Reversal of severe osteoporosis with vitamin B12 and etidronate therapy in a patient with pernicious anemia

Pernicious anemia has recently been recognized as a risk factor for osteoporosis and fructures. Although vitamin B12 is important for osteoblast function, the effect of vitamin B12 replacement in states of vitamin B12 deficiency on bone density and fracture incidence is not known. We report 2-year follow-up data from a patient with severe osteoporosis, multiple vertebral compression fractures, and pernicious anemia who exhibited a dramatic response to treatment with vitamin B12 and cyclic etidronate. Serial bone density measurements demonstrated a 15% and 17% increase in the lumbar and greater trochanter regions, respectively, and a 79% increase in the femoral neck region over the 2-year follow-up period. In addition to normalization of bone density compared with age-matched controls, no subsequent vertebral fractures were noted in the 2-year period following initiation of vitamin B12 and etidronate therapy. This case demonstrates that osteoporosis associated with pernicious anemia may be markedly improved by vitamin B12 replacement and cyclic etidronate therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31684/1/0000620.pd

Developments at the Advanced Design Technologies Testbed

A report presents background and historical information, as of August 1998, on the Advanced Design Technologies Testbed (ADTT) at Ames Research Center. The ADTT is characterized as an activity initiated to facilitate improvements in aerospace design processes; provide a proving ground for product-development methods and computational software and hardware; develop bridging methods, software, and hardware that can facilitate integrated solutions to design problems; and disseminate lessons learned to the aerospace and information technology communities

A Graduate Student Mentoring Program to Develop Interest in Research

Objective. To assess the impact of a graduate student mentoring program on student interest in research and postgraduate education and on graduate student confidence in mentoring. Methods. Undergraduate and pharmacy students (mentees) and graduate students (mentors) were matched and participated in the study, which required them to engage in at least 2 discussions regarding research and careers. Mentees completed a pre- and post-assessment of their perceptions of research, postgraduate training plans, and perceptions about mentors. Mentors completed a pre- and post-assessment of their perceptions about themselves as mentors and their confidence in mentoring. Results. Although there were no significant differences among the mentees’ perceptions of research or the mentors’ confidence in mentoring, qualitative analysis indicated that the mentees’ perceptions of research improved and that the mentors believed their mentoring skills improved. Conclusions. Based on the results of the qualitative analysis, implementing a graduate student mentoring program may help improve students’ perceptions of research and graduate students’ confidence in mentoring, which could increase student interest in postgraduate education and prepare mentors for future leadership roles

IL-17A produced by αβ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction.

Emerging evidence suggests that the T helper 17 (T(H)17) subset of αβ T cells contributes to the development of allergic asthma. In this study, we found that mice lacking the αvβ8 integrin on dendritic cells did not generate T(H)17 cells in the lung and were protected from airway hyper-responsiveness in response to house dust mite and ovalbumin sensitization and challenge. Because loss of T(H)17 cells inhibited airway narrowing without any obvious effects on airway inflammation or epithelial morphology, we examined the direct effects of T(H)17 cytokines on mouse and human airway smooth muscle function. Interleukin-17A (IL-17A), but not IL-17F or IL-22, enhanced contractile force generation of airway smooth muscle through an IL-17 receptor A (IL-17RA)-IL-17RC, nuclear factor κ light-chain enhancer of activated B cells (NF-κB)-ras homolog gene family, member A (RhoA)-Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling cascade. Mice lacking integrin αvβ8 on dendritic cells showed impaired activation of this pathway after ovalbumin sensitization and challenge, and the diminished contraction of the tracheal rings in these mice was reversed by IL-17A. These data indicate that the IL-17A produced by T(H)17 cells contributes to allergen-induced airway hyper-responsiveness through direct effects on airway smooth muscle

Indications and Relative Utility of Lower Endoscopy in the Management of Clostridium difficile Infection

Background. Diagnosis and management of Clostridium difficile infection (CDI) rely upon clinical assessments and diagnostic studies. Among diagnostic tests, lower gastrointestinal (GI) endoscopy in the setting of CDI remains controversial. Objective. To describe the role of lower endoscopy in CDI management. Methods. Retrospective study of lower endoscopies in CDI at four metropolitan hospitals, July 2005 through December 2007. Results. Of 1760 CDI inpatients, 45 lower endoscopies were performed on 43 patients. Most common indications were ruling out other etiologies (42%), inconclusive stool studies (36%), and worsening course (11%). Most endoscopies (73%) had positive findings, including pseudomembranous colitis (49%) and nonspecific colitis (24%). Biopsies were performed in 31 cases, more with nonspecific colitis (10/11, 92%) compared to pseudomembranous colitis (14/22, 64%). Conclusion. While not recommended as a primary screening tool, lower GI endoscopy can add valuable information in CDI when other colonic pathologies may exist, studies are inconclusive, or clinical status worsens

The Iowa Homemaker vol.10, no.2

Coeds of the Naughty Ninties by Mary Morrison Beyer, page 1 Color in the Garden by Edna Rhoades, page 2 The Tragedy of Errors by Marjorie W. Smith, page 3 Where Toothbrushes Grow on Trees by Nellie Goethe, page 3 Architectural Features in Small Gardens by Margaret Jane Walker, page 4 Y. W. C. A.’s Fortieth Birthday by Ila Woodburn, page 5 4-H Club by Helen Melton, page 6 State Association by Marcia E. Turner, page 8 Child Health May Day by Anafred Stephenson, page 10 Editorial, page 11 Alumnae News by Dorothy B. Anderson, page 12 Tid Bits for Home Economics by Edith Roberts and Nellie Goethe, page 1

The Iowa Homemaker vol.10, no.4

Help Fight Goiter With Seaweed by Sarah Field, page 1 Let’s Talk Collegiate Styles by Jerry Martin, page 2 The Friendly House with White Pillars by Ila Woodburn, page 2 “Chicago – Hog Butcher” by Mary Morrison Beyer, page 3 Is Your Room an Adventure? by Margaret McDonough, page 3 Manicure That Precious Antique by Nora Workman, page 4 “Prep Dorm” Has Vivid History by Madge McGlade, page 4 4-H Club by Helen Melton, page 6 I Want to Be Beautiful! by A. Co-ed, page 6 State Association by Marcia E. Turner, page 8 Why Buy Baker’s Cakes? by Nellie Goethe, page 9 Editorial, page 11 Alumnae News by Dorothy B. Anderson, page 12 Who Wants a Hole-in-the-Wall? By Edith Graham et al, page 1

FACTS-international year 2

Summary Objectives:  To compare alendronate 70 mg once weekly (OW) with risedronate 35 mg OW with respect to change in bone mineral density (BMD), biochemical markers and upper gastrointestinal (UGI) tolerability over 24 months. Methods:  This was a 12-month extension to the Fosamax® Actonel® Comparison Trial international study (FACTS). Postmenopausal women with osteoporosis randomly assigned to either alendronate 70 mg OW or risedronate 35 mg OW for the 12-month base study continued taking the same double-blind study medication. Efficacy measurements were BMD at the hip trochanter, lumbar spine, total hip, and femoral neck and levels of four bone turnover markers at 24 months. The primary hypothesis was that alendronate would produce a greater mean per cent increase from baseline in hip trochanter BMD at 24 months. Results:  Trochanter BMD increased significantly from baseline to month 24 in both groups, with a significantly larger increase with alendronate: adjusted mean treatment difference of 1.50% (95% confidence interval: 0.74%, 2.26%; p < 0.001). Similar results were seen at all BMD sites. Significant geometric mean per cent decreases (p < 0.001) from baseline were seen for all four bone turnover markers in both groups, with significantly larger decreases (p < 0.001) with alendronate: adjusted mean treatment differences ranged from 8.9% to 25.3%. No significant differences were seen in incidence of UGI or other adverse events. Conclusions:  Alendronate 70 mg OW yielded significantly greater BMD gains and larger decreases in bone turnover marker levels than risedronate 35 mg OW over 24 months, with no difference in UGI tolerability

Transforming growth factor-[beta]1 regulates steady-state PTH/PTHrP receptor mRNA levels and PTHrP binding in ROS 17/2.8 osteosarcoma cells

The effect of transforming growth factor [beta]1 (TGF-[beta]1) on the expression of mRNA for the parathyroid hormone receptor and binding of iodinated parathyroid hormone-related protein in ROS 17/2.8 osteosarcoma cells was evaluated. TGF-[beta]1 stimulated a 2-7-fold increase in steady state mRNA levels for the parathyroid hormone receptor at a maximal dose of 5 ng/ml, with increased levels of expression at 6 h of TGF-[beta]1-incubation, and peak levels at 8-24 h. Receptor binding studies revealed a significant increase in PTHrP-specific binding with TGF-[beta]1 doses as low as 0.5 ng/ml and a 55% increase in numbers of receptors with no alteration in binding affinity with 5.0 ng/ml TGF-[beta]1. Time course studies indicated that receptor binding was increased at 24 h with peak levels reached at 48 h of treatment. PTH-stimulated cAMP levels were significantly increased in ROS 17/2.8 cells treated with TGF-[beta]1 (0.5 ng/ml) for 48 h. These data indicate that TGF-[beta]1 upregulates steady-state mRNA, ligand binding and PTH/PTHrP receptor signaling in rat osteosarcoma cells. The effects of TGF-[beta]1 on bone may be attributed in part to regulation of the PTH/PTHrP receptor at the molecular level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31617/1/0000549.pd

Tai Chi for osteopenic women: design and rationale of a pragmatic randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Post-menopausal osteopenic women are at increased risk for skeletal fractures. Current osteopenia treatment guidelines include exercise, however, optimal exercise regimens for attenuating bone mineral density (BMD) loss, or for addressing other fracture-related risk factors (e.g. poor balance, decreased muscle strength) are not well-defined. Tai Chi is an increasingly popular weight bearing mind-body exercise that has been reported to positively impact BMD dynamics and improve postural control, however, current evidence is inconclusive. This study will determine the effectiveness of Tai Chi in reducing rates of bone turnover in post-menopausal osteopenic women, compared with standard care, and will preliminarily explore biomechanical processes that might inform how Tai Chi impacts BMD and associated fracture risks.</p> <p>Methods/Design</p> <p>A total of 86 post-menopausal women, aged 45-70y, T-score of the hip and/or spine -1.0 and -2.5, have been recruited from primary care clinics of a large healthcare system based in Boston. They have been randomized to a group-based 9-month Tai Chi program plus standard care or to standard care only. A unique aspect of this trial is its pragmatic design, which allows participants randomized to Tai Chi to choose from a pre-screened list of community-based Tai Chi programs. Interviewers masked to participants' treatment group assess outcomes at baseline and 3 and 9 months after randomization. Primary outcomes are serum markers of bone resorption (C-terminal cross linking telopeptide of type I collagen), bone formation (osteocalcin), and BMD of the lumbar spine and proximal femur (dual-energy X-ray absorptiometry). Secondary outcomes include health-related quality-of-life, exercise behavior, and psychological well-being. In addition, kinetic and kinematic characterization of gait, standing, and rising from a chair are assessed in subset of participants (n = 16) to explore the feasibility of modeling skeletal mechanical loads and postural control as mediators of fracture risk.</p> <p>Discussion</p> <p>Results of this study will provide preliminary evidence regarding the value of Tai Chi as an intervention for decreasing fracture risk in osteopenic women. They will also inform the feasibility, value and potential limitations related to the use of pragmatic designs for the study of Tai Chi and related mind-body exercise. If the results are positive, this will help focus future, more in-depth, research on the most promising potential mechanisms of action identified by this study.</p> <p>Trial registration</p> <p>This trial is registered in Clinical Trials.gov, with the ID number of NCT01039012.</p