Under-diagnosis of mood disorders in Canada.

AIMS: Under-diagnosis of mood disorders occurs worldwide. In this study, we characterized and compared Canadians with symptoms compatible with a mood disorder by diagnosis status; and described the associated health impacts, use of health services and perceived need for care. METHODS: Respondents to the 2012 Canadian Community Health Survey - Mental Health, a nationally representative sample of Canadians age ≥15 years were assessed for symptoms compatible with mood disorders based on a Canadian adaptation of the World Health Organization Composite International Diagnostic Interview (n = 23 504). Descriptive and multivariate regression analyses were performed. RESULTS: In 2012, an estimated 5.4% (1.5 million) Canadians aged 15 years and older reported symptoms compatible with a mood disorder, of which only half reported having been professionally diagnosed. The undiagnosed individuals were more likely to be younger (mean age: 36.2 v. 41.8), to be single (49.5 v. 32.7%), to have less than a post-secondary graduation (49.8 v. 41.1%) and to have no physical co-morbidities (56.4 v. 35.7%), and less likely to be part of the two lower income quintiles (49.6 v. 62.7%) compared with those with a previous diagnosis. Upon controlling for all socio-demographic and health characteristics, the associations with age and marital status disappeared. While those with a previous diagnosis reported significantly greater health impacts and were more likely to have consulted a health professional for their emotional and mental health problems in the previous 12 months compared with those undiagnosed (79.4 v. 31.0%), about a third of both groups reported that their health care needs were only partially met or not met at all. CONCLUSIONS: Mood disorders are prevalent and can profoundly impact the life of those affected, however, their diagnosis remains suboptimal and health care use falls short of apparent needs. Improvements in mental health literacy, help-seeking behaviours and diagnosis are needed. In light of the heterogeneity of mood disorders in terms of symptoms severity, impacts and prognosis, interventions must be tailored accordingly.

Health status, activity limitations, work-related restrictions and level of disability among Canadians with mood and/or anxiety disorders. / État de santé, limitations d'activité, restrictions professionnelles et degré d'invalidité chez les Canadiens atteints d'un trouble de l'humeur ou d'anxiété.

INTRODUCTION: This study provides the first overview of the perceived general and mental health, activity limitations, work-related restrictions and level of disability, as well as factors associated with disability severity, among Canadian adults with mood and/or anxiety disorders, using a population-based household sample. METHODS: We used data from the 2014 Survey on Living with Chronic Diseases in Canada- Mood and Anxiety Disorders Component. The sample consists of Canadians aged 18 years and older with self-reported mood and/or anxiety disorders from the 10 provinces (n = 3361; response rate 68.9%). We conducted descriptive and multinomial multivariate logistic regression analyses. RESULTS: Among Canadian adults with mood and/or anxiety disorders, over one-quarter reported "fair/poor" general (25.3%) and mental (26.1%) health; more than one-third (36.4%) reported one or more activity limitations; half (50.3%) stated a job modification was required to continue working; and more than one-third (36.5%) had severe disability. Those with concurrent mood and anxiety disorders reported poorer outcomes: 56.4% had one or more activity limitations; 65.8% required a job modification and 49.6% were severely disabled. Upon adjusting for individual characteristics, those with mood and/or anxiety disorders who were older, who had a household income in the lowest or lower-middle adequacy quintile or who had concurrent disorders were more likely to have severe disability. CONCLUSION: Findings from this study affirm that mood and/or anxiety disorders, especially concurrent disorders, are associated with negative physical and mental health outcomes. Results support the role of public health policy and programs aimed at improving the lives of people living with these disorders, in particular those with concurrent disorders.

INTRODUCTION: Cette étude fournit, au moyen d'un échantillon de ménages fondé sur la population, le premier aperçu, chez des Canadiens adultes atteints de troubles de l'humeur ou d'anxiété, de leur état de santé globale et de santé mentale perçu, de leurs limitations fonctionnelles, de leurs restrictions professionnelles et de leur degré d'invalidité, ainsi que des facteurs associés à une invalidité grave. MÉTHODOLOGIE: Nous avons obtenu les données de l'Enquête sur les personnes ayant une maladie chronique au Canada ­ Composante des troubles de l'humeur et d'anxiété. L'échantillon est composé de Canadiens âgés de 18 ans et plus, atteints d'un trouble de l'humeur ou d'anxiété autodéclaré et habitant l'une des 10 provinces (n = 3 361; taux de réponse 68,9 %). Nous avons mené des analyses de régression logistiques multidimensionnelles multinomiales et descriptives. RÉSULTATS: Parmi les Canadiens adultes atteints d'un trouble de l'humeur ou d'anxiété, plus d'un quart ont rapporté un état de santé globale (25,3 %) et de santé mentale (26,1 %) « passable ou médiocre ¼, plus du tiers (36,4 %) ont mentionné avoir une ou plusieurs limitations fonctionnelles, la moitié (50,3 %) ont déclaré qu'une modification de leur emploi a été nécessaire pour continuer à travailler et plus du tiers (36,5 %) souffrait d'une invalidité grave. Les personnes avec troubles de l'humeur et d'anxiété concomitants ont mentionné de moins bons résultats : 56,4 % avaient une ou plusieurs limitations fonctionnelles, 65,8 % ont mentionné qu'une modification de leur emploi a été nécessaire et 49,6 % souffraient d'une invalidité grave. Après ajustement pour les caractéristiques individuelles, les personnes atteintes d'un trouble de l'humeur ou d'anxiété qui étaient plus âgées, dont le revenu familial était situé dans le quintile du plus faible revenu ou du revenu faible à moyen ou qui avaient des troubles concomitants étaient plus susceptibles d'avoir une invalidité grave. CONCLUSION: Les résultats de cette étude confirment que les troubles de l'humeur ou d'anxiété, surtout dans le cas de troubles concomitants, sont associés à des résultats en santé physique et mentale négatifs. Ces constats soutiennent les actions en politique et programmes de santé publique qui visent à améliorer la vie des personnes atteintes de ces troubles, surtout celles qui sont atteintes de troubles concomitants.

Report summary - Mood and Anxiety Disorders in Canada, 2016. / Note de synthèse - Les troubles anxieux et de l'humeur au Canada, 2016.

Mood and Anxiety Disorders in Canada, 2016 is the first publication to include administrative health data from the Canadian Chronic Disease Surveillance System (CCDSS) for the national surveillance of mood and anxiety disorders among Canadians aged one year and older. It features nationally complete CCDSS data up to fiscal year 2009/10, as well as trend data spanning over a decade (1996/97 to 2009/10). The data presented in this report, and subsequent updates, can be accessed via the Public Health Agency of Canada's Chronic Disease Infobase Data Cubes at www.infobase.phac-aspc.gc.ca. Data Cubes are interactive databases that allow users to quickly create tables and graphs using their Web browser. The report demonstrates the Public Health Agency of Canada's commitment to improving data collection and reporting about mental illness, as recommended within Changing Directions, Changing Lives - The Mental Health Strategy for Canada.

RÉSUMÉ: Le rapport Les troubles anxieux et de l'humeur au Canada, 2016 est la première publication à présenter des données administratives sur la santé tirées du Système canadien de surveillance des maladies chroniques (SCSMC) pour la surveillance nationale des troubles de l'humeur et d'anxiété chez les Canadiens d'un an ou plus. Il présente les données nationales complètes les plus récentes du SCSMC jusqu'à l'exercice 2009-2010 ainsi que des données sur les tendances couvrant plus d'une décennie (de 1996-1997 à 2009-2010). Les données présentées ici et leurs mises à jour subséquentes sont consultable à partir des cubes de données de l'Infobase des maladies chroniques de l'Agence de la santé publique du Canada à www.infobase.phac-aspc.gc.ca. Les cubes de données sont des bases de données interactives qui permettent aux utilisateurs de créer rapidement des tableaux et graphiques à l'aide de leur navigateur Web. Le rapport témoigne de l'engagement de l'Agence de la santé publique du Canada à améliorer la collecte de données et la production de rapports sur les troubles mentaux, conformément aux recommandations de Changer les orientations, changer des vies : Stratégie en matière de santé mentale pour le Canada.

Describing the population health burden of depression: health-adjusted life expectancy by depression status in Canada. / Description du fardeau de la dépression sur la santé de la population au Canada : utilisation de l'espérance de vie ajustée en fonction de la santé.

INTRODUCTION: Few studies have evaluated the impact of depression in terms of losses to both premature mortality and health-related quality of life (HRQOL) on the overall population. Health-adjusted life expectancy (HALE) is a summary measure of population health that combines both morbidity and mortality into a single summary statistic that describes the current health status of a population. METHODS: We estimated HALE for the Canadian adult population according to depression status. National Population Health Survey (NPHS) participants 20 years and older (n = 12 373) were followed for mortality outcomes from 1994 to 2009, based on depression status. Depression was defined as having likely experienced a major depressive episode in the previous year as measured by the Composite International Diagnostic Interview Short Form. Life expectancy was estimated by building period abridged life tables by sex and depression status using the relative risks of mortality from the NPHS and mortality data from the Canadian Chronic Disease Surveillance System (2007-2009). The Canadian Community Health Survey (2009/10) provided estimates of depression prevalence and Health Utilities Index as a measure of HRQOL. Using the combined mortality, depression prevalence and HRQOL estimates, HALE was estimated for the adult population according to depression status and by sex. RESULTS: For the population of women with a recent major depressive episode, HALE at 20 years of age was 42.0 years (95% CI: 40.2-43.8) compared to 57.0 years (95% CI: 56.8-57.2) for women without a recent major depressive episode. For the population of Canadian men, HALE at 20 was 39.0 years (95% CI: 36.5-41.5) for those with a recent major depressive episode compared to 53.8 years (95% CI: 53.6-54.0) for those without. For the 15.0-year difference in HALE between women with and without depression, 12.3 years can be attributed to the HRQOL gap and the remaining 2.7 years to the mortality gap. The 14.8 fewer years of HALE observed for men with depression equated to a 13.0-year HRQOL gap and a 1.8-year mortality gap. CONCLUSION: The population of adult men and women with depression in Canada had substantially lower healthy life expectancy than those without depression. Much of this gap is explained by lower levels of HRQOL, but premature mortality also plays a role.

INTRODUCTION: Peu d'études ont évalué, dans l'ensemble d'une population, les conséquences de la dépression en matière de pertes dues à la mortalité prématurée d'une part et à la qualité de vie liée à la santé (QVLS) d'autre part. L'espérance de vie ajustée en fonction de la santé (EVAS) est une mesure synthétique de la santé de la population qui combine la morbidité et la mortalité en une seule statistique succincte décrivant l'état de santé d'une population à un moment donné. MÉTHODOLOGIE: Nous avons estimé la QVLS de la population canadienne adulte en fonction de la présence ou non de dépression. Nous avons effectué un suivi de la mortalité, de 1994 à 2009, des participants à l'Enquête nationale sur la santé de la population (ENSP) (n = 12 373) de 20 ans et plus, là aussi en fonction de la présence ou non de dépression. La dépression a été définie comme l'état d'une personne susceptible d'avoir connu au cours de l'année précédente un épisode dépressif majeur au sens du formulaire abrégé de l'Entrevue composite diagnostique internationale. L'espérance de vie a été estimée en créant des tables abrégées de mortalité selon le sexe et l'état dépressif à l'aide des risques relatifs de mortalité de l'ENSP et des données sur la mortalité du Système canadien de surveillance des maladies chroniques (2007 à 2009). L'Enquête sur la santé dans les collectivités canadiennes (2009-2010) a fourni des estimations de la prévalence de la dépression, et l'indice de l'état de santé Health Utilities Index a permis de mesurer la QVLS. L'EVAS de la population adulte a été mesurée en fonction de la présence ou non de dépression et en fonction du sexe à l'aide des estimations combinées de la mortalité, de la prévalence de la dépression et de la QVLS. RÉSULTATS: Chez les femmes ayant connu récemment un épisode de dépression majeure, l'EVAS à 20 ans était de 42,0 ans (IC à 95 % : 40,2 à 43,8), contre 57,0 ans (IC à 95 % : 56,8 à 57,2) chez les femmes n'ayant pas vécu récemment d'épisode de dépression majeure. Au sein de la population masculine canadienne, l'EVAS à 20 ans était de 39,0 ans (IC à 95 % : 36,5 à 41,5) chez ceux qui avaient connu récemment un épisode de dépression majeure, contre 53,8 ans (IC à 95 % : 53,6 à 54,0) chez ceux n'ayant pas connu récemment d'épisode de dépression majeure. La différence de 15 ans dans l'EVAS des femmes avec et sans épisode récent de dépression majeure peut se décomposer en 12,3 ans attribuables à l'écart de la QVLS et 2,7 ans à l'écart observé en matière de mortalité. Les 14,8 années de moins d'EVAS chez les hommes ayant souffert de dépression correspondent à un écart de la QVLS de 13 ans et à un écart de mortalité de 1,8 an. CONCLUSION: La population canadienne adulte atteinte de dépression au Canada avait une espérance de vie en santé considérablement plus faible que celle ne souffrant pas de dépression, chez les hommes comme chez les femmes. Si la majeure partie de cet écart s'explique par des niveaux moins élevés de la QVLS, la mortalité prématurée joue également un rôle.

Monitoring positive mental health and its determinants in Canada: the development of the Positive Mental Health Surveillance Indicator Framework.

INTRODUCTION: The Mental Health Strategy for Canada identified a need to enhance the collection of data on mental health in Canada. While surveillance systems on mental illness have been established, a data gap for monitoring positive mental health and its determinants was identified. The goal of this project was to develop a Positive Mental Health Surveillance Indicator Framework, to provide a picture of the state of positive mental health and its determinants in Canada. Data from this surveillance framework will be used to inform programs and policies to improve the mental health of Canadians. METHODS: A literature review and environmental scan were conducted to provide the theoretical base for the framework, and to identify potential positive mental health outcomes and risk and protective factors. The Public Health Agency of Canada's definition of positive mental health was adopted as the conceptual basis for the outcomes of this framework. After identifying a comprehensive list of risk and protective factors, mental health experts, other governmental partners and non-governmental stakeholders were consulted to prioritize these indicators. Subsequently, these groups were consulted to identify the most promising measurement approaches for each indicator. RESULTS: A conceptual framework for surveillance of positive mental health and its determinants has been developed to contain 5 outcome indicators and 25 determinant indicators organized within 4 domains at the individual, family, community and societal level. This indicator framework addresses a data gap identified in Canada's strategy for mental health and will be used to inform programs and policies to improve the mental health status of Canadians throughout the life course.

TITRE: Surveillance de la santé mentale positive et de ses facteurs déterminants au Canada : élaboration d'un cadre d'indicateurs de surveillance de la santé mentale positive. INTRODUCTION: D'après la Stratégie en matière de santé mentale pour le Canada, la collecte de données sur la santé mentale au Canada a besoin d'être améliorée. La mise en place de systèmes de surveillance sur la maladie mentale n'a pas suffi à combler toutes les lacunes statistiques relevant de la santé mentale positive et de ses facteurs déterminants au Canada. L'objectif de ce projet était d'élaborer un Cadre d'indicateurs de surveillance de la santé mentale positive, dans le but de dresser un portrait de la santé mentale positive au Canada, ainsi que de ses facteurs déterminants. Les données recueillies grâce à ce cadre de surveillance serviront de référence pour l'établissement des programmes et des politiques d'amélioration de la santé mentale des Canadiens. MÉTHODOLOGIE: Un examen de la littérature et une analyse contextuelle ont été réalisés afin de fournir une base théorique au cadre et de sélectionner divers critères d'évaluation de la santé mentale positive et de ses facteurs de risque et de protection. La définition de la santé mentale positive adoptée par l'Agence de la santé publique du Canada a servi de référence conceptuelle lors de l'élaboration du cadre. À partir de la liste exhaustive des risques et des facteurs de protection qui a été réalisée, des experts en santé mentale, des partenaires gouvernementaux et des intervenants indépendants ont été invités à classer les indicateurs choisis par ordre de priorité. Ces groupes ont ensuite été invités à sélectionner les méthodes de mesure les plus prometteuses pour chacun des indicateurs. RÉSULTATS: Le cadre conceptuel de surveillance de la santé mentale positive et de ses facteurs déterminants qui a été ainsi élaboré contient 5 indicateurs de résultats et 25 indicateurs de déterminants, répartis en 4 niveaux contextuels : « individu ¼, « famille ¼, « communauté ¼ et « société ¼. Ce cadre d'indicateurs vise à combler les lacunes en matière de données relevées par la Stratégie en matière de santé mentale pour le Canada, et il servira de référence pour l'établissement des programmes et des politiques d'amélioration de la santé mentale des Canadiens tout au long de leur vie.

Comparison of the estimated prevalence of mood and/or anxiety disorders in Canada between self-report and administrative data.

BACKGROUND: To compare trends in the estimated prevalence of mood and/or anxiety disorders identified from two data sources (self-report and administrative). Reviewing, synthesising and interpreting data from these two sources will help identify potential factors that underlie the observed estimates and inform public health action. METHOD: We used self-reported, diagnosed mood and/or anxiety disorder cases from the Canadian Community Health Survey (CCHS) across a 5-year span (from 2003 to 2009) to estimate the prevalence among the Canadian population aged ≥15 years. We also estimated the prevalence of mood and/or anxiety disorders using the Canadian Chronic Disease Surveillance System (CCDSS), which identified cases using ICD-9/-10-CA codes from physician billing claims and hospital discharge records during the same time period. The prevalence rates for mood and/or anxiety disorders were compared across the CCHS and CCDSS by age and sex for all available years of data from 2003 to 2009. Summary rates were age-standardised to the Canadian population as of 1 October 1991. RESULTS: In 2009, the prevalence of mood and/or anxiety disorders was 9.4% using self-reported data v. 11.3% using administrative data. Prevalence rates obtained from administrative data were consistently higher than those from self-report for both men and women. However, due to an increase in the prevalence of self-reported cases, these differences decreased over time (rate ratios for both sexes: 1.6-1.2). Prevalence estimates were consistently higher among females compared with males irrespective of data source. While differences in the prevalence estimates between the two data sources were evident across all age groups, the reduction of these differences was greater among adolescent, young and middle-aged adults compared with those 70 years and older. CONCLUSIONS: The overall narrowing of differences over time reflects a convergence of information regarding the prevalence of mood and/or anxiety disorders trends between self-report and administrative data sources. While the administrative data-based prevalences remained relatively stable, the self-reported prevalences increased over time. These observations may reflect positive societal changes in the perceptions of mental health (declining stigma) and/or increasing mental health literacy. Additional research using non-ecological data is required to further our understanding of the observed findings and trends, including a data linkage exercise permitting a comparison of prevalence estimates and population characteristics from these two data sources both separately and merged.

Status Report--Retracing the history of the early development of national chronic disease surveillance in Canada and the major role of the Laboratory Centre for Disease Control (LCDC) from 1972 to 2000.

TITRE: Rapport d'étape - Historique des débuts de la surveillance nationale des maladies chroniques au Canada et rôle majeur du Laboratoire de lutte contre la maladie (LLCM) de 1972 à 2000. INTRODUCTION: La surveillance de la santé consiste en l'utilisation systématique et continue de données sur la santé recueillies régulièrement en vue d'orienter les mesures de santé publique en temps opportun. Ce document décrit la création et l'essor des systèmes nationaux de surveillance au Canada et les répercussions de ces systèmes sur la prévention des maladies chroniques et des blessures. En 2008, les auteurs ont commencé à retracer l'historique des débuts de la surveillance nationale des maladies chroniques au Canada, en commençant à 1960, et ils ont poursuivi leur examen jusqu'en 2000. Une publication de 1967 a retracé l'historique de la création du Laboratoire d'hygiène de 1921 à 1967. Notre étude fait suite à cette publication et décrit l'historique de l'établissement de la surveillance nationale des maladies chroniques au Canada, à la fois avant et après la création du Laboratoire de lutte contre la maladie (LCDC).

The development of national indicators for the surveillance of osteoporosis in Canada.

INTRODUCTION: The Public Health Agency of Canada, in collaboration with bone health and osteoporosis experts from across Canada (n = 12), selected a core set of indicators for the public health surveillance of osteoporosis using a formal consensus process. METHODS: A literature review identified candidate indicators that were subsequently categorized into an osteoporosis-specific indicator framework. A survey was then administered to obtain expert opinion on the indicators' public health importance. Indicators that scored less than 3 on a Likert scale of 1 (low) to 5 (high) were excluded from further consideration. Subsequently, a majority vote on the remaining indicators' level of public health importance was sought during a face-to-face meeting. RESULTS: The literature yielded 111 indicators, and 88 were selected for further consideration via the survey. At the face-to-face meeting, more than half the experts considered 39 indicators to be important from the public health perspective. CONCLUSION: This core set of indicators will serve to inform the development of new data sources and the integration, analysis and interpretation of existing data into surveillance products for the purpose of public health action.

Life with arthritis in Canada: a personal and public health challenge.

"Arthritis" describes more than 100 conditions that affect the joints, the tissues that surround joints and other connective tissue. These conditions range from relatively mild forms of tendonitis and bursitis to systemic illnesses, such as rheumatoid arthritis. Life with arthritis in Canada: a personal and public health challenge presents the latest knowledge about arthritis in the Canadian population and its wide-ranging impact. It provides an overview of the impact of arthritis, and is designed to increase public awareness of the importance of prevention and timely management. Although progress has been made on interventions, arthritis remains common, disabling and costly. Increasing participation in physical activity and maintaining a healthy body weight may help to mitigate the effects of arthritis.

Asthma in children: Management practices among paediatricians and family physicians.

OBJECTIVE: To ascertain the variation in asthma management practices among paediatricians and family physicians to determine how to improve care. DESIGN: Questionnaire study of paediatricians and family physicians that focused on the use of beta(2)-agonists, inhaled corticosteroids, patient asthma education, quantitative measurements of airflow and diagnostic investigations for asthma. Case scenarios were used in the questionnaire. RESULTS: The response rate was 66% (415 of 632) among paediatricians and 42% (1156 of 2750) among family physicians. In general, both groups followed consensus guidelines. There were some differences in management practices among paediatricians and family physicians. Paediatricians were more likely to develop an action plan and less likely to use xanthines or inhaled anticholinergic agents. However, family physicians were more likely to use spirometry or home peak expiratory flow rates to make a diagnosis of asthma. CONCLUSION: Family physicians and paediatricians require a different focus on educational interventions to improve the care of children with asthma.

Physician asthma management practices in Canada.

OBJECTIVES: To establish national baseline information on asthma management practices of physicians, to compare the reported practices with the Canadian Consensus recommendations and to identify results potentially useful for interventions that improve physician asthma management practices. DESIGN: National, stratified cross-sectional survey. SETTINGS: The 10 provinces and two territories of Canada, from 1996 to 1997. PARTICIPANTS: Questionnaires were sent to 4489 physicians stratified by province/territory and specialty group (family/general practice, respirology, internal medicine, pediatrics and allergy/immunology); 2605 responses were received. OUTCOME MEASURES: Methods for the diagnosis, treatment, education and follow-up of patients with asthma ('asthma management practices'). RESULTS: Significant variations existed among the five specialty groups in asthma management practices. A low use of objective measures of airflow limitation to assist with diagnosis was found among some respondents (mostly family physicians). Up to 40% of physicians regarded the daily fixed dosing (three or four times a day) of inhaled, short acting beta2-agonist as 'first-line therapy' for moderate to severe asthma. A minority of physicians reported using written action plans for patients or referring them to other health professionals for asthma education. Insufficient time during appointments and a perceived lack of appropriate educational materials were frequently cited as reasons for not providing asthma education. The perceived knowledge of the Canadian Consensus recommendations varied among physicians but was lowest among nonspecialists. CONCLUSIONS: The survey showed variations in certain aspects of the management of asthma by physicians. The findings will help to target specific areas for future physician education programs and other behavioural change strategies.

Noninvasive urodynamics: a study of male voiding dysfunction.

A group of 26 patients was tested for isovolumetric pressure and optimal flow rate by means of the cuff-uroflow (CUF) technique. The same patients were also examined in the clinic, and a diagnosis was recorded. The two processes were performed independently in a statistically double-blind manner. Standard statistical comparisons were made, and it was shown that there exists substantial correlation between the results of clinical examination and the cuff-uroflow procedure. It was also shown that the CUF technique converged more rapidly to a correct diagnosis than standard clinical procedures. Surgical treatment and watchful waiting were examined and it was shown, as expected, that surgical treatment resulted in substantial improvement in most cases, but that watchful waiting generated no statistically significant change.

Objective noninvasive evaluation of benign prostatic hypertrophy.

An objective noninvasive procedure has been developed to evaluate the urodynamics of benign prostatic hypertrophy. The test uses pneumatic occlusive cuffs similar to those used for blood pressure measurements and the electrical engineering concepts of open-circuit, short-circuit, and transient response measurements. The cuff is first inflated to measure pressure, then rapidly released, yielding the transient response and subsequent unimpeded flow. From the pressure and flowrate recordings as functions of time, objective evaluations of bladder strength and urethral obstruction are extracted.

Noninvasive quantitative method for measuring isovolumetric bladder pressure and urethral resistance in the male: I. Experimental validation of the theory.

Noninvasive measurement of intravesical pressure, impulsive flow rate, and localized urethral resistance is achieved by clamping the penis immediately above the glans with a pneumatic cuff and then instructing the patient to initiate voiding. The cuff is then deflated slowly until urinary flow of at least 1 ml/s is detected and is then released rapidly to permit unimpeded flow. Cuff pressure, voided volume, and flow rate are recorded as functions of time. From the resulting tracings it is possible to determine the isovolumetric bladder pressure, the impulsive flow rate, and the flow pattern specific to the test. We studied 53 male patients demonstrating that data thus obtained are reproducible and that the cuff pressure at the initiation of voiding does measure the bladder pressure at this moment. We then modeled the lower urinary tract by an analog electrical circuit which facilitated the analysis of the urodynamic data. This analysis suggests that it is possible to separate the effects of bladder dysfunction from the effects of urethral resistance and to localize the resistance to the proximal or distal urethra without invasive testing.

Changes in receptor occupancy and growth factor responsiveness induced by treatment of a transformed mouse embryo cell line with N,N-dimethylformamide.

Treatment of the transformed mouse embryo fibroblast cell line (AKR-MCA) with N,N-dimethylformamide (DMF) results in a reversion to the nontransformed AKR-2B cell line phenotype. AKR-MCA cells grown in the presence of 1% DMF showed a 2-fold increase in the sites for epidermal growth factor (EGF) binding. However, most of these sites were occupied by an endogenous ligand. The EGF receptor was unoccupied in untreated AKR-MCA cells. The increased receptor occupation was paralleled by an increase in the mitogenic response to EGF. Treatment of these cells with 1% DMF resulted in a 6-fold stimulation of mitogenesis by EGF. The ability to respond to nutrient replenishment (a property of growth-arrested AKR-MCA cells) was lost within 24 h of DMF treatment. Upon removal of DMF from the cells, both the mitogenic response to EGF and the occupation of the EGF receptor by endogenous ligands were lost. Treatment of the AKR-2B cell line with DMF had little effect on its growth properties. Therefore, DMF altered the growth control response and growth factor binding of AKR-MCA cells in a reversible, noncytotoxic manner.

Identification of endogenous inhibitory growth factors from a human colon carcinoma cell line.

A line of human colon carcinoma cells, designated MOSER, was established which synthesized tumor-inhibitory factor (TIF) and transforming growth factor (TGF) activity. Both activities were found in serum-free conditioned medium and in cell extracts. The activities coelute on Bio-Gel P-10 in acetic acid, but can be completely separated by reverse-phase high-pressure liquid chromatography. The TIF and TGF activities were acid and heat stable and were sensitive to trypsin and dithiothreitol. MOSER cell TIF prevented the anchorage-independent growth of the more differentiated colon carcinoma cell lines tested but did not affect the less differentiated lines. Using anchorage-dependent growth conditions, the effect of TIF appeared to be noncytotoxic and partially reversible. Purified TGF stimulated the growth of normal rat kidney fibroblasts and the slow-growing CBS colon carcinoma cell line but did not stimulate MOSER cell growth. MOSER cells contain both positive (TGF) and negative (TIF) factors with relative concentrations that may be important parameters in the regulation of cell growth.

Elevated growth factor levels in transformed mouse embryo cells treated with N,N-dimethylformamide.

The transformed mouse embryo fibroblast cell line AKR-MCA, produces several transforming growth factor (TGF) activities which can be identified in cell extracts and serum-free conditioned medium. Treatment of these transformed cells with 1% N,N-dimethylformamide resulted in a more normal phenotype and an increased level of TGFs in cell extracts and conditioned medium. In addition, an 11-fold increase in an epidermal growth factor receptor-competing activity was observed in cell extracts and conditioned medium compared to control untreated cells. Fractionation of the conditioned medium on Bio-Gel P-100 showed that the same size classes of TGFs were present in N,N-dimethylformamide-treated as well as untreated cells. The increased EGF-receptor-competing activity was eluted in two peaks at Mr 6500 and Mr 4000. The Mr 6500 peak did not coelute with a TGF peak in the N,N-dimethylformamide-treated cells.

Disulfiram implantation: a dose response trial.

Alcoholic volunteers (N = 120) were assigned at random to receive an 800 mg, 1200 mg, or 1600 mg subcutaneous disulfiram implant. Patients were followed for a 2-year period. Although all groups showed an increase in sobriety following implantation, there was no significant dose-response relationship. There were no significant between-group differences in the incidence of disulfiram-ethanol reaction.

Restoration of normal growth control and membrane antigen composition in malignant cells by N,N-dimethylformamide.

The effects of the differentiation agent, N,N-dimethylformamide (DMF), on malignant AKR-MCA cells were studied. The properties of DMF-treated AKR-MCA cells were compared to those of the normal parental AKR-2B mouse embryo fibroblasts. AKR-MCA cells grown in 1% DMF were found to be more similar to their normal counterparts than to untreated AKR-MCA cells by several criteria. These criteria included the loss of the transformed morphology, a 2-fold reduction of doubling time, a 10-fold reduction of saturation density, and the complete loss of the ability to grow with anchorage independence. The expression of high-molecular-weight membrane antigens (Mr 110,000 to 450,000), which was found to be greatly reduced in AKR-MCA cells in comparison to normal AKR-2B cells, was restored by treatment of AKR-MCA cells with DMF. The expression of a low-molecular-weight AKR-MCA cell-associated membrane antigen, on the other hand was found to be suppressed. Studies on the mitogenic response of these cells indicated that AKR-MCA and AKR-2B cells may be regulated by different types of growth control. Growth-arrested AKR-MCA cells did not respond to epidermal growth factor, but responded to nutrient replenishment. AKR-2B cells, on the other hand, responded to epidermal growth factor, but did not respond to nutrient replenishment. Treatment of AKR-MCA cells with DMF restored their ability to respond to epidermal growth factor, while their ability to respond to nutrient replenishment was lost. The results of this study indicated that DMF treatment induced the normalization of malignant AKR-MCA cells with regard to membrane antigen composition and growth control properties.