Publications

OBJECTIVE

To detect matrix metalloproteinase (MMP)-9 in serum and CSF and determine relationships between MMP activity and severity of disease, duration of clinical signs, and duration of hospitalization in dogs with acute intervertebral disk disease (IVDD).

ANIMALS

35 dogs with acute IVDD and 8 clinically normal control dogs.

PROCEDURE

CSF and serum were collected from affected and control dogs. Zymography was used to detect MMP-9.

RESULTS

Activity of MMP-9 in CSF was detected in 6 of 35 dogs with IVDD; activity was significantly more common in dogs with duration of signs < 24 hours. Paraplegic dogs were more likely to have MMP-9 activity in the CSF than non-paraplegic dogs. No significant difference in hospitalization time was detected in dogs with IVDD between those with and without activity of MMP-9 in the CSF. Serum MMP-9 was detected more frequently in dogs with IVDD than in control dogs.

CONCLUSIONS AND CLINICAL RELEVANCE

Data were consistent with results of experimental rodent spinal cord injury studies that indicate that MMP-9 is expressed early during secondary injury.

BACKGROUND

Maintaining independence in daily functioning is an important health outcome in older adults. A key measure of functional independence in elders is the ability to do activities of daily living (ADL) without the assistance of another person. However, few prognostic indices have been developed that stratify elders into groups at variable risk for developing ADL dependence.

OBJECTIVE

We sought to develop and validate a prognostic index that distinguishes between elders at different risk of ADL dependence.

RESEARCH DESIGN, SUBJECTS, AND MEASURES

We studied subjects enrolled in Asset and Health Dynamics Among the Oldest Old (AHEAD), a nationally representative cohort of elders older than the age of 70. We included 5239 subjects (mean age, 77) reporting that they could do each of 5 ADL (bathing, dressing, toileting, transferring, and eating) without the assistance of another person at baseline. Subjects were divided into development (n = 3245) and validation (n = 1994) samples based on region of the United States. Our primary outcome was the need for help (dependence) with at least one ADL at 2 years. We used logistic regression to select among predictor variables encompassing several domains: demographic characteristics, comorbid conditions, functional status, cognitive status, and general health indicators.

RESULTS

The 9 independent predictors of 2-year ADL dependence were age older than 80, diabetes, difficulty walking several blocks, difficulty bathing or dressing, need for help with personal finances, difficulty lifting 10 pounds, inability to name the Vice President, history of falling, and low body mass index. We created a risk score by assigning 1 point to each risk factor. In the development sample, rates of 2-year ADL dependence in subjects with 0, 1, 2, 3, 4, and 5 or more risk factors were 1.3%, 2.8%, 3.8%, 10%, 22%, and 33%, respectively (P < 0.001, roc area = 0.79). In the validation sample, the rates were 0.7%, 4.3%, 8.7%, 11%, 18%, and 40% (P < 0.001, roc area = 0.77). The risk score also discriminated between subjects at variable risk for a combined outcome of either ADL decline or death (4.3%, 7.6%, 15%, 21%, 30%, and 47%).

CONCLUSION

Using data available from patient reports, we validated a simple risk index that distinguished between elders at variable risk of ADL dependence. This index may be useful for identifying elders at high risk of poor outcomes or for risk adjustment.

Single short-term exposures to ozone are known to cause acute changes in pulmonary function and neutrophilic airway inflammation. The respiratory health effects of repeated exposures are not as well studied. Pulmonary function decrements are known to attenuate, but it is less clear how injury and inflammation are affected. Using sputum induction (SI) to sample respiratory tract lining fluid after single- and multiday exposures, we designed a study to test the hypothesis that neutrophils would increase after multiday exposure compared with single-day exposure. In a randomized, crossover design, 15 normal healthy subjects were exposed to O3 (0.2 ppm) under two conditions: for 4 hr for 1 day (1D) and for 4 hr for 4 consecutive days (4D). Pulmonary function testing was performed immediately before and after each 4-hr exposure. The SI was performed 18 hr after the end of the 1D and 4D conditions. The symptom and pulmonary function data followed a pattern seen in other multiday O3 exposure studies, with the greatest changes occurring on the second day. In contrast to previous studies using bronchoalveolar lavage, however, there was a significant increase in the percentage of neutrophils and a significant decrease in the percentage of macrophages after the 4D condition compared with the 1D condition. Given that SI likely samples proximal airways better than distal lung, these results add to the body of evidence that differential airway compartmental responses to O3 occur in humans and other species.

A longstanding hypothesis is that individuals who exhibit large increases in blood pressure during psychological stress are at risk for atherosclerosis. We tested whether blood pressure changes during psychological stress predict subsequent coronary calcification (CaC) in young healthy adults. We evaluated 2816 healthy black and white women, 20 to 35 years of age, from the Coronary Artery Risk Development in Young Adults Study, who were not using medication for hypertension or diabetes in 1987-1988. Participants completed video game and star tracing tasks while their blood pressure was recorded. Thirteen years later (2000-2001), they completed computed tomography measures of CaC. Overall 9.3% (261 of 2816) had CaC present at follow-up. Each 10 mm Hg change in systolic blood pressure during the video game was associated with a 24% increased odds of having CaC at follow-up (unadjusted odds ratio, 1.24; 95% CI, 1.06 to 1.46; P=0.008). This association persisted after adjustment for age, race, sex, education, smoking, alcohol, family history of myocardial infarction, smoking, daily alcohol consumption, body mass index, and resting or baseline blood pressure (odds ratio, 1.31; 95% CI, 1.08 to 1.58; P=0.006). Blood pressure changes during the star tracing task were not associated with subsequent CaC. Blood pressure changes during a video game predicted the presence of CaC 13 years later. To our knowledge, this is the first study that reports blood pressure reactivity to a stressor being related to calcification in the coronary arteries. Blood pressure reactivity may provide useful prognostic information about future risk beyond standard risk factors.

Recently, the field of tissue engineering has progressed rapidly, but poor vascularization remains a major obstacle in bioengineering cell-dense tissues, limiting the viable size of constructs due to hypoxia, nutrient insufficiency, and waste accumulation. Therefore, new technologies for fabricating functional tissues with a well-organized vasculature are required. In the present study, neonatal rat cardiomyocytes were harvested as intact sheets from temperature-responsive culture dishes and stacked into cell-dense myocardial tissues. However, the thickness limit for layered cell sheets in subcutaneous tissue was approximately 80 microm (3 layers). To overcome this limitation, repeated transplantation of triple-layer grafts was performed at 1, 2, or 3 day intervals. The two overlaid grafts completely synchronized and the whole tissues survived without necrosis in the 1 or 2 day interval cases. Multistep transplantation also created approximately 1 mm thick myocardium with a well-organized microvascular network. Furthermore, functional multilayer grafts fabricated over a surgically connectable artery and vein revealed complete graft perfusion via the vessels and ectopic transplantation of the grafts was successfully performed using direct vessel anastomoses. These cultured cell sheet integration methods overcome long-standing barriers to producing thick, vascularized tissues, revealing a possible solution for the clinical repair of various damaged organs, including the impaired myocardium.