PrPC Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features.

Bank vole is a rodent species that shows differential susceptibility to the experimental transmission of different prion strains. In this work, the transmission features of a panel of diverse prions with distinct origins were assayed both in bank vole expressing methionine at codon 109 (Bv109M) and in transgenic mice expressing physiological levels of bank vole PrPC (the BvPrP-Tg407 mouse line). This work is the first systematic comparison of the transmission features of a collection of prion isolates, representing a panel of diverse prion strains, in a transgenic-mouse model and in its natural counterpart. The results showed very similar transmission properties in both the natural species and the transgenic-mouse model, demonstrating the key role of the PrP amino acid sequence in prion transmission susceptibility. However, differences in the PrPSc types propagated by Bv109M and BvPrP-Tg407 suggest that host factors other than PrPC modulate prion strain features. IMPORTANCE: The differential susceptibility of bank voles to prion strains can be modeled in transgenic mice, suggesting that this selective susceptibility is controlled by the vole PrP sequence alone rather than by other species-specific factors. Differences in the phenotypes observed after prion transmissions in bank voles and in the transgenic mice suggest that host factors other than the PrPC sequence may affect the selection of the substrain replicating in the animal model.

Water response to ganglioside GM1 surface remodelling.

BACKGROUND: Gangliosides are biological glycolipids participating in rafts, structural and functional domains of cell membranes. Their headgroups are able to assume different conformations when packed on the surface of an aggregate, more lying or standing. Switching between different conformations is possible, and is a collective event. Switching can be induced, in model systems, by concentration or temperature increase, then possibly involving ganglioside-water interaction. In the present paper, the effect of GM1 ganglioside headgroup conformation on the water structuring and interactions is addressed. METHODS: Depolarized Rayleigh Scattering, Raman Scattering, Quasielastic Neutron Scattering and NMR measurements were performed on GM1 ganglioside solutions, focusing on solvent properties. RESULTS: All used techniques agree in evidencing differences in the structure and dynamics of solvent water on different time-and-length scales in the presence of either GM1 headgroup conformations. CONCLUSIONS: In general, all results indicate that both the structural properties of solvent water and its interactions with the sugar headgroups of GM1 respond to surface remodelling. The extent of this modification is much higher than expected and, interestingly, ganglioside headgroups seem to turn from cosmotropes to chaotropes upon collective rearrangement from the standing- to the lying-conformation. SIGNIFICANCE: In a biological perspective, water structure modulation could be one of the physico-chemical elements contributing to the raft strategy, both for rafts formation and persistence and for their functional aspects. In particular, the interaction with approaching bodies could be favoured or inhibited or triggered by complex-sugar-sequence conformational switch. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo.

Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study.

UNLABELLED: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year. INTRODUCTION: Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure. METHODS: We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95% confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91-180), past (181-364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out. RESULTS: In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95% CI, 1.59-2.43). CONCLUSION: In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.

Assessing the risk of osteonecrosis of the jaw due to bisphosphonate therapy in the secondary prevention of osteoporotic fractures.

SUMMARY: There is evidence that the use oral bisphosphonates can lead to osteronecrosis of the jaws (ONJ). Although the occurrence of ONJ appears rare among oral bisphosphonates (BPs) users, it is important to know that it exists and can be opportunely minimized. INTRODUCTION: The purpose of this study is to evaluate the association between BPs prescribed for the secondary prevention of osteoporotic fractures and the occurrence of ONJ. METHODS: An Italian record linkage claims database with a target population of around 18 million individuals (6 million over 55 years of age) constituted the data source. We conducted a nested case-control study within a cohort of individuals aged 55+ years old, who were discharged from hospitals with a primary diagnosis of incident osteoporotic fracture. The date related to the discharge diagnosis of ONJ was the index date. Conditional logistic regression for matched data was fitted to estimate the odds ratio (OR) along with 95 % confidence intervals (95 % CI) for the likely association between use of BPs and the risk of ONJ. RESULTS: Any one of the 61 ascertained cases of ONJ (incidence rate, 36.6 per 100,000 person-years) was matched to 20 controls for a total of 1120 controls. When the exposure to BPs was modeled according to recency (i.e., exposure time window prior to the index date) of use, the adjusted OR (95 % CI) for current users was 2.8 (1.3-5.9) against never users. The cumulative use of BPs has shown to increase the incidence of ONJ among patients with primary osteoporotic fractures, although not statistically significant risk has been observed. CONCLUSIONS: Although the risk of BP-related ONJ appears low in non-oncological indications, it is important to be aware that it exists and to know how it may be predicted and possibly minimized.

Microbiological quality assessment of sand and water from three selected beaches of South Coast, São Paulo State, Brazil.

This study aimed to assess the sanitary quality of water, and wet and dry sand from three beaches located in the South Coast region of São Paulo State, Brazil, selected taking into account the frequency of tourists and the water quality (good, fair and poor). Thirty-six water samples each of wet and dry sand and seawater were collected monthly over a period of one year and analyzed for fecal indicator bacteria (FIB: thermotolerant coliforms, Escherichia coli, and enterococci), presumptive Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and dermatophytes. The results revealed FIB concentrations more elevated in dry sand followed by wet sand and water. P. aeruginosa and presumptive S. aureus were detected with a similar frequency in water and sand samples, but maximum concentrations and geometric means were higher in dry sand. C. albicans was detected only in water samples whereas the dermatophyte Microsporum sp. was isolated exclusively from dry and wet sand samples. This evaluation showed also that the environment had a significant influence on P. aeruginosa but not on presumptive S. aureus concentrations. According to threshold values proposed in the literature for E. coli and enterococci dry sand densities, none of the beaches would be considered of sufficient quality for recreational activities.

Elastic incoherent neutron scattering as a probe of high pressure induced changes in protein flexibility.

We report here the results of elastic incoherent neutron scattering experiments on three globular proteins (trypsin, lysozyme and beta-lactoglobulin) in different pressure intervals ranging from 1 bar to 5.5 kbar. A decrease of the mean square hydrogen fluctuations, u(2), has been observed upon increasing pressure. Trypsin and beta-lactoglobulin behave similarly while lysozyme shows much larger changes in u(2). This can be related to different steps in the denaturing processes and to the high propensity of lysozyme to form amyloids. Elastic incoherent neutron scattering has proven to be an effective microscopic technique for the investigation of pressure induced changes in protein flexibility.

Is suboptimal prescribing a risk factor for poor health outcomes in community-dwelling elders? The ICARe Dicomano study.

PURPOSE: Mostly because of comorbidity and drugs consumption, older persons are often exposed to an increased risk of sub-optimal prescribing (SP). At present, few studies investigated the association between SP and long-term health outcomes. We examined the relation between SP and the risk of mortality and hospitalization in Italian older community-dwellers. METHODS: Older (65+ years) community-dwelling residents of a small town in Tuscany were enrolled in a longitudinal study. SP was defined as polypharmacy (use of 5+ drugs), prescription of inappropriate drugs (ID) according to Beers' criteria, and of potentially interacting drugs (PID), evaluated in 1995 and 1999. These three forms of SP were entered as time-dependent exposures into multivariable Cox regression analysis models, whose outcomes were mortality and hospitalizations through 2003. RESULTS: Of 1022 participants (mean age 73.0 +/- 6.8, 57% women), 220 were evaluated in 1995, 234 in 1999 and 568 in both waves. In univariate analysis, mortality was two-fold higher in participants with polypharmacy (73.4/1000 person/years, 95% CI 58.2-92.4 vs. 34.1, 95% CI 29.7-39.2; p < 0.001) or PID (72.7/1000 person/years, 95% CI 46.3-113.9 vs. 38.0, 95% CI 33.5-43.1; p < 0.001), whereas it was unrelated to the presence of ID. Hospitalization rates were independent of any form of SP. In multivariable models, polypharmacy, ID, and PID were no longer associated with an increased risk of death, and ID predicted a slightly increased risk of hospitalizations (HR 1.03, 95% CI 1.0-1.06, p = 0.048). CONCLUSIONS: In this cohort, SP was not associated with an excess risk of poor health outcomes.

Msx2 induces epithelial-mesenchymal transition in mouse mammary epithelial cells through upregulation of Cripto-1.

Epithelial-mesenchymal transition (EMT) is a process occurring during both embryogenesis and early stages of invasive cancer. Epithelial cells that undergo EMT become more migratory and invasive with a mesenchymal morphology. Herein we assess EMT induction in a mouse mammary epithelial cell line driven by Msx2, a homeobox-containing transcription factor important during mammary gland development. NMuMG cells, a normal mouse mammary epithelial cell line, stably transfected with a Msx2 cDNA showed downregulation of an epithelial marker E-cadherin and upregulation of the mesenchymal markers vimentin and N-cadherin. Furthermore, overexpression of Cripto-1, a member of the epidermal growth factor-CFC protein family already known to be involved in EMT, was detected in Msx2-transfected cells. The expression of Cripto-1 was accompanied by activation of the tyrosine kinase c-Src pathway and an increase in the invasive ability of the cells. Functional assays also demonstrated inhibition of the invasive behavior of the Msx2-transfected cells by a c-Src specific inhibitor. Moreover, immunohistochemistry of human infiltrating breast carcinomas showed positive staining for Msx2 only in the infiltrating tumor cells while the non-infiltrating tumor cells were negative. These results suggest that Msx2 may play a significant role in promoting EMT in epithelial cells that acquire properties involved in tumor invasion. J. Cell. Physiol. 219: 659-666, 2009. Published 2009 Wiley-Liss, Inc.

Quantitative profiling of the pathological prion protein allotypes in bank voles by liquid chromatography-mass spectrometry.

The conversion of the cellular prion protein (PrP(C)) into a misfolded isoform (PrP(TSE)) that accumulates in the brain of affected individuals is the key feature of transmissible spongiform encephalopaties (TSEs). Susceptibility to TSEs is influenced by polymorphisms of the prion gene suggesting that the presence of certain amino acid residues may facilitate the pathological conversion. In this work, we describe a quantitative, fast and reliable HPLC-MS method that allowed to demonstrate that in the brain of 109(Met/Ile) heterozygous bank voles infected with the mouse adapted scrapie strain 139A, there are comparable amounts of PrP(TSE) with methionine or isoleucine in position 109, suggesting that in this TSE model the two allotypes have similar rates of accumulation. This method can be easily adapted for the quantitative determination of PrP allotypes in the brain of other natural or experimental TSE models.

Formation of self-organized nanoparticles by lecithin/chitosan ionic interaction.

In this work the production of auto-assembled nanoparticles obtained by the mixing of chitosan and lecithin is presented. The size and surface charge of the nanoparticles were studied as function of the weight ratio between components, the viscosity of the polysaccharide and the pH of the colloidal suspension. In order to elucidate the structure of nanoparticles, micro-FT-IR and elastic neutron scattering experiments have been performed. Results evidenced a strong electrostatic interaction between components and a structure that is neither that of homogeneous spheres nor of coated unilamellar vesicles. Preliminary encapsulation experiments with progesterone, as model lipophilic drug, showed good encapsulation efficiencies.

Synchronous colon and gastric advanced carcinomas.

An unusual case of advanced synchronous colon and gastric carcinoma is described. A 36 year old female was admitted to our Department with a stenosing right colon cancer diagnosed at endoscopy which was performed for lower crampy abdominal pain and gross blood in the stool. Multiple colon polyps, distal to the tumor, were also detected. On preoperative abdominal computed tomography, a stenosing right colon cancer, without evidence of abdominal diffusion, was confirmed. At laparotomy, in addition to colon cancer, an antral gastric cancer was incidentally found. En bloc hemigastrectomy and subtotal colectomy were performed. Digestive continuity was restored by gastrojejunal and ileosigmoid anastomoses. At histology, a poorly differentiated gastric adenocarcinoma with signet ring-cell component (pT2, pN0; stage IB) and a moderately differentiated colon adenocarcinoma with a tubulovillous component (pT3, pN1; stage III, Stage Dukes C) were revealed. Both tumors showed a low expression of p53 and c-erb2 oncoproteins. No genetic defect was identified in the APC and MMR genes. The patient is alive, without recurrence, two years after the operation.

Type 2 diabetes in older well-functioning people: who is undiagnosed? Data from the Health, Aging, and Body Composition study.

OBJECTIVE: To assess, in an older population, the prevalence of diagnosed and undiagnosed diabetes, the number needed to screen (NNTS) to identify one individual with undiagnosed diabetes, and factors associated with undiagnosed diabetes. RESEARCH DESIGN AND METHODS: Socioeconomic and health-related factors were assessed at the baseline examination of the Health, Aging, and Body Composition (Health ABC) Study, a cohort of 3,075 well-functioning people aged 70-79 years living in Memphis, Tennessee and Pittsburgh, Pennsylvania (42% blacks and 48% men). Diabetes was defined according to the 1985 World Health Organization criteria (fasting glucose > or =7.8 mmol/l or 2-h glucose > or =11.1 mmol/l) and the 1997 American Diabetes Association criteria (fasting glucose > or =7.0 mmol/l). RESULTS: The prevalence of diagnosed and undiagnosed diabetes was 15.6 and 8.0%, respectively, among all participants (NNTS 10.6), 13.9 and 9.1% among white men (NNTS 9.5), 7.8 and 7.4% among white women (NNTS 12.4), 22.7 and 9.1% among black men (NNTS 8.5), and 21.6 and 6.2% among black women (NNTS 12.6). In multivariate analyses, compared with individuals without diabetes, individuals with undiagnosed diabetes were more likely to be men and were more likely to have a history of hypertension, higher BMI, and larger waist circumference. NNTS was lowest in men (9.1), individuals with hypertension (8.7), individuals in the highest BMI quartile (6.9), and individuals in the largest waist circumference quartile (6.8). CONCLUSIONS: In approximately one-third of all older people with diabetes, the condition remains undiagnosed. Screening for diabetes may be more efficient among men and individuals with hypertension, high BMI, and large waist circumference.

Operationalization of the physical frailty & sarcopenia syndrome: rationale and clinical implementation.

Over the years, different operational definitions have been elaborated to identify frail older persons, but none of them has received unanimous consensus. This, in turn, has hampered the clinical implementation of frailty as well as the design of targeted interventions. To overcome the current limitations in the field, a novel operationalization of physical frailty (PF) is proposed which grounds its roots in the recognition of sarcopenia as its central biological substrate. This conceptualization is based on the fact that the clinical picture of PF overlaps substantially with that of sarcopenia. The two conditions may therefore be merged into a new clinical entity, the PF & sarcopenia (PF&S) syndrome, in which muscle loss represents both the biological substrate for the development of PF and a major pathway whereby the negative health outcomes of PF occur. All of the components defining the PF&S syndrome are measurable in an objective manner, which will facilitate its incorporation into standard practice. The recognition of a precise biological substratum for PF&S (i.e., skeletal muscle decline) also opens new venues for the development of preventive and therapeutic interventions.

Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP).

OBJECTIVE: To assess longitudinally the association of serum uric acid and its change due to diuretic treatment with cardiovascular events in hypertensive patients. DESIGN: Cohort study in a randomized trial. SETTING: Cohort of hypertensive patients. PARTICIPANTS: A total of 4327 men and women, aged > or = 60 years, with isolated systolic hypertension, randomized to placebo or chlorthalidone, with the addition of atenolol or reserpine if needed, were observed for 5 years. MAIN OUTCOME MEASURES: Major cardiovascular events, coronary events, stroke and all-cause mortality. RESULTS: Cardiovascular event rates for quartiles of baseline serum uric acid were: I, 32.7 per 1000 person-years; II, 34.5 per 1000 person-years; III, 38.1 per 1000 person-years; and IV, 41.4 per 1000 person-years (P for trend = 0.02). The adjusted hazard ratio (HR), of cardiovascular events for the highest quartile of serum uric acid versus the lowest quartile was 1.32 (95% CI, 1.03-1.69). The benefit of active treatment was not affected by baseline serum uric acid. After randomization, an increase of serum uric acid < 0.06 mmol/l (median change) in the active treatment group was associated with a HR of 0.58 (0.37-0.92) for coronary events compared with those with a serum uric acid increase > or = 0.06 mmol/l. This difference was not explained by blood pressure effects. Those with a serum uric acid increase > or = 0.06 mmol/l in the active treatment group had a similar risk of coronary events as the placebo group. CONCLUSIONS: Serum uric acid independently predicts cardiovascular events in older persons with isolated systolic hypertension. Monitoring serum uric acid change during diuretic treatment may help to identify patients who will most benefit from treatment.

Undertreatment of hypertension in community-dwelling older adults: a drug-utilization study in Dicomano, Italy.

OBJECTIVE: To define: (1) the prevalence of and (2) factors associated with undertreatment of hypertension in older persons; and (3) the prevalence of specific drug regimens and reasons for their selection. PARTICIPANTS: Cross-sectional survey of persons aged > or =65 years living in Dicomano, Italy. MAIN OUTCOME MEASURES: Prevalence of untreated and uncontrolled hypertension, both defined on the basis of two blood pressure (BP) cut-off points (> or =140/90 and > or =160/90 mm Hg) and of the presence of pharmacological treatment Predictors of undertreatment were analysed for the higher BP cut-off only. RESULTS: Five hundred of 692 (72.3%) and 380/692 (54.9%) participants met the 140/90 and the 160/90 mm Hg BP criterion, respectively. Of the latter, 162 (42.6%) were untreated, 119 (31.3%) had uncontrolled and 99 (26.1%) controlled hypertension. Women [odds ratio (OR), 0.4; 95% confidence interval (CI), 0.2-0.7], participants with coronary artery disease (CAD) (OR, 0.2; 95% CI, 0.1-0.6), stroke (OR, 0.3; 95% CI, 0.1-0.7), and preserved cognitive status (Mini Mental State Examination score >21: 0.3; 95% CI, 0.2-0.7) were more frequently treated. Uncontrolled hypertension was less likely in women (OR, 0.5; 95% CI, 0.3-1.0) and CAD patients (OR, 0.3; 95% CI, 0.1-0.7). Angiotensin converting enzyme (ACE)-inhibitors (55%), calcium (Ca)-antagonists (31%) and diuretics (20%) were the drugs most commonly prescribed. ACE-inhibitors were preferred, and diuretics rarely used, in diabetic subjects. Ca-antagonists were used mostly in CAD participants. CONCLUSIONS: Hypertension is undertreated in the majority of noninstitutionalized older adults, especially in men with impaired cognition and no vascular disease. Drug regimens are mostly based on ACE-inhibitors and Ca-antagonists, as a result of associated clinical conditions, requiring individualized treatment.

Age-related hemodynamic effects of intravenous nitroglycerin for acute myocardial infarction and left ventricular failure.

Acute hemodynamic effects of intravenous nitroglycerin (NTG) were assessed in 24 patients with acute myocardial infarction and left ventricular failure, and results were compared between 2 groups of different age (group A--65 years or less, n = 12; group B--75 years or more, n = 12). Overall, hemodynamic effects of NTG consisted of an increase in stroke volume index and left ventricular stroke work index (+21 and +23%), coupled with a 16% reduction in systemic vascular resistance, and of a marked decrease in right atrial and pulmonary artery (PA) pressures. The hemodynamic end-point (5 to 10% reduction in mean systemic arterial pressure) used for NTG titration was achieved with a significantly lower dose in group B, in which a greater percent reduction in mean PA and mean PA wedge pressures was also observed. However, because effects of NTG on systemic vascular resistance were similar in groups A and B, it was concluded that the vasodilating action of NTG is maintained in advanced age, as opposed to what has been demonstrated for beta-adrenergic agents.

Hemodynamic and electrocardiographic effects of fructose-1,6-diphosphate in acute myocardial infarction.

Acute hemodynamic and electrocardiographic effects of fructose-1,6-diphosphate (FDP), an agent that is supposed to restore anaerobic glycolytic flux in the ischemic myocardium, were studied in 40 patients with acute myocardial infarction who were grouped into 4 subsets: subset 1, normal (15 mm Hg or less) pulmonary artery (PA) wedge pressure and normal (35 g-m/m2 or greater) left ventricular (LV) stroke work index; subset 2, elevated (more than 15 mm Hg) PA wedge pressure and normal LV stroke work index; subset 3, normal PA wedge pressure and reduced (less than 35 g-m/m2) LV stroke work index; subset 4, elevated PA wedge pressure and LV stroke work index moderately reduced to a range between 16 and 34 g-m/m2. Patients were randomized into an FDP (250 mg/kg body weight in isotonic saline solution intravenously in 20 minutes) and into a placebo group. Each subset contained 5 FDP- and 5 placebo-treated patients. After basal measurements, hemodynamic measurements were reassessed at 60, 90 and 120 minutes from the infusions, while a standard 12-lead electrocardiogram was recorded in the basal state and 120 minutes after infusion. Nonsignificant hemodynamic change was observed in the placebo subsets, and FDP failed to exert any effect in subsets 1, 2 and 3. A 24% (p less than 0.02) increase in cardiac index occurred 60 minutes after FDP in subset 4. LV stroke work index also increased, while PA wedge pressure remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Features of excessive alcohol drinking in older adults distinctively captured by behavioral and biological screening instruments. An epidemiological study.

The entire > or =65-year-old population living in a small Italian town, where alcohol use is almost ubiquitous, was assessed with a frequency-quantity questionnaire for alcohol intake and with two screening instruments for alcohol problems, the CAGE questionnaire and the MCV-gammaGT test. Aim of the study was to assess whether these instruments identify different subsets of subjects with alcohol problems. Of the 649 participants, 19.1% were at-risk drinkers (average intake > 40 g/day in men and > 20 g/day in women). Both the screening instruments were positive in only a minority of participants. Of the 377 drinkers, 53 gave > or =1 affirmative response to the CAGE questionnaire, whereas 24 had a positive MCV-gammaGT test. The concordance between positive CAGE questionnaire and MCV-gammaGT test was limited to seven subjects (kappa = 0.10), and these tests identified subjects who differed for several health and psychosocial characteristics. Participants aged > or =75 years drank less, but had similar prevalence of CAGE and MCV-gammaGT positive markers as compared to younger participants. In conclusion, excessive drinking is common in the elderly. Screening tests based on behavioral and biological markers identify two different sets of subjects with possible alcohol problems. This might indicate the opportunity to use these instruments in conjunction.

Glycemic control of older adults with type 2 diabetes: findings from the Third National Health and Nutrition Examination Survey, 1988-1994.

BACKGROUND: Although nearly half of all people who have diabetes are aged 65 or older, glycemic control of older adults with diabetes has not been well described. METHODS: We conducted a cross-sectional study of 1,482 participants with self-reported type 2 diabetes in the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III), a nationally representative sample of the US noninstitutionalized civilian population. Variables included in this analysis included age, sociodemographic factors, drug treatment, and level of glycemic control. RESULTS: The mean % (+/-SE) HbA1c was 7.78 +/- 0.21, 7.64 +/- 0.18, 7.71 +/- 0.14, and 7.27 +/- 0.14 in persons aged 20 to 54, 55 to 64, 65 to 74 and > or = 75 years, respectively. The mean mg/dL (+/-SE) fasting plasma glucose (FPG) was 175.9 +/- 7.6, 164.5 +/- 6.1, 183.3 +/- 5.3, and 158.5 +/- 5.5 in the four age groups and older, respectively. When controlling for race, gender, education, and duration of diabetes, age was not significantly associated with levels of HbA1c [P (trend) =0.17] or FPG [P (trend) =0.19]. Among NHANES III participants aged 65 or older, ADA guidelines for glycemic control (HbA1c < 7%) were achieved by 71%, 44%, and 27% of persons using no drug therapy, oral hypoglycemic agents, and insulin, respectively. CONCLUSIONS: Although many older adults with type 2 diabetes do not achieve targets for glucose control, there is no evidence to suggest that community-dwelling older adults with diabetes are treated less vigorously than younger persons with diabetes.

Immediate and long-term survival after intra-aortic balloon pumping: is advanced age an independent, unfavorable prognostic factor?

OBJECTIVE: To determine whether advanced age is an independent prognostic factor that may increase the risk of complications and reduce the immediate and long-term survival after treatment with intra-aortic balloon pumping (IABP) for acute ischemic heart disease. DESIGN: Retrospective analysis of a clinical series and long-term follow-up study. PATIENTS: A total of 142 patients (age range 23-86 years) in whom IABP was indicated following a standardized protocol. MEASUREMENTS: Univariate analysis of the association between age and anamnestic, clinical, and hemodynamic data significantly affecting prognosis; multivariate logistic regression analysis of variables showing significant associations. RESULTS: IABP-related complications were independent of age. At univariate analysis, pre-existing, noncardiac, associated conditions (chronic renal failure, stroke, bronchopulmonary disease) (P < .001), an indication to IABP for hemodynamic complications of acute myocardial infarction rather than for medically refractory myocardial ischemia (P < .001), a lack in hemodynamic response to IABP (P < .002), a prolonged delay to IABP initiation (P < .003), and advanced age (P < .025) were all predictors of in-hospital mortality. However, older patients were also more frequently affected by chronic comorbid conditions and by acute left ventricular failure as an indication to IABP. When these variables were entered into logistic regression models, the association between age and mortality was no longer statistically significant. Similarly, advancing age was associated (P < .012) with an increased mortality rate during an average follow-up of 94 +/- 9 months, but, again, such a significant association disappeared when simultaneously adjusting for New York Heart Association functional class, which was the single most important predictor of long-term mortality. CONCLUSIONS: Several anamnestic and clinical variables, rather than advanced age itself, are independent, prognostic factors negatively affecting the outcome of treatment with IABP. Technique-related complications are independent of age. Thus, old age should not be considered as a criterion to exclude any patient, a priori, from the potential benefits of this type of cardiocirculatory assistance.