Surgical removal of intestinal foreign bodies using a laparotomy-assisted endoscopic approach in dogs and cats and comparison with enterotomy.

OBJECTIVES: To describe a novel surgical technique for intestinal foreign body removal without enterotomy using a laparotomy-assisted endoscopic approach and compare short-term outcomes to enterotomy. MATERIALS AND METHODS: Medical records of dogs and cats with intestinal foreign bodies that underwent attempted treatment with a laparotomy-assisted endoscopic approach between June 2019 and July 2021 were extracted. The approach consisted in manoeuvring the intestinal foreign body into the stomach during laparotomy and then removing it via a gastroscopy. If the foreign body was unmovable, an enterotomy was performed. RESULTS: Fifty-eight cases were enrolled and foreign bodies were successfully removed in 25 cases using a laparotomy-assisted endoscopic approach. The median distance between the pylorus and the proximal part of the foreign body was 55 cm (range: 0 to 300). The mean surgical time and median endoscopic time were 49 minutes (±sd 12.8) and 5 minutes (range: 2 to 28), respectively. All but two cases were discharged 1 day postoperatively. In 20 cases, the foreign body was not easily movable, and an enterotomy was performed. In three of these cases, conversion to enterotomy was required due to serosal tears that occurred as a consequence of the attempted retrograde manipulation of the foreign body. Foreign body width, length and distance to pylorus were not significantly different between the two techniques. Mean surgical time was significantly shorter for laparotomy-assisted endoscopic approach compared to enterotomy: 49 minutes (±SD 12.8) versus 61.7 minutes (±SD 14.6). CLINICAL SIGNIFICANCE: Surgical removal of intestinal foreign bodies through a laparotomy-assisted endoscopic approach is a feasible technique that offers satisfactory outcomes and shorter surgical time than enterotomy. Retrograde manipulation of the intestinal foreign body may result in serosal tears.

Reporting health research translation and impact in the curriculum vitae: a survey.

BACKGROUND: Increasingly, health researchers must demonstrate the impact and real-life applications of their research. We investigated how health researchers with expertise in knowledge translation report research translation activities and impact on their curriculum vitae (CV). METHODS: We conducted a cross-sectional survey of health researchers with expertise in knowledge translation as we anticipated best practices in CV reporting from this specialized group. Our survey asked participants about their reporting of research translation and impact activities on their CVs, intention to report, and barriers and facilitators to reporting such activities on their CVs. We calculated univariate descriptive statistics for all quantitative data. Linear regression models determined predictors of researchers' intention to report research translation and impact activities on their CVs. We analyzed open-ended qualitative responses using content analysis. RESULTS: One hundred and fifty-three health researchers responded to the survey (response rate = 29%). Most respondents were Canadian, were female, and had a doctoral degree. Eighty-two percent indicated they reported at least one research translation and/or impact indicator on their CVs. Of those, health researchers commonly reported the following: advisory/regulatory committee membership related to research program (83%), research translation award(s) (61%), and academic performance assessments (59%). Researchers least commonly indicated the following: citation metric scores (31%), summaries of impact (21%), and requests to use research materials and/or products (19%). Fewer than half of the health researchers intended to report knowledge translation (43%) and impact (33%) on their CVs. Strong beliefs about capabilities and consequences of reporting research translation and/or impact were significant predictors of intention. Main barriers were as follows: CV templates do not include research translation and impact activities, participants perceived employers do not value research translation and impact activities, and lack of metrics to evaluate research translation and impact. Ninety-six percent were unaware of a CV template formatted to include research translation and/or impact reporting. CONCLUSIONS: Knowledge translation and impact indicators on the CV are inconsistently reported by our sample of health researchers. Modifiable barriers should be addressed to support more consistent reporting of such activities, including providing a CV template that includes research translation and impact as well as clear metrics to quantify them.

Building an integrated knowledge translation (IKT) evidence base: colloquium proceedings and research direction.

BACKGROUND: Integrated knowledge translation (IKT) is a model of research co-production, whereby researchers partner with knowledge users throughout the research process and who can use the research recommendations in practice or policy. IKT approaches are used to improve the relevance and impact of research. As an emerging field, however, the evidence underpinning IKT is in active development. The Integrated Knowledge Translation Research Network represents a collaborative interdisciplinary team that aims to advance the state of IKT science. METHODS: In 2017, the Integrated Knowledge Translation Research Network issued a call to its members for concept papers to further define IKT, outline an IKT research agenda, and inform the Integrated Knowledge Translation Research Network's special meeting entitled, Integrated Knowledge Translation State of the Science Colloquium, in Ottawa, Canada (2018). At the colloquium, authors presented concept papers and discussed knowledge-gaps for a research agenda and implications for advancing the IKT field. We took detailed field notes, audio-recorded the meeting and analysed the data using qualitative content analysis. RESULTS: Twenty-four participants attended the meeting, including researchers (n = 11), trainees (n = 6) and knowledge users (n = 7). Seven overarching categories emerged from these proceedings - IKT theory, IKT methods, IKT process, promoting partnership, definitions and distinctions of key IKT terms, capacity-building, and role of funders. Within these categories, priorities identified for future IKT research included: (1) improving clarity about research co-production/IKT theories and frameworks; (2) describing the process for engaging knowledge users; and (3) identifying research co-production/IKT outcomes and methods for evaluation. CONCLUSION: The Integrated Knowledge Translation State of the Science Colloquium initiated a research agenda to advance IKT science and practice. Next steps will focus on building a theoretical and evidence base for IKT.

Patient experiences of a physiotherapy-led multidisciplinary rehabilitative intervention after successful treatment for oesophago-gastric cancer.

PURPOSE: To qualitatively explore the perceived impact of a 12-week rehabilitative intervention for oesophago-gastric cancer survivors on their physical, mental and social wellbeing. METHODS: Of the 21 participants who completed the intervention, 19 took part in a semi-structured focus group interview. Four audio-taped focus groups were held, ranging in size from two to eight participants. Focus groups were transcribed and analysed using a descriptive qualitative approach. RESULTS: At recruitment, participants were 23.5 ± 15.2 months post-surgery and all had suboptimal fitness levels. Participants reported improvements in their physical capacity and ability to carry out activities of daily living during the intervention. These improvements led to increased confidence and social connectivity. Other participants were a valuable source of information and reassurance, while support from family members was variable. Future interventions should educate participants on how to maintain gains achieved during the intervention. CONCLUSIONS: Participating in an exercise-based multidisciplinary rehabilitative intervention reduces isolation and helps oesophago-gastric cancer survivors to safely negotiate their physical, emotional and social needs as they move further down the path of recovery.

Impact of patient decision aids on appropriate and timely access to hip or knee arthroplasty for osteoarthritis: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of patient decision aids (PtDA) compared to usual education on appropriate and timely access to total joint arthroplasty in patients with osteoarthritis. METHOD: A randomized controlled trial (RCT) with patients undergoing orthopedic screening. Control and intervention arms received usual education; intervention arm also received a PtDA and a surgeon preference report. Wait times (primary outcome) were described using stratified Kaplan-Meier survival curves with patients censored at the time of death or loss to follow-up, and multivariable Cox proportional hazards regression. Secondary outcomes were compared using stratified Cochran-Mantel-Haenszel chi-squared tests. RESULTS: 343 patients were randomized to intervention (n = 174) or control (n = 169). The typical patient was 66 years old, retired, living with someone, and 51% had high school education or less. The intervention was associated with a trend towards reduction in wait time (hazard ratio (HR) 1.25, 95% confidence interval (CI) 0.99-1.60, P = 0.0653). Median wait times were 3 weeks shorter in intervention than in control at the community site with no difference at the academic site. Good decision quality was reached by 56.1% intervention and 44.5% control (Relative risk (RR) 1.25; 95% CI 1.00-1.56, P = 0.050). Surgery rates were 73.2% intervention and 80.5% controls (RR 0.91: 95% CI 0.81-1.03) with 12 intervention (7.3%) and eight control participants (4.9%) returning to have surgery within 2 years (P = 0.791). CONCLUSION: Compared to controls, decision aid recipients had shorter wait times at one site, fewer surgeries, and were more likely to reach good decision quality, but overall effect was not statistically significant. TRIALS REGISTRATION: The full trial protocol is available at ClinicalTrials.Gov (NCT00911638).

Care everywhere, a point-to-point HIE tool: utilization and impact on patient care in the ED.

BACKGROUND: Emergency departments (EDs) routinely struggle with gaps in information when providing patient care. A point to point health information exchange (HIE) model has the potential to effectively fill those gaps. OBJECTIVE: To examine the utility, perceived and actual, of a point-to-point HIE tool called Care Everywhere (CE) and its impact on patient care in the ED. METHODS: This mixed methods study was performed at four large hospital EDs between January 2012 and November 2012. Retrospective data was extracted from the electronic health record (EHR) to evaluate CE utilization since implementation. ED notes data were extracted from ED visits occurring between January 2012 and June 2012 and were reviewed to evaluate the impact of exchanged information on patient care. RESULTS: Per focus group discussions, physicians thought the information received via CE was of value to patient care, particularly laboratory results, imaging, medication lists, discharge summaries and ECG interpretations. They feel the greatest impact of HIE is the avoidance of duplicative diagnostic testing and the identification of drug-seeking behavior. Nursing and ancillary staff expressed somewhat less enthusiasm but still felt HIE positively impacted patient care. Over a period of six months, CE was used in approximately 1.46% of ED encounters. A review of ED provider notes over that time period revealed CE use resulted in 560 duplicate diagnostic procedures being avoided and 28 cases of drug seeking behavior identified. CONCLUSION: Our study provides insight into the perceived value of HIE from the point of view of our ED physicians and staff. It also demonstrates that a point-to-point HIE tool such as Epic System's Care Everywhere has the potential to generate greater efficiencies within the ED and impact to patient care through elimination of duplicative diagnostic imaging or testing and resource utilization associated with those procedures.

Reduced polymerization stress of MAPO-containing resin composites with increased curing speed, degree of conversion and mechanical properties.

OBJECTIVES: The degree and rate of photopolymerization in resin-based dental composites will significantly affect polymer network formation and resultant material properties that may determine their clinical success. This study investigates the mechanical properties, the generation of stress from polymerization, tooth cusp deflection and marginal integrity of experimental resin composites that contain different photoinitiators. METHODS: Experimental light-activated resin composites (60vol% particulate filled in 50/50mass% bis-GMA/TEGDMA) were formulated using a monoacylphosphine oxide (MAPO) photoinitiator and compared with a conventional camphoroquinone (CQ)-based system. Similar radiant exposure was used (18Jcm(-2)) for polymerization of each material although the curing protocol was varied (400mWcm(-2) for 45s, 1500mWcm(-2) for 12s and 3000mWcm(-2) for 6s). Degree and rate of polymerization was calculated in real-time by near infrared spectroscopy and the generation of stress throughout polymerization measured using a cantilever beam method. Flexural strength and modulus were acquired by three-point bend tests. Standardized cavities in extract pre-molar teeth were restored with each material, the total cuspal deflection measured and post-placement marginal integrity between the tooth and restoration recorded. RESULTS: Generally, MAPO- exhibited a significantly higher degree of conversion (72±0.8 to 82±0.5%) compared with CQ-based materials (39±0.7 to 65±1.6%) regardless of curing protocol (p<0.05) and MAPO-based materials exhibited less difference in conversion between curing protocols. CQ-based materials exhibited between ∼85 and 95% of the maximum rate of polymerization at <15% conversion, whereas MAPO-based RBCs did not approach the maximum rate until >50% conversion. Higher irradiance polymerization had a significant deleterious effect on the mechanical properties of CQ-based materials (p<0.05) whereas MAPO-based materials exhibited increased strength and modulus and were less affected by the curing method. Total cuspal deflection in restored extracted teeth was higher for CQ- compared with MAPO-based materials cured at the lowest irradiance curing protocol (12.9±4.0 and 8.3±1.5µm) and similar at 3000mWcm(-1) for 6s (10.1±3.5 and 9.0±1.5µm). A significant decrease in marginal integrity was observed for CQ-based RBCs cured at high irradiance for short exposure time compared with that of the MAPO-based RBC cured using a similar protocol (p=0.037). SIGNIFICANCE: Polymer network formation dictates the final properties of the set composite and the use MAPO photoinitiators may provide an effective restorative material that exhibits higher curing speeds, increased degree of conversion, strength and modulus without compromise in terms of polymerization stress and marginal integrity between tooth and restoration.

MMP-2 as an early synovial biomarker for cranial cruciate ligament disease in dogs.

OBJECTIVES: To measure the activity of matrix metalloproteinases (MMP)-2 and -9 in synovial fluid from the stifle joints of dogs with cranial cruciate ligament (CrCL) rupture and to compare that to values from contralateral stifle joints and dogs with clinically normal stifle joints. Additionally, the C-reactive protein (CRP) levels were also measured. METHODS: Fourteen large breed dogs with unilateral CrCL rupture and 11 large breed normal dogs were included in this prospective clinical study. Synovial fluid was collected from CrCL-ruptured stifle joints, contralateral clinically normal stifle joints of the same dogs, and stifle joints of normal dogs. Serum was also collected. Synovial fluid activities of MMP-2 and MMP-9 and serum CRP level were measured. RESULTS: The MMP-2 activity in synovial fluid was significantly higher in CrCL-ruptured joints compared to contralateral joints and to stifles from normal dogs. There was no significant difference in activity of MMP-2 in contralateral joints of CrCL-ruptured dogs compared to normal dogs. Both serum CRP level and MMP-9 activity did not differ significantly between the studied conditions. CLINICAL SIGNIFICANCE: It was confirmed that MMP-2 activity is significantly related to CrCL rupture, but there was a failure to demonstrate any significant increase in the contralateral joints compared to the stifle joints of normal dogs. The MMP-2 involvement in progressing CrCL disease still has to be defined.

Cats with inflammatory bowel disease and intestinal small cell lymphoma have low serum concentrations of 25-hydroxyvitamin D.

BACKGROUND: Inflammatory bowel disease (IBD) and intestinal small cell lymphoma (ISCL) are common diseases in cats. The prevalence of alterations in the serum concentrations of fat soluble vitamins, such as vitamin D, in cats with IBD and ISCL is unknown. HYPOTHESIS/OBJECTIVES: The objective of this study was to measure serum 25 hydroxyvitamin D (25[OH]D) concentrations in cats with IBD or ISCL. Serum 25(OH)D also was measured in healthy cats, and in hospitalized ill cats with nongastrointestinal diseases. ANIMALS: Eighty-four cats were included in the study: 23 in the healthy group, 41 in the hospitalized ill group, and 20 in the IBD/ISCL group. METHODS: Retrospective study. Serum samples for vitamin D analysis were frozen at -20°C until serum 25(OH)D was measured by high-performance liquid chromatography (HPLC). RESULTS: Although there was overlap in serum 25(OH)D concentrations among the 3 groups, serum 25(OH)D concentrations were significantly lower in the cats with IBD or ISCL compared to healthy cats (P < .0001) and hospitalized ill cats (P = .014). In the IBD/ISCL group, there was a significant moderate positive correlation between serum albumin and 25(OH)D concentrations (r = 0.58, P = .018). CONCLUSION AND CLINICAL IMPORTANCE: The median serum concentration of 25(OH)D was significantly lower in cats with IBD/ISCL than in healthy cats and in hospitalized ill cats. Additional studies are required to elucidate the mechanism of hypovitaminosis D in cats with gastrointestinal diseases, to define the best management strategy to treat this complication, and to investigate its potential prognostic implications.

Prospective study of subclinical atherosclerosis as a risk factor for venous thromboembolism.

BACKGROUND: Whether atherosclerotic disease predisposes to venous thrombosis is uncertain. OBJECTIVE: To determine whether subclinical atherosclerosis, manifested as increased carotid intima-media thickness (IMT) or presence of carotid plaque, is associated with increased incidence of venous thromboembolism (VTE). PATIENTS AND METHODS: The Atherosclerosis Risk in Communities study is a prospective cohort of adults aged 45-64 years, examined at baseline (1987-89) and followed for cardiovascular events. Bilateral carotid ultrasound for IMT measurements was done at baseline for portions of the common and internal carotid arteries, and carotid bifurcation and also to detect the presence of carotid plaque. Exclusion criteria included baseline anticoagulant use, history of coronary heart disease, stroke, or VTE, and incomplete data. First VTE during follow-up was validated using abstracted medical records. RESULTS: Among 13,081 individuals followed for a mean of 12.5 years, 225 first VTE events were identified. Unadjusted hazard ratios (HR) (95% CI) of VTE across quartiles of baseline IMT were 1.0, 1.16 (0.77-1.75), 1.64 (1.12-2.40), and 1.52 (1.03-2.25). However, this association disappeared after adjustment for age, sex, and ethnicity (HRs: 1.0, 1.06, 1.40, and 1.18). Further adjustment for body mass index and diabetes weakened the relative risks even further. Presence of carotid plaque at baseline also was not associated with VTE occurrence; adjusted HR = 0.97, 95% CI = 0.72-1.29. CONCLUSION: Increased carotid IMT or presence of carotid plaque was not associated with an increased incidence of VTE in this middle-aged cohort, suggesting subclinical atherosclerosis itself is not a VTE risk factor.

Stability of haemoglobin A1c (HbA1c) measurements from frozen whole blood samples stored for over a decade.

OBJECTIVE: Haemoglobin A1c (HbA1c), a measure of long-term glycaemic control, is at the centre of the clinical management of diabetes mellitus. However, the reproducibility of HbA1c measurements from whole blood samples which have been in long-term storage is unknown. We undertook this study to assess the reproducibility of HbA1c measurements from whole blood samples that had been in storage at -70 degrees C for over a decade. RESEARCH DESIGN AND METHODS: Three hundred and thirty-six samples of frozen whole blood from the Atherosclerosis Risk in Communities (ARIC) Study, stored at -70 degrees C for 11-14 years assayed for HbA1c using a dedicated ion-exchange HPLC assay (Tosoh A1c 2.2 Plus HPLC) were compared with measurements on these same samples conducted prior to storage (in 1990-92) using a Diamat (Bio-Rad) HPLC instrument. RESULTS: HbA1c measurements from long-term stored samples were strongly correlated with values obtained prior to long-term storage (r=0.97). The difference between HbA1c from long- and short-term stored samples had a mean of 0.35% HbA1c (sd=0.35) and a CV of 5.8%, which was approximately three times that of duplicate assays (CV 1.3 to 2.5%). CONCLUSIONS: These data demonstrate that highly correlated but more variable and slightly higher HbA1c results were obtained from frozen whole blood samples that have been in storage for more than a decade. This highly reproducible assay performance would lead to comparable ranking of individuals and unbiased estimates of relative risks and odds ratios in epidemiological studies (case-control and cohort designs), but results should be realigned when the absolute value is of interest. These results have important implications for epidemiological studies and clinical trials which have stored whole blood specimens.

Alcohol consumption and the risk of type 2 diabetes mellitus: atherosclerosis risk in communities study.

Evidence regarding the association between alcohol consumption and type 2 diabetes risk remains inconsistent, particularly with regard to male-female differences. The authors conducted a prospective study of type 2 diabetes risk associated with alcohol consumption in a cohort of 12,261 middle-aged participants of the Atherosclerosis Risk in Communities Study (1990-1998), who were followed between 3 and 6 years. Alcohol consumption at baseline was characterized into lifetime abstainers, former drinkers, and current drinkers of various levels. Incident diabetes was determined by blood glucose measurements and self-report. After adjustment for potential confounders, an increased risk of diabetes was found in men who drank >21 drinks/week when compared with men who drank < or =1 drink/week (odds ratio = 1.50, 95% confidence interval: 1.02, 2.20) while no significant association was found in women. This increased diabetes risk among men who drank >21 drinks/week was predominantly related to spirits rather than to beer or wine consumption. The relative odds of incident diabetes in a comparison of men who drank >14 drinks of spirits per week with men who were current drinkers but reported no regular use of spirits, beer, or wine were 1.82 (95% confidence interval: 1.14, 2.92). Results of this study support the hypothesis that high alcohol intake increases diabetes risk among middle-aged men. However, more moderate levels of alcohol consumption do not increase risk of type 2 diabetes in either middle-aged men or women.

Kinetic analysis of open- and closed-state inactivation transitions in human Kv4.2 A-type potassium channels.

1. We studied the gating kinetics of Kv4.2 channels, the molecular substrate of neuronal somatodendritic A-type currents. For this purpose wild-type and mutant channels were transiently expressed in the human embryonic kidney (HEK) 293 cell line and currents were measured in the whole-cell patch-clamp configuration. 2. Kv4.2 channels inactivated from pre-open closed state(s) with a mean time constant of 959 ms at -50 mV. This closed-state inactivation was not affected by a deletion of the Kv4.2 N-terminus (Delta2-40). 3. Kv4.2 currents at +40 mV inactivated with triple-exponential kinetics. A fast component (tau = 11 ms) accounted for 73 %, an intermediate component (tau = 50 ms) for 23 % and a slow component (tau = 668 ms) for 4 % of the total decay. 4. Both the fast and the intermediate components of inactivation were slowed by a deletion of the Kv4.2 N-terminus (tau = 35 and 111 ms) and accounted for 33 and 56 %, respectively, of the total decay. The slow component was moderately accelerated by the truncation (tau = 346 ms) and accounted for 11 % of the total Kv4.2 current inactivation. 5. Recovery from open-state inactivation and recovery from closed-state inactivation occurred with similar kinetics in a strongly voltage-dependent manner. Neither recovery reaction was affected by the N-terminal truncation. 6. Kv4.2 Delta2-40 channels displayed slowed deactivation kinetics, suggesting that the N-terminal truncation leads to a stabilization of the open state. 7. Simulations with an allosteric model of inactivation, supported by the experimental data, suggested that, in response to membrane depolarization, Kv4.2 channels accumulate in the closed-inactivated state(s), from which they directly recover, bypassing the open state.

Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study.

Disordered breathing during sleep is associated with acute, unfavorable effects on cardiovascular physiology, but few studies have examined its postulated association with cardiovascular disease (CVD). We examined the cross-sectional association between sleep- disordered breathing and self-reported CVD in 6,424 free-living individuals who underwent overnight, unattended polysomnography at home. Sleep-disordered breathing was quantified by the apnea-hypopnea index (AHI)-the average number of apneas and hypopneas per hour of sleep. Mild to moderate disordered breathing during sleep was highly prevalent in the sample (median AHI: 4.4; interquartile range: 1.3 to 11.0). A total of 1,023 participants (16%) reported at least one manifestation of CVD (myocardial infarction, angina, coronary revascularization procedure, heart failure, or stroke). The multivariable-adjusted relative odds (95% CI) of prevalent CVD for the second, third, and fourth quartiles of the AHI (versus the first) were 0.98 (0.77-1.24), 1.28 (1.02-1.61), and 1.42 (1.13-1.78), respectively. Sleep-disordered breathing was associated more strongly with self-reported heart failure and stroke than with self-reported coronary heart disease: the relative odds (95% CI) of heart failure, stroke, and coronary heart disease (upper versus lower AHI quartile) were 2.38 (1.22-4.62), 1.58 (1.02- 2.46), and 1.27 (0.99-1.62), respectively. These findings are compatible with modest to moderate effects of sleep-disordered breathing on heterogeneous manifestations of CVD within a range of AHI values that are considered normal or only mildly elevated.

Cardiovascular risk factors and cognitive decline in middle-aged adults.

OBJECTIVE: To perform serial neuropsychological assessments to detect vascular risk factors for cognitive decline in the Atherosclerosis Risk in Communities cohort, a large biracial, multisite, longitudinal investigation of initially middle-aged individuals. METHODS: The authors administered cognitive assessments to 10,963 individuals (8,729 white individuals and 2,234 black individuals) on two occasions separated by 6 years. Subjects ranged in age at the first assessment from 47 to 70 years. The cognitive assessments included the delayed word recall (DWR) test, a 10-word delayed free recall task in which the learning phase included sentence generation with the study words, the digit symbol subtest (DSS) of the Wechsler Adult Intelligence Scale-Revised and the first-letter word fluency (WF) test using letters F, A, and S. RESULTS: In multivariate analyses (controlling for demographic factors), the presence of diabetes at baseline was associated with greater decline in scores on both the DSS and WF (p < 0.05), and the presence of hypertension at baseline was associated with greater decline on the DSS alone (p < 0.05). The association of diabetes with cognitive decline persisted when analysis was restricted to the 47- to 57-year-old subgroup. Smoking status, carotid intima-media wall thickness, and hyperlipidemia at baseline were not associated with change in cognitive test scores. CONCLUSIONS: Hypertension and diabetes mellitus were positively associated with cognitive decline over 6 years in this late middle-aged population. Interventions aimed at hypertension or diabetes that begin before age 60 might lessen the burden of cognitive impairment in later life.

Hypertension and arterial stiffness: the Atherosclerosis Risk in Communities Study. ARIC Investigators.

Our objective was to describe the relationship of arterial stiffness and hypertension in a large, population-based sample of men and women. Hypertension-related increases in arterial stiffness may reflect the distending pressure and/or structural alterations in the artery. Included were 10,712 participants, ages 45 to 64 years, of the Atherosclerosis Risk in Communities Study, free of prevalent cardiovascular disease. Hypertension was classified as systolic or diastolic blood pressure (BP) > or =140/90 mm Hg, respectively, or the current use of antihypertensive medications. Common carotid arterial diameter change was measured using B-mode ultrasound and an electronic device that utilized radio frequency signals to track the motion of the arterial walls. Using statistical models to control for diastolic BP and pulse pressure, arterial diameter change was calculated separately in normotensive/ nonmedicated and medicated hypertensives. Hypertension was associated with a smaller adjusted diameter change (ie, greater stiffness) in comparison to optimal blood pressure (BP < 120/80 mm Hg): normotensive/nonmedicated men, 0.33 versus 0.43 mm (P < 0.001); medicated men, 0.34 versus 0.42 mm (P < 0.001); normotensive/ nonmedicated women, 0.34 versus 0.40 mm (P < 0.001), and medicated women, 0.33 versus 0.40 mm (P < 0.001). The relationship between pulse pressure and diameter change (ie, the slope of pulse pressure and diameter change) did not differ between hypertensives and normotensives. These cross-sectional data suggest that hypertension is associated with carotid arterial stiffness; however, these differences in the calculated stiffness appear to be the effect of distending pressure rather than structural changes in the carotid artery.

Inferomedial placement of a single-entry subpalpebral lavage tube for treatment of equine eye disease.

The objective of this study was to describe method of placement, and frequency and severity of complications associated with a subpalpebral lavage system placed in the medial aspect of the equine inferior eyelid. The inferomedial subpalpebral lavage (ISPL) tube is positioned deep in the medial aspect of the inferior conjunctival fornix so that the footplate lies flat between the lower eyelid and the anterior surface of the nictitans. Retrospective data from the placement of 92 ISPL systems placed in 86 horses during a 31-month period were examined. Tube placement was performed using sedation and regional anesthesia only in 59% of horses. The median duration of tube placement was 19 days (range: 1-61 days). Seventy-one horses were treated for up to 55 days following discharge from hospital with an ISPL tube in place. No complications were reported with 59% of ISPL systems. Non-ocular complications were found in 38% of ISPL systems and included tube displacement from the conjunctival fornix (18%), suture loss requiring resuturing of the system to the horse's head (14%), and damage necessitating replacement of the injection port (6%). Ocular complications were recorded in 3% of horses and were limited to inferior eyelid swelling. Vision was retained in 88% of horses. The ISPL system is easily and safely placed, and well tolerated for extended periods. It appears to be associated with infrequent and minor complications when compared with placement of subpalpebral lavage tubes in the superior eyelid.

Protein kinase C inhibits Kv1.1 potassium channel function.

The regulation by protein kinase C (PKC) of recombinant voltage-gated potassium (K) channels in frog oocytes was studied. Phorbol 12-myristate 13-acetate (PMA; 500 nM), an activator of PKC, caused persistent and large (up to 90%) inhibition of mouse, rat, and fly Shaker K currents. K current inhibition by PMA was blocked by inhibitors of PKC, and inhibition was not observed in control experiments with PMA analogs that do not activate PKC. However, site-directed substitution of potential PKC phosphorylation sites in the Kv1.1 protein did not prevent current inhibition by PMA. Kv1.1 current inhibition was also not accompanied by changes in macroscopic activation kinetics or in the conductance-voltage relationship. In Western blots, Kv1.1 membrane protein was not significantly reduced by PKC activation. The injection of oocytes with botulinum toxin C3 exoenzyme blocked the PMA inhibition of Kv1. 1 currents. These data are consistent with the hypothesis that PKC-mediated inhibition of Kv1.1 channel function occurs by a novel mechanism that requires a C3 exoenzyme substrate but does not alter channel activation gating or promote internalization of the channel protein.

Episodic ataxia/myokymia mutations functionally expressed in the Shaker potassium channel.

Episodic ataxia type 1 is a rare, autosomal dominant neurological disorder caused by missense mutations of the Kv1.1 gene from the Shaker K+ channel subfamily. To study the functional effects of the disease-causing mutations in a robust K+ channel background, we introduced seven different episodic ataxia type 1 substitutions into the corresponding, conserved residues of the Shaker K+ channel. K+ channel currents expressed in Xenopus oocytes were studied by electrophysiology. All episodic ataxia type 1 mutations produced functional K+ channels. In a Shaker N-terminal deletion mutant with fast inactivation removed, current amplitudes were significantly reduced in channels harboring an episodic ataxia type 1 mutation. Six of the seven mutations also showed depolarizing shifts (+9 to +36 mV) in the conductance voltage dependence. One mutation (F307I) shifted the midpoint of the conductance-voltage relationship by 23 mV in the hyperpolarizing direction. Episodic ataxia type 1 mutations were also expressed in ShakerH4 with intact N-terminal inactivation. In this construct, current amplitudes for episodic ataxia type 1 mutants were not significantly different from wild-type channels. All mutations altered the voltage range of steady-state inactivation; most changes were coupled to the changes in activation gating. Some episodic ataxia type 1 mutants also caused significant changes in the kinetics of N-type (F307I, E395D) or C-type (F307I, E395D, V478A) inactivation. These results suggest that episodic ataxia type 1 mutations may change K+ channel function by two mechanisms: (i) reduced channel expression and (ii) altered channel gating.

Docosahexaenoic acid and smoking-related chronic obstructive pulmonary disease. The Atherosclerosis Risk in Communities Study Investigators.

If the inflammatory response to inhalation of cigarette smoke causes chronic obstructive pulmonary disease (COPD), suppression of that natural response might be beneficial. We hypothesized that a smoker's risk of developing COPD is inversely related to physiologic levels of two fatty acids that have antiinflammatory properties: eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6). The proportion of each fatty acid in plasma lipids was measured in 2,349 current or former smokers. COPD was identified and defined by clinical symptoms and/or spirometry. After adjustment for smoking exposure and other possible confounders, the prevalence odds of COPD were inversely related to the DHA (but not to the EPA) content of plasma lipid components in most of the models. For example, as compared with the first quartile of the DHA distribution, the prevalence odds ratios (ORs) for chronic bronchitis were 0.98, 0.88, and 0.69 for the second, third, and fourth quartiles, respectively (p for linear trend = 0.09). The corresponding ORs for COPD as defined spirometrically, were 0.65, 0.51, and 0.48 (p < 0. 001). Among 543 current heavy smokers, adjusted mean values of FEV1 (lowest to highest DHA quartile) were 2,706, 2,785, 2,801, and 2,854 ml. DHA may have a role in preventing or treating COPD and other chronic inflammatory conditions of the lung. Pilot testing of that hypothesis in experimental models seems warranted.