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PubMed1995

Teaching ophthalmology to primary care physicians. The Association of University Professors of Ophthalmology Education Committee.

The evolution of our health care system toward managed care has placed primary care "gatekeeper" physicians in a position where they must examine and treat patients with diseases that are ordinarily treated by medical and surgical subspecialists. Many of these physicians may be poorly prepared to accept this new responsibility. The Association of University Professors of Ophthalmology (AUPO) has published a Policy Statement on Medical Student Education that suggests the minimum level of competence expected of general physicians when dealing with ophthalmologic problems. A recent survey of directors of residency programs in family practice, internal medicine, and pediatrics revealed that the training of primary care physicians (as opposed to academicians or subspecialists) has become a nearly universal programmatic goal. Most program directs believe that less than half of their residents meet the AUPO standard at the completion of medical school, and a significant minority do not meet the AUPO standard at the completion of their residency. An overwhelming majority of program directors believe that additional training in ophthalmology and other subspecialties should be incorporated into the training programs of primary care physicians. Ophthalmologists and other subspecialists should develop programs at the medical student level directed toward the education of primary care physicians, and should participate in the training of primary care physicians, as well as their own subspecialty residents. In the future, the primary care physician must be considered part of the "eye care team." Enhancing the ophthalmologic education of primary care physicians is in the best interest of quality patient care.

Family Practice↗
PubMed1998

Identification of psychosocial problems in pediatric primary care: do family attitudes make a difference?

OBJECTIVE: To evaluate the affect of families' attitudes about the appropriateness of discussing psychosocial concerns on pediatric providers' identification of psychosocial problems. DESIGN: These data were collected as part of the Greater New Haven Child Health Study, New Haven, Conn. The study design was a prospective cohort. SETTING: Families were recruited from a stratified random sample of all primary care practices in the greater New Haven area. Nineteen of 23 invited practices agreed to participate including 2 prepaid practices, 2 neighborhood health centers, and 7 fee-for-service group and 8 fee-for-service solo practices. PARTICIPANTS: All families of children aged 4 to 8 years who attended these practices during 2 separate 3-week periods (1 in fall 1987 and 1 in spring 1988) were invited to participate in the study. Families were invited to participate only once, on the first contact with any eligible child, using approved procedures. Of 2006 eligible families, 1886 (94%) chose to participate. MAIN OUTCOME MEASURE: The outcome variable for these analyses is the identification of any behavioral, emotional, or developmental problem by the pediatrician on the 13-category checklist. Overall, pediatric clinicians identified 27.5% of children with 1 or more psychosocial problems. RESULTS: Our data suggest that there is a great deal of discrepancy between what parents report is appropriate to do when their children have psychosocial problems and what they actually do when they recognize such problems in their children. Most (81.1%) believed it was appropriate to discuss 4 or more of the 6 hypothetical situations with their children's physician, while only 40.9% actually did discuss any of these problems with a physician when a problem occurred. Given the correlates of parents who intended to discuss such problems (higher education, older age, Euro-American ethnicity, higher income, married, availability of medical insurance) the possibility that parents are providing socially acceptable responses to such questions seems likely. Further, our data indicate that parents' actual reports of discussions of psychosocial problems is unrelated to whether physicians identified those problems in children. CONCLUSIONS: Pediatricians'judgments about the presence of psychosocial problems in their young patients seem to be based on their own observations rather than on what parents report. Physician-parent communication about psychosocial problems will be increasingly important as primary care physicians assume their role as gatekeepers to more expensive services such as mental health interventions.

Affective Symptoms↗
PubMed2003

Referral of children to specialists in the United States and the United kingdom.

OBJECTIVE: To compare the rates and patterns of children's specialty referrals in the United States (US) and the United Kingdom (UK). DESIGN: Retrospective cohort analysis of health care claims/encounter data obtained in 1996 (US) and 1997 (UK). SETTING: Children in the US were selected from 5 managed health plans that used primary care physicians as gatekeepers: 2 health maintenance organizations and 3 point-of-service plans. Point-of-service plans allow patient self-referral at increased out-of-pocket costs. In the UK, the General Practice Research Database provided data from 211 general practices. PARTICIPANTS: Children, from birth to the age of 17 years, with no cost sharing for physician services in the US (n = 135,092) and who were registered with general practitioners, all of whom authorize patients' access to specialty care, in the UK (n = 221,312). MAIN OUTCOME MEASURE: Annual percentage of children referred to a specialist. RESULTS: Across the 5 US plans, 18.6% to 28.8% of the patients per year were referred vs 8.7% of the patients per year in the UK sample. Referral rates were not significantly different between a health maintenance organization and a point-of-service plan administered by a single insurer. Compared with patients in the UK sample, those in the US plans were 1.9 times more commonly referred to medical specialists and 3.2 times more commonly referred to surgical specialists. There was considerable cross-national variation in specialty-specific referral rates for children with selected conditions. CONCLUSIONS: Children in US managed care plans are between 2 and 3 times as likely to be referred to specialists compared with counterparts in the UK. Although these referral rate differences are substantial, our findings cannot be construed to mean that the US referral rates are too high or that the UK rates are too low. The greater supply of specialists and higher expectations for direct access to specialty care in the US, compared with the UK, are likely explanations for these differences in children's specialty referral rates.

Adolescent↗
PubMed1992

Parental behavior in relation to physical activity and fitness in 9-year-old children.

OBJECTIVE: To examine the relationship between parental behaviors and physical activity and fitness in elementary school-aged children. DESIGN: Cross-sectional survey of students and parents. SETTING: Seven public elementary schools in a suburban southern California city. PARTICIPANTS: One hundred forty-eight fourth-grade girls and 149 fourth-grade boys and their parents. Eighty-four percent were white. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Children's physical activity was indicated by self-report, data obtained from a monitor (accelerometer), and results of the mile run/walk. Multiple regression analysis, controlling for ethnicity and body mass index, was conducted separately for girls and boys to explain variation in child activity and fitness. Parents' reported physical activity was not associated with child activity or fitness. However, availability of transportation by parents to sport and fitness activities was significant (or nearly so) in two regressions for boys and in one regression for girls. Parents who played with their children had more active boys, based on self-report, but verbal encouragement to be active was not significant in any model. CONCLUSION: The parental role as gatekeeper of access to activity and sport facilities deserves further study.

Behavior↗
PubMed1998

Patients' views of direct access to specialists: an Israeli experience.

CONTEXT: Surveys carried out among users of medical services can be a useful tool for health care organizations in designing proper services. Specifically, patients' views of direct access to specialists can be useful to health organizations considering the gatekeeper model. OBJECTIVE: To assess patients' opinions about direct access to specialists and referral to specialists through their primary care physician. DESIGN: An intercept survey, in which patients were interviewed at the randomly selected service provision sites, was carried out in 3 districts in Israel during 1995. A total of 1445 and 1289 patients were interviewed in primary care and specialty clinics, respectively. SETTING: Primary care and specialty clinics in 3 regions in Israel serving 750000 members of Kupat Holim Clalit, Israel's largest sick fund. PARTICIPANTS: Hebrew-speaking members of Kupat Holim Clalit who visited the primary care or specialty clinics in the 3 regions during the study period. MAIN OUTCOME MEASURES: Rate of preferences for direct access to specialists and preferences for referral through primary care physician. RESULTS: Fifty-two percent of the respondents preferred direct access to specialists, while 48% preferred a referral from their primary care physician. Multivariate logistic regression analysis indicated that the preference for direct access was significantly lower among patients older than 45 years (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.62-0.91); patients whose primary care physician was a specialist in family medicine (OR, 0.80; 95% CI, 0.67-0.97); and patients who were satisfied with their primary care physician (OR, 0.34; 95% CI, 0.27-0.44). Preference for direct access was significantly higher among more highly educated patients (OR, 1.38; 95% CI, 1.16-1.65) and patients residing in Jerusalem (OR, 2.46; 95% CI, 2.05-2.95) and those younger than 45 years who were dissatisfied with their family physician or a primary care physician who was not board certified. If direct access was not available, 33% of respondents would leave the sick fund and 48% would remain; 19% did not know. CONCLUSIONS: Informing sick fund members, particularly the younger and more educated among them, about the advantages of consulting with the primary care physician, as well as providing specialty training in family medicine to primary care physicians, may reduce patients' preference for direct access to specialists.

Adult↗
PubMed2001

Self-referral in point-of-service health plans.

CONTEXT: Most health maintenance organizations offer products with loosened restrictions on patients' access to specialty care. One such product is the point-of-service (POS) plan, which combines "gatekeeping" arrangements with the ability to self-refer at increased out-of-pocket costs. Few data are available from formal evaluations of this new type of plan. OBJECTIVES: To comprehensively describe the self-referral process in POS plans by quantifying rates of self-referral, identifying patients most likely to self-refer, characterizing patients' reasons for self-referral, and assessing satisfaction with specialty care. DESIGN: Retrospective cohort analysis using administrative databases composed of members aged 0 to 64 years who were enrolled in 3 POS health plans in the Midwest (n = 265 843), Northeast (n = 80 292), and mid-Atlantic (n = 39 888) regions for 6 to 12 months in 1996, and a 1997 telephone survey of specialty care users (n = 606) in the midwestern plan. MAIN OUTCOME MEASURES: Self-referred service use and charges, reasons for self-referral, and satisfaction with specialty care. RESULTS: Overall, 8.8% of enrollees in the midwestern POS plan, 16.7% in the northeastern plan, and 17.3% in the mid-Atlantic plan self-referred for at least 1 physician or nonphysician clinician visit. The proportions of enrollees self-referring to generalists (4.7%-8.5%) were slightly higher than the proportions self-referring to specialists (3.7%-7.2%) across all 3 plans. Nine percent to 16% of total charges were due to self-referral. The chances of self-referral to a specialist were increased for patients with chronic and orthopedic conditions, higher cost sharing for physician-approved services, and less continuity with their regular physician. Patients who self-referred to specialists preferred to access specialty care directly (38%), reported relationship problems with their regular physicians (28%), had an ongoing relationship with a specialist (23%), were confused about insurance rules (8%), and did not have a regular physician (3%). Compared with those referred to specialists by a physician, patients who self-referred were more satisfied with the specialty care they received. CONCLUSIONS: Having the option to self-refer is enough for most POS plan enrollees; 93% to 96% of enrollees did not exercise their POS option to obtain specialty care via self-referral during a 1-year interval. The potential downside of uncoordinated, self-referred service use in POS health plans is limited and counterbalanced by higher patient satisfaction with specialist services.

Adolescent↗
PubMed1998

APC mutations in human colorectal adenomas: analysis of the mutation cluster region with temperature gradient gel electrophoresis and clinicopathological features.

To date, the earliest mutations in colorectal adenomas have been found in the adenomatous polyposis coli (APC) gene, considered the 'gatekeeper' in tumourigenesis. To study the types of APC gene mutations and their relation to clinicopathological features which are associated with malignant potential, the mutation cluster region of the APC gene was analysed in a series of 32 human sporadic colorectal adenomas from 22 patients. DNA was extracted from frozen sections and two overlapping fragments which cover the mutation cluster region were amplified using the polymerase chain reaction (PCR). Mutations were screened with temperature gradient gel electrophoresis and identified by DNA sequencing. Mutations were found in 14 samples (44 per cent) from 11 patients. The changes could be characterized as point mutations (n = 7), deletions of one or more nucleotides (n = 6), and insertions (n = 1). From five patients, multiple adenoma samples were obtained and the adenomas from two of these patients showed a heterogeneous mutation pattern in the APC gene. All detected mutations are predicted to result in a truncated APC protein. Genetic alterations in the mutation cluster region of the APC gene occurred significantly more frequently in large adenomas and showed a trend towards an increase in villous adenomas and adenomas with moderate and severe dysplasia. It is concluded that an increased proportion of APC gene mutations were found in the adenomas showing clinicopathological features associated with increased proliferation but not with characteristics of malignant potential. The results suggest that in a significant proportion of adenomas, other (genetic) alterations are involved in early tumourigenesis.

Adenoma↗
PubMed1998

The black box of health care expenditure growth determinants.

In this paper, the determinants of growth of aggregate health expenditures are investigated. The study departs from previous literature in that it looks at differences across countries in growth (and not levels) of health care expenditures. Estimation is made for 24 OECD countries. Health system characteristics usually believed to influence health expenditures growth, like population ageing, the type of health system (public reimbursement, public contract or integrate) and existence of gatekeepers, are found to be non-significant. Nevertheless, there is evidence that health expenditures experienced a clear slower growth in the last decade. The explanation for this slowdown could not be found in the proposed model and should stimulate further research.

Aged↗
PubMed1999

Managed behavioral health care and supply-side economics. 1998 Carl Taube Lecture.

BACKGROUND: Within the past decade, the mental health care system in the United States has undergone a significant transformation in terms of delivery, financing and work force configuration. Contracting between managed care organizations (MCOs) and providers has become increasingly prevalent, paralleling the trend in health care in general. These managed care carve-outs in behavioral health depend on networks of providers who agree to capitated rates or discounted fees for service for those patients covered by the carve-out contracts. Moreover, the carve-outs use a broader array of mental health providers than is typically found in traditional indemnity plans, encourage time-limited versus long-term treatments and favor providers who are engaged in outpatient care. This phenomenal growth in managed behavioral health care over the past decade includes the rapid growth and quick consolidation of mental health MCOs. The period 1992-1998 shows steady and substantial annual increases in the number of enrollees in mental health MCOs, the figure more than doubling from 78.1 million people in 1992 to a projected 156.6 million in 1998, or 70% of insured lives. Moreover, these vast numbers of enrollees are becoming increasingly consolidated into a smaller number of firms. In 1997, 12 companies controlled nearly 85% of the managed behavioral health care market, with 60% of the market held by the three largest firms. STUDY AIMS: This article reviews empirical data and draws policy implications from the literature on managed behavioral health care in the United States. Starting with spending and spending trend estimates that show the average annual growth rate of mental health expenditures to be lower than that of health care expenditures in general over the past decade, the author examines utilization and price factors that may account for managed-care-induced cost reductions in behavioral health care, with special attention to hospital use patterns, fee discounting and the supply and earnings patterns of various types of mental health provider. In addition, data on staffing ratios and provider mixes of health maintenance organizations and mental health MCOs are reviewed as they reveal at least part of the dynamics of reconfiguration of the mental health work force in this era of managed care. CONCLUSIONS: As measured by changes in utilization and price, widespread application of "classic" managed care techniques such as preadmission review (gatekeeping), concurrent review, case management, standardized clinical guidelines and protocols, volume purchase of services and fee discounting appears to have led to significant cost reductions for providers of both impatient and outpatient mental health services. However, amidst a complex flux of market variables such as risk shifting, changing financial incentives and intensity of competition, not all of the reduction or slowdown in spending can be clearly and purely attributed to managed care. The data on the ongoing reconfiguration of the mental health work force are clearer in their implications: with an oversupply of all types of mental health providers, managed care has significant potential to increase the incidence of provider substitutions and spur the growth of integrated group practices. IMPLICATIONS FOR FURTHER RESEARCH: The current body of empirical and policy literature in mental health economics suggests several salient areas of follow-up. Is the proportionately greater impact of managed care on the annual growth rate of mental health care spending a temporary phenomenon or does it signal an enduring difference in the rates of increase between behavioral health care and health care in general? Beyond industry downsizing, what are the substitutions among mental health providers that are going on, and will go on, to produce cost-effective practices? What are the new financial or risk-sharing arrangements between providers and MCOs that will produce appropriate and high-quality mental health services?

Journal Article↗
PubMed1999

Controlling the urge for a Ca(2+) surge: all-or-none Ca(2+) release in neurons.

Changes in the intracellular calcium concentration ([Ca2+]i) convey signals that are essential to the life and death of neurons. Ca(2+)-induced Ca(2+)-release (CICR), a process in which a modest elevation in [Ca2+]i is amplified by a secondary release of Ca2+ from stores within the cell, plays a prominent role in shaping neuronal [Ca2+]i signals. When CICR becomes regenerative, an explosive increase in [Ca2+]i generates a Ca2+ wave that spreads throughout the cell. A discrete threshold controls activation of this all-or-none behavior and cellular context adjusts the threshold. Thus, the store acts as a switch that determines whether a given pattern of electrical activity will produce a local or global Ca2+ signal. This gatekeeper function seems to control some forms of Ca(2+)-triggered plasticity in neurons.

Animals↗
PubMed2003

The role of dendritic cells in regulating mucosal immunity and tolerance.

The intestinal immune system discriminates between invasive pathogens and antigens that are harmless, such as food proteins and commensal bacteria. The latter groups of antigens normally induce tolerance and a breakdown in this homeostatic process can lead to diseases such as coeliac disease or Crohn's disease. The nature ofthe intestinal immune response depends on how antigen is presented to CD4+ T cells by dendritic cells (DCs). Both oral tolerance and priming are influenced by the numbers and activation status of DCs in the gut and its draining lymphoid tissues, and our current work indicates that dietary proteins are taken up preferentially by DCs in the lamina propria of the small intestine. These then migrate to interact with antigen-specific CD4+ T cells in the mesenteric lymph node. In vivo and in vitro studies using purified lamina propria DCs suggest these may play a unique role in the regulation of intestinal immune responses. We propose that local DCs are the gatekeepers of the mucosal immune system, inducing tolerance under physiological conditions, but being sufficiently responsive to inflammatory stimuli to allow T cell priming and protective immunity when necessary. In addition, we will discuss evidence that adjuvant vectors such as ISCOMS may be effective mucosal vaccines due to an ability to activate intestinal DCs.

Animals↗
PubMed2000

Somatic Apc mutations are selected upon their capacity to inactivate the beta-catenin downregulating activity.

The APC gene, originally identified as the gene for familial adenomatous polyposis (FAP), is now considered as the true "gatekeeper" of colonic epithelial proliferation. Its main tumor suppressing activity seems to reside in the capacity to properly regulate intracellular beta-catenin signaling. Most somatic APC mutations are detected between codons 1286 and 1513, the mutation cluster region (MCR). This clustering can be explained either by the presence of mutation-prone sequences within the MCR, or by the selective advantage provided by the resulting truncated polypeptides. Here, a Msh2-deficient mouse model (Msh2(delta 7N) ) was generated and bred with Apc(1638N) and Apc(Min) that allowed the comparison of the somatic mutation spectra along the Apc gene in the different allelic combinations. Mutations identified in Msh2(delta 7N/delta 7N) tumors are predominantly dinucleotide deletions at simple sequence repeats leading to truncated Apc polypeptides that partially retain the 20 a.a. beta-catenin downregulating motifs. In contrast, the somatic mutations identified in the wild type Apc allele of Msh2(delta 7N/delta 7N) /Apc(+/1638N) and Msh2(delta 7N/delta 7N) /Apc(+/Min) tumors are clustered more to the 5' end, thereby completely inactivating the beta-catenin downregulating activity of APC. These results indicate that somatic Apc mutations are selected during intestinal tumorigenesis and that inactivation of the beta-catenin downregulating function of APC is likely to represent the main selective factor.

Adenomatous Polyposis Coli↗
PubMed1993

Channels and vehicles of communication: the asbestos awareness campaign.

In April 1978, the U.S. Department of Health, Education, and Welfare launched a multimedia campaign to inform doctors, workers, and others about the increased risks of asbestos exposure. Unlike most worker notification efforts, this one has no lists of workers or even of workplaces but faced the challenge of locating people who had worked in the shipbuilding industries more than 30 years earlier. Multiple mass media channels were used, but since most messages were distributed as public service announcements, gatekeepers were critical to the success of the campaign. Some campaign messages were aired, but mostly at hours other than prime time, and the coverage focused more on the controversial, fast-breaking events rather than on estimates of risk or on behaviors to reduce risk. The campaign was effective in increasing the number of people who believed they were at risk, but was less successful with older Americans than with manual laborers.

Advertising↗
PubMed1988

Prenatal diagnosis and the Canadian collaborative randomized trial of chorionic villi sampling: the physician's view.

Women eligible for the Canadian randomized trial of chorionic villi sampling (CVS) often cite physician influence as a reason for refusing to participate. To measure directly physicians' attitudes to and knowledge of prenatal diagnosis (PND), amniocentesis, CVS, randomized trials, and the Canadian trial, a 3-page questionnaire was mailed to all registered obstetricians in British Columbia (BC) and in Montreal (Mtl). The overall response rate was 70%. Most physicians thought PND was important and that it was their role to discuss and advise PND to their patients. Physicians were split in their preferences for amniocentesis or CVS (32% vs. 34%); reasons for their preferences paralleled those given by women studied previously by us. Physicians who thought CVS was too experimental, who were hesitant about the trial or who were less likely to discuss the study with patients were older, less likely to have participated in a randomized trial previously and less comfortable with randomization and discussing uncertain risks with patients. Mtl physicians were less aware and more hesitant about the Canadian trial than those in BC. Moreover, Mtl physicians were more likely to consider the ongoing trial inappropriate and too experimental than BC physicians. Because physicians act as "gatekeepers," educating them about new technologies and about randomized studies is essential for ensuring both participant's access to a new procedure and success of the randomized trial.

Attitude of Health Personnel↗
PubMed1990

Structure and function of the nuclear pore complex: new perspectives.

The double membrane of the nuclear envelope is a formidable barrier separating the nucleus and cytoplasm of eukaryotic cells. However, movement of specific macromolecules across the nuclear envelope is critical for embryonic development, cell growth and differentiation. Transfer of molecules between the nucleus and cytoplasm occurs through the aqueous channel formed by the nuclear pore complex (NPC). Although small molecules may simply diffuse across the NPC, transport of large proteins and RNA requires specific transport signals and is energy dependent. A family of pore glycoproteins modified by O-linked N-acetylglucosamine moieties are essential for transport through the NPC. Recent evidence suggests that the regulation of nuclear transport may also involve the interaction of RNA and nuclear proteins with specific binding proteins that recognize these transport signals. Are these nuclear pore glycoproteins and signal binding proteins the 'gatekeepers' that control access to the genetic material? Recent evidence obtained from a combination of biochemical and genetic approaches suggests--perhaps.

Animals↗
PubMed2004

A gene signature of inhibitory MHC receptors identifies a BDCA3(+) subset of IL-10-induced dendritic cells with reduced allostimulatory capacity in vitro.

Dendritic cells (DC) are crucial gatekeepers in regulating immunity. Whereas mature immunostimulatory myeloid DC (DC(ims)) potently promote immune responses, IL-10-induced myeloid DC (DC-IL-10) counteract T cell activation. To elucidate the molecular repertoire by which DC-IL-10 secure reduced T cell activation, comparative gene expression profiling was done using Affymetrix U133A microarrays. Among the genes overexpressed in DC-IL-10, eight immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing inhibitory molecules (ILT2, ILT3, ILT4, ILT5, DCIR, PILRA, FcgammaRIIB, SLAM) were found. Phenotypic analysis of DC-IL-10 defined an ILT(high) DC subset further characterized by expression of CD14, TLR2, DC-SIGN, and CD123 and the lack of lymphocyte, monocyte/macrophage, and plasmacytoid DC markers such as CD3, CD8, and CD68. A unique feature of the ILT(high) DC subset was expression of the novel DC marker BDCA3, which was not detected on monocytes, immature DC, DC(ims), or ILT(low) DC-IL-10. While the allogeneic T cell proliferation induced by the entire DC-IL-10 population was approximately 30% of that stimulated by DC(ims), allogeneic MLR responses driven by the ILT(high) DC subset were reduced to 8% of the allostimulatory capacity of DC(ims), although secretion of the inhibitory cytokine IL-10 and other Th1/Th2-associated cytokines was similar in these cells.

Cytokines↗
PubMed2005

Factors affecting timely recognition and diagnosis of dementia across Europe: from awareness to stigma.

BACKGROUND: Timely recognition and diagnosis of dementia is the pre-condition for improving dementia care, but diagnosis often occurs late in the disease process. OBJECTIVE: To compare facilitators and obstacles to the timely recognition of dementia across eight European Union states, in order to implement established policies for earlier diagnosis. METHODS: A modified focus group technique, including a pre and posterior procedure. RESULTS: Twenty-three participants from different disciplines, purposively sampled for professional expertise in dementia research and innovative practice, attended two focus groups. Stigma in ageing and dementia, accompanied by a sense that there is little to offer until later on in the disease, underpinned the widespread reluctance of GPs to recognise dementia at an early stage and were major obstacles to the timely diagnosis of dementia across all eight countries. Dementia care services varied widely across Europe. Countries with the greatest development of dementia health care services were characterised by national guidelines, GPs fulfilling a gatekeeper function, multi-disciplinary memory clinics and innovative programmes that stimulated practice and new services. Dementia-related stigma was perceived as being less prominent in these countries. CONCLUSIONS: Overcome of delays in the timely diagnosis of dementia needs more than specialist services. They should address the processes associated with stigma, age and dementia, especially where these relate to physician practice and diagnostic disclosure. Stigma is perceived as variable across European States, with a promising finding that its impact is relatively small in countries with the widest range of dementia care services.

Dementia↗
PubMed2006

Phenotype-genotype correlation: challenge of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses.

BACKGROUND: Intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinuses shows microscopic features indistinguishable from colorectal cancer. Our aim was to verify whether the morphologic resemblances mirror genetic profile similarities. METHODS: Twenty consecutive surgically treated ITAC cases, previously investigated for p16(INK4a) and TP53, were investigated for hMLH1, hMSH2, and beta-catenin immunoreactivity, and for adenomatous polyposis coli (APC), K-ras, and BRAF gene mutations. RESULTS: One case was immunonegative for both hMLH1 and hMSH2, and 12 tumors (40%) revealed a strong beta-catenin overexpression. No BRAF and APC truncating mutations were identified, whereas K-ras mutations were detected in 9 ITACs (50%). CONCLUSIONS: Our data confirm the phenotypic similarities at the genetic level between colorectal cancer and ITACs showing deregulation of K-Ras/BRAF and loss of heterozygosity (LOH) of chromosome 18q. By contrast, both frequency rate and type of inactivation of the APC-beta-catenin pathway differ in the 2 tumors, suggesting different gatekeeper events in the early development of ITAC (p16(INK4a) and TP53) and colorectal cancer (APC).

Adaptor Proteins, Signal Transducing↗