Effect of blockade of TNF-alpha and interleukin-1 action on bone resorption in early postmenopausal women.

After acute estrogen withdrawal in postmenopausal women, administration of anakinra or etanercept, specific blockers of IL-1 and TNF-alpha, respectively, reduced the rise in bone resorption markers to about one half of that in controls. This is consistent with an important role for these immune cytokines in mediating the effect of estrogen deficiency on bone. INTRODUCTION: Studies in rodents have implicated increased production of interleukin (IL)-1 beta and TNF-alpha as mediators of bone loss after ovariectomy, but their roles are unclear in humans whose immune system differs markedly from that of rodents. MATERIALS AND METHODS: We administered transdermal estradiol, 0.1 mg/d, for 60 days to 42 early postmenopausal women. Estrogen treatment was discontinued, and subjects were randomly assigned to intervention groups receiving 3 wk of injections with 0.9% saline, anakinra 100 mg/d, or etanercept 25 mg/twice weekly. Bone turnover was assessed by measuring serum carboxyl-terminal telopeptide of type 1 collagen (CTX) and amino-terminal telopeptide of type 1 collagen (NTX), markers for bone resorption, and serum amino-terminal propeptide of type 1 collagen (P1NP), a marker for bone formation. Results were expressed as percent change in markers from baseline (last 2 days of estrogen treatment and days 20 and 21 of intervention). RESULTS: The percent changes from baseline during intervention for serum CTX, urine NTX, and serum PINP, respectively, were 43.3 +/- 8.0%, 12.0 +/- 7.1%, and -41.0 +/- 2.5% for the control group; 25.9 +/- 6.3%, 9.5 +/- 4.0%, and -37.8 +/- 3.0% for the anakinra group; and 21.7 +/- 5.0%, 0.32 +/- 3.82%, and -34.5 +/- 3.9% for the etanercept group. Compared with the control group, the blunting of the increase in serum CTX fell just below the level of significance (p=0.10) after anakinra treatment, whereas the blunting of the increase in serum CTX (p=0.034) and in urine NTX (p=0.048) were significant after etanercept treatment. Other changes were not significant. CONCLUSIONS: The data are consistent with a role for TNF-alpha, and possibly for IL-1 beta, in mediating increased bone resorption during estrogen deficiency in women. Although either cytokine blocker reduced serum CTX by about one half, the effect of combined blockade could not be tested because of concerns about toxicity. The data do not exclude direct or indirect contributory roles for RANKL or for other cytokines.     

Late-onset and Recurrent Neonatal Group B Streptococcal Disease Associated with Breast-milk Transmission

The purpose of the study was to determine the epidemiological relationships in three unrelated cases of neonatal late-onset Group B streptococcal (GBS) disease and maternal breast-milk infection with GBS. All deliveries were by cesarean section; case 1 was at term, and cases 2 and 3 were at 32- and 33-wk gestation, respectively. Case 1 relates to a mother with clinical mastitis and recurrent GBS infection in a 20-day-old male infant. Following antibiotic therapy and cessation of breast-feeding, the infant recovered without sequelae. Case 2 refers to a mother with clinical mastitis and the occurrence of late-onset GBS disease in 5-wk-old male twins. Despite intervention, one infant died and the second became ill. Following antibiotic therapy and cessation of breast-feeding, the surviving infant recovered without sequelae. Case 3 refers to a mother with sub-clinical mastitis and late-onset GBS infection occurring in a 6-day-old female twin. Following intervention, the infant recovered but suffered a bilateral thalamic infarction resulting in developmental delay and a severe seizure disorder. Following recovery of GBS from an inapparent mastitis and cessation of breast-feeding, the second infant remained well. Blood cultures from all affected infants and maternal breast milk were positive for GBS. Epidemiological relationships between neonatal- and maternal-derived GBS isolates were confirmed by a random amplified polymorphic DNA polymerase chain reaction assay (RAPD-PCR). This study is significant in that it has demonstrated that maternal milk (in cases of either clinical or sub-clinical mastitis) can be a potential source of infection resulting in either late-onset or recurrent neonatal GBS disease.     

Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment.

In a population-based cross-sectional study, we examined effects of sex and age on bone microstructure at the wrist using high-resolution 3-D pQCT. Compared with women, men had thicker trabeculae in young adulthood and had less microstructural damage with aging. These findings may contribute to the virtual immunity of men to age-related increases in wrist fractures. INTRODUCTION: Although changes in bone microstructure contribute to fracture risk independently of BMD, it has not heretofore been possible to assess this noninvasively in population-based studies. MATERIALS AND METHODS: We used high-resolution 3-D pQCT imaging (voxel size, 89 mum) to define, in a random sample of women (n = 324) and men (n = 278) 21-97 years of age, sex and age effects on bone microstructure at the wrist. RESULTS: Relative to young women (age, 20-29 years), young men had greater trabecular bone volume/tissue volume (BV/TV; by 26%, p = 0.001) and trabecular thickness (TbTh; by 28%, p < 0.001) but similar values for trabecular number (TbN) and trabecular separation (TbSp). Between ages 20 and 90 years, cross-sectional decreases in BV/TV were similar in women (-27%) and in men (-26%), but whereas women had significant decreases in TbN (-13%) and increases in TbSp (+24%), these parameters had little net change over life in men (+7% and -2% for TbN and TbSp, respectively; p < 0.001 versus women). However, TbTh decreased to a greater extent in men (-24%) than in women (-18%; p = 0.010 versus men). CONCLUSIONS: Whereas decreases with age in trabecular BV/TV are similar in men and women, the structural basis for the decrease in trabecular volume is quite different between the sexes. Thus, over life, women undergo loss of trabeculae with an increase in TbSp, whereas men begin young adult life with thicker trabeculae and primarily sustain trabecular thinning with no net change in TbN or TbSp. Because decreases in TbN have been shown to have a much greater impact on bone strength compared with decreases in TbTh, these findings may help explain the lower life-long risk of fractures in men, and specifically, their virtual immunity to age-related increases in distal forearm fractures.     

Pharmacy Fill Patterns in Young Urban Children with Persistent Asthma

Background. Medication adherence impacts healthcare utilization. Pharmacy records are useful to establish fill patterns. Objective. Use pharmacy records to establish medication patterns fill patterns for comparison to healthcare utilization. Methods. Pharmacy records of 175 children with persistent asthma were collected and compared to healthcare utilization. Results. Majority of subjects had significant healthcare utilization, low numbers of rescue medications, and poor controller medication fill rates. Those with more rescue medications had more healthcare utilization and more controller medications. Conclusions. Pharmacy fill patterns demonstrate few rescue and/or controller medication fills. Those with more rescue medications reported increased healthcare utilization despite controller medications.     

Dynamics of saccadic adaptation: differences between athletes and nonathletes.

PURPOSE: The aim of the study was to delineate differences in saccadic adaptation characteristics between a population of racquet sports athletes and nonathletes. METHODS: Eye movements were recorded at 120 Hz using a video-based eye tracker (ELMAR 2020) in a sample of 27 athletes (varsity badminton and squash players) and 14 nonathletes (<3 hours/week participation in recreational sports). Responses to negative positional error and positive positional error were studied in two sessions on separate days. Negative positional errors were induced by displacing the stimuli backwards by 3 degrees from the initial target step (12 degrees). Likewise, positive positional errors were induced by displacing the stimuli forward by 3 degrees . Amplitude gains were calculated for trials before, during, and after the adaptation phase. The magnitude and the rate of change of saccadic adaptation were determined from the amplitude gains. Differences between the groups were compared using regression analysis. RESULTS: No significant differences were found between the two groups in the magnitude of saccadic adaptation, both for negative (athletes -60%, nonathletes -57%) and positive (athletes +26%, and nonathletes +27%) positional error. Racquet sports athletes showed a significantly faster rate of adaptation for the positive positional error. A significant difference was not observed in the rate of adaptation for the negative positional error. CONCLUSIONS: Racquet sports athletes and nonathletes adapt to positional error signals by similar amounts. However, racquet sports athletes respond to positive positional errors at a faster rate, suggesting that a strategic component or environmental influences (such as practice) may play a role in saccadic adaptation.     

Assessing the Stiffness of Spinal Fusion in Animal Models

The clinical goal of spinal fusion is to reduce motion and the associated pain. Therefore, measuring motion under loading is critical. The purpose of this study was to validate four-point bending as a means to mechanically evaluate simulated fusions in dog and rabbit spines. We hypothesized that this method would be more sensitive than manual palpation and would be able to distinguish unilateral vs bilateral fusion. Spines from four mixed breed dogs and four New Zealand white rabbits were used to simulate posterolateral fusion with polymethyl methacrylate as the fusion mass. We performed manual palpation and nondestructive mechanical testing in four-point bending in four planes of motion: flexion, extension, and right and left bending. This testing protocol was used for each specimen in three fusion modes: intact, unilateral, and bilateral fusion. Under manual palpation, all intact spines were rated as not fused, and all unilateral and bilateral simulated fusions were rated as fused. In four-point bending, dog spines were significantly stiffer after unilateral fusion compared with intact in all directions. Additionally, rabbit spines were stiffer in flexion and left bending after unilateral fusion. All specimens exhibited significant differences between intact and bilateral fusion except the rabbit in extension. For unilateral vs bilateral fusion, significant differences were present for right bending in the dog model and for flexion in the rabbit. Unilateral fusion can provide enough stability to constitute a fused grade by manual palpation but may not provide structural stiffness comparable to bilateral fusion.     

Toward a VA women’s health research agenda: Setting evidence-based priorities to improve the health and health care of women veterans

The expansion of women in the military is reshaping the veteran population, with women now constituting the fastest growing segment of eligible VA health care users. In recognition of the changing demographics and special health care needs of women, the VA Office of Research & Development recently sponsored the first national VA Women’s Health Research Agenda-setting conference to map research priorities to the needs of women veterans and position VA as a national leader in Women’s Health Research. This paper summarizes the process and outcomes of this effort, outlining VA’s research priorities for biomedical, clinical, rehabilitation, and health services research.     

Distance-adjusted motor threshold for transcranial magnetic stimulation.

OBJECTIVE: To examine the relationship between coil-cortex distance and effective cortical stimulation using transcranial magnetic stimulation (TMS) in the left and right motor cortex. We also compare the effect of coil-cortex distance using 50 and 70 mm figure-eight stimulating coils. METHODS: Coil-cortex distance was manipulated within each participant using 5 and 10 mm acrylic separators placed between the coil and scalp surface. The effect of cortical stimulation was indexed by resting motor threshold (MT). RESULTS: Increasing distance between the coil and underlying cortex was associated with a steep linear increase in MT. For each additional millimetre separating the stimulating coil from the scalp surface, an additional approximately 2.8% of absolute stimulator output (approximately 0.062 T) was required to reach MT. The gradient of the observed distance effect did not differ between hemispheres, and no differences were observed between the 50 and 70 mm TMS coils. CONCLUSIONS: Coil-cortex distance directly influences the magnitude of cortical stimulation in TMS. The relationship between TMS efficacy and coil-cortex distance is well characterised by a linear function, providing a simple and effective method for scaling stimulator output to a distance adjusted MT. SIGNIFICANCE: MT measured at the scalp-surface is dependent on the underlying scalp-cortex distance, and therefore does not provide an accurate index of cortical excitability. Distance-adjusted MT provides a more accurate index of cortical excitability, and improves the safety and efficacy of MT-calibrated TMS.     

Development of a new Adolescent Patient-Provider Interaction Scale (APPIS) for youth at risk for STDs/HIV

PurposeAlthough an adult model of patient-provider mutual exchange of information has been proposed, there is no guiding model for adolescents or measurement methodology. Our purpose was to develop a new scale of patient-provider interaction for adolescents accessing reproductive health care and at risk for sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV), and assess the reliability and validity of the scale.MethodsThe Adolescent Patient-Provider Interaction Scale (APPIS) was developed from the Roter and Hall theory of doctor-patient relationships, previously validated adolescent satisfaction and communication scales, and focus group and individual elicitation interviews. To assess construct validity, the new nine-item APPIS was compared with the satisfaction scale used by the Young Adult Health Care Survey (YAHCS), and Kahn’s Provider Communication Scale. Pearson correlation coefficients were used to examine convergence across scales, and factor analysis of the APPIS was performed.ResultsThe study recruited 192 African American girls aged 17.9 ± 1.7 years (range 15–21 years) from three sites: a county STD clinic (n = 51), urban adolescent clinic (n = 99), and a family planning clinic (n = 42). Most participants (85%) rated their overall health care highly (≥ 7 on a 10-point scale); 49% felt that both the provider and patient were “in charge” of the visit, and 88% “strongly agreed” or “agreed” that there was an equal “exchange of information” during the visit. The APPIS showed good internal consistency (Cronbach alpha = .75), and moderate convergence with the six-item YAHCS scale (r = .57, p < .001) and seven-item Kahn scale (r = .48, p < .001). Three factors emerged from exploratory factor analyses, supporting our conceptualization of patient-provider interaction as being multi-dimensional.ConclusionsA new theory-based scale of adolescent patient-provider interaction compares favorably with previous scales of health care satisfaction and communication. The new APPIS may be useful for evaluating approaches to improve health care outcomes for adolescents at-risk for STDs and HIV.     

Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.