TASK DEFINITION: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: To examine the effect of a single spinal manipulation therapy (SMT) on the in vitro production of inflammatory cytokines, tumor necrosis factor alpha, and interleukin (IL) 1beta, in relation to the systemic (in vivo) levels of neurotransmitter substance P (SP).', 'Sixty-four asymptomatic subjects were assigned to SMT, sham manipulation, or venipuncture control group. SMT subjects received a single adjustment in the thoracic spine. Blood and serum samples were obtained from subjects before and then at 20 minutes and 2 hours after intervention. Whole-blood cultures were activated with lipopolysaccharide (LPS) for 24 hours. Cytokine production in culture supernatants and serum SP levels were assessed by specific immunoassays.', 'Over the study period, a significant proportion (P </= .05) of sham and control subjects demonstrated progressive increases in the synthesis of tumor necrosis factor alpha and IL-1beta. Conversely, in a comparable proportion of cultures from SMT-derived subjects, the production of both cytokines decreased gradually. Normalization of the observed alterations to reflect the changes relative to self-baselines demonstrated that, within 2 hours after intervention, the production of both cytokines increased significantly (P < .001 to .05) in both controls. In contrast, a significant (P < .001 to .05) reduction of proinflammatory cytokine secretion was observed in cultures from SMT-receiving subjects. In all study groups, serum levels of SP remained unaltered within 2 hours after intervention.

SOLUTION: Does spinal manipulative therapy reduce inflammatory cytokines but not substance P production in normal subjects?

PROBLEM: Evaluation of right ventricular (RV) function in patients with pulmonary regurgitation (PR) after tetralogy repair remains challenging because of abnormal RV loading conditions.', 'We examined 124 patients, aged 21+/-11.4 years, who had tetralogy repair at 3.7+/-3.5 years. By Doppler echocardiography, 33 patients had mild, 22 moderate, and 69 severe PR; 55 had significant tricuspid regurgitation (TR). Myocardial velocities, myocardial acceleration during isovolumic contraction (IVA), strain, and strain rate were measured at RV and LV base. Tricuspid valve annulus was measured in a 4-chamber view. QRS, QT, and JT intervals and their dispersions were measured from 12-lead electrocardiogram. IVA in the RV was lower in all patients compared with controls (0.8+/-0.4 versus 1.8+/-0.5, P<0.0001) and correlated with the severity of PR (r=-0.43, P<0.0001), whereas myocardial velocities, and strain/strain rate did not. LV IVA correlated with PR (r=-0.32, P<0.001) and with RV IVA (r=0.28, P<0.003). Patients with severe PR had a higher incidence of TR (r=0.69, P<0.0001) and lower RV IVA (1.0+/-0.4 versus 0.6+/-0.3, P<0.0001), a larger tricuspid valve ring diameter (P<0.0001), and prolonged electrical depolarization (P<0.001). Age at surgery or examination did not correlate with PR and with RV function assessed by IVA. In the RV, IVA correlated inversely with QRS duration (P<0.01).

SOLUTION: Is pulmonary regurgitation an important determinant of right ventricular contractile dysfunction in patients with surgically repaired tetralogy of Fallot?

PROBLEM: To examine the effect of glyceryl trinitrate (GTN), a nitric oxide (NO) donor compound, on the concurrent progression of cartilage and subchondral bone changes in an ovine meniscectomy model of osteoarthritis (OA).', 'Bilateral lateral meniscectomy (MX) was performed on 12 ewes to induce OA. Six were treated with topical GTN (0.7mg/kg twice weekly) (MX+GTN). Six other sheep formed non-operated controls (NOC). After sacrifice at six months, the subchondral bone density (BMD) of the lateral and medial femoral condyles (LFC, MFC) and tibial plateau (LTP, MTP) was assessed by DEXA. Dynamic biomechanical testing was performed across the MTP and LTP. Histological sections from each region were scored qualitatively and the thickness of the subchondral bone plate (SCB) was determined by image analysis.', 'MX+GTN displayed significantly greater SCB thickness relative to MX in the LFC (mean increase +88% and +42%, respectively) and the MFC. SCB BMD was 10-12% greater in MX+GTN relative to MX in the LFC, LTP and MTP. MX+GTN sheep also showed greater increases in some histopathology variables, greater central erosion of the LTP, and changes in dynamic stiffness (decreased) and phase lag (increased) in the outer zone of the LTP.

SOLUTION:
Does the nitric oxide donor glyceryl trinitrate increase subchondral bone sclerosis and cartilage degeneration following ovine meniscectomy?