Risk of subsequent fracture after prior fracture among older women.

Among 377,561 female Medicare beneficiaries who sustained a fracture, 10% had another fracture within 1 year, 18% within 2 years, and 31% within 5 years. Timely management to reduce risk of subsequent fracture is warranted following all nontraumatic fractures, including nonhip nonvertebral fractures, in older women. INTRODUCTION: Prior fracture is a strong predictor of subsequent fracture; however, postfracture treatment rates are low. Quantifying imminent (12-24 month) risk of subsequent fracture in older women may clarify the need for early postfracture management. METHODS: This retrospective cohort study used Medicare administrative claims data. Women ≥ 65 years who sustained a clinical fracture (clinical vertebral and nonvertebral fracture; index date) and were continuously enrolled for 1-year pre-index and ≥ 1-year (≥  2 or ≥ 5 years for outcomes at those time points) post-index were included. Cumulative incidence of subsequent fracture was calculated from 30 days post-index to 1, 2, and 5 years post-index. For appendicular fractures, only those requiring hospitalization or surgical repair were counted. Death was considered a competing risk. RESULTS: Among 377,561 women (210,621 and 10,969 for 2- and 5-year outcomes), cumulative risk of subsequent fracture was 10%, 18%, and 31% at 1, 2, and 5 years post-index, respectively. Among women age 65-74 years with initial clinical vertebral, hip, pelvis, femur, or clavicle fractures and all women ≥ 75 years regardless of initial fracture site (except ankle and tibia/fibula), 7-14% fractured again within 1 year depending on initial fracture site; risk rose to 15-26% within 2 years and 28-42% within 5 years. Risk of subsequent hip fracture exceeded 3% within 5 years in all women studied, except those < 75 years with an initial tibia/fibula or ankle fracture. CONCLUSIONS: We observed a high and early risk of subsequent fracture following a broad array of initial fractures. Timely management with consideration of pharmacotherapy is warranted in older women following all fracture types evaluated.

Identification, localization, and functional implications of an abundant nematode annexin.

Cultures of the nematode C. elegans were examined for the presence of calcium-dependent, phospholipid-binding proteins of the annexin class. A single protein of apparent mass on SDS-polyacrylamide gels of 32 kD was isolated from soluble extracts of nematode cultures on the basis of its ability to bind to phospholipids in a calcium-dependent manner. After verification of the protein as an annexin by peptide sequencing, an antiserum to the protein was prepared and used to isolate a corresponding cDNA from an expression library in phage lambda gt11. The encoded protein, herein referred to as the nex-1 annexin, has a mass of 35 kD and is 36-42% identical in sequence to 10 known mammalian annexins. Several unique modifications were found in the portions of the sequence corresponding to calcium-binding sites. Possible phosphorylation sites in the NH2-terminal domain of the nematode annexin correspond to those of mammalian annexins. The gene for this annexin (nex-1) was physically mapped to chromosome III in the vicinity of the dpy-17 genetic marker. Two other annexin genes (nex-2 and nex-3) were also identified in chromosome III sequences reported by the nematode genomic sequencing project (Sulston, J., Z. Du, K. Thomas, R. Wilson, L. Hillier, R. Staden, N. Halloran, P. Green, J. Thierry-Mieg, L. Qiu, et al. 1992. Nature (Lond.). 356:37-41). The nex-1 annexin was localized in the nematode by immunofluorescence and by electron microscopy using immunogold labeling. The protein is associated with membrane systems of the secretory gland cells of the pharynx, with sites of cuticle formation in the grinder in the pharynx, with yolk granules in oocytes, with the uterine wall and vulva, and with membrane systems in the spermathecal valve. The presence of the annexin in association with the membranes of the spermathecal valve suggests a novel function of the protein in the folding and unfolding of these membranes as eggs pass through the valve. The localizations also indicate roles for the annexin corresponding to those proposed in mammalian systems in membrane trafficking, collagen deposition, and extracellular matrix formation.

Structural changes and airway remodelling in occupational asthma at a mean interval of 14 years after cessation of exposure.

BACKGROUND: Occupational asthma (OA) may cause alterations of airways with inflammation and remodelling after cessation of exposure. Although the long-term clinical, functional and induced sputum sequelae have been examined in workers removed from exposure, the long-term pathological outcomes are unknown. OBJECTIVE: We aimed to investigate whether airway inflammation and remodelling were present in bronchial biopsies of subjects with prior OA but without evidence of persisting asthma at a mean interval of 14 years after cessation of exposure. METHODS: Ten clinically and functionally asymptomatic subjects with a prior diagnosis of OA were recruited and underwent bronchoscopy, bronchoalveolar lavage and bronchial biopsy. Comparisons were made with biopsies from normal control subjects. Epithelial detachment, epithelial metaplasia, mucous gland and airway smooth muscle (ASM) areas as well as the distance between the epithelium and ASM were measured by image analysis. The amount of collagen present was assessed by van Gieson staining. The numbers of TGF-beta1- and eosinophil cationic protein (ECP)-positive cells were evaluated by specific immunostaining. RESULTS: Statistically significant increases were found in the numbers of TGF-beta1- and ECP-positive cells and in the amount of subepithelial fibrosis present in the biopsies of subjects with prior OA compared with control biopsies. The distance between the epithelium and ASM was significantly reduced in the OA group. Increases in epithelial metaplasia, ASM mass, mucous gland numbers, collagen deposition and eosinophilia in the OA group were not statistically significant. There was no evidence of ongoing inflammation in the group with prior OA as assessed by the number of T lymphocytes present. CONCLUSION: Some aspects of airway inflammation and remodelling persist in subjects with prior OA long after cessation of exposure even in the absence of clinical, sputum and functional abnormalities. These findings are relevant to the assessment of long-term sequelae in subjects with OA when reviewed after cessation of exposure.

Mercury release from deforested soils triggered by base cation enrichment.

The Brazilian Amazon has experienced considerable colonization in the last few decades. Family agriculture based on slash-and-burn enables millions of people to live in that region. However, the poor nutrient content of most Amazonian soils requires cation-rich ashes from the burning of the vegetation biomass for cultivation to be successful, which leads to forest ecosystem degradation, soil erosion and mercury contamination. While recent studies have suggested that mercury present in soils was transferred towards rivers upon deforestation, little is known about the dynamics between agricultural land-use and mercury leaching. In this context, the present study proposes an explanation that illustrates how agricultural land-use triggers mercury loss from soils. This explanation lies in the competition between base cations and mercury in soils which are characterized by a low adsorption capacity. Since these soils are naturally very poor in base cations, the burning of the forest biomass suddenly brings high quantities of base cations to soils, destabilizing the previous equilibrium amongst cations. Base cation enrichment triggers mobility in soil cations, rapidly dislocating mercury atoms. This conclusion comes from principal component analyses illustrating that agricultural land-use was associated with base cation enrichment and mercury depletion. The overall conclusions highlight a pernicious cycle: while soil nutrient enrichment actually occurs through biomass burning, although on a temporary basis, there is a loss in Hg content, which is leached to rivers, entering the aquatic chain, and posing a potential health threat to local populations. Data presented here reflects three decades of deforestation activities, but little is known about the long-term impact of such a disequilibrium. These findings may have repercussions on our understanding of the complex dynamics of deforestation and agriculture worldwide.

Vitamin D and incident urinary incontinence in older adults.

BACKGROUND/OBJECTIVES: The aim of this study is to determine whether vitamin D status is associated with incident urinary incontinence (UI) among community-dwelling older adults. SUBJECTS/METHODS: The University of Alabama at Birmingham Study of Aging is a prospective cohort study of community-dwelling Medicare enrollees. Standardized assessment of UI was conducted using the validated Incontinence Severity Index. The analysis of 25-hydroxyvitamin D [25(OH)D] levels was performed on stored baseline sera. UI was assessed every 6-12 months for up to 42 months. The analyses included multivariable logistic regression and Cox proportional hazard models. RESULTS: Of 350 participants (175 male, 147 black, mean age 73.6±5.8), 54% (189/350) were vitamin D deficient (25(OH)D <20 ng/ml) and 25% (87/350) were vitamin D insufficient (25(OH)D: 20 ng/ml to <30 ng/ml). Among the 187 subjects with no UI at baseline, 57% (107/187) were vitamin D deficient and 24% (45/187) were vitamin D insufficient. A total of 175 of the 187 subjects had follow-up evaluation for incident UI over 42 months, and incident UI occurred in 37% (65/175). After adjustment, cumulative incident UI at 42 months was associated with baseline vitamin D insufficiency (P=0.03) and demonstrated a trend association with deficiency (P=0.07). There was no association between baseline vitamin D status and the time to incident UI. CONCLUSIONS: These preliminary results support an association between vitamin D and incident UI in community-dwelling older adults. Future studies may target specific at-risk groups, such as men with BPH or women with pelvic floor disorders for evaluation of the impact of vitamin D supplementation on urinary symptoms.

PSE-like turkey breast enhancement through adjunct incorporation in a chunked and formed deli roll.

A randomized complete block design with five treatments (100% pale, soft, and exudative-like (PSE-like), 100% PSE-like+1.5% collagen, 100% PSE-like+0.30% κ-/ι-carrageenan, 100% PSE-like+1.5% soy protein concentrate, and 100% Normal) and six replications was utilized to test the effects of meat raw material, turkey collagen (TC), soy protein concentrate (SPC), and carrageenan (CG) on protein functionality in the formulation of chunked and formed turkey breast. Addition of 1.5% SPC and 1.5% TC both decreased (P<0.05) cooking loss and increased (P<0.005) the protein bind of treatments formulated with 100% PSE-like raw material. Purge loss decreased (P<0.05) in PSE-like raw material when 1.5% TC, 1.5% SPC, or 0.30% CG were utilized, and no differences (P>0.05) existed in consumer acceptability among treatments. This research demonstrates the potential to increase the water holding capacity and improve the texture of deli rolls from PSE-like raw material through the incorporation of collagen, soy protein, or carrageenan.

[Operating room assistance: an innovative practice]. / L'assistance opératoire: une pratique innovatrice.

Professional practice changes in the operating room have led to the development of a new role for nurses--as surgical assistants. Essentially, the surgical assistant nurse helps ensure the patient's safety while providing technical and clinical assistance to the surgeon in such areas as exposing and manipulating tissues, suturing fascia and using various specialized instruments. The surgical assistant nurse function is being implemented through a pilot project at the Institut de cardiologie de Montréal. Developed by representatives of the nursing and surgical departments there, the project was approved by the Collège des médecins du Québec in April 1995 and subsequently by the institute's council of physicians, dentists and pharmacists. It has also gained recognition from the Ordre des infirmières et infirmiers du Québec (OIIQ). The pilot project incorporated a 186-hour training program, which was delivered from May to September 1995 according to three distinct learning modules: maintenance of a safe environment for the patient, clinical assistance and technical assistance. A tutorial approach to learning included individual and team work, simulation exercises, technical courses, lab work and practical training in the operating room. At the end of the training program, two surgical assistant nurses began practising in their new role. An evaluation of the project will be performed in September 1996.

Nurse first assistant: an evolving project in Québec.

Changes in the work environment, quotas imposed on the number of resident physicians, scientific and technological advances, and nurses having to play two roles, that of scrub nurse and of nurse first assistant, have all contributed to the development of a new role, that of nurse first assistant. For the purpose of providing optimal quality care to patients and at the request of its surgeons, the Montreal Heart Institute has presented a project to the Ordre des infirmières et infirmiers du Québec and the Professional Corporation of Physicians of Québec. The project was accepted by both bodies. The OIIQ moved in favour of recognizing the function of nurse first assistant in September, 1994, and the PCPQ gave its approval for the project on March 30, 1995. A 186 hour training program was developed. The two selected nurses have been trained and have been integrated into a medico-surgical team since February, 1996. The Nurse First Assistant pilot project will be evaluated in February, 1997.

Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l.

The t(10;11)(p12;q23) translocation and the t(10;11)(p12;q14) translocation, which encode the MLL (mixed lineage leukemia)-AF10 and CALM (clathrin assembly lymphoid myeloid leukemia)-AF10 fusion oncoproteins, respectively, are two recurrent chromosomal rearrangements observed in patients with acute myeloid leukemia and acute lymphoblastic leukemia. Here, we demonstrate that MLL-AF10 and CALM-AF10-mediated transformation is dependent on the H3K79 methyltransferase Dot1l using genetic and pharmacological approaches in mouse models. Targeted disruption of Dot1l using a conditional knockout mouse model abolished in vitro transformation of murine bone marrow cells and in vivo initiation and maintenance of MLL-AF10 or CALM-AF10 leukemia. The treatment of MLL-AF10 and CALM-AF10 transformed cells with EPZ004777, a specific small-molecule inhibitor of Dot1l, suppressed expression of leukemogenic genes such as Hoxa cluster genes and Meis1, and selectively impaired proliferation of MLL-AF10 and CALM-AF10 transformed cells. Pretreatment with EPZ004777 profoundly decreased the in vivo spleen-colony-forming ability of MLL-AF10 or CALM-AF10 transformed bone marrow cells. These results show that patients with leukemia-bearing chromosomal translocations that involve the AF10 gene may benefit from small-molecule therapeutics that inhibit H3K79 methylation.

Assessment of impairment/disability due to occupational asthma through a multidimensional approach.

Subjects with occupational asthma (OA) are often left with permanent sequelae after removal from exposure, and assessing their impairment/disability should utilise various tools. The aim of the present study was to examine whether: 1) assessment of inflammation in induced sputum is relevant to impairment; and 2) use of questionnaires on quality of life and psychological factors can be useful for the evaluation of disability. In total, 40 subjects were prospectively assessed for permanent impairment/disability due to OA 2 yrs after cessation of exposure. Impairment was assessed as follows: 1) need for asthma medication; 2) asthma severity; 3) airway calibre and responsiveness; and 4) degree of inflammation in induced sputum. Disability was assessed according to quality of life and psychological distress. There was a significant improvement in airway responsiveness and inflammation from diagnosis to the present assessment. Sputum eosinophils > or =2% and neutrophils >60% were present in eight (20%) and 12 (30%) out of all subjects, respectively, one or the other feature being the only abnormalities in 15% of subjects. Quality of life was moderately affected and there was a prevalence of depression and anxiety close to 50%. In the assessment of subjects with occupational asthma, information on airway inflammation and psychological impacts are relevant to the assessment of impairment/disability, although these findings need further investigation.

Transcription, biochemistry and localization of nematode annexins.

The transcription of three annexin genes in the nematode, Caenorhabditis elegans, was detected by reverse transcriptase/polymerase chain reaction amplification of messenger RNAs. The highest level of expression was from the nex-1 gene, with lower levels detected for the nex-2 and nex-3 genes. The expression of nex-1 was reduced in the Dauer larval stage relative to the other annexins, correlating with the absence of the spermathecal valves, a major site of nex-1 protein localization. Recombinant nex-1 protein was expressed in yeast, isolated by calcium-dependent binding to acidic phospholipids, and its membrane binding and aggregating activities characterized using bovine chromaffin granules as a representative intracellular substrate. Binding to granule membranes was promoted by calcium with half-maximal binding seen at 630 microM calcium. Chromaffin granule aggregation was similarly promoted by the nex-1 protein at 630 microM calcium. This low sensitivity to calcium suggests the annexin can only be activated in vivo near the plasma membrane or other sources of calcium. Sequences including the nex-1 promoter were fused to the gene for green fluorescent protein and this construct was introduced into nematodes by microinjection. Examination of transgenic offspring revealed specific nex-1 promoter activity in the pharynx, the hypodermal cells, the vulva, and the spermathecal valve, locations in which the annexin may function in collagen secretion/deposition and membrane-membrane interactions. A sensitive anti-nex-1 antibody labelled with rhodamine was injected into body cavities of the nematode but did not detect extracellular nex-1 protein. Therefore, this annexin is apparently cytosolic and may function on the cytoplasmic side of the plasma membrane of the spermathecal valve to chaperon the folding of this membrane during the opening and closing of the valve.