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Incompetency--Massachusetts applies substituted judgment to probate court sterilization proceedings--In re Moe, 385 Mass. 555, 432 N.E.2d 712 (1982)
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A Multidisciplinary Approach to Locoregional Management of the Axilla for Primary Operable Breast Cancer.
BACKGROUND: Lymph node metastasis is the single most important factor in assessing breast cancer prognosis and planning systemic therapy. However, lymph node dissection portends significant morbidity, with little or no therapeutic benefit if the nodes prove to be negative for cancer. METHODS: The authors review indications for avoiding axillary dissection, and they analyze the results from lower-level axillary lymphadenectomy together with the morbidity from full axillary dissection. RESULTS: Limited level I dissection depends on surgical technique and limits prognostic information. Three approaches have evolved to identify the sentinel node in breast cancer: perilesional breast injection of radiocolloid alone, blue dye alone, or a combination of radiocolloid and blue dye. These techniques provide high diagnostic accuracy, few false-negative results, and less morbidity. CONCLUSIONS: Knowledge of axillary status is critical to current breast cancer management and cannot be foregone in the preponderance of patients with advanced breast cancer. Results from lymphatic mapping and sentinel node biopsy are highly encouraging.
Drinking water contamination in Walkerton, Ontario: positive resolutions from a tragic event.
In May 2000, Escherichia coli O157:H7 and Campylobacter jejuni contaminated the drinking water supply in Walkerton, Ontario. Seven people died and over 2,000 were ill as a result. The Ontario Provincial Government set up a judicial Inquiry into the circumstances surrounding the outbreak and also moved quickly to introduce a new Drinking Water Regulation that incorporated some significant requirements for drinking water providers. The Inquiry itself was in three parts: (a) part 1 related to the events that occurred in Walkerton and why the water contamination occurred; (b) part 1A related specifically to the role of the Provincial Government in the event; and (c) part 2 related to the future of drinking water safety in Ontario with potential to influence regulation on a wider basis. A number of other actions were taken after Walkerton. In August 2000, the Ontario Government, through the Regulatory body, the Ontario Ministry of the Environment (MOE) (a) re-issued and revised the Ontario Drinking Water Objectives (ODWO) as the Ontario Drinking Water Standards (ODWS) and (b) introduced new regulations governing drinking water in Ontario--the Ontario Drinking Water Protection Regulation. One of the key features of the Drinking Water Protection Regulation was the requirement to produce an independent Engineers' Report on all water systems. This paper provides a unique perspective on the Walkerton tragedy and its aftermath. The author was active in many aspects of the resulting activity (Chair of the Ontario Water Works Association's (a section of the AWWA) Special Committee involved in Part 2 of the Walkerton Inquiry; author of several of the Engineers' Reports mandated by Regulation; reviewer on behalf of the Regulator of Engineers' Reports submitted by others). The Engineers' Reports were of interest because (1) the drinking water providers (mostly municipalities) were mandated by regulation to complete the Reports by specific dates and are paying for the Reports, (2) the work had to be done by a registered professional engineer who is not an employee of the owner or the operator if a different entity and (3) the engineer had to sign a declaration that the Regulator could rely on the accuracy of the Report. In other words, the Municipality retained the Engineer and paid them to produce the Report--the Engineer essentially carried the liability while the Regulator had the final say in the acceptability of the Report, a sort of eternal triangle of responsibilities. The paper will outline how the drinking water profession in North America worked together to provide the Walkerton Inquiry with the benefit of its experience and knowledge of best practices to the benefit of consumers and the drinking water providers. It will also outline the procedures adopted to produce the independent Engineers' Reports and how the findings are being applied to further improve drinking water safety in Ontario, across Canada and in similar situations around the world.
[Bilateral massive ovarian edema: a case report including MR findings and etiology].
A 42-year-old woman with bilateral massive ovarian edema (MOE) is presented. MOE is usually seen in women 6 to 33 years of age. Therefore, accurate re-operative assessment of MOE is important to avoid unnecessary oophorectomy procedures. MR findings of MOE are characteristic and reflect very well the diffuse stromal edema noted on microscopy. The etiology and MR findings of MOE are discussed.
A mathematical model of parasystole and its application to clinical arrhythmias.
A ventricular parasystolic focus capable of generating manifest ectopic beats should not be totally insulated from the electrical events that accompany depolarization in the surrounding tissue; the intrinsic cycle length of the ectopic discharge may be modulated by electrotonic influences transmitted across the zone of "protection." To study the nature of the interaction, response patterns were examined in a mathematical model programmed to simulate an ectopic pacemaker protected, but not divorced from ventricular responses to the normal pacemaker. Computer runs covered a wide range of heart rates, and a wide range of magnitudes of the simulated electrotonic influence. Application of the results obtained in the model to published examples of complex arrhythmias revealed a remarkably close fit to many clinical examples. This findings suggests that many patterns attributed to a re-entrant "extrasystolic" rhythm may, in fact, represent the modulated activity of a parasystolic focus.
The case for modulated parasystole.
Several recently published tracings of parasystolic rhythms with unusual features were studied to determine whether the biphasic response curve characteristic of modulated parasystole could be extracted from the patterns of arrhythmia. Even in cases in which the possibility of modulation had been rejected, the phase response curves could be derived by inverse analysis of the ectopic intervals. When the derived curves were inserted into the program of the computer model, almost exact matches for the clinical patterns were recorded. In one case, in which the right atrium was driven at increasing rates, the patterns of manifest ectopic ventricular responses appeared to be re-entrant rather than parasystolic. In this case, similar patterns as a function of heart rate were recorded from a mathematical model of reflection.
Worker exposure standard for phosphine gas.
The 1998 U.S. Environmental Protection Agency Office of Pesticide Programs (OPP) re-registration eligibility decision (RED) for phosphine fumigants has generated much interest in defining safe levels of exposure for workers and worker bystanders. This report summarizes the pertinent literature on phosphine toxicity, including animal inhalation studies and human epidemiology studies, and also describes a margin-of-exposure (MOE) analysis based on available worker exposure data. In addition, a safe occupational exposure limit is estimated using typical OPP assumptions, after determination of appropriate uncertainty factors, based on quality of data in the principal study and pharmacokinetic considerations. While a conservative 8-hour time-weighted average (TWA) of 0.1 ppm was calculated, the overall weight of evidence, from a risk-management perspective, supports a conclusion that an occupational TWA of 0.3 ppm provides adequate health protection. In addition, a 15-minute short-term exposure limit (STEL) of 3 ppm was estimated. Finally, in contrast to the MOE analysis described in the OPP's phosphine RED, the MOE analysis described herein does not indicate that fumigation workers are currently being exposed to unacceptable levels of phosphine. Collectively, these findings support the occupational exposure limits of 0.3 ppm (8-hour TWA) and 1 ppm (STEL) established in the updated applicator's manuals for phosphine-generating products, which recently received approval from OPP.
[Circadian variations and modification of ventricular parasystole].
As shown by Jalife and Moe, brief subliminar depolarizations induced upstreams of the protection zone may predictably modify the discharge from a parasystolic focus. In the biological and mathematical models of parasystole, numerous arrhythmias which do not fulfil the classical criteria of parasystole have been identified, some of them even mimicking a re-entry mechanism. In this paper we report the electrocardiograms of three patients in whom an electrotonic modulation mechanism may be involved. In the first patient the classical pattern of continuous parasystole without exit block was observed throughout daytime. However, between 1 and 5 a.m. non parasystolic beats lengthened or shortened the parasystolic rhythm, depending on their time-related position in the cycle. Later, the usual continuous parasystole pattern reappeared. In the second patient the patent 1:1 entrainment of parasystole by sinus beats resulted in long episodes of ventricular bigeminy with fixed coupling. A sudden slowing down of the cardiac rate disrupting the harmony of the two rhythms and, consequently, the regular entrainment of the ectopic focus, shortened the parasystolic cycle and suppressed bigeminy. In the third patient ventricular stimulation produced a hisian parasystolic rhythm resembling intermittent parasystole on surface ECG. It is concluded that, as suggested by experimental models, many disorders of cardiac rhythm which do not fulfil the criteria of parasystole can be explained in terms of modulated parasystole.
On the effect of vinblastine on ameloblasts of rat incisors in vivo. 2. Protracted effect on secretory ameloblasts. A light microscopical study.
The effects of vinblastine sulphate at a dosage of 0.2 mg per 100 g body weight on the secretory ameloblasts of rat incisors were studied 3, 6 and 24 hours and 3 and 7 days after administration of the drug. The vinblastine affected the secretion profoundly, caused a reduction in size of the cells and death of many ameloblasts. Most of the surviving ameloblasts restored initially-induced loss of polarity. Many also resumed secretion and deposition of enamel matrix. The Tomes' processess were extremely sensitive to vinblastine and all matrix deposited after administration of the drug appeared abnormal in structure. Ameloblasts not resuming secretory activity were less than half the size (height) of normal cells. In some areas all the ameloblasts were destroyed with the exception of a varying number of surviving ameloblasts parts consisting only of a nucleus and a small amount of cytoplasm. The ameloblasts which had re-established secretory activity, and most of the ameloblasts which had not, retained their ability to transform into transporting ameloblasts. Large amounts of ameloblast debris present 3 and 6 hours after administration of the vinblastine were effectively engulfed and digested by the cells of the striatum intermedium within 24 hours.
Iron metabolism in end stage renal failure: rationale for re-evaluation of parenteral iron therapy.
PURPOSE OF REVIEW: In this article we will examine the basis for using chronic high dose parenteral iron therapy in dialysis patients. RECENT FINDINGS: There are increasing data that dialysis patients fare better in many respects if they have higher hematocrit values although the real optimal hematocrit has not been defined. There is an increasing tendency to use parenteral iron to achieve this goal. SUMMARY: Although parenteral iron achieves seemingly favourable short results, there are no data for its safety in the long term. On the contrary, there are reasons to suggest possible iron overload with chronic use.
Epitopes recognized by a nonautoreactive murine anti-N-propionyl meningococcal group B polysaccharide monoclonal antibody.
The capsular polysaccharide of Neisseria meningitidis group B (MBPS) is a polymer of alpha (2-->8) N-acetyl neuraminic acid. The polysaccharide is chemically identical to an autoantigen, polysialic acid (PSA), and is a poor immunogen, even when conjugated to protein carriers. Immunization of mice with MBPS-protein conjugate vaccines, in which N-acetyl groups have been replaced by propionyl groups (N-Pr MBPS), elicits serum bactericidal antibodies. A subpopulation of these antibodies do not cross-react with human PSA. The reasons for the increased immunogenicity of N-Pr MBPS and the antigenic targets of the bactericidal nonautoreactive antibodies are unknown. In this study, we investigated the antigenic targets of a protective murine monoclonal antibody (MAb) prepared against a N-Pr MBPS-tetanus toxoid conjugate vaccine. Binding of the MAb to N-Pr MBPS (as demonstrated by an enzyme-linked immunosorbent assay) and bactericidal activity were inhibited by de-N-acetylated MBPS and re-N-acetylated MBPS, which indicate that N-propionyl groups are not obligatory determinants for binding. The results of affinity selection from a preparation of N-Pr MBPS and matrix-assisted laser desorption ionization-time of flight mass spectroscopic analysis indicated that the minimal epitope recognized by the MAb is a MBPS disaccharide containing one de-N-acetylated residue. Thus, the bacterial capsular epitope recognized by this bactericidal, nonautoreactive, anti-group-B MAb likely contains de-N-acetyl residues.
Correlating a protein structure with function of a bacterial mechanosensitive channel.
MscL, a mechanosensitive channel found in many bacteria, protects cells from hypotonic shock by reducing intracellular pressure through release of cytoplasmic osmolytes. First isolated from Escherichia coli, this protein has served as a model for how a protein senses and responds to membrane tension. Recently the structure of a functionally uncharacterized MscL homologue from Mycobacterium tuberculosis was solved by x-ray diffraction to a resolution of 3.5 A. Here we demonstrate that the protein forms a functional MscL-like mechanosensitive channel in E. coli membranes and azolectin proteoliposomes. Furthermore, we show that M. tuberculosis MscL crystals, when re-solubilized and reconstituted, yield wild-type channel currents in patch clamp, demonstrating that the protein does not irreversibly change conformation upon crystallization. Finally, we apply functional clues acquired from the E. coli MscL to the M. tuberculosis channel and show a mechanistic correlation between these channels. However, the inability of the M. tuberculosis channel to gate at physiological membrane tensions, demonstrated by in vivo E. coli expression and in vitro reconstitution, suggests that the membrane environment or other additional factors influence the gating of this channel.