The information needs and media preferences of Canadian cancer specialists regarding breast cancer treatment related arm morbidity.

The information needs and media preferences of Canadian cancer specialists regarding breast cancer treatment related arm morbidity. Breast cancer treatment related arm morbidity is a common but pernicious condition that is under-recognised, under-diagnosed, and can result in long-term impairment and disability. Despite the prevalence of this condition, little is known about breast cancer specialists' information needs and media preferences around this issue. In-depth telephone interviews with 14 Canadian cancer specialists were conducted, and were coded and analysed using a grounded theory approach. Findings revealed that cancer specialists were open to receiving all types of information about treatment related arm morbidity, and have preferences for particular types of media formats. However, barriers that could problematise the uptake of research findings into clinical practice were also noted and included gaps in specialists' knowledge of the complex nature of treatment related lymphoedema. Hence providing specialists with summary information about arm morbidity will not suffice, and an educational campaign around this condition, including the importance of physician vigilance in regularly monitoring patients for early and latent indications of this morbidity may be necessary.

Effects of IKr and IKs heterogeneity on action potential duration and its rate dependence: a simulation study.

BACKGROUND: A growing body of evidence suggests that heterogeneity of ion channel expression and electrophysiological characteristics is an important property of the ventricular myocardium. The 2 components of the delayed rectifier potassium current, IKr (rapid) and IKs (slow), play a dominant role in the repolarization of the action potential and are important determinants of its duration. METHODS AND RESULTS: In this report, the effects of heterogeneities of IKr and IKs on action potential duration (APD) and its rate dependence (adaptation) are studied with the use of the LRd model of a mammalian ventricular cell. Results demonstrate the importance of IKs density variations in heterogeneity of repolarization. Cells with reduced IKs (eg, mid-myocardial M cells) display long APD and steep dependence of APD on rate. Mechanistically, accumulation of IKs activation and increased sodium calcium exchange current, INaCa, secondary to Na+ accumulation at a fast rate underlie the steep APD-rate relation of these cells. When cells are electrotonically coupled in a multicellular fiber through resistive gap junction, APD differences are reduced. The results demonstrate strong dependence of APD heterogeneity on the degree of intercellular coupling even in the normal physiological range. Highly reduced coupling maximizes APD heterogeneity. CONCLUSIONS: Heterogeneity of IKs:IKr density strongly influences APD and its rate dependence. However, in the intact myocardium, the degree of gap-junction coupling may be an important factor that determines the manifestation of APD heterogeneity and dispersion of repolarization. The clinical significance of this study is in the context of repolarization abnormalities and associated arrhythmias (eg, long QT syndrome and torsade de pointes).

Ionic mechanisms of propagation in cardiac tissue. Roles of the sodium and L-type calcium currents during reduced excitability and decreased gap junction coupling.

In cardiac tissue, reduced membrane excitability and reduced gap junction coupling both slow conduction velocity of the action potential. However, the ionic mechanisms of slow conduction for the two conditions are very different. We explored, using a multicellular theoretical fiber, the ionic mechanisms and functional role of the fast sodium current, INa, and the L-type calcium current, ICa(L), during conduction slowing for the two fiber conditions. A safety factor for conduction (SF) was formulated and computed for each condition. Reduced excitability caused a lower SF as conduction velocity decreased. In contrast, reduced gap junction coupling caused a paradoxical increase in SF as conduction velocity decreased. The opposite effect of the two conditions on SF was reflected in the minimum attainable conduction velocity before failure: decreased excitability could reduce velocity to only one third of control (from 54 to 17 cm/s) before failure occurred, whereas decreased coupling could reduce velocity to as low as 0.26 cm/s before block. Under normal conditions and conditions of reduced excitability, ICa(L) had a minimal effect on SF and on conduction. However, ICa(L) played a major role in sustaining conduction when intercellular coupling was reduced. This phenomenon demonstrates that structural, nonmembrane factors can cause a switch of intrinsic membrane processes that support conduction. High intracellular calcium concentration, [Ca]i, lowered propagation safety and caused earlier block when intercellular coupling was reduced. [Ca]i affected conduction via calcium-dependent inactivation of ICa(L). The increase of safety factor during reduced coupling suggests a major involvement of uncoupling in stable slow conduction in infarcted myocardium, making microreentry possible. Reliance on ICa(L) for this type of conduction suggests ICa(L) as a possible target for antiarrhythmic drug therapy.

Electrophysiologic effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration.

OBJECTIVE: To study the ionic mechanisms of electrophysiologic changes in cell excitability and action potential duration during the acute phase of myocardial ischemia. METHODS: Using an ionic-based theoretical model of the cardiac ventricular cell, the dynamic LRd model, we have simulated the three major component conditions of acute ischemia (elevated [K]o, acidosis and anoxia) at the level of individual ionic currents and ionic concentrations. The conditions were applied individually and in combination to identify ionic mechanisms responsible for reduced excitability at rest potentials, delayed recovery of excitability, and shortened action potential duration. RESULTS: Increased extracellular potassium ([K]o) had the major effect on cell excitability by depolarizing resting membrane potential (Vrest), causing reduction in sodium channel availability. Acidosis caused a [K]o-independent reduction in maximum upstroke velocity, (dVm/dt)max. A transition from sodium-current dominated to calcium-current dominated upstroke occurred, and calcium current alone was able to sustain the upstroke, but only after sodium channels were almost completely (97%) inactivated. Acidic conditions prevented the transition to calcium dominated upstroke by acidic reduction of both sodium and calcium currents. Anoxia, simulated by lowering [ATP]i and activating the APT-dependent potassium current, IK(ATP), was the only process that could decrease action potential duration by more than 50% and reproduce AP shape changes that are observed experimentally. Acidic or anoxic depression of the L-type calcium current could not reproduce the observed action potential shape changes and APD shortening. Delayed recovery of excitability, known as 'post-repolarization refractoriness', was determined by the voltage-dependent kinetics of sodium channel recovery; Vrest depolarization caused by elevated [K]o increased the time constant of (dVm/dt)max recovery from tau = 10.3 ms at [K]o = 4.5 mM to tau = 81.4 ms at [K]o = 12 mM, reflecting major slowing of sodium-channel recovery. Anoxia and acidosis had little affect on tau. CONCLUSIONS: The major conditions of acute ischemia, namely elevated [K]o, acidosis and anoxia, applied at the ionic channel level are sufficient to simulate the major electrical changes associated with ischemia. Depression of membrane excitability and delayed recovery of excitability in the single, unloaded cell are caused by elevated [K]o with additional excitability depression by acidosis. Major changes in action potential duration and shape can only be accounted for by anoxia-dependent opening of IK(ATP).

Cardiac excitation: an interactive process of ion channels and gap junctions.

Theoretical simulations were performed to study the interplay between membrane ionic currents and gap-junction coupling in determining cardiac conduction. Results demonstrate that a much slower conduction velocity can be achieved with reduced gap-junction coupling than with reduced membrane excitability. Also, uniform reduction in intercellular coupling increases spatial asymmetries of excitability and, consequently, the vulnerability to unidirectional block.

Electrophysiologic effects of acute myocardial ischemia. A mechanistic investigation of action potential conduction and conduction failure.

A multicellular ventricular fiber model was used to determine mechanisms of slowed conduction and conduction failure during acute ischemia. We simulated the three major pathophysiological component conditions of acute ischemia: elevated [K+]o, acidosis, and anoxia. Elevated [K+]o was the major determinant of conduction, causing supernormal conduction, depressed conduction, and conduction block as [K+]o was gradually increased from 4.5 to 14.4 mmol/L. Only elevated [K+]o caused conduction failure when varied within the range reported for acute ischemia. Before block, depressed upstrokes consisted of two distinct components: the first to the fast Na+ current (INa) and the second to the L-type Ca2+ current (ICa(L)). Even in highly depressed conduction, excitability was maintained by INa, with conduction block occurring at 95% INa inactivation. However, because ICa(L) supported the later phase of the depressed upstroke, ICa(L) enhanced conduction and delayed block by increasing the electrotonic source current. At [K+]o = 18 mmol/L, slow action potentials generated by ICa(L) were obtained with 10% ICa(L) augmentation. However, in the presence of acidosis and anoxia, significantly larger (120%) ICa(L) augmentation was required. The depressant effect was due mostly to anoxic activation of outward ATP-sensitive K+ current, which counteracts inward ICa(L) and, by lowering the action potential amplitude, decreases the electrotonic current available to depolarize downstream cells. The simulations highlight the interactive nature of electrophysiological ischemic changes during propagation and demonstrate that both membrane changes and load factors (by downstream fiber) must be considered.

A preliminary study of the effects of laser radiation on collagen metabolism in cell culture.

A low power Ga-As pulse laser was used to stimulate cultured human embryonic fibroblast cells. Energy fluencies varied from 0-1 J/cm2 over a period of 1-4 days. Fibroblast procollagen production was monitored by the synthesis of [3H] hydroxyproline, and DNA replication was assessed by [3H] thymidine incorporation. Following laser treatment, controlled pepsin digestion measured the increase in cell biostimulation. Maximum increase in collagen production and cell biostimulation occurred after 4 episodes of laser treatment at 24-hour intervals. Laser doses between 0.099 and 0.522 J/cm2 had the most significant stimulatory effects on fibroblast function. Clinical efficacy of the low power Ga-As pulse laser may be related to enhanced connective tissue repair.

Collagen type in dysfunctional temporomandibular joint disks.

Controlled studies were undertaken to ascertain the nature of the fibrous tissue component of surgically removed dysfunctional human temporomandibular joint disks. Each disk was divided into several parts and dissociative methods were used to extract collagenous residues. The resultant residues were digested with cyanogen bromide and the obtained soluble peptides were characterized by their electrophoretic mobility on polyacrylamide slab gels. The separated peptides were then scanned on a laser densitometer. Type III collagen was identified in samples taken from both the women's and the men's posterior disk attachment tissues. The amount of type III collagen in the women's attachments was approximately twice that found in the men's and both of these quantities were greater than those previously found in nondysfunctional tissues. The finding that there was more type III collagen in the posterior attachments of the women's chronically damaged disks may indicate that these tissues in women are less able to withstand functional loading.

The vulnerable window for unidirectional block in cardiac tissue: characterization and dependence on membrane excitability and intercellular coupling.

INTRODUCTION: Unidirectional block is a requisite event in the initiation of reentry in cardiac tissue, but its initiation and behavior in the presence of tissue pathologies remain poorly understood. Previous experimental and theoretical reports on vulnerability to unidirectional block under conditions of reduced cellular coupling and reduced membrane excitability have varied due to differences in experimental and simulation protocols. METHODS AND RESULTS: We have addressed the issue of vulnerability to unidirectional block using the recent Luo-Rudy membrane model and computer simulations of propagation in a one-dimensional cardiac fiber. The vulnerable window (VW) of unidirectional block from premature stimulation is expressed in units of time, VWtime, and as a range of membrane potentials at the stimulus site, VWpot. VWpot and VWtime were quantified over a range of membrane excitability and gap junction resistances (intercellular coupling). With normal membrane excitability and intercellular coupling, VWpot and VWtime were small (VWpot = 0.44 mV, VWtime = 0.39 msec). A uniform reduction (0.25x) in the degree of intercellular coupling increased VWtime and VWpot by factors of 3.6 and 4.7, respectively, whereas a uniform decrease (0.25x) in membrane excitability (same resulting velocity) increased VWtime by only a factor of 0.4 and decreased VWpot to negligible levels. When inhomogeneities in fiber properties were introduced (intercellular coupling and membrane excitability), VWtime increased more due to inhomogeneity in membrane excitability (VWtime = 4.5 msec) than to inhomogeneity in intercellular coupling (VWtime = 1.5 msec). The simulations also clarify the dependence of the VW on the dimensions of the stimulating electrode. The length of the stimulating electrode added a factor, equal to the propagation time across the electrode length, to the intrinsic VW of the fiber. CONCLUSIONS: VWpot and VWtime are both important parameters for quantifying vulnerability to unidirectional block. In an environment with uniform distribution of fiber and membrane properties, reduced intercellular coupling has a greater effect on the VW than reduced membrane excitability. Inhomogeneous reduction of membrane excitability can significantly enhance vulnerability to unidirectional block, much more so than inhomogeneous reduction of intercellular coupling. Theoretically, stimulation at a point should be used to define the VW. Finite electrode dimensions introduce a geometrical factor that affects the measurement of the VW.

Age-related changes to the surface ultrastructure of the rabbit temporomandibular disc.

The ultrastructural characteristics of the temporomandibular disc were investigated by transmission electron microscopy in rabbits, aged from 7 d to 6 y. The disc is interposed between the head of the mandibular condyle below, and the squamous temporal bone above, within the temporomandibular joint. A single layer of flattened mesenchymal cells covered the articular surface of the disc during early postnatal development. Gradual disappearance of this cell layer was succeeded by the development of an articular surface lamina. The first appearance of the lamina coincided with the transition from suckling to adult masticatory function. With advancing age, the lamina increased in thickness from 0.3 to 1.0 micron in adulthood, and was well demarcated from the subsurface tissue. The lamina was a continuous, smooth, electron-dense layer, that reacted biochemically as proteoglycan complex. The surface lamina may be responsible for the low frictional properties associated with articular movement and load, and the selective passage of molecules bidirectionally across the cartilage-fluid interface. Variations in lamina thickness occurred topographically across the disc and were attributed to site concentration of shearing stress. Beneath the articular surface lamina were cells surrounded by collagenous intercellular stroma. Chondrocytic, fibrocytic and fibrochondrocytic cellular phenotypes were present. Subsurface cellular debris accumulated within the rabbit disc from the commencement of mastication. Mature adult disc contained expanses of debris, attributed to cell death in situ. Foci of mineral precipitates were found within ageing discal tissue.

The effects of mandibular hypofunction on the development of the mandibular disc in the rabbit.

The effect of a reduced functional dentition on the development of the mandibular disc in young rabbits was studied by measuring cell proliferation within the disc following tooth extraction. Maxillary and mandibular incisor teeth were extracted from 18 animals at 5 weeks of age. At 12 weeks the rabbits received 0.25 mg/kg vincristine sulphate. Groups of three animals were killed 1.5, 3, 6, 12, 24 and 48 h after the injection of vincristine and the mitotic rate determined across the anterior, intermediate and posterior bands of the disc. Eighteen age- and sex-matched control rabbits with intact dentitions were treated in parallel. In the absence of incisor teeth, reflex gnawing and incising failed to develop, resulting in altered jaw movements and muscle force requirements. The mitotic rate in the anterior band was reduced significantly (p = 0.0117); rates for the intermediate and posterior bands were not significantly affected. There was an associated reduction in alveolar bone mass and deformation of the developing craniomandibular complex. As the lateral pterygoid inserts into the anterior band of the mandibular disc, it is proposed that altered activity within this muscle, combined with a modified loading of the joints, both secondary to incisor removal, resulted in a reduced mitotic rate in the anterior band of the developing mandibular disc.

The effects of induced dental malocclusion on the fibrocartilage disc of the adult rabbit temporomandibular joint.

Unilateral cast occlusal splints were fitted to the mandibular posterior teeth of adult rabbits, for periods of 1-28 days. The reactivity of the mandibular disc was examined by the effect on cell proliferation across the anterior, intermediate and posterior discal bands, as measured by metaphase arrest using vincristine sulphate. The effect on the disc was to activate cell proliferation on the splinted side. Intensity of response varied according to the length of time after fitting the splint, and the site involved. The findings suggested that the adult mandibular disc may participate in compensatory change at a cellular level and thus respond to changing functional loads placed upon the adult temporomandibular joints.

Normative dental treatment needs of Alzheimer patients.

The results of this survey show that the dental needs of non-institutionalized Alzheimer patients are quite high--three out of four requiring dental treatment. This concurs with the results of the only other similar study published. Physicians should be made aware of the extent of the problem and the importance of advising dental referral soon after a patient is diagnosed.

Monitoring behavioural stress control using a craniomandibular index.

This study was concerned with the practical value of relaxation training in helping an individual reduce anxiety and its physical manifestations. Twenty-five subjects learned and practised transcendental meditation for a period of three months. Subjects were clinically examined before and after meditation training, and a craniomandibular index (CMI) was used to objectively assess criteria pertaining to mandibular function. Baseline and outcome CMI scores were compared for the group and shown to be significantly different. Deep relaxation achieved through transcendental meditation alleviated intramuscular tension and fatigue, promoting balanced, co-ordinated muscle function.

Prosthetic management of hypohydrotic ectodermal dysplasia with anodontia. Case report.

The patient in this report is a young boy with hypohydrotic ectodermal dysplasia. His case is exceptional in that anodontia was complete in both deciduous and permanent dentitions. A brief review of this condition is presented along with the prosthetic management of the case which emphasizes the need for regular modification and replacement of dentures worn by growing child.