Utility of immediate hemoglobin A1c in children with type I diabetes mellitus

Agus MSD, Alexander JL, Wolfsdorf JI. Utility of immediate hemoglobin A1c in children with type I diabetes mellitus. Objective: Immediate feedback (IFB) of hemoglobin A1c (HbA1c) results to adults with type 1 and 2 diabetes allows more appropriate care decisions at the clinic visit and may improve glycemic control. Our objective is to determine whether IFB of HbA1c results to children with type 1 diabetes will improve patient care and glycemic control. Methods: In this prospective randomized controlled trial, children under 18 years of age were randomly assigned to receive HbA1c results during their diabetes clinic visit by point‐of‐care fingerstick testing (immediate) or several days after by venipuncture and laboratory assessment (conventional). HbA1c levels, therapy changes, and painfulness of testing were recorded at baseline and every follow‐up appointment for a year. Results: The 215 patients studied had similar baseline characteristics including initial HbA1c (7.90 ± 1.24% vs. 7.81 ± 1.13%, p = 0.25). IFB improved HbA1c at 3 months (?0.20 ± 0.66%, p = 0.005) with a return to baseline for the remainder of the study. Subjects receiving conventional feedback had increased HbA1c results at 12 months (+0.27 ± 1.05%, p = 0.048). Less frequent patient–clinician communication between visits was reported with IFB (0.29 ± 0.48 vs. 0.38 ± 0.49 contacts/visit, p = 0.043). Subjects rated fingersticks as less painful than conventional venipuncture (0.30 ± 0.66 vs. 3.9 ± 2.6, p < 0.001). Conclusions: IFB of HbA1c is a more acceptable method of HbA1c determination in children with type 1 diabetes mellitus. Although sustained improvements in glycemic control did not result from this intervention alone, IFB testing resulted in more efficient patient–clinician communication and was less painful.     

Intraoperative CT navigation for glenoid component fixation in reverse shoulder arthroplasty

CT navigation has been shown to improve component positioning in total shoulder arthroplasty. The technique can be useful in achieving strong initial fixation of the metal backed glenoid in reverse shoulder arthroplasty. We report a 61 years male patient who underwent reverse shoulder arthroplasty for rotator cuff arthropathy. CT navigation was used intraoperatively to identify best possible glenoid bone and to maximize the depth of the fixation screws that anchor the metaglene portion of the metal backed glenoid component. Satisfactory positioning of screws and component was achieved without any perforation or iatrogenic fracture in the scapula. CT navigation can help in maximizing the purchase of the fixation screws that dictate the initial stability of the glenoid component in reverse shoulder arthroplasty. The technique can be extended to improve glenoid component position [version and tilt] with the availability of appropriate software.     

Production of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor by human mononuclear cells stimulated with granulocyte- macrophage colony-stimulating factor [see comments]

Recent studies have examined the synergistic effects of granulocyte- macrophage colony-stimulating factor (GM-CSF) and hematopoietin-1 (now identified as Interleukin-1, IL-1) on bone marrow colony formation. In the present report, human peripheral blood mononuclear cells (MNCs) were stimulated in vitro with recombinant human GM-CSF (rGM-CSF) and production of IL-1 alpha, IL-1 beta, and tumor necrosis factor (TNF) was measured by specific radioimmunoassays. In the MNCs of 20 individuals, rGM-CSF's ability to induce the three cytokines was variable. Nearly all donors responded to low-dose rGM-CSF (0.02 to 2 ng/mL) with production of TNF, whereas some individuals did not produce IL-1 alpha or IL-1 beta. The MNCs from some subjects stimulated with high-dose rGM-CSF (10 to 80 ng/mL) produced as much cytokine as in response to 10 ng/mL endotoxin. Localization (ie, extracellular or cell- associated cytokine) was specific for the cytokine rather than the stimulus. Indomethacin increased the amount of cytokine produced in response to rGM-CSF for IL-1 beta and TNF but not for IL-1 alpha. In addition, interferon-gamma (INF-gamma) upregulated the amount of TNF induced by rGM-CSF in all donors examined, with variable effect on IL-1 alpha and IL-1 beta. Suboptimal levels of endotoxin incubated with rGM- CSF did not alter the amount of IL-1 produced as compared with cells stimulated with rGM-CSF alone, whereas TNF production showed either no change or a slight decrease in production. These data suggest that GM- CSF may play an important role in the host defense response by stimulating production of these cytokines.     

Improvement in migraine-specific quality of life in a clinical trial of rizatriptan

A validated migraine-specific questionnaire (24-h Migraine Quality of Life Questionnaire1: 24-h MQoLQ) was used to assess the impact of migraine and migraine therapy on health related quality of life during an acute migraine attack. Male and female migraineurs aged 18-55 years were randomized to placebo ( n = 41), rizatriptan 2.5 mg ( n = 47), 5 mg ( n = 74), or 10 mg ( n = 85) in a triple-blind, placebo-controlled clinical trial. Rizatriptan 5 mg and 10 mg were significantly more efficacious than placebo on pain relief and functional disability. After accounting, for multiple comparisons to placebo, rizatriptan 10 mg showed significantly better responses compared to placebo on three of five domains of 24-h MQoLQ (social functioning, migraine symptoms, and feelings/concerns). The O'Brien's Rank Sum Test statistic showed a statistically significant overall difference on the 24-h MQoLQ between the 10 mg rizatriptan and placebo groups ( p = 0.005) and for the overall close trend ( p 0.001).     

Ineffectiveness of neurokinin-1 antagonist in acute migraine: a crossover study

Lanepitant is a high-affinity selective neurokinin⁻¹ receptor (NK-1) and is effective in the dural inflammation model of acute migraine. Lanepitant 30, 80, and 240 mg given orally was evaluated in a double-blind, placebo-controlled crossover study to determine its effect in reducing migraine pain and severity of associated symptoms. Outpatients treated four migraine headaches of moderate or severe pain intensity with study drug according to a randomization schedule. They recorded their pain intensity and severity of migraine-associated symptoms at 30, 60, 90, and 120 min. Although 53 patients were randomly allocated to a treatment sequence, only 40 patients , completed all treatments. There was no statistically significant difference in improvement in migraine pain at any time for any of the treatments. Additionally, there was no change in severity of migraine associated symptoms associated with lanepitant therapy. No adverse events could be attributed to lanepitant Lanepitant was ineffective orally in treating acute migraine in this trial. This may be due to poor bioavailability during a migraine attack. Alternatively, the neurogenic inflammation hypothesis may not apply to migraine.     

Echography of the Cervix and Uterus during the Proliferative and Secretory Phases of the Menstrual Cycle in Bonnet Monkeys (Macaca radiata)

We undertook the present study to investigate the echographic characteristics of the uterus and cervix of female bonnet monkeys (Macaca radiata) during the proliferative and secretory phases of the menstrual cycle. The cervix was tortuous in shape and measured 2.74 ± 0.30 cm (mean ± SD) in width by 3.10 ± 0.32 cm in length. The cervical lumen contained 2 or 3 colliculi, which projected from the cervical canal. The echogenicity of cervix varied during proliferative and secretory phases. The uterus was pyriform in shape (2.46 ± 0.28 cm × 1.45 ± 0.19 cm) and consisted of serosa, myometrium, and endometrium. The endometrium generated a triple-line pattern; the outer and central lines were hyperechogenic, whereas the inner line was hypoechogenic. The endometrium was significantly thicker during the secretory phase (0.69 ± 0.12 cm) than during the proliferative phase (0.43 ± 0.15 cm). Knowledge of the echogenic changes in the female reproductive organs of bonnet monkeys during a regular menstrual cycle may facilitate understanding of other physiologic and pathophysiologic changes.Ultrasound imaging is a noninvasive, atraumatic, and simple method to assess various organs in humans and nonhuman primates.¹¹ Ultrasonography has been used to detect fetal growth, endometrial thickness, and endometriosis in rhesus macaques (Macaca mulatta),^17,20,26 and color Doppler ultrasonography has used for characterizing uteroplacental hemodynamics and assessing fetal and placental blood flow in that species.^22,29 In cynomolgus macaques (Macaca fascicularis), ultrasound techniques have been applied in transfundal uterine sperm recovery, follicular fluid aspiration, assessment of endometrial changes during the menstrual cycle, evaluation of folliculogenesis, and ovulation induction studies.^5,33-35 Other primates species wherein ultrasound techniques have been used are vervet monkeys (Cercopithecus aethiops),³¹ owl monkeys (Aotus nancymaae),³⁰ and common marmosets (Callithrix jacchus).^9,12Bonnet macaques (Macaca radiata) have been used as an animal model for research on contraceptive agents,^6,23,24 endometrial biology,^18,27,28 and assisted reproductive technologies.¹⁰ Although bonnet macaques bear close similarity with rhesus macaques, ultrasound profile of cervix and uterus in these species has not yet been characterized. We undertook the present study to evaluate the echographic profile of the cervix and uterus in regularly cycling bonnet macaques in the proliferative (days 6 through 13 after overt bleeding) and secretory phases (days 16 through 21) of menstrual cycle. Knowledge of the normal ultrasonographic profiles of the female reproductive organs may facilitate the identification of pathophysiological changes during natural or stimulated cycles in bonnet monkeys.     

Down-regulation of cell-surface CD4 co-receptor expression and modulation of experimental allergic encephalomyelitis

Pre-immunization with autoantigens confers resistance in experimental models of autoimmune diseases. Since non-self molecules can also be protective, it is conceivable that part of the effect rests on a non- specific attenuation of the immune response. This study is aimed at identifying mechanisms by which pre-immunization with a moiety suspended in incomplete Freund's adjuvant (IFA) protects from experimental allergic encephalomyelitis (EAE). Lewis rats were immunized with each of either concanavalin A, lipopolysaccharide, bovine serum albumin, 70 or 65 kDa heat shock proteins, or myelin basic protein. All moieties were given in IFA 3 weeks prior to EAE induction. Serial cytofluorimetric monitoring of B cells and of the alpha beta TCR+, CD4+, CD8+, CD45high and CD45low cells was performed. IFN-gamma and IgG1 production was evaluated in parallel. All moieties were able to attenuate or abrogate the clinical signs of EAE. At day 4 and 10 after EAE induction, the surface expression of the CD4 molecule was down-regulated on T lymphocytes. This down-regulation was most evident in animals with the highest degree of clinical protection. By day 21 post-immunization, CD4 expression was restored. The same animals also showed an increase in the B cell percentage and Th2-related IgG1 production while IFN-gamma secretion was reduced. Pre-immunization with diverse antigens suspended in IFA confers resistance to EAE induction. The down-regulation of the CD4 co-receptor accompanied by events suggestive of an immune deviation may be a general mechanism that contributes to the protection.