Adiponectin Is a Candidate Biomarker of Lower Extremity Bone Density in Men With Chronic Spinal Cord Injury

Adipose tissue is a major regulator of bone metabolism and in the general population obesity is associated with greater bone mineral density (BMD). However, bone‐fat interactions are multifactorial, and may involve pathways that influence both bone formation and resorption with competing effects on the skeleton. One such pathway involves adipocyte production of adipokines that regulate bone metabolism. In this study we determined the association between BMD, walking status, and circulating adipokines (adiponectin and leptin) in 149 men with chronic spinal cord injury (SCI). Although adipokine levels did not vary significantly based on walking status, there was a significant inverse association between adiponectin and BMD in wheelchair users independent of body composition. We found no association between adiponectin and BMD in the walkers and no association between leptin and BMD in either group. These findings suggest that for subjects with chronic SCI, walking may mitigate the effect of adiponectin mediated bone loss. For wheelchair users, adipose‐derived adiponectin may contribute to SCI‐induced osteoporosis because the osteoprotective benefits of obesity appear to require mechanical loading during ambulation. © 2014 American Society for Bone and Mineral Research.     

Evaluation in monkey of two candidate PET radioligands, [11C]RX‐1 and [18F]RX‐2, for imaging brain 5‐HT4 receptors

The serotonin subtype‐4 (5‐HT₄) receptor, which is known to be involved physiologically in learning and memory, and pathologically in Alzheimer's disease, anxiety, and other neuropsychiatric disorders—has few radioligands readily available for imaging in vivo. We have previously reported two novel 5‐HT₄ receptor radioligands, namely [methoxy‐¹¹C](1‐butylpiperidin‐4‐yl)methyl 4‐amino‐3‐methoxybenzoate; [¹¹C]RX‐1), and the [¹⁸F]3‐fluoromethoxy analog ([¹⁸F]RX‐2), and in this study we evaluated them by PET in rhesus monkey. Brain scans were performed at baseline, receptor preblock or displacement conditions using SB 207710, a 5‐HT₄ receptor antagonist, on the same day for [¹¹C]RX‐1 and on different days for [¹⁸F]RX‐2. Specific‐to‐nondisplaceable ratio (BP_ND) was measured with the simplified reference tissue model from all baseline scans. To determine specific binding, total distribution volume (V_T) was also measured in some monkeys by radiometabolite‐corrected arterial input function after ex vivo inhibition of esterases from baseline and blocked scans. Both radioligands showed moderate to high peak brain uptake of radioactivity (2–6 SUV). Regional BP_ND values were in the rank order of known 5‐HT₄ receptor distribution with a trend for higher BP_ND values from [¹⁸F]RX‐2. One‐tissue compartmental model provided good fits with well identified V_T values for both radioligands. In the highest 5‐HT₄ receptor density region, striatum, 50–60% of total binding was specific. The V_T in receptor‐poor cerebellum reached stable values by about 60 min for both radioligands indicating little influence of radiometabolites on brain signal. In conclusion, both [¹¹C]RX‐1 and [¹⁸F]RX‐2 showed positive attributes for PET imaging of brain 5‐HT₄ receptors, validating the radioligand design strategy. Synapse 68:613–623, 2014 . © 2014 Wiley Periodicals, Inc.     

Male Breast Cancer: A Population-Based Comparison with Female Breast Cancer in Hong Kong,Southern China: 1997–2006

Background

Male breast cancer (MBC) is uncommon. As a result, there is limited availability of studies and reviews and even fewer reports from Asia. This is the largest population-based study to compare Chinese MBC patients with female patients during a 10-year period in Hong Kong, Southern China.

Methods

A retrospective review of medical records of 132 male and 8,118 female breast cancer patients between year 1997 and 2006 in Hong Kong was performed. Each MBC patient was matched with three female breast cancer patients for further analysis. Different characteristics, overall, breast-cancer specific, and disease-free survivals (DFS) were compared.

Results

Mean age at diagnosis of male and female patients was 64.5 and 52.7 years respectively. Male patients showed lower histological grade, overall stage, smaller tumor size, and more positive sensitivity in hormone receptors. They were more likely to die of causes other than breast cancer. Matched analysis found that the 5-year overall survival (OS), breast-cancer–specific mortality, and DFS for male and female patients were 78.7, 90.5, 90.5, and 77.9, 86.4, and 81.4 % respectively. Male patients had poorer OS at early overall stage but better breast-cancer—specific mortality rates at any age (p < 0.01). Male patients had a significant risk of dying due to any cause in the presence of distant relapse and had less risk of dying when tumor was ER-positive and HER2-positive.

Conclusions

Chinese male breast cancer patients tend to have poorer OS but better breast-cancer—specific survival compared with their female counterparts.     

Discriminant Analysis of the Self-Administered Alcoholism Screening Test

For a sample of 1156 patients (520 alcoholics and 636 nonalcoholics), discriminant function analyses were performed on the total score, a nine-item version, and a two-item version of the Self-Administered Alcoholism Screening Test (SAAST). With sensitivities set at 90 and 95%, specificities for the total score and nine-item versions ranged from 96.4 to 99.4%. Cross-validation of the nine-item version with the "jackknife" procedure resulted in only one additional misclassification of the 1156 subjects. Separate analyses of the male and female samples revealed that more items entered the discriminant function for women than for men and resulted in a higher, although clinically nonsignificant, percentage of correct classification for women. The results strongly support the use of either the total score or the nine-item version of the SAAST in large-scale screening for alcoholism in a medical patient population.     

Results of a phase I/II trial of recombinant human granulocyte- macrophage colony-stimulating factor in very low birthweight neonates: significant induction of circulatory neutrophils, monocytes, platelets, and bone marrow neutrophils

Neonates, especially those of very low birthweight (VLBW), have an increased risk of nosocomial infections secondary to deficiencies in development. We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) production and mRNA expression from stimulated neonatal mononuclear cells are significantly less than that from adult cells. Recombinant murine GM-CSF administration to neonatal rats has resulted in neutrophilia, increased neutrophil production, and increased survival of pups during experimental Staphylococcus aureus sepsis. In the present study, we sought to determine the safety and biologic response of recombinant human (rhu) GM-CSF in VLBW neonates. Twenty VLBW neonates (500 to 1,500 g), aged < 72 hours, were randomized to receive either placebo (n = 5) or rhuGM-CSF at 5.0 micrograms/kg once per day (n = 5), 5.0 micrograms/kg twice per day (n = 5), or 10 micrograms/kg once per day (n = 5) given via 2-hour intravenous infusion for 7 days. Complete blood counts, differential, and platelet counts were obtained, and tibial bone marrow aspirate was performed on day 8. Neutrophil C3bi receptor expression was measured at 0 and 24 hours. GM-CSF levels were measured by a sandwich enzyme-linked immunosorbent assay at 2, 4, 6, 12, and 24 hours after the first dose of rhuGM-CSF. At all doses, rhuGM-CSF was well tolerated, and there was no evidence of grade III or IV toxicity. Within 48 hours of administration, there was a significant increase in the circulating absolute neutrophil count (ANC) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day, which continued for at least 24 hours after discontinuation of rhuGM-CSF. When the ANC was normalized for each patient's first ANC, there was a significant increase in the ANC on days 6 and 7 at each dose level. By day 7, all tested doses of rhuGM- CSF resulted in an increase in the absolute monocyte count (AMC) compared with placebo-treated neonates. In those receiving rhuGM-CSF 5.0 micrograms/kg twice per day, there was additionally a significant increase in the day 7 and 8 platelet count. Tibial bone marrow aspirates demonstrated a significant increase in the bone marrow neutrophil storage pool (BM NSP) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day. Neutrophil C3bi receptor expression was significantly increased 24 hours after the first dose of rhuGM-CSF at 5.0 micrograms/kg once per day. The elimination half-life (T1/2) of rhuGM-CSF was 1.4 +/- 0.8 to 3.9 +/- 2.8 hours.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pelvic ring fractures: has mortality improved following the implementation of damage control resuscitation?

Background

Over the last 10 years, the paradigm of damage control resuscitation (DCR) has been associated with improved patient outcomes. This study investigates the outcomes of both closed and open pelvic ring fractures at a single institution before and after the formal implementation of DCR principles.

Methods

A retrospective chart review was performed in an urban level I trauma center of all patients who sustained open or closed pelvic ring fractures between 2002 and 2012.

Results

Two thousand two hundred forty-seven patients presented with pelvic fractures between 2002 and 2012. Overall mortality was 10% (n = 212). Only 8% of all patients with closed fractures required DCR compared with 28% of patients with open fractures. There was no difference in mortality when comparing DCR and pre-DCR cohorts for either open or closed pelvic fractures.

Conclusions

Interestingly, although DCR seems to lead to more efficient initial resuscitations, further improvements in patient mortality were not realized with formal implementation of DCR principles.     

Muscular adaptations and insulin‐like growth factor‐1 responses to resistance training are stretch‐mediated

Introduction: Modulation of muscle characteristics was attempted through altering muscle stretch during resistance training. We hypothesized that stretch would enhance muscle responses. Methods: Participants trained for 8 weeks, loading the quadriceps in a shortened (SL, 0–50° knee flexion; n = 10) or lengthened (LL, 40–90°; n = 11) position, followed by 4 weeks of detraining. Controls (CON; n = 10) were untrained. Quadriceps strength, vastus lateralis architecture, anatomical cross‐sectional area (aCSA), and serum insulin‐like growth factor‐1 (IGF‐1) were measured at weeks 0, 8, 10, and 12. Results: Increases in fascicle length (29 ± 4% vs. 14 ± 4%), distal aCSA (53 ± 12% vs. 18 ± 8%), strength (26 ± 6% vs. 7 ± 3%), and IGF‐1 (31 ± 6% vs. 7 ± 6%) were greater in LL compared with SL muscles (P < 0.05). No changes occurred in CON. Detraining decrements in strength and aCSA were greater in SL than LL muscles (P < 0.05). Conclusions: Enhanced muscle in vivo (and somewhat IGF‐1) adaptations to resistance training are concurrent with muscle stretch, which warrants its inclusion within training. Muscle Nerve 49 : 108–119, 2014