Nifedipine and propranolol: A beneficial drug interaction

The antianginal effects of two active drugs, nifedipine and propranolol, alone and in combination, were compared with those of placebo in a double-blind clinical trial that included 16 patients with chronic stable angina triggered by exertion. A low dose and a high dose of the active drugs were used (nifedipine, 30 and 60 mg/day; propranolol, 240 and 280 mg/day). Precordial exercise mapping and continuous electrocardiographic recordings were used to assess objective response to therapy, and the patients were asked to keep a diary of episodes of chest pain and consumption of nitroglycerin tablets for subjective appraisal. Both frequency of chest pain and nitroglycerin consumption were significantly reduced by each of the active drugs when compared with placebo, and the combination of nifedipine and propranolol added significantly to the effectiveness. Reductions in area of ischemia and number of episodes of ST segment depression on 48-hour ambulatory electrocardiographic monitoring corroborated the efficacy of each active treatment with respect to placebo. Nearly 60 percent of all episodes of ST segment depression were painless and responded to the active treatment in the same manner as did the episodes associated with chest pain. Side effects were mild and all treatments were well tolerated. The objective methods used allowed for clear-cut differentiation of treatment effects with the various regimens. Although the two drugs alone were significantly more effective than placebo, their combination provided an even greater improvement (p < 0.005), and therefore it appears to be a safe and effective form of treatment for chronic stable angina.     

All-ceramic inlay-retained fixed dental prostheses for replacing posterior missing teeth: A systematic review

Purpose

To evaluate the current status of all-ceramic inlay-retained fixed dental prostheses (CIR-FDPs) for the replacement of posterior teeth.

How do short-term rates of femorotibial cartilage change compare to long-term changes? Four year follow-up data from the osteoarthritis initiative

OBJECTIVE: To compare unbiased estimates of short- vs long-term cartilage loss in osteoarthritic knees. METHOD: 441 knees [216 Kellgren Lawrence (KL) grade 2, 225 KL grade 3] from participants of the Osteoarthritis Initiative were studied over a 4-year period. Femorotibial cartilage thickness was determined using 3?T double echo steady state magnetic resonance imaging, the readers being blinded to time points. Because common measurement time points bias correlations, short-term change (year-1 to year-2: Y1?→?Y2) was compared with long-term change (baseline to year-4: BL?→?Y4), and initial (BL?→?Y1) with subsequent (Y2?→?Y4) observation periods. RESULTS: The mean femorotibial cartilage thickness change (standardized response mean) was?-1.2%/-0.8% (-0.42/-0.28) over 1 (BL?→?Y1/Y1?→?Y2),?-2.1%/-2.5% (-0.56/-0.55) over 2 (BL?→?Y2/Y2?→?Y4),?-3.3% (-0.63) over 3 (Y1?→?Y4), and?-4.5% (-0.78) over 4 years. Spearman correlations were 0.33 for Y1?→?Y2 vs BL?→?Y4, and 0.17 for BL?→?Y1 vs Y2?→?Y4 change. Percent agreement between knees showing progression during Y1?→?Y2 vs BL?→?Y4 was 59%, and 64% for BL?→?Y1 vs Y2?→?Y4. The area under the receiver operating characteristic curve was 0.66 for using Y1?→?Y2 to predict BL?→?Y4, and 0.59 for using BL?→?Y1 to predict Y2?→?Y4 change. CONCLUSION: Weak to moderate correlations and agreement were observed between individual short- vs long-term cartilage loss, and between initial and subsequent observation periods. Hence, longer observation periods are recommended to achieve robust results on cartilage loss in individual knees. At cohort and subcohort level (e.g., KLG3 vs KLG2 knees), the mean cartilage loss increased almost linearly with the length of the observation period and was constant throughout the study.     

Analysis of Human Biologics With a Mouse Skin Transplant Model in Humanized Mice

Preclinical testing of human therapeutic monoclonal antibodies has been limited in murine models due to species differences in pharmacokinetics and biologic responses. To overcome these constraints we developed a murine skin transplant model in humanized mice and used it to test human monoclonal antibody therapy. Neonatal NOD/SCID/IL2Rγc^null mice (NSG) were reconstituted with human CD34⁺ hematopoietic stem cells (hNSG). When adult, these mice rejected MHC mismatched murine C57BL/6J skin grafts. Rejection required adequate reconstitution with human cells. There was diffuse infiltration of the epidermis and dermis with hCD8 and hCD4 cells in rejected grafts by immunohistochemistry. Studies with B6/MHC class I and II knockout mice donors indicated that neither is required for rejection. Graft rejection was associated with the development of effector and central memory T cells and an increase in serum immunoglobulins. We also tested the effects of teplizumab (anti‐CD3 mAb) and found it could delay skin graft rejection, whereas ipilimumab (anti‐CTLA‐4 [cytotoxic T‐lymphocyte antigen‐4] mAb) treatment accelerated rejection. These findings demonstrate that hNSG mice reliably and predictably reject a xenogenic mouse skin graft by a human T cell mediated mechanism. The model can be utilized to investigate the ability of human immunotherapies to enhance or suppress functional human immune responses.     

Standardization of assay methods reduces variability of total PSA measurements: an Irish study

Study Type – Diagnosis (quality control) Level of Evidence 2b What's known on the subject? and What does the study add? Today, numerous assays for PSA detection are available from various manufacturers. However, these various assays do not detect PSA equally and several studies have demonstrated variability between them. In order to harmonise PSA results and reduce the discrepancies, reference materials are available for assay calibration. We have demonstrated significantly variability between 6 different assay methods currently in use in 9 hospitals despite assay calibration. Variability in PSA values was reduced with the standardisation of the assay method in 4 hospitals. Our results highlight the dilemma of PSA assay variability and stress the need for nationwide standardisation of PSA testing.

OBJECTIVE

• ? To determine whether standardization of total prostate‐specific antigen (tPSA) assay methods reduces variability in tPSA measurements.

PATIENTS AND METHODS

• ? Blood samples from 84 patients attending a single urology department were distributed across nine hospitals selected throughout Ireland for the independent determination of tPSA under the same conditions.
• ? The selected hospitals collectively used six different assay methods for tPSA detection: Beckman Hybritech WHO Calibrated (used as reference method), Tosoh AIA 1800, Roche E170 (used in three hospitals), Abbott AxSYM, Immulite 2500 2nd Generation (used in two hospitals) and Siemens ADVIA Centaur.
• ? The method of tPSA detection was next standardized in a subset of four hospitals using the same assay method and the measurements were repeated.
• ? The difference in mean tPSA in the cohort across the hospitals tested was determined and the Bland–Altman test was used to assess the agreement between each test. Analysis was performed over both the full (0.5–30 µg/L, N= 84) and a narrow (3–7 µg/L, n= 25) tPSA range.

RESULTS

• ? The range and the mean tPSA of the full cohort were inflated across the eight test hospitals, when compared with the reference hospital.
• ? The poorest agreement between assay methods was associated with a bias of 2.2 ± 2.4 µg/L. The variability in tPSA measurements between assay methods was inconsistent across the range of tPSA values tested and increased with increasing mean tPSA.
• ? Agreement in reported tPSA was excellent after standardization of tPSA assay methods (bias <0.2 µg/L).
• ? Over the narrow 3–7 µg/L PSA range, 12/25 (48%) patients had a tPSA range of values across all hospitals in excess of 2 µg/L. Following standardization of the tPSA assay method, patient tPSA ranges were <0.5 µg/L for 13/25 (52%) patients.

CONCLUSIONS

• ? We have shown that the lack of standardization of tPSA assay methods across a panel of Irish hospitals leads to significant variability in the measured tPSA values for the same patient samples.
• ? Variability in tPSA values was reduced with the standardization of the assay method in four hospitals.
• ? Standardization of PSA testing on a nationwide scale is warranted.

     

Short-Term Jump Activity on Bone Metabolism in Female College-Aged Nonathletes

There have been few studies examining the short-term effect of high-impact activities on bone metabolism measured by bone serum marker concentrations. The purpose of this study was to examine the effect of short-term high-impact jump activity on bone turnover in female college-aged non-athletes. Twenty six healthy females were randomly assigned to a control or jump group. The subjects jumped 5 days per week for 2 weeks. The participants completed 10 jumps per session. A general health questionnaire and a bone-specific physical activity assessment instrument (BPAQ) were completed. BPAQ scores were calculated based on the past history of exercise. Blood draws were taken in both groups before and after the two-week experimental period. The vertical ground reaction force (VGRF) of all jumps and jump height were measured for each subject daily and the osteogenic index (OI) was measured. Concentrations of serum osteocalcin (OC), Bone Specific Alkaline Phosphatase (BAP), C-Terminal Telopeptides of Type I Collagen (CTX) and plasma Tartrate-Resistant Acid Phosphatase (TRAP5b) were assessed pre and post jump protocol to measure bone formation and resoprtion respectively. A significant interaction (time x group) was found in TRAP5b, and BAP values (p < 0.05). There was a significant decrease in CTX and BAP values in the jump group (p < 0.05) after the two week jump protocol. No significant interactions or changes were observed in OC values for either the jump or the control group. Two weeks of jump activity consisting of 10 jumps/day for 5 days/week with a weekly osteogenic index of 52.6 significantly decreased markers of bone resorption (TRAP5b and CTX) and bone formation (BAP) in young female non-athletes.

Key points

• Please provide 3-5 bullet points of the study.
• Inductive qualitative methodologies can encourage the much-needed voice of female youth in sport and physical activity research.
• Vignettes serve, not only as a method to illustrate data, but also as a medium to teach contextually relevant information to participants and sport science service providers.
• The barriers and solutions to female youth engagement in physical activity are best understood through the perspectives of the intended participant.
• Female youth can serve as central informants in the development and analysis of research projects relating to female youth physical activity.

Key words: Jump exercise, vertical ground reaction force, bone serum markers, randomized controlled study