Cortical Bone Porosity in Rabbit Models of Osteoporosis

Cortical bone porosity is intimately linked with remodeling, is of growing clinical interest, and is increasingly accessible by imaging. Thus, the potential of animal models of osteoporosis (OP) to provide a platform for studying how porosity develops and responds to interventions is tremendous. To date, rabbit models of OP have largely focused on trabecular microarchitecture or bone density; some such as ovariectomy (OVX) have uncertain efficacy and cortical porosity has not been extensively reported. Our primary objective was to characterize tibial cortical porosity in rabbit-based models of OP, including OVX, glucocorticoids (GC), and OVX + GC relative to controls (SHAM). We sought to: (i) test the hypothesis that intracortical remodeling is elevated in these models; (ii) contrast cortical remodeling and porosity in these models with that induced by parathyroid hormone (1–34; PTH); and (iii) contrast trabecular morphology in the proximal tibia across all groups. Evidence that an increase in cortical porosity occurred in all groups was observed, although this was the least robust for GC. Histomorphometric measures supported the hypothesis that remodeling rate was elevated in all groups and also revealed evidence of uncoupling of bone resorption and formation in the GC and OVX + GC groups. For trabecular bone, a pattern of loss was observed for OVX, GC, and OVX + GC groups, whereas the opposite was observed for PTH. Change in trabecular number best explained these patterns. Taken together, the findings indicated rabbit models provide a viable and varied platform for the study of OP and associated changes in cortical remodeling and porosity. Intriguingly, the evidence revealed differing effects on the cortical and trabecular envelopes for the PTH model. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..     

Relation of salivary cotinine to blood pressure in middle-aged cigarette smokers

BACKGROUND: In laboratory research, nicotine administration is associated with increases in blood pressure. In epidemiologic research, however, the amount of reported cigarette smoking has no consistent relation with blood pressure. The objective of this study was to examine the relation of a nicotine metabolite (salivary cotinine) to systolic and diastolic blood pressure in current smokers being screened for entry to a clinical trial. METHODS AND RESULTS: Data were obtained from 5164 middle-aged cigarette smokers during screening for the Lung Health Study. Multiple linear regression was used to examine the association of salivary cotinine and number of cigarettes smoked per day to systolic and diastolic blood pressure with age, body mass, years of education, alcohol intake, and recent caffeinated beverage use controlled in all analyses. Although smoking frequency was unrelated to blood pressure, salivary cotinine was related to greater systolic blood pressure in both men and women and greater diastolic blood pressure in men. CONCLUSIONS: The association between salivary cotinine and blood pressure in these analyses suggests that long-term nicotine exposure may be related to modest elevations in blood pressure in cigarette smokers.     

Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.     

PRIME: impact of previous mental health problems on health-related quality of life in women with childbirth trauma

We investigated the impact of pre-existing mental ill health on postpartum maternal outcomes. Women reporting childbirth trauma received counselling (Promoting Resilience in Mothers' Emotions; n?=?137) or parenting support (n?=?125) at birth and 6 weeks. The EuroQol Five dimensional (EQ-5D)-measured health-related quality of life at 6 weeks, 6 and 12 months. At 12 months, EQ-5D was better for women without mental health problems receiving PRIME (mean difference (MD) 0.06; 95 % confidence interval (CI) 0.02 to 0.10) or parenting support (MD 0.08; 95 % CI 0.01 to 0.14). Pre-existing mental health conditions influence quality of life in women with childbirth trauma.     

Extracorporeal membrane oxygenation in pregnancy

We describe the use of extracorporeal membrane oxygenation in pregnancy. There were no major complications, and the outcome was successful for mother and baby.