Improving the Gastrointestinal Tolerability of Aspirin in Older People

Interventions to reduce mortality and disability in older people are vital. Aspirin is cheap and effective and known to prevent cardiovascular and cerebrovascular disease, many cancers, and Alzheimer dementia. The widespread use of aspirin in older people is limited by its gastrointestinal side effects. Understanding age-related changes in gastrointestinal physiology that could put older people at risk of the side effects of aspirin may direct strategies to improve tolerance and hence lead to greater numbers of older people being able to take this effective intervention.     

Corticotropin releasing factor-like peptides produce selective dilatation of the dog mesenteric circulation

Three synthetic peptides, ovine corticotropin-releasing factor, sauvagine, and urotensin I, contain homologous amino acid residues. In the anesthetized dog, all three produce marked and selective dilatation of the mesenteric circulation; none of the peptides influenced blood flow in the renal, femoral, carotid, or even celiac arteries. The mesenteric vasodilatation appeared to be unrelated to the common ability of these peptides to release corticotropin and beta-endorphin, and cannot be abolished or attenuated by conventional blocking agents or inhibitors. The unique action of these peptides suggests that there may be a related peptide in the intestine that acts to regulate intestinal blood flow. The peptides may also prove useful therapeutically in nonocclusive ischemia, if this unusual action is also present in humans.     

Studies in homosexual patients with and without lymphadenopathy. Relationships to the acquired immune deficiency syndrome

We studied the immunologic function of 19 sexually active homosexual men, ten of whom had persistent lymphadenopathy. Analysis of mononuclear cell populations distinguished homosexuals from heterosexual controls since, as a group, homosexuals had increased percentages of natural killer cells (Leu 7+), decreased helper-inducer T lymphocytes (OKT-4+), increased suppressor/cytotoxic (OKT-8+) T lymphocytes, low OKT-4:OKT-8 ratios, and depressed mitogenic responses. Homosexuals without lymphadenopathy were distinguishable from controls by increased percentages of Ia+ cells, decreased OKT-4+ cells, and decreased OKT-4:OKT-8 ratios. Four had positive findings simultaneously for hepatitis B surface antigen (HBsAg) and surface antibody, and five had positive findings for HBsAg alone. Homosexuals with lymphadenopathy were distinguishable from controls by increased percentages of Leu 7+ cells, increased total lymphocyte numbers per cubic millimeter, decreased percentages of both OKT-4+ and OKT-8+ cells, abnormal OKT-4:OKT-8 ratios, and depressed mitogenic responses. Only histories of larger numbers of sexually acquired diseases, higher numbers of OKT-8+ cells per cubic millimeter, and lower mitogenic responses in homosexuals with lymphadenopathy distinguished this group from homosexuals without lymphadenopathy. Furthermore, none of the nine patients tested in this group was HBsAg positive. We conclude that homosexuals without lymphadenopathy are distinguishable from those with lymphadenopathy by both immunologic and serologic abnormalities.     

Regulation of vertebrate forelimb development and wing reduction in the flightless emu

The vertebrate limb is a dynamic structure which has evolved into many diverse forms to facilitate complex behavioral adaptations. The principle molecular and cellular processes that underlie development of the vertebrate limb are well characterized. However, how these processes are altered to drive differential limb development between vertebrates is less well understood. Several vertebrate models are being utilized to determine the developmental basis of differential limb morphogenesis, though these typically focus on later patterning of the established limb bud and may not represent the complete developmental trajectory. Particularly, heterochronic limb development can occur prior to limb outgrowth and patterning but receives little attention. This review summarizes the genetic regulation of vertebrate forelimb diversity, with particular focus on wing reduction in the flightless emu as a model for examining limb heterochrony. These studies highlight that wing reduction is complex, with heterochronic cellular and genetic events influencing the major stages of limb development. Together, these studies provide a broader picture of how different limb morphologies may be established during development.     

Development of a conceptual model of oral health for malocclusion patients

Objectives:To provide an empirical test of the applicability of Locker''s conceptual model of oral health for malocclusion patients, and to suggest alternative models of the effect of malocclusion on well-being.Materials and Methods:Data from a survey of 323 adolescents attending for orthodontic treatment were analyzed to develop a new oral health model for malocclusion patients. Oral health–related quality of life (OHRQoL) was measured using the 14-item Oral Health Impact Profile; malocclusion was measured using the Dental Health Component (DHC) of the Index of Orthodontic Treatment Need (IOTN). Using structural equation modeling, the relationship between conceptual domains in Locker''s model was explored and three models of their interrelationship tested for goodness of fit.Results:Fit indexes for Locker''s model indicated that it did not fit the data well. Therefore, a modified model was developed to incorporate additional paths between other levels to better fit the data. The best fit was provided by a model in which the direct effects of malocclusion on pain, discomfort, and handicapping—and the direct effect of pain on disability—were removed. A direct effect of functional limitation on disability was allowed. The modified Oral Health Impact Profile model proved to be a good fit to the data (root mean square error of approximation  =  0.069).Conclusion:The pathways identified in Locker''s (1988) conceptual model of oral health may not be appropriate for describing the relationships between OHRQoL constructs in individuals with malocclusion. An alternative model is proposed.     

Preventable Major Cardiovascular Events Associated With Uncontrolled Glucose,Blood Pressure,and Lipids and Active Smoking in Adults With Diabetes With and Without Cardiovascular Disease: A Contemporary Analysis

OBJECTIVEThe objective of this study was to assess the incidence of major cardiovascular (CV) hospitalization events and all-cause deaths among adults with diabetes with or without CV disease (CVD) associated with inadequately controlled glycated hemoglobin (A1C), high LDL cholesterol (LDL-C), high blood pressure (BP), and current smoking.RESULTSMean (SD) age at baseline was 59 (14) years; 48% of subjects were female, 45% were white, and 31% had CVD. Mean follow-up was 59 months. Event rates per 100 person-years for adults with diabetes and CVD versus those without CVD were 6.0 vs. 1.7 for MI/ACS, 5.3 vs. 1.5 for stroke, 8.4 vs. 1.2 for HF, 18.1 vs. 40 for all CV events, and 23.5 vs. 5.0 for all-cause mortality. The percentages of CV events and deaths associated with inadequate risk factor control were 11% and 3%, respectively, for those with CVD and 34% and 7%, respectively, for those without CVD.CONCLUSIONSAdditional attention to traditional CV risk factors could yield further substantive reductions in CV events and mortality in adults with diabetes.     

Randomized Controlled Trial of Insulin Supplementation for Correction of Bedtime Hyperglycemia in Hospitalized Patients With Type 2 Diabetes

OBJECTIVE

Clinical guidelines recommend point-of-care glucose testing and the use of supplemental doses of rapid-acting insulin before meals and at bedtime for correction of hyperglycemia. The efficacy and safety of this recommendation, however, have not been tested in the hospital setting.

RESEARCH DESIGN AND METHODS

In this open-label, randomized controlled trial, 206 general medicine and surgery patients with type 2 diabetes treated with a basal-bolus regimen were randomized to receive either supplemental insulin (n = 106) at bedtime for blood glucose (BG) >7.8 mmol/L or no supplemental insulin (n = 100) except for BG >19.4 mmol/L. Point-of-care testing was performed before meals, at bedtime, and at 3:00 a.m. The primary outcome was the difference in fasting BG. In addition to the intention-to-treat analysis, an as-treated analysis was performed where the primary outcome was analyzed for only the bedtime BG levels between 7.8 and 19.4 mmol/L.

RESULTS

There were no differences in mean fasting BG for the intention-to-treat (8.8 ± 2.4 vs. 8.6 ± 2.2 mmol/L, P = 0.76) and as-treated (8.9 ± 2.4 vs. 8.8 ± 2.4 mmol/L, P = 0.92) analyses. Only 66% of patients in the supplement and 8% in the no supplement groups received bedtime supplemental insulin. Hypoglycemia (BG <3.9 mmol/L) did not differ between groups for either the intention-to-treat (30% vs. 26%, P = 0.50) or the as-treated (4% vs. 8%, P = 0.37) analysis.

CONCLUSIONS

The use of insulin supplements for correction of bedtime hyperglycemia was not associated with an improvement in glycemic control. We conclude that routine use of bedtime insulin supplementation is not indicated for management of inpatients with type 2 diabetes.