Optimal care for the management of older people non-weight bearing after lower limb fracture: a consensus study.

BACKGROUND: Older people who are non-weight-bearing after a lower limb fracture are at risk of poor outcomes but there are no clinical guidelines for this group of patients. Given the paucity of the research evidence base, we conducted a consensus exercise to ascertain expert opinion about the management of this group. METHODS: A three-round e-Delphi technique was planned to use the online JISC survey tool with a multidisciplinary panel of health professionals. Panellists were invited by email via professional organisations and UK NHS Trusts. The initial statements for this study were prepared by the authors based upon the findings of their scoping review. Consensus required >/= 70% agreement with statements. RESULTS: Only 2 survey rounds were required. Ninety panellists, representing seven clinical disciplines, reached consensus for 24 statements about general issues (osteoporosis detection and management, falls risk reduction and nutrition) and specific non-weight bearing issues (such as the need for activity to be promoted during this period). CONCLUSIONS: These findings can be used in the generation of a clinical guideline for this group of patients.

A difficult case of recurrent hypoglycaemia: role of insulin assays in establishing the diagnosis.

BACKGROUND: Insulin assays are designed to detect endogenous insulin, however, insulin assays produced by different manufacturers may detect exogenous recombinant insulin, with varying degrees of cross-reactivity between different assays. We report a fascinating and difficult case of recurrent hypoglycaemia, where the final diagnosis was established with the help of insulin assays using different platforms. CASE REPORT: A 24-year-old female presented with recurrent hypoglycaemic episodes on a background of Type 1 diabetes mellitus and a completely resected synovial sarcoma of the right hip several years previously. She reported significant physical, sexual and emotional abuse leading to reduced appetite and weight loss. Despite withdrawing insulin therapy, she experienced profound hypoglycaemic episodes with detectable C-peptide and inappropriately elevated insulin levels, suggesting endogenous hyperinsulinaemic hypoglycaemia; however, localization studies were negative and finally she was found to have exogenous hyperinsulinaemia after discordant insulin levels were detected using two different insulin assays. The C-peptide level was elevated as a result of stimulation by parenteral dextrose and was suppressed after dextrose was ceased. Her Type 1 diabetes mellitus was fabricated and she had factitious hypoglycaemia. CONCLUSIONS: Factitious hypoglycemia is difficult to diagnose and treat. A low blood glucose level, suppressed C-peptide level and an inappropriately elevated insulin level is the classic finding. We were able to make a diagnosis in the present case after discordant insulin levels were detected on the two different insulin assays, signifying cross-reactivities of the recombinant insulin with the assays. A multidisciplinary team approach with psychiatric input is needed to treat such cases.

Impulsivity as a Multifaceted Construct Related to Excessive Drinking Among UK Students.

AIMS: A substantial number of university students exceed alcohol guidelines. Impulsivity has been repeatedly implicated in heavy alcohol use, yet despite knowledge that impulsivity is multifaceted, there have previously been few studies applying multiple measures of self-report and behavioural impulsivity to examine the relationship with excessive student drinking. This results in a limited understanding of the relationship of various facets of impulsivity to student drinking. METHODS: Participants completed a comprehensive battery of impulsivity measures: the Barratt Impulsiveness Scale as a self-report index and the Stop Signal Task, Information Sampling Task and Monetary Choice Questionnaire as behavioural measures of three facets of impulsivity. Participants who exceeded UK drinking guidelines were compared to those who did not on measures of impulsivity. Hierarchical linear regression was then employed to test whether indices of impulsivity were associated with the average units consumed per week. RESULTS: Participants who exceeded UK guidelines reported increased impulsivity in facets of self-report impulsivity. They also displayed performance deficits in normal adjustment of Go responses on the Stop Signal Task. In the regression model, nonplanning impulsivity on the Barratt Impulsiveness Scale was seen to predict quantity of alcohol consumed per month. CONCLUSIONS: The study applies a comprehensive selection of behavioural and self-report measures of impulsivity and indicates that excessive drinkers are more impulsive in some but not all aspects. The results indicate that the wide range of deficits apparent in alcohol-dependent individuals are not evident in this younger, heavy drinking population, but that specific performance and self-identified deficits are already apparent.

Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas.

BACKGROUND: This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions. TYPES OF STUDIES REVIEWED: The panel members conducted a systematic search of MEDLINE, identifying 332 systematic reviews and 1,499 recent clinical studies. They selected 5 systematic reviews and 4 clinical studies to use as a basis for developing recommendations. RESULTS: The panel concluded that screening by means of visual and tactile examination to detect potentially malignant and malignant lesions may result in detection of oral cancers at early stages of development, but that there is insufficient evidence to determine if screening alters disease-specific mortality in asymptomatic people seeking dental care. CLINICAL IMPLICATIONS: The panel suggested that clinicians remain alert for signs of potentially malignant lesions or early-stage cancers while performing routine visual and tactile examinations in all patients, but particularly in those who use tobacco or who consume alcohol heavily. Additional research regarding oral cancer screening and the use of adjuncts is needed.

Establishing an antiracism framework for dental education through critical assessment of accreditation standards.

PURPOSE: The purpose of this manuscript is to establish an antiracism framework for dental education. Since the accreditation process is an influential driver of institutional culture and policy in dental education, the focus of the framework is the Commission on Dental Accreditation (CODA) standards for predoctoral education. METHODS: The authors of this manuscript reviewed each CODA predoctoral standard for opportunities to incorporate antiracism strategies. Eight standards were identified under themes of diversity (Standards 1-3, 1-4, 4-4), curriculum development (Standards 2-17, 2-26), and faculty recruitment and promotion (Standards 3-1, 3-4, 3-5). Guided primarily by National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care, a logic model approach was used to critically assess those standards for opportunities to establish antiracism strategies, with anticipated outcomes and impacts. RESULTS: Strategies highlighted a need to improve recruitment, admissions, and accountability among dental schools to address the low numbers of historically underrepresented racial and ethnic (HURE) students and faculty. They emphasized the inclusion of racism in curricula geared toward training dental students to provide care to HURE populations. Finally, there are opportunities to improve accountability that dental schools are providing equitable opportunities for career advancement among HURE faculty, with consideration of conflicting demands for scholarship with HURE student mentoring, role modeling, teaching, and/or service. CONCLUSIONS: The framework identifies gaps in CODA standards where racism may be allowed to fester, provides specific antiracism strategies to strengthen antiracism through the accreditation process, and offers dental education programs, a process for evaluating and establishing their own antiracism strategies.

Identification and extraction of proteins that compose the triad junction of skeletal muscle.

Treatment of both transverse tubules and terminal cisternae with a combination of Triton X-100 and hypertonic K cacodylate causes dissolution of nonjunctional proteins and selective retention of membrane fragments which are capable of junction formation. Treatment of vesicles with Triton X-100 and either KCl or K gluconate causes complete dissolution of all components. Therefore K cacodylate exerts a specific preservative action on the junctional material. The membrane fragment from treatment of transverse tubules with Triton X-100 + cacodylate contains a protein of Mr = 80,000 in SDS gel electrophoresis as the predominant protein while lipid composition is enriched in cholesterol. The membrane fragment retains in electron microscopy the trilaminar appearance of the intact vesicles. Freeze fracture of transverse tubule fragments reveals a high density of low-profile, intercalated particles, which frequently form strings or occasional small arrays. The fragments from Triton X-100 plus cacodylate treatment of terminal cisternae include the protein of Mr = 80,000 as well as the spanning protein of the triad, calsequestrin, and some minor proteins. The fragments are almost devoid of lipid and display an amorphous morphology suggesting membrane disruption. The ability of the transverse tubular fragment, which contains predominantly the Mr = 80,000 protein, to form junctions with terminal cisternae fragments suggests that it plays a role in anchoring the membrane to the junctional processes of the triad. The junctional proteins may be solubilized in a combination of nonionic detergent and hypertonic NaCl. Subsequent molecular sieve chromatography gives an enriched preparation of the spanning protein. This protein has subunits of Mr = 300,000, 270,000 and 140,000 and migrates in the gel as a protein of Mr = 1.2 X 10(6) indicating a polymeric structure.

Identification of a constituent of the junctional feet linking terminal cisternae to transverse tubules in skeletal muscle.

This study describes the biochemical composition of junctional feet in skeletal muscle utilizing a fraction of isolated triad junctions. [3H]Ouabain entrapment was employed as a specific marker for T-tubules. The integrity of the triad junction was assayed by the isopycnic density of [3H]ouabain activity (24-30% sucrose for free T-tubules, 38-42% sucrose for intact triads). Trypsin, chymotrypsin, and pronase all caused separation of T-tubules from terminal cisternae, indicating that the junction is composed as least in part of protein. Trypsin and chymotrypsin hydrolyzed four proteins: the Ca2+ pump, a doublet 325,000, 300,000, and an 80,000 Mr protein. T-tubules which had been labeled covalently with 125I were joined to unlabeled terminal cisternae by treatment with K cacodylate. The reformed triads were separated from free T-tubules and then severed by passage through a French press. When terminal cisternae were separated from T-tubules, some 125I label was transferred from the labeled T-tubules to the unlabeled terminal cisternae. Gel electrophoresis showed that, although T-tubules were originally labeled in a large number of different proteins, only a single protein doublet was significantly labeled in the originally unlabeled terminal cisternae. This protein pair had molecular weights of 325,000 and 300,000 daltons. Transfer of label did not occur to a substantial degree without K cacodylate treatment. We propose that the transfer of 125I label from T-tubules to terminal cisternae during reformation and breakage of the triad junction is a property of the protein which spans the gap between T-tubules and terminal cisternae.

Isolation, characterization, and localization of the spanning protein from skeletal muscle triads.

A monoclonal antibody has been developed against the putative junctional protein or spanning protein (SP) from skeletal muscle triads. By immuno-affinity chromatography, we have purified this protein. The native protein has a molecular mass of 630-800 kD, as determined by gel filtration and rate zonal centrifugation. Within the limits of the methods used, the basic unit of the SP appears to be a dimer. In electron micrographs, it is shown to exhibit a circular profile with a diameter of approximately 100 A. In thin section analysis, the protein is frequently observed as parallel tracks of electron-dense particles bordering a translucent core. We suggest that the basic unit of the junctional structure is a dimer of 300-kD subunits and that four such entities constitute the intact SP. The purified protein has been used to develop polyclonal antibodies. By immunoelectron microscopy using immunogold probes, the SP has been localized to the junctional gap of the triad. By attaching the SP to an affinity resin, three proteins have been identified as forming associations with the SP. The Mrs of the proteins are 150, 62, and 38 kD; the 62-kD protein is calsequestrin.

Ultrastructural observations of isolated intact and fragmented junctions of skeletal muscle by use of tannic acid mordanting.

Tannic acid mordanting during fixation of isolated vesicles from skeletal muscle enhanced the resolution of the images. Isolated triadic junctions displayed two characteristic features not previously described: (a) a clear gap separated terminal cisternae from transverse tubules; (b) this gap was bridged by a separating array of structures which resembled the "feet" of intact muscle. When the triad was broken in a French press and subsequently reassembled by joining the two organelles, a similar gap was seen but the structure of the feet was less well defined. When the membrane of the triad was extracted by Triton X-100, the junctional region was retained and a similar gap between the two organelles could be discerned. The terminal cisternae characteristically displayed a thickening of the cytoplasmic leaflet of the membrane in select areas in which electron-dense material was apposed on the luminal leaflet. This thickened membrane was not observed in longitudinal reticulum or in terminal cisternae regions distal to the electron-dense matter. This thickened leaflet was not invariably associated with the junction, and some junctional regions did not display discernible thickening of the membrane. When the triad was treated with KCl, the electron-dense aggregate was dispersed and the thickened leaflet of the terminal cisternae dissipated, whereas the triadic junctional region with its feet remained unchanged. KCl treatment caused dissolution of three proteins of Mr = 77,000, 43,000, and 38,000. Treatment of Triton-resistant vesicles with KCl caused the loss of electron-dense aggregate but did not otherwise influence the appearance of the junction. A good degree of correlation both qualitatively and in quantitative parameters between the isolated vesicles and the intact muscle was observed.

Triad formation: organization and function of the sarcoplasmic reticulum calcium release channel and triadin in normal and dysgenic muscle in vitro.

Excitation-contraction (E-C) coupling is thought to involve close interactions between the calcium release channel (ryanodine receptor; RyR) of the sarcoplasmic reticulum (SR) and the dihydropyridine receptor (DHPR) alpha 1 subunit in the T-tubule membrane. Triadin, a 95-kD protein isolated from heavy SR, binds both the RyR and DHPR and may thus participate in E-C coupling or in interactions responsible for the formation of SR/T-tubule junctions. Immunofluorescence labeling of normal mouse myotubes shows that the RyR and triadin co-aggregate with the DHPR in punctate clusters upon formation of functional junctions. Dysgenic myotubes with a deficiency in the alpha 1 subunit of the DHPR show reduced expression and clustering of RyR and triadin; however, both proteins are still capable of forming clusters and attaining mature cross-striated distributions. Thus, the molecular organization of the RyR and triadin in the terminal cisternae of SR as well as its association with the T-tubules are independent of interactions with the DHPR alpha 1 subunit. Analysis of calcium transients in dysgenic myotubes with fluorescent calcium indicators reveals spontaneous and caffeine-induced calcium release from intracellular stores similar to those of normal muscle; however, depolarization-induced calcium release is absent. Thus, characteristic calcium release properties of the RyR do not require interactions with the DHPR; neither do they require the normal organization of the RyR in the terminal SR cisternae. In hybrids of dysgenic myotubes fused with normal cells, both action potential-induced calcium transients and the normal clustered organization of the RyR are restored in regions expressing the DHPR alpha 1 subunit.

Immunolocalization of sarcolemmal dihydropyridine receptor and sarcoplasmic reticular triadin and ryanodine receptor in rabbit ventricle and atrium.

The subcellular distribution of sarcolemmal dihydropyridine receptor (DHPR) and sarcoplasmic reticular triadin and Ca2+ release channel/ryanodine receptor (RyR) was determined in adult rabbit ventricle and atrium by double labeling immunofluorescence and laser scanning confocal microscopy. In ventricular muscle cells the immunostaining was observed primarily as transversely oriented punctate bands spaced at approximately 2-micron intervals along the whole length of the muscle fibers. Image analysis demonstrated a virtually complete overlap of the staining patterns of the three proteins, suggesting their close association at or near dyadic couplings that are formed where the sarcoplasmic reticulum (SR) is apposed to the surface membrane or its infoldings, the transverse (T-) tubules. In rabbit atrial cells, which lack an extensive T-tubular system, DHPR-specific staining was observed to form discrete spots along the sarcolemma but was absent from the interior of the fibers. In atrium, punctate triadin- and RyR-specific staining was also observed as spots at the cell periphery and image analysis indicated that the three proteins were co-localized at, or just below, the sarcolemma. In addition, in the atrial cells triadin- and RyR-specific staining was observed to form transverse bands in the interior cytoplasm at regularly spaced intervals of approximately 2 micron. Electron microscopy suggested that this cytoplasmic staining was occurring in regions where substantial amounts of extended junctional SR were present. These data indicate that the DHPR codistributes with triadin and the RyR in rabbit ventricle and atrium, and furthermore suggest that some of the SR Ca2+ release channels in atrium may be activated in the absence of a close association with the DHPR.

Does muscle activation occur by direct mechanical coupling of transverse tubules to sarcoplasmic reticulum?

Our knowledge of the physiological and biochemical constituents of skeletal muscle excitation has increased greatly during the last few years but this has not led to a consensus of the physiological mode of muscle activation. Three hypotheses of transmission, involving either transmitter-receptor interaction or direct mechanical coupling, are still under active consideration. The hypothesis of direct mechanical coupling currently being evaluated proposes that the dihydropyridine receptor in the transverse tubules serves as a voltage sensor that communicates directly with the junctional foot protein/Ca2+ channel of sarcoplasmic reticulum to initiate opening of the channel.

A model for selection and assessment of community-based sites for dental students' extramural clinical experiences.

As a recipient of the Robert Wood Johnson's Pipeline, Profession, and Practice: Community-Based Dental Education grant, the Extramural Education Program (EEP) at the University of Illinois at Chicago College of Dentistry was charged with developing partnerships with community-based oral health programs throughout Illinois. These programs are to be used for clinical service-learning rotations for fourth-year dental students, relying on the utilization of the dentists employed at the community site as preceptors for the students. Because the College of Dentistry had essentially no community-based service-learning experiences prior to the Robert Wood Johnson grant, procedures and protocols needed to be developed to standardize a process for site and preceptor selection. An administrative process was developed to engage, recruit, and partner with community-based oral health programs that provided direct clinical services. This article will discuss the development of criteria used to select sites and preceptors for extramural clinical rotations; the development of a set of standardized assessment instruments; and the credentialing process for community-based adjunct faculty that leads to the affiliation agreements. These community-based rotations have been integrated into the College of Dentistry curriculum as a required extramural service-learning course referred to as Extramural Clinical Experience (DADM 325).

The role of dental schools in the issues of access to care.

Some individuals emphasize dentistry as the provision of services; others concentrate on achieving specified levels of oral health. One's vision of dentistry affects how the issue of access is viewed. The University of Illinois at Chicago College of Dentistry has been the recipient of a Profession and Practice: Community-Based Dental Education project (the Pipeline) grant to promote oral health in underserved communities and to train students to function effectively in such settings. The School's Extramural Clinical Experience is described. This involves 60 days of providing care in seventeen sites for students in their fourth year of training. Students must qualify for these rotations based on clinical competency and they must document their experiences. The positive effects observed so far in this program are described.

Clinical and Community-Based Education in U.S. Dental Schools.

This review of U.S. dental schools' clinical curricula suggests that the basic structure of clinical education has not changed significantly in the past 60 years, although important developments include the introduction of competency-based education and community-based clinical education. Most dental schools still have a two-year preclinical curriculum and a two-year clinical curriculum, and most schools still operate a large clinical facility where students receive the bulk of their clinical education and assessment for graduation. In those clinics, dental students are the main providers of patient treatment, with faculty serving in supervisory roles. In addition, a major portion of the entire dental curriculum continues to be dedicated to student education on the restoration of a single tooth or replacement of teeth. This article was written as part of the project "Advancing Dental Education in the 21st Century."

Eliminating oral health disparities: Ethics workshop reactor comments.

Oral health encompasses dentistry and is broader in concept. Dentistry alone appears insufficient to ensure oral health for the population at large. Troubling disparities in oral health status and access to care have been documented. The segment of the population that has little or no access to care is growing; aging baby-boomers are adding to this problem. As suggested in Oral Health in America: A Report of the Surgeon General, partnerships and collaboration are essential to improving oral health. The ethics of dental practice and the profession are being called into question. Who will provide the necessary leadership to address and resolve these issues, so that oral health is attainable by all?

Evidence that ecto-nucleoside-triphosphate pyrophosphatase serves in the generation of extracellular inorganic pyrophosphate in human bone and articular cartilage.

Extracellular inorganic pyrophosphate (PPi) is important in the regulation of mineralisation of bone, and in the pathogenesis of chondrocalcinosis, an arthritic disease in which calcium pyrophosphate dihydrate crystals form in articular cartilage. Nucleoside-triphosphate pyrophosphatase, which catalyses the formation of PPi, was previously observed at the surface of human articular chondrocytes in culture. A similar enzyme has been identified in osteoblast-like human bone cells in culture, and is active towards purine and pyrimidine nucleoside triphosphates. The enzyme has high affinity for ATP and is located on the cell surface, and thus could serve in the generation of extracellular PPi. Moreover, no other mechanism for the catabolism of small amounts of exogenous ATP is present in human bone cells. Further evidence for ecto-nucleoside-triphosphate pyrophosphatase serving in the generation of extracellular PPi in articular cartilage and bone was obtained by studying the ability of alternative substrates (which do not yield PPi) to inhibit generation of PPi from ATP. In both articular chondrocytes and bone cells, the enzyme exhibited an apparent preference for ATP over dinucleotide and phosphodiester substrates. Some potential inhibitors of the enzyme activity were also studied in both cell types. ADP moderately inhibited the activity but two bisphosphonate drugs were only slightly inhibitory.