Anti-inflammatory drugs protect against Alzheimer disease at low doses

CONTEXT: Anti-inflammatory medications have an inverse association with Alzheimer disease (AD). OBJECTIVES: To examine at what doses this anti-inflammatory drug effect occurs and whether other medications and/or International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses affect the association. DESIGN: Subjects 75 years and older from a random population sample were classified by consensus using International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses. Drug associations with different types of dementia with and without the International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses as well as dosage data were analyzed. SETTING: The Centre for Education and Research on Aging, Concord Hospital, Concord, Australia. PATIENTS: The Sydney Older Persons Study recruited 647 subjects (average age, 81 years). A total of 163 patients were given diagnoses placing them in different dementia categories and were compared with 373 control subjects. Of the patients with dementia, 78 had AD without vascular dementia, 45 had vascular dementia (permissive of other dementia diagnoses), and 40 had other dementia diagnoses (without AD or vascular dementia). MAIN OUTCOME MEASURES: Fifty drugs or drug groups were subjected to a 2 (drug used vs drug not used) x 4 (dementia and control groups) chi(2) analysis. Drugs with inverse associations were identified and potential confounders (logistic regression) and dosage data (exact small sample 1-tailed tests) analyzed. RESULTS: As expected, there was an inverse association between nonsteroidal anti-inflammatory drugs and aspirin (and unexpectedly angiotensin-converting enzyme inhibitors) and AD. This association was not observed with vascular dementia or any other diagnoses. Analysis showed no evidence for a dosage effect, ie, responses were equivalent for low and high doses. CONCLUSIONS: This study does not support a high-dose anti-inflammatory action of nonsteroidal anti-inflammatory drugs or aspirin in AD. Potential mechanisms for the beneficial effects of these medications are discussed.     

The effect of the nitric oxide donor glyceryl trinitrate on global and regional cerebral blood flow in man

Despite their potential use as cerebral vasodilatory agents there are few studies of the effect of nitric oxide (NO) donors on the cerebral circulation in non-anaesthetised man. We determined the effect of the NO donor glyceryl trinitrate (GTN) at clinically relevant doses on global and regional cerebral blood flow (CBF) in healthy non-anaesthetised volunteers, using H(2)(15)O PET, ultrasonic colour velocity flow imaging of carotid artery flow, and transcranial Doppler (TCD) of middle cerebral artery velocities (MCAv). Three rates of GTN infusion (0.1, 0.4, 1.0 microg/kg/min) were used. There was no significant change in common or internal carotid artery flow following GTN administration although a dose dependent fall in MCAv post GTN was observed. There was no significant change in either global or regional CBF following GTN. Thus intravenous GTN at therapeutic doses in awake humans does not alter global or regional CBF. However it does produce basal cerebral artery vasodilatation as evidenced by a fall in MCAv in the absence of a change in internal carotid artery flow.     

The effect of circumferential taping on flexor tendon pulley failure in rock climbers

The purpose of this study was to determine whether circumferential taping of the base of the finger increases the A2 pulley's load to failure in a model simulating a rock climber's grip. Nine pairs of fresh-frozen cadaveric hands, 20 to 47 years of age, were rigidly mounted in a specialized jig that maintained the finger in the climber's "crimp" position. Two of the four fingers of each hand were reinforced over the A2 pulley with three wraps of cloth adhesive tape. The flexor digitorum profundus and superficialis tendons were distracted until pulley or tendon failure. Overall, A2 pulley strength was greater in male specimens than in female specimens, and the A2 pulley of the small finger was the weakest tested. The A2 pulley failed simultaneously with the A3 and A4 pulleys in 55% of the tests. In the remaining trials, a single pulley failed initially followed by the remainder of the sheath. Of the 72 fingers studied, complete data were available for comparison of 22 pairs of fingers. No statistically significant difference in load to A2 pulley failure was noted between the taped and untaped finger pairs. Based on our findings we do not support taping the base of the fingers as a prophylactic measure against flexor tendon sheath injury in the climbing athlete.     

Impact of Institution of a Stroke Program Upon Referral Bias at a Rural Academic Medical Center

ABSTRACT: Context: Referral bias reflecting the preferential hospital transfer of patients with intracerebral hemorrhage (ICH) has been demonstrated as the major contributing factor for an observed high nonrisk-adjusted in-hospital crude acute stroke mortality rate at a rural academic medical center. Purpose: This study was done to assess the impact of a clinical acute stroke program upon referral bias in August 2000. Methods: A chart review of acute stroke (DRG 14) discharges during 2001 from a rural academic medical center was compared with the same data from 1999. Results: The odds ratio of ICH in hospital-transfer patients compared with nonhospital-transfer patients decreased from 11.7 in 1999 to 3.2 in 2001 (P<.035). Conclusions: This study demonstrated the rapid magnitude and significance that clinical programs can have upon referral bias. Changes in referral bias may be more rapid at rural academic medical centers because of the relative lack of health care delivery competition.     

Monitoring neuroprotection and restorative therapies in Parkinson's disease with PET

In this article the role of functional imaging (PET and SPECT) as a surrogate marker for following the progression of Parkinson's disease (PD) is discussed. The potential value of PET and SPECT for assessing the efficacy of putative neuroprotective agents in PD is considered and a review of 18F-dopa PET findings in transplantation trials involving implantation of human and procine fetal mesencephalic tissue is presented. It is concluded that functional imaging provides a valuable adjunct to clinical assessment when judging the efficacy of neuroprotective and restorative approaches to PD.     

Green tea extract modulates actin remodeling via Rho activity in an in vitro multistep carcinogenic model.

Alteration of actin polymerization and loss of actin filaments is a marker of cellular dedifferentiation and early malignant transformation. To study this phenomenon, an in vitro human urothelial model consisting of two cell lines, HUC-PC and MC-T11, were incorporated into the study design. These two cell lines have different malignant transformation potential. The effect of green tea extract (GTE), a potential anticancer agent, on actin remodeling was investigated. Upon exposure to the carcinogen 4-aminobiphenyl (4-ABP), the untransformed HUC-PC undergoes malignant transformation whereas the transformed MC-T11 progresses from noninvasive to invasive tumor. GTE induces actin polymerization in MC-T11 cells in a dose-responsive manner, but this effect is less obvious in the untransformed, more differentiated HUC-PC cells, which natively have higher actin polymerization status. In contrast, GTE antagonizes carcinogen 4-ABP induced actin depolymerization and stress fiber disruption in HUC-PC cells. In MC-T11 cells, GTE inhibits 4-ABP induced motility by increasing cell adhesion and focal adhesion complex formation. The effect of GTE on actin remodeling seems to be mediated by the stimulation of small GTP-binding protein Rho activity, because C3 exoenzyme, a specific inhibitor for Rho, blocks GTE-mediated Rho activation and stress fiber formation in MC-T11 cells. This study shows that GTE exerts an effect on cytoskeletal actin remodeling and provides further support for the use of GTE as a chemopreventive agent.     

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults,Canada, 2015–2019

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.