the spontaneous nystagmus was consistent with the primary-secondary sequence of nystagmus that occurs with relatively prolonged stimulation of the normal vestibulo-oculomotor system. To evaluate this nystagmus pattern further, spontaneous nystagmus was monitored in eight patients using DC electronystagmography during an acute Meniere's attack. All showed an initial contralateral nystagmus during the acute phase of the attack with reversal to an ipsilateral (or recovery) nystagmus, as the acute symptoms subsided. Such a pattern of nystagmus occurring over a few hours is a helpful diagnostic aid, and when surgery is being considered, it provides objective evidence of the ear with active disease.

Characterization of the membrane fraction isolated by the fluorescein mercuric acetate technique of Barland and Schroeder.

Using scanning electron microscopy we have demonstrated that tha membrane fraction isolated by the fluorescein mercuric acetate technique of Barland and Schroeder (Barland, P. and Schroeder, E.A. (1975) J. Cell Biol. 45, 662-668) represents a topologically distinct membrane which circumscribes the cell nucleus. Our data suggest that not all the cells within a non-synchronized cell population release a membrane fraction after treatment according to the technique of Barland and Schroeder, but rather that the efficiency of membrane release achieved using this preparative technique is dependent on the morphology of individual cells. Our work has also demonstrated that the peptide composition of the membrane fraction isolated by the technique of Barland and Schroeder differs from the peptide composition of the plasma membrane-enriched fraction isolated by the technique of Brunette and Till (Brunette, D.M. and Till, J.E. (1971) J. Membrane Biol. 5, 215-224). This difference in peptide composition is particularly noticeable among the higher molecular weight proteins, glycoproteins and iodineateable membrane components. The data which we have accumulated suggest that the compositional differences noted between the two membrane isolates do not result from differential extraction of membrane components during the ZnCl2-fluorescein mercuric acetate treatments required in the isolation technique originally described by Barland and Schroeder. However, our data do clearly demonstrate that the membrane isolation technique of Barland and Schroeder cannot be used to study the general composition of the plasma membrane.