Showing papers by "Mayo Clinic published in 2004"
TL;DR: It is suggested that the diagnosis of mild cognitive impairment can be made in a fashion similar to the clinical diagnoses of dementia and AD, and an algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI.
Abstract: The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.
6,382 citations
TL;DR: Effective weight loss was achieved in morbidly obese patients after undergoing bariatric surgery, and a substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or improvement.
Abstract: ContextAbout 5% of the US population is morbidly obese. This disease remains
largely refractory to diet and drug therapy, but generally responds well to
bariatric surgery.ObjectiveTo determine the impact of bariatric surgery on weight loss, operative
mortality outcome, and 4 obesity comorbidities (diabetes, hyperlipidemia,
hypertension, and obstructive sleep apnea).Data Sources and Study SelectionElectronic literature search of MEDLINE, Current Contents, and the Cochrane
Library databases plus manual reference checks of all articles on bariatric
surgery published in the English language between 1990 and 2003. Two levels
of screening were used on 2738 citations.Data ExtractionA total of 136 fully extracted studies, which included 91 overlapping
patient populations (kin studies), were included for a total of 22 094
patients. Nineteen percent of the patients were men and 72.6% were women,
with a mean age of 39 years (range, 16-64 years). Sex was not reported for
1537 patients (8%). The baseline mean body mass index for 16 944 patients
was 46.9 (range, 32.3-68.8).Data SynthesisA random effects model was used in the meta-analysis. The mean (95%
confidence interval) percentage of excess weight loss was 61.2% (58.1%-64.4%)
for all patients; 47.5% (40.7%-54.2%) for patients who underwent gastric banding;
61.6% (56.7%-66.5%), gastric bypass; 68.2% (61.5%-74.8%), gastroplasty; and
70.1% (66.3%-73.9%), biliopancreatic diversion or duodenal switch. Operative
mortality (≤30 days) in the extracted studies was 0.1% for the purely restrictive
procedures, 0.5% for gastric bypass, and 1.1% for biliopancreatic diversion
or duodenal switch. Diabetes was completely resolved in 76.8% of patients
and resolved or improved in 86.0%. Hyperlipidemia improved in 70% or more
of patients. Hypertension was resolved in 61.7% of patients and resolved or
improved in 78.5%. Obstructive sleep apnea was resolved in 85.7% of patients
and was resolved or improved in 83.6% of patients.ConclusionsEffective weight loss was achieved in morbidly obese patients after
undergoing bariatric surgery. A substantial majority of patients with diabetes,
hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete
resolution or improvement.
6,373 citations
Thomas Jefferson University1, Cincinnati Children's Hospital Medical Center2, Yeshiva University3, Alfred I. duPont Hospital for Children4, University of Michigan5, Harvard University6, University of Iowa7, Mayo Clinic8, University of Texas Health Science Center at Houston9, Wake Forest University10, University of Minnesota11, University of Pennsylvania12, National Institutes of Health13, American Institutes for Research14
5,707 citations
Karolinska Institutet1, Johns Hopkins University2, Tohoku University3, Uppsala University4, University of Gothenburg5, New York University6, University of California, Davis7, University of Helsinki8, University of Geneva9, National Institutes of Health10, Mayo Clinic11, Australian National University12, French Institute of Health and Medical Research13, Erasmus University Rotterdam14, Maastricht University15
TL;DR: A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics.
Abstract: The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.
4,206 citations
Columbia University1, University of Michigan2, University of California, Davis3, Baylor College of Medicine4, University of Massachusetts Medical School5, Mayo Clinic6, University of Washington7, University of Arkansas for Medical Sciences8, University of California, San Francisco9, Cleveland Clinic10, University of Colorado Denver11
TL;DR: The improvement in median survival of nearly two months with docetaxel and estramustine, as compared with mitoxantrone and prednisone, provides support for this approach in men with metastatic, androgen-independent prostate cancer.
Abstract: background Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive androgen-independent prostate cancer. We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic, hormoneindependent prostate cancer. methods We randomly assigned 770 men to one of two treatments, each given in 21-day cycles: 280 mg of estramustine three times daily on days 1 through 5, 60 mg of docetaxel per square meter of body-surface area on day 2, and 60 mg of dexamethasone in three divided doses before docetaxel, or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily. The primary end point was overall survival; secondary end points were progression-free survival, objective response rates, and post-treatment declines of at least 50 percent in serum prostate-specific antigen (PSA) levels. results Of 674 eligible patients, 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone. In an intention-to-treat analysis, the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone (17.5 months vs. 15.6 months, P=0.02 by the log-rank test), and the corresponding hazard ratio for death was 0.80 (95 percent confidence interval, 0.67 to 0.97). The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone (P<0.001 by the log-rank test). PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients, respectively (P<0.001), and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease, respectively (P=0.30). Grade 3 or 4 neutropenic fevers (P=0.01), nausea and vomiting (P<0.001), and cardiovascular events (P=0.001) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone. Pain relief was similar in both groups. conclusions The improvement in median survival of nearly two months with docetaxel and estramustine, as compared with mitoxantrone and prednisone, provides support for this approach in men with metastatic, androgen-independent prostate cancer.
3,554 citations
TL;DR: Differences in incidence across age, time, and geographic region suggest that environmental factors significantly modify the expression of Crohn's disease and ulcerative colitis.
2,911 citations
National Institutes of Health1, Baylor University Medical Center2, University of California, San Francisco3, Ohio State University4, Thomas Jefferson University5, Mayo Clinic6, French Institute of Health and Medical Research7, University of Texas Health Science Center at Houston8, McGill University9, Karolinska Institutet10, Creighton University11, University of Helsinki12, Fred Hutchinson Cancer Research Center13, Harvard University14
TL;DR: This commentary summarizes the Workshop presentations on HNPCC and MSI testing; presents the issues relating to the performance, specificity, and specificity of the Bethesda Guidelines; outlines the revised Bethesda Guidelines for identifying individuals at risk for H NPCC; and recommend criteria for MSI testing.
Abstract: Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI). Because cancers with MSI account for approximately 15% of all colorectal cancers and because of the need for a better understanding of the clinical and histologic manifestations of HNPCC, the National Cancer Institute hosted an international workshop on HNPCC in 1996, which led to the development of the Bethesda Guidelines for the identification of individuals with HNPCC who should be tested for MSI. To consider revision and improvement of the Bethesda Guidelines, another HNPCC workshop was held at the National Cancer Institute in Bethesda, MD, in 2002. In this commentary, we summarize the Workshop presentations on HNPCC and MSI testing; present the issues relating to the performance, sensitivity, and specificity of the Bethesda Guidelines; outline the revised Bethesda Guidelines for identifying individuals at risk for HNPCC; and recommend criteria for MSI testing.
2,899 citations
TL;DR: NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the blood-brain barrier that distinguishes neuromyleitis opticas from multiple sclerosis.
2,793 citations
TL;DR: High-resolution recombination mapping and candidate gene sequencing in 46 families found six disease-segregating mutations in a gene encoding a large, multifunctional protein, LRRK2 (leucine-rich repeat kinase 2), which may be central to the pathogenesis of several major neurodegenerative disorders associated with parkinsonism.
2,757 citations
TL;DR: It is shown that although deletion of IKKbeta in intestinal epithelial cells does not decrease inflammation, it leads to a dramatic decrease in tumor incidence without affecting tumor size, which is linked to increased epithelial apoptosis during tumor promotion.
2,366 citations
TL;DR: The nature and extent of CD4+ T cell depletion in lymphoid tissue is defined and mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5+ CD4- T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation are pointed to.
Abstract: The mechanisms underlying CD4+ T cell depletion in human immunodeficiency virus (HIV) infection are not well understood. Comparative studies of lymphoid tissues, where the vast majority of T cells reside, and peripheral blood can potentially illuminate the pathogenesis of HIV-associated disease. Here, we studied the effect of HIV infection on the activation and depletion of defined subsets of CD4+ and CD8+ T cells in the blood, gastrointestinal (GI) tract, and lymph node (LN). We also measured HIV-specific T cell frequencies in LNs and blood, and LN collagen deposition to define architectural changes associated with chronic inflammation. The major findings to emerge are the following: the GI tract has the most substantial CD4+ T cell depletion at all stages of HIV disease; this depletion occurs preferentially within CCR5+ CD4+ T cells; HIV-associated immune activation results in abnormal accumulation of effector-type T cells within LNs; HIV-specific T cells in LNs do not account for all effector T cells; and T cell activation in LNs is associated with abnormal collagen deposition. Taken together, these findings define the nature and extent of CD4+ T cell depletion in lymphoid tissue and point to mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5+ CD4+ T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation.
TL;DR: The clinical phenotype of SNCA duplication closely resembles idiopathic Parkinson's disease, which has a late age-of-onset, progresses slowly, and in which neither cognitive decline nor dementia are prominent, and suggest a direct relation between S NCA gene dosage and disease progression.
Albert Einstein College of Medicine1, Agency for Healthcare Research and Quality2, Harvard University3, United States Department of Veterans Affairs4, Icahn School of Medicine at Mount Sinai5, University of Birmingham6, University of California, Los Angeles7, MedStar Washington Hospital Center8, University of Texas at San Antonio9, University of Texas Southwestern Medical Center10, Mayo Clinic11, Loyola University Chicago12, Georgetown University13
TL;DR: The strength of the evidence that untreated subclinical thyroid disease is associated with clinical symptoms and adverse clinical outcomes was assessed and recommendations for clinical practice developed and insufficient evidence to support population-based screening was found.
Abstract: ContextPatients with serum thyroid-stimulating hormone (TSH) levels outside
the reference range and levels of free thyroxine (FT4) and triiodothyronine
(T3) within the reference range are common in clinical practice.
The necessity for further evaluation, possible treatment, and the urgency
of treatment have not been clearly established.ObjectivesTo define subclinical thyroid disease, review its epidemiology, recommend
an appropriate evaluation, explore the risks and benefits of treatment and
consequences of nontreatment, and determine whether population-based screening
is warranted.Data SourcesMEDLINE, EMBASE, Biosis, the Agency for Healthcare Research and Quality,
National Guideline Clearing House, the Cochrane Database of Systematic Reviews
and Controlled Trials Register, and several National Health Services (UK)
databases were searched for articles on subclinical thyroid disease published
between 1995 and 2002. Articles published before 1995 were recommended by
expert consultants.Study Selection and Data ExtractionA total of 195 English-language or translated papers were reviewed.
Editorials, individual case studies, studies enrolling fewer than 10 patients,
and nonsystematic reviews were excluded. Information related to authorship,
year of publication, number of subjects, study design, and results were extracted
and formed the basis for an evidence report, consisting of tables and summaries
of each subject area.Data SynthesisThe strength of the evidence that untreated subclinical thyroid disease
is associated with clinical symptoms and adverse clinical outcomes was assessed
and recommendations for clinical practice developed. Data relating the progression
of subclinical to overt hypothyroidism were rated as good, but data relating
treatment to prevention of progression were inadequate to determine a treatment
benefit. Data relating a serum TSH level higher than 10 mIU/L to elevations
in serum cholesterol were rated as fair but data relating to benefits of treatment
were rated as insufficient. All other associations of symptoms and benefit
of treatment were rated as insufficient or absent. Data relating a serum TSH
concentration lower than 0.1 mIU/L to the presence of atrial fibrillation
and progression to overt hyperthyroidism were rated as good, but no data supported
treatment to prevent these outcomes. Data relating restoration of the TSH
level to within the reference range with improvements in bone mineral density
were rated as fair. Data addressing all other associations of subclinical
hyperthyroid disease and adverse clinical outcomes or treatment benefits were
rated as insufficient or absent. Subclinical hypothyroid disease in pregnancy
is a special case and aggressive case finding and treatment in pregnant women
can be justified.ConclusionsData supporting associations of subclinical thyroid disease with symptoms
or adverse clinical outcomes or benefits of treatment are few. The consequences
of subclinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0 mIU/L)
are minimal and we recommend against routine treatment of patients with TSH
levels in these ranges. There is insufficient evidence to support population-based
screening. Aggressive case finding is appropriate in pregnant women, women
older than 60 years, and others at high risk for thyroid dysfunction.
Lund University1, University of Colorado Denver2, University of California, San Diego3, University of Grenoble4, Mayo Clinic5, University of Hawaii6, University of Washington7, University of Portland8, University of Melbourne9, University of Medicine and Dentistry of New Jersey10, University of Lyon11, University of Edinburgh12, University College London13, University of Michigan14
TL;DR: The CEAP classification for chronic venous disorders was developed in 1994 by an international ad hoc committee of the American Venous Forum, endorsed by the Society for Vascular Surgery, and incorporated into "Reporting Standards in Venous Disease" in 1995.
TL;DR: In this community-based cohort, the incidence ofheart failure has not declined during 2 decades, but survival after onset of heart failure has increased overall, with less improvement among women and elderly persons.
Abstract: ContextThe epidemic of heart failure has yet to be fully investigated, and
data on incidence, survival, and sex-specific temporal trends in community-based
populations are limited.ObjectiveTo test the hypothesis that the incidence of heart failure has declined
and survival after heart failure diagnosis has improved over time but that
secular trends have diverged by sex.Design, Setting, and ParticipantsPopulation-based cohort study using the resources of the Rochester Epidemiology
Project conducted in Olmsted County, Minnesota. Patients were 4537 Olmsted
County residents (57% women; mean [SD] age, 74 [14] years) with a diagnosis
of heart failure between 1979 and 2000. Framingham criteria and clinical criteria
were used to validate the diagnosisMain Outcome MeasuresIncidence of heart failure and survival after heart failure diagnosis.ResultsThe incidence of heart failure was higher among men (378/100 000
persons; 95% confidence interval [CI], 361-395 for men; 289/100 000 persons;
95% CI, 277-300 for women) and did not change over time among men or women.
After a mean follow-up of 4.2 years (range, 0-23.8 years), 3347 deaths occurred,
including 1930 among women and 1417 among men. Survival after heart failure
diagnosis was worse among men than women (relative risk, 1.33; 95% CI, 1.24-1.43)
but overall improved over time (5-year age-adjusted survival, 43% in 1979-1984
vs 52% in 1996-2000, P<.001). However, men and
younger persons experienced larger survival gains, contrasting with less or
no improvement for women and elderly persons.ConclusionIn this community-based cohort, the incidence of heart failure has not
declined during 2 decades, but survival after onset of heart failure has increased
overall, with less improvement among women and elderly persons.
TL;DR: The transient left ventricular apical ballooning syndrome, also known as takotsubo cardiomyopathy, is characterized by transient wall motion abnormalities involving the left ventric apex and mid-ventricle in the absence of obstructive epicardial coronary disease as mentioned in this paper.
Abstract: The transient left ventricular apical ballooning syndrome, also known as takotsubo cardiomyopathy, is characterized by transient wall-motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of obstructive epicardial coronary disease. In this paper, we review case series that report on patients with the transient left ventricular apical ballooning syndrome to better characterize patients presenting with the syndrome. We identified 7 case series that reported on at least 5 consecutive patients with the transient left ventricular apical ballooning syndrome. The syndrome more often affects postmenopausal women (82% to 100%) (mean age, 62 to 75 years). Patients commonly present with ST-segment elevation in the precordial leads, chest pain, relatively minor elevation of cardiac enzyme and biomarker levels, and transient apical systolic left ventricular dysfunction despite the absence of obstructive epicardial coronary disease. An episode of emotional or physiologic stress frequently precedes presentation with the syndrome. The in-hospital mortality rate seems to be low, as does the risk for recurrence.
TL;DR: A direct correlation between the concentration of Aβ42 and the rate of amyloid deposition is demonstrated and suggests that PS1 variants do not simply alter the preferred cleavage site for γ-secretase, but rather that they have more complex effects on the regulation of ιsecretase and its access to substrates.
Abstract: Amyloid precursor protein (APP) is endoproteolytically processed by BACE1 and γ-secretase to release amyloid peptides (Aβ40 and 42) that aggregate to form senile plaques in the brains of patients with Alzheimer's disease (AD). The C-terminus of Aβ40/42 is generated by γ-secretase, whose activity is dependent upon presenilin (PS 1 or 2). Missense mutations in PS1 (and PS2) occur in patients with early-onset familial AD (FAD), and previous studies in transgenic mice and cultured cell models demonstrated that FAD-PS1 variants shift the ratio of Aβ40 : 42 to favor Aβ42. One hypothesis to explain this outcome is that mutant PS alters the specificity of γ-secretase to favor production of Aβ42 at the expense of Aβ40. To test this hypothesis in vivo, we studied Aβ40 and 42 levels in a series of transgenic mice that co-express the Swedish mutation of APP (APPswe) with two FAD-PS1 variants that differentially accelerate amyloid pathology in the brain. We demonstrate a direct correlation between the concentration of Aβ42 and the rate of amyloid deposition. We further show that the shift in Aβ42 : 40 ratios associated with the expression of FAD-PS1 variants is due to a specific elevation in the steady-state levels of Aβ42, while maintaining a constant level of Aβ40. These data suggest that PS1 variants do not simply alter the preferred cleavage site for γ-secretase, but rather that they have more complex effects on the regulation of γ-secretase and its access to substrates.
TL;DR: It is concluded that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD.
TL;DR: Questionnaire data are of greatest value in life-threatening, acute-onset diseases and chronic disorders requiring ongoing management and are more accurate in young women and better-educated subjects.
TL;DR: This cross-sectional study compared GFR estimated by the MDRD equation with GFR measured by iothalamate clearance in 320 patients with chronic kidney disease and 580 healthy kidney donor candidates, and developed a new GFR prediction equation based on both healthy persons and patients with Chronic kidney disease.
Abstract: The Modification of Diet in Renal Disease equation for glomerular filtration rate (GFR) substantially underestimates GFR in healthy persons A new equation developed with patients with chronic kidn
TL;DR: It is found that a strong association exists between OSA and AF, such that OSA is strikingly more prevalent in patients with AF than in high-risk patients with multiple other cardiovascular diseases.
Abstract: Background— Obstructive sleep apnea (OSA) is associated with recurrent atrial fibrillation (AF) after electrocardioversion. OSA is highly prevalent in patients who are male, obese, and/or hypertens...
TL;DR: The results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS and suggest that OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.
Abstract: Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line th...
Vita-Salute San Raffaele University1, National University of Singapore2, University of Buenos Aires3, University of California, San Francisco4, University of Miami5, Wake Forest Institute for Regenerative Medicine6, University of Western Ontario7, Mayo Clinic8, Johns Hopkins University9, Duke University10, Karolinska University Hospital11, Aristotle University of Thessaloniki12, Tulane University13, Erasmus University Rotterdam14, London Bridge Hospital15, Istanbul University16, Rush University Medical Center17, Georgia Regents University18, University of Florence19, Deakin University20, Cleveland Clinic21, University of Milan22, Memorial Sloan Kettering Cancer Center23, Concordia University Wisconsin24, Valparaiso University25, University of Medicine and Dentistry of New Jersey26, Maimonides Medical Center27, Ludwig Maximilian University of Munich28, Rambam Health Care Campus29, Emory University30
TL;DR: Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronie's disease; and priapism.
TL;DR: Pulmonary arterial hypertension is diagnosed by various investigations that are essential for making the diagnosis, and by additional tests to clarify the category of pulmonary hypertension (PH).
TL;DR: Patients with high-risk resected colon cancer obtain benefit from FU-based therapy across subsets of age, sex, location, T stage, nodal status, and grade, which may improve patients' and physicians' understanding of the potential benefits of adjuvant therapy.
Abstract: Purpose Although it is well-established that fluorouracil- (FU-) based adjuvant therapy improves survival for patients with resected high-risk colon cancer, the magnitude of adjuvant therapy benefit across specific subgroups and for individual patients has been uncertain. Patients and Methods Using a pooled data set of 3,302 patients with stage II and III colon cancer from seven randomized trials comparing FU + leucovorin or FU + levamisole to surgery alone, we performed an analysis based on a Cox proportional hazards regression model. Treatment, age, sex, tumor location, T stage, nodal status, and grade were tested for both prognostic and predictive significance. Model derived estimates of 5-year disease-free survival and overall survival (OS) for surgery alone and surgery plus FU-based therapy were calculated for a range of patient subsets. Results Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS. Age was significant only f...
University of Maryland Medical Center1, University of Chicago2, NewYork–Presbyterian Hospital3, Cleveland Clinic4, Beth Israel Deaconess Medical Center5, Wake Forest University6, Mayo Clinic7, Baylor College of Medicine8, University of California, San Francisco9, University of Wisconsin-Madison10, MedStar Washington Hospital Center11
TL;DR: Young ε4 carriers and noncarriers did not differ significantly in their sex, age, educational level, clinical ratings, or neuropsychological test scores, and an aggregate surface-projection map was generated that compared regional PET measurements in the two groups.
Abstract: Fluorodeoxyglucose positron emission tomography (PET) studies have found that patients with Alzheimer's dementia (AD) have abnormally low rates of cerebral glucose metabolism in posterior cingulate, parietal, temporal, and prefrontal cortex We previously found that cognitively normal, late-middle-aged carriers of the apolipoprotein E epsilon4 allele, a common susceptibility gene for late-onset Alzheimer's dementia, have abnormally low rates of glucose metabolism in the same brain regions as patients with probable AD We now consider whether epsilon4 carriers have these regional brain abnormalities as relatively young adults Apolipoprotein E genotypes were established in normal volunteers 20-39 years of age Clinical ratings, neuropsychological tests, magnetic resonance imaging, and PET were performed in 12 epsilon4 heterozygotes, all with the epsilon3/epsilon4 genotype, and 15 noncarriers of the epsilon4 allele, 12 of whom were individually matched for sex, age, and educational level An automated algorithm was used to generate an aggregate surface-projection map that compared regional PET measurements in the two groups The young adult epsilon4 carriers and noncarriers did not differ significantly in their sex, age, educational level, clinical ratings, or neuropsychological test scores Like previously studied patients with probable AD and late-middle-aged epsilon4 carriers, the young epsilon4 carriers had abnormally low rates of glucose metabolism bilaterally in the posterior cingulate, parietal, temporal, and prefrontal cortex Carriers of a common Alzheimer's susceptibility gene have functional brain abnormalities in young adulthood, several decades before the possible onset of dementia
TL;DR: Digital hyperemic response, as measured by RH-PAT, is attenuated in patients with coronary microvascular endothelial dysfunction, suggesting a role for RH- PAT as a noninvasive test to identify patients with this disorder.
University of California, San Diego1, Mayo Clinic2, New York University3, Georgetown University4, Rush University Medical Center5, University of Michigan6, Baylor College of Medicine7, Oregon Health & Science University8, Columbia University9, Eli Lilly and Company10, McGill University11, University of California, Irvine12, Yale University13, Medical University of South Carolina14, University of Alabama at Birmingham15, Brown University16
TL;DR: Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings.
Abstract: Background Mild cognitive impairment (MCI) represents a transitional state between the cognitive changes of normal aging and very early dementia and is becoming increasingly recognized as a risk factor for Alzheimer disease (AD). The Memory Impairment Study (MIS) is a multicenter clinical trial in patients with MCI designed to evaluate whether vitamin E or donepezil is effective at delaying the time to a clinical diagnosis of AD. Objective To describe the baseline characteristics of patients with MCI recruited for the MIS and compare them with those of elderly controls and patients with AD in another clinical trial. Design Descriptive and comparative study of patients with MCI participating in a multicenter clinical trial. Setting Memory disorder centers in the United States and Canada. Patients A total of 769 patients with MCI, 107 cognitively normal elderly controls, 122 patients with very mild AD (Clinical Dementia Rating [CDR] 0.5), and 183 patients with mild AD (CDR 1.0) were evaluated. Patients in the MIS met operational criteria for amnestic MCI. Controls were recruited in parallel with the MCI group, underwent the same assessments, and had a CDR of 0. Main Outcome Measures Clinical, neuropsychologic, functional, neuroimaging, and genetic measures. Results Mean ± SD Alzheimer's Disease Assessment Scale–Cognitive Subscale scores were 5.6 ± 3.3 for controls, 11.3 ± 4.4 for patients with MCI, 18.0 ± 6.2 for the AD CDR 0.5 group, and 25.2 ± 8.8 for the AD CDR 1.0 group. Compared with controls, patients with MCI were most impaired on memory tasks, with less severe impairments in other cognitive domains. Patients with MCI were more likely than controls but less likely than patients with AD to carry the apolipoprotein E ϵ4 allele. Patients with MCI had hippocampal volumes that were intermediate between those of controls and patients with AD. Conclusions Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings. These results demonstrate the successful implementation of operational criteria for this unique group of at-risk patients in a multicenter clinical trial.