Leukocyte-Rich Platelet-Rich Plasma Is Predominantly Anti-inflammatory Compared With Leukocyte-Poor Platelet-Rich Plasma in Patients With Mild-Moderate Knee Osteoarthritis: A Prospective, Descriptive Laboratory Study.

BACKGROUND: Platelet-rich plasma (PRP) has been used extensively in clinical practice to treat patients with symptomatic knee osteoarthritis (OA). Leukocyte-poor PRP (LP-PRP) has been clinically preferred over leukocyte-rich PRP (LR-PRP); however, it is unclear which cytokine mediators of pain and inflammation are present in LR-PRP and LP-PRP from patients with mild to moderate knee OA in order to rationalize a specific formulation. HYPOTHESIS: LP-PRP would be predominantly anti-inflammatory and have reduced nociceptive pain mediators compared with LR-PRP from the same individual with mild to moderate knee OA. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 24 unique samples of PRP were prepared in order to assess 48 samples of LR-PRP and LP-PRP taken from 12 patients (6 male and 6 female) with symptomatic knee OA of Kellgren-Lawrence grade 2 to 3. Patients underwent blood collection for LR-PRP and LP-PRP preparation through a double-spin protocol to obtain baseline whole blood, platelet concentration, and white blood cell subtypes. LR-PRP and LP-PRP from the same patient were produced at the same time and underwent a comprehensive panel through Luminex (multicytokine profiling) to assess key mediators of inflammation: interleukin 1 receptor antagonist (IL-1Ra), interleukin 4, 6, 8, and 10 (IL-4, IL-6, IL-8, and IL-10), IL-1ß, tissue necrosis factor α (TNF-α), and matrix metalloproteinase 9 (MMP-9). To assess mediators of nociceptive pain, nerve growth factor (NGF) and tartrate resistant acid phosphatase 5 (TRAP5) were also assessed. RESULTS: LR-PRP from patients with mild to moderate knee OA expressed significantly more IL-1Ra, IL-4, IL-8, and MMP-9 compared with LP-PRP formulations from the same patients. No significant differences were found between LR-PRP and LP-PRP in mediators of nociceptive pain-namely, NGF and TRAP5. Other mediators including TNF-α, IL-1ß, IL-6, and IL-10 were also found to have no significant expression differences between LR-PRP and LP-PRP. CONCLUSION: LR-PRP expressed significantly more IL-1Ra, IL-4, and IL-8, suggesting that LR-PRP may be more anti-inflammatory than LP-PRP. MMP-9 was expressed in higher concentrations in LR-PRP, suggesting that LR-PRP may be more chondrotoxic than LP-PRP. CLINICAL RELEVANCE: LR-PRP was found to have a robust expression of anti-inflammatory mediators compared with LP-PRP and may be beneficial to patients with long-term knee OA where chronic low-grade inflammation is present. Mechanistic clinical trials are needed to elucidate the key mediators in both LR-PRP and LP-PRP to assess their effect on long-term progression of knee OA.

The Influence of Health Education Teacher Characteristics on Students' Health-Related Knowledge Gains.

BACKGROUND: Studies have examined relationships between teacher characteristics and student achievement in courses such as math and science. This study is among the first to examine effects of teacher characteristics on student knowledge in a health course. METHODS: Student (N = 6143) pretest and posttest data were linked to teacher (N = 67) data. Changes in student knowledge scores from pre- to postcourse were explored using mixed-effects linear models. Teacher characteristics included professional development (PD) attendance, having a dedicated classroom, certification type, educational background, years' experience, and athletic coaching status. RESULTS: Teacher characteristics associated with greater student knowledge gains included: being certified to teach health versus not certified (p < .001), having a dedicated classroom versus no classroom (p = .017), and for middle school teachers, having attended ≥3 PD sessions versus ≤2 (p = .023). Less knowledge gain was associated with teachers that coached versus noncoaches (p = .040) and having a health degree versus no health degree (p = .049). Post hoc analyses revealed the negative effect of health degree was only significant among coaches (p = .026). CONCLUSIONS: Findings suggest opportunities for maximizing student knowledge gains through tailored selection of health teachers and provision of appropriate teaching support.

BMEC-1: a human bone marrow microvascular endothelial cell line with primary cell characteristics.

Bone marrow microvascular endothelial cells (BMEC) are a functional component of the bone marrow stroma and have been shown to release hematopoietic regulatory factors as well as to selectively adhere and support the proliferation and differentiation of CD34+ hematopoietic progenitors. An early passage of these cells was immortalized by transfection with a vector (pSVT) encoding the large T antigen of SV40. The transformed cell line (CDC/CU.BMEC-1) expresses the SV40 transcript, retains the primary cell expression of Ulex europeaus and vWF/ FVIII, and incorporates acetylated low-density lipoprotein. In addition, BMEC-1 mirrors the phenotype of the primary cells with only a few exceptions. Both cell populations express the cellular adhesion molecules ICAM-1 and PECAM and also VCAM-1 and ELAM-1 after upregulation by tumor necrosis factor-alpha. The fibronectin receptor, hyaluronate receptor, collagen receptor, integrins VLA-alpha 3, VLA-alpha 4, and beta 4, endoglin, collagen IV, CD58, and CD61 are also expressed. The only differences are that BMEC-1 expresses higher levels of ICAM-1, CD58, CD34, CD36, and c-kit than the primary cells. The supernatants of primary cell and BMEC-1 contain stem cell factor, interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 alpha, IL-11, and G-CSF. The functional significance of these hematopoietic cytokines was demonstrated in transwell cultures. Both cell populations supported the expansion of progeny from CD34+ cell-enriched cord blood mononuclear cells suspended in the upper chamber. These characteristics, plus the fact that BMEC-1 can be maintained independently of exogenous growth factors and exhibit contact inhibition, indicate that this cell line can be used to further define the role of BMEC in hematopoiesis.

Selective inhibition of adhesion molecule expression by edelfosine (ET-18-OCH3) on human umbilical vein or microvascular endothelium.

An abundance of data is accumulating that suggest that if one can block endothelial cell-leukocyte binding or inhibit cell adhesion molecules (CAM), inflammatory events can be greatly diminished. In this report, we demonstrate that an alkyl-lysophospho-lipid compound (ET-18-OCH3) can decrease adhesion molecule expression on cultured human micro- and macrovascular endothelial cell lines. ET-18 selectively decreased CAM expression; CD31 was decreased, however. Vascular CAM-1 tumor necrosis factor-alpha-induced expression was not altered. Intercellular adhesion molecule 1 expression was decreased, but endoglin expression was not affected. Thus, we have demonstrated nontoxic downmodulation of vascular CAM expression in vitro. Whether this compound will have anti-inflammatory properties needs to be clarified in animal models.

Panendoscopy in screening for synchronous primary malignancies.

The entire upper aerodigestive tract must be evaluated at the time of initial tumor evaluation in patients with squamous cell carcinoma of the head and neck. The necessity of panendoscopy (laryngoscopy, bronchoscopy, esophagoscopy) in this evaluation has not been demonstrated convincingly. Between January 1, 1984 and December 31, 1985, 208 patients with previously untreated squamous cell carcinoma of the head and neck were analyzed prospectively. These patients underwent head and neck examination, chest radiograph, barium esophagram, and panendoscopy. Fifteen (7.2%) had synchronous malignancies of the upper aerodigestive tract. In four patients (1.9%) the synchronous primary tumor was found only by endoscopy. Three patients (1.4%) had cancers of the hypopharynx. One patient (0.5%) had a bronchial cancer detected only on bronchoscopy. No tumors were detected by esophagoscopy that were not also seen on barium esophagram. We conclude that endoscopic examination of the hypopharynx is very helpful in screening for additional tumors in head and neck cancer patients, but routine esophagoscopy cannot be supported. Screening bronchoscopy cannot be strongly supported due to its very low yield.