A randomized controlled trial of oropharyngeal therapy with mother's own milk for premature infants.

OBJECTIVE: To determine if oropharyngeal therapy with mother's own milk (OPT-MOM) reduces late-onset sepsis (L-OS; primary outcome), NEC, death, length of stay, time to full enteral nutrition (FEN) and full oral feeds in preterm infants (BW < 1250 g). DESIGN: Infants (N = 220) were randomized to Group A (milk) or B (placebo) and received 0.2 mL every 2 h for 48 h, then every 3 h until 32 weeks CGA. RESULTS: There were no significant differences in L-OS, NEC or death. Group A trended towards an 8-day reduction in stay, 8-day reduction in time to FEN and a 6-day reduction in time to full oral feeds, compared to B. While clinically relevant, due to large variability in outcomes and lack of power, p values were > 0.05. CONCLUSION: OPT-MOM did not reduce L-OS, NEC or death. Group A trended towards a reduced stay and better nutritional outcomes, but results were not statistically significant. CLINICALTRIALS: GOV: NCT02116699.

Oropharyngeal administration of mother's colostrum, health outcomes of premature infants: study protocol for a randomized controlled trial.

BACKGROUND: Extremely premature (birth weight < 1250 g) infants are at high risk for acquiring late-onset sepsis and necrotizing enterocolitis, which are associated with significant mortality and morbidity. Own mother's milk contains protective (immune and trophic) biofactors which provide antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory functions, enhance intestinal microbiota, and promote intestinal maturation. Many of these biofactors are most highly concentrated in the milk expressed by mothers of extremely premature infants. However, since extremely premature infants do not receive oral milk feeds until 32 weeks post-conceptional age, they lack the potential benefit provided by milk (biofactor) exposure to oropharyngeal immunocompetent cells, and this deficiency could contribute to late-onset sepsis and necrotizing enterocolitis. Therefore, oropharyngeal administration of own mother's milk may improve the health outcomes of these infants. OBJECTIVES: To compare the effects of oropharyngeal administration of mother's milk to a placebo, for important clinical outcomes, including (1A) reducing the incidence of late-onset sepsis (primary outcome) and (1B) necrotizing enterocolitis and death (secondary outcomes). To identify the biomechanisms responsible for the beneficial effects of oropharyngeal mother's milk for extremely premature infants, including; (2A) enhancement of gastrointestinal (fecal) microbiota (2B) improvement in antioxidant defense maturation or reduction of pro-oxidant status, and (2C) maturation of immunostimulatory effects as measured by changes in urinary lactoferrin. METHODS/DESIGN: A 5-year, multi-center, double-blind, randomized controlled trial designed to evaluate the safety and efficacy of oropharyngeal mother's milk to reduce the incidence of (1A) late-onset sepsis and (1B) necrotizing enterocolitis and death in a large cohort of extremely premature infants (n = 622; total patients enrolled). Enrolled infants are randomly assigned to one of 2 groups: Group A infants receive 0.2 mL of own mother's milk, via oropharyngeal administration, every 2 hours for 48 hours, then every 3 hours until 32 weeks corrected-gestational age. Group B infants receive a placebo (0.2 mL sterile water) following the same protocol. Milk, urine, oral mucosal swab, and stool samples are collected at various time points, before, during and after the treatment periods. Health outcome and safety data are collected throughout the infant's stay. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02116699 on 11 April 2014. Last updated: 26 May 2015.

Oropharyngeal administration of mother's milk to prevent necrotizing enterocolitis in extremely low-birth-weight infants: theoretical perspectives.

The oropharyngeal administration of mother's milk-placing drops of milk onto the infant's oral mucosa-may serve as a preventative strategy against necrotizing enterocolitis (NEC) for extremely low-birth-weight (ELBW: birth weight <1000 g) infants. Necrotizing enterocolitis is a devastating gastrointestinal disorder which is associated with significant mortality for ELBW infants. Survivors are at risk for costly and handicapping morbidities, including severe neurological impairment. The oropharyngeal administration of mother's milk to ELBW infants may serve to expose the infant's oropharynx to protective (immune and trophic) biofactors (also present in amniotic fluid) and may protect the infant against NEC. Emerging evidence suggests that this intervention may have many benefits for extremely premature infants including protection against bacteremia, NEC, and ventilator-associated pneumonia, an earlier attainment of full enteral feeds, enhanced maturation of oral feeding skills, improved growth, and enhanced breast-feeding outcomes. While more research is needed to definitively establish safety and efficacy of this intervention, this article will examine biological plausibility and will describe the theoretical mechanisms of protection against NEC for ELBW infants who receive this intervention. Nurses play a key role in advancing the science and practice of this intervention. Future directions for research and implications for nursing practice will also be presented.

Six to success: improving primary care management of pediatric overweight and obesity.

INTRODUCTION: Despite the existence of established guidelines addressing pediatric obesity, many primary care providers fail to successfully implement recommendations. This study measured the impact of Six to Success, a weight management program based on the Chronic Care Model, on primary care provider adherence to pediatric weight management guidelines. METHOD: We used comprehensive pre- and postimplementation chart audits (N = 396) to conduct a quality improvement study at a hospital-based pediatric outpatient clinic. Charts of patients with a body mass index percentile at or above the 85th percentile (preimplementation, n = 90; postimplementation, n = 97) were audited for 23 identification, assessment, and prevention measures recommended in the care of the pediatric overweight/obese patient. RESULTS: Statistically significant improvements to clinical guideline adherence were found in the following areas: correct diagnosis, physical examination, lifestyle assessment, use of motivational interviewing, and prevention strategies. DISCUSSION: These findings suggest that Six to Success can be an effective method of improving primary care provider adherence to established pediatric weight management guidelines.

Sinus augmentation using rhBMP-2/ACS in a mini-pig model: relative efficacy of autogenous fresh particulate iliac bone grafts.

BACKGROUND: Implant dentistry in the posterior maxilla often requires bone augmentation. The gold standard, autogenous bone graft, requires additional surgery with associated morbidity, while bone biomaterials may not support relevant bone formation. Recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS), however, induces significant, clinically relevant bone formation in several settings including the maxillary sinus floor. OBJECTIVE: The objective of this study was to compare local bone formation and osseointegration following maxillary sinus augmentation using rhBMP-2/ACS or a particulate autogenous cancellous bone graft obtained from the iliac crest in conjunction with immediate placement of dental implants. MATERIALS AND METHODS: Bilateral sinus augmentation using an extraoral approach including rhBMP-2 (0.43 mg/ml)/ACS or the autogenous bone graft, alternated between left and right sinus cavities in five adult male Yucatan mini-pigs, was performed. Two 12-mm dental implants were inserted into the sinus wall protruding approximately 8 mm into the sinus cavity. Surgical sites were closed and sutured in layers; block biopsies collected for histometric analysis at 8 weeks. RESULTS: rhBMP-2/ACS induced bone of significantly greater and consistent quality compared with the iliac crest autogenous bone graft; bone density averaging 51.9 ± 3.0% vs. 32.9 ± 2.5% (P = 0.01). However, there were only numerical differences in augmented bone height (9.3 ± 0.5 vs. 8.6 ± 0.7 mm) and bone-implant contact (37.4 ± 3.0% vs. 30.7 ± 5.9%) between treatments. CONCLUSION: rhBMP-2/ACS induces bone of superior quality compared with an iliac crest particulate autogenous cancellous bone graft when used for maxillary sinus augmentation, and should perhaps be considered the new standard for this indication.

Evaluation of a novel calcium phosphate-coated titanium porous oxide implant surface: a study in rabbits.

PURPOSE: To evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous oxide implant surface. MATERIALS AND METHODS: Twenty adult male New Zealand White rabbits were used. Each animal received two titanium porous oxide-surfaced implants (benchmark control: TiUnite, Nobel Biocare) and two novel CaP-coated titanium porous oxide-surfaces implants; they were randomly allocated to contralateral tibia implant sites. The animals were sacrificed after 2 or 4 weeks, and tissues were evaluated histometrically. RESULTS: Healing was generally uneventful. A removal torque analysis showed significantly higher mean (± SE) peak values for the control implants than for the test implants at 2 weeks (31.4 ± 2.5 Ncm versus 20.4 ± 1.8 Ncm) and 4 weeks (48.4 ± 5.5 Ncm versus 30.3 ± 3.9 Ncm). Light microscopy showed no significant differences in local bone density around control and test implants at 2 and 4 weeks (range, 85% to 91% within the thread area and 91% to 95% immediately outside the threads). At 2 weeks, bone-implant contact for control and test implants averaged 81.8% ± 2.8% and 75.7% ± 4.6%, respectively, and at 4 weeks the bone-implant contact values were 79.4% ± 2.8% and 73.5% ± 4.2%, respectively; these differences were not significant. Backscatter scanning electron microscopy also showed no significant differences in local bone density at control and test implants at 2 and 4 weeks (range, 55% to 72% within the thread area and 75% to 81% immediately outside the threads). At 2 weeks, bone-implant contact for control and test implants averaged 66.4% ± 2.9% and 61.5% ± 5.1%, respectively, and at 4 weeks mean values were 60.1% ± 4.2% and 53.3% ± 4.6% (differences not significant). CONCLUSIONS: The results suggest that the novel CaP-coated surface effectively supports osseointegration.

A pilot study to determine the safety and feasibility of oropharyngeal administration of own mother's colostrum to extremely low-birth-weight infants.

UNLABELLED: Own mother's colostrum is rich in cytokines and other immune agents that may stimulate oropharyngeal-associated lymphoid tissue if administered oropharyngeally to extremely low-birth-weight (ELBW) infants during the first days of life when enteral feeding is contraindicated. However, the safety and feasibility of the oropharyngeal route for the administration of colostrum have not been determined. PURPOSE: To determine the safety of oropharyngeal administration of own mother's colostrum to ELBW infants in first days of life. A secondary purpose was to investigate the feasibility of (1) delivering this intervention to ELBW infants in the first days of life and (2) measuring concentrations of secretory immunoglobulin A and lactoferrin in tracheal aspirate secretions and urine of these infants. SUBJECTS: Five ELBW infants (mean birth weight and gestational age = 657 g and 25.5 weeks, respectively). DESIGN: Quasi-experimental, 1 group, pretest-posttest design. METHODS: Subjects received 0.2 mL of own mother's colostrum administered oropharyngeally every 2 hours for 48 consecutive hours, beginning at 48 hours of life. Concentrations of secretory immunoglobulin A and lactoferrin were measured in tracheal aspirates and urine of each subject at baseline, at the completion of the intervention and again 2 weeks later. RESULTS: All infants completed the entire treatment protocol, each receiving 24 treatments. A total of 15 urine specimens were collected and 14 were sufficient in volume for analysis. A total of 15 tracheal aspirates were collected, but only 7 specimens (47%) were sufficient in volume for analysis. There was wide variation in concentrations of secretory immunoglobulin A and lactoferrin in urine and tracheal aspirates among the 5 infants; however, several results were outside the limits of assay detection. All infants began to suck on the endotracheal tube during the administration of colostrum drops. Oxygen saturation measures remained stable or increased slightly during each of the treatment sessions. There were no episodes of apnea, bradycardia, hypotension, or other adverse effects associated with the administration of colostrum. CONCLUSIONS: Oropharyngeal administration of own mother's colostrum is easy, inexpensive, and well-tolerated by even the smallest and sickest ELBW infants. Future research should continue to examine the optimal procedure for measuring the direct immune effects of this therapy, as well as the clinical outcomes such as infections, particularly ventilator-associated pneumonia.

Evaluation of an injectable rhGDF-5/PLGA construct for minimally invasive periodontal regenerative procedures: a histological study in the dog.

AIM: To evaluate the injectability, biocompatibility, safety, and periodontal wound healing/regeneration following application of a novel bioresorbable recombinant human growth/differentiation factor-5 (rhGDF-5)/poly(lactic-co-glycolic acid) (PLGA) construct. MATERIAL AND METHODS: Periodontal pockets (3 x 6 mm, width x depth) were surgically created over the buccal roots of the second and fourth mandibular pre-molars in eight adult Hound Labrador mongrel dogs. Surgeries including injection of the rhGDF-5/PLGA construct into the pockets were sequenced that four animals provided 2-/4-week and four animals 6-/8-week observations of sites receiving rhGDF-5/PLGA or serving as sham-surgery control. RESULTS: The rhGDF-5/PLGA construct was easy to prepare and apply. Approximately 0.2 ml (93 microg rhGDF-5)/tooth was used. Clinical and radiographic healing was exemplary without adverse events. Healing was characterized by a non-specific connective tissue attachment, acellular/cellular cementum, periodontal ligament (PDL), bone regeneration, and a junctional epithelium. PLGA fragments were observed in 4/7, 2/8, and 1/8 sites at 2, 4, and 6 weeks, respectively. Associated inflammatory reactions exhibited no limiting effect on periodontal wound healing/regeneration. Root resorption/ankylosis was not observed. Bone formation showed apparent increased maturity (lamellar bone) at 6 weeks in sites receiving rhGDF-5/PLGA compared with the control. Both protocols exhibited significant increases in PDL, cementum, and bone regeneration over time, without significant differences between treatments. In time, PDL and cementum regeneration was twofold greater for the control at 4 weeks (p=0.04) while increased bone formation was observed at sites receiving rhGDF-5/PLGA (p<0.01). CONCLUSIONS: In conclusion, the rhGDF-5/PLGA construct appears to be a safe technology for injectable, ease-of-use application of rhGDF-5-stimulated periodontal wound healing/regeneration. Additional work to optimize the polymer carrier and rhGDF-5 release kinetics/dose might be required before evaluating the efficacy of this technology in clinical settings using minimally invasive approaches.

Periodontal wound healing/regeneration following the application of rhGDF-5 in a beta-TCP/PLGA carrier in critical-size supra-alveolar periodontal defects in dogs.

AIM: The objective of this study was to evaluate the effect of a novel recombinant human GDF-5 (rhGDF-5) construct intended for onlay and inlay indications on periodontal wound healing/regeneration. METHODS: Contralateral, surgically created, critical-size, 6-mm, supra-alveolar periodontal defects in five adult Hound Labrador mongrel dogs received rhGDF-5 coated onto beta-tricalcium phosphate (beta-TCP) particles and immersed in a bioresorbable poly(lactic-co-glycolic acid) (PLGA) composite or the beta-TCP/PLGA carrier alone (control). The rhGDF-5 and control constructs were moulded around the teeth and allowed to set. The gingival flaps were then advanced; flap margins were adapted 3-4 mm coronal to the teeth and sutured. The animals were euthanized at 8 weeks post-surgery when block biopsies were collected for histometric analysis. RESULTS: Healing was generally uneventful. A few sites exhibited minor exposures. Three control sites and one rhGDF-5 site (in separate animals) experienced more extensive wound dehiscencies. The rhGDF-5 and control constructs were easy to apply and exhibited adequate structural integrity to support the mucoperiosteal flaps in this challenging onlay model. Limited residual beta-TCP particles were observed at 8 weeks for both rhGDF-5/beta-TCP/PLGA and beta-TCP/PLGA control sites. The rhGDF-5/beta-TCP/PLGA sites showed significantly greater cementum (2.34 +/- 0.44 versus 1.13 +/- 0.25 mm, p=0.02) and bone (2.92 +/- 0.66 versus 1.21 +/- 0.30 mm, p=0.02) formation compared with the carrier control. Limited ankylosis was observed in four of five rhGDF-5/beta-TCP/PLGA sites but not in control sites. CONCLUSIONS: Within the limitations of this study, the results suggest that rhGDF-5 is a promising candidate technology in support of periodontal wound healing/regeneration. Carrier and rhGDF-5 dose optimization are necessary before further advancement of the technology towards clinical evaluation.

Disparities in medical care among commercially insured patients with newly diagnosed breast cancer: opportunities for intervention.

BACKGROUND: African-American women have increased breast cancer mortality compared with white women. Diagnostic and treatment gaps may contribute to this disparity. METHODS: In this retrospective, longitudinal cohort study, Southern US health plan claims data and linked medical charts were used to identify racial disparities in the diagnoses, treatment, and mortality of commercially insured women with newly diagnosed breast cancer. White women (n = 476) and African-American women (n = 99) with newly diagnosed breast cancer were identified by breast cancer claims codes (International Classification of Diseases, Ninth Revision, Clinical Modification codes 174, 233.0, 238.3, and 239.3) between January 2000 and December 2004. Race, diagnoses (breast cancer stage, estrogen/progesterone receptor [ER/PR]-positive status), treatment (breast-conserving surgery, antiestrogen therapy, and chemotherapy interruption or reduction), and all-cause mortality were assessed from medical charts. Multivariate regression analyses were adjusted for age, geography, and socioeconomic status to test the association of race with diagnoses/treatment. RESULTS: White women were older (P < .001) and had higher rates of diagnosis at stage 0/I (55.2% vs 38.4%; P < .05) than African-American women. More white women had positive ER/PR status (75% vs 56% African-American; P = .001) and received antiestrogen therapy if they were positive (37.2% vs 27.3% African-American; P < .001). White women received slightly more breast-conserving surgery and chemotherapy dose modification than African-American women (P value nonsignificant). African-American women had a higher mortality rate (8.1%) than white women (3.6%; P = .06). In adjusted analyses, African-American women were diagnosed at later stages (odds ratio, 1.71; P = .02), and white women received more antiestrogen therapy (odds ratio, 2.1; P = .03). CONCLUSIONS: Disparities in medical care among patients with newly diagnosed breast cancer were evident between African-American women and white women despite health plan insurance coverage. Interventions that address the gaps identified are needed.

Retrieval of rhesus monkey (Macaca mulatta) oocytes by ultrasound-guided needle aspiration: problems and solutions.

Oocytes of nonhuman primates such as rhesus monkeys are excellent models for diverse studies on developmental biology, epigenetics, human reproduction, and assisted reproductive technologies, as well as on transgenics. Such studies require numerous oocytes that can be retrieved after controlled ovarian stimulation. Currently, most primate centers use laparoscopic aspiration or laparotomy followed by aspiration to collect rhesus oocytes, although the ultrasound-guided needle aspiration is more advantageous due to reduced infection risk, less injury, and a shorter recovery period. Yet, some initial difficulties associated with the ultrasound-guided needle aspiration limit its broader application. The objective of the present study was to address these obstacles. By presenting practical solutions to the initial difficulties, results from our study show that it is possible to collect a mean number of 38 +/- 10 rhesus oocytes per hormonally stimulated female. These results compare favorably to the average number of rhesus oocytes collected using the laparoscopic approach and suggest that when initial obstacles are overcome, the ultrasound-guided oocyte retrieval represents a good alternative to more invasive approaches.

Anomaly in aortic arch alters pathological outcome of transient global ischemia in Rhesus macaques.

We investigated a non-human primate (NHP) transient global ischemia (TGI) model which was induced by clipping the arteries originating from the aortic arch. Previously we demonstrated that our TGI model in adult Rhesus macaques (Macaca mulatta) results in marked neuronal cell loss in the hippocampal region, specifically the cornu Ammonis (CA1) region. However, we observed varying degrees of hippocampal cell loss among animals. Here, we report for the first time an anomaly of the aortic arch in some Rhesus macaques that appears as a key surgical factor in ensuring the success of the TGI model in this particular NHP. Eleven adult Rhesus macaques underwent the TGI surgery, which involved 10-15-minute clipping of both innominate and subclavian arteries. Animals were allowed to survive between 1 day and 28 days after TGI. Because of our experience and knowledge that Japanese macaques exhibited only innominate and subclavian arteries arising from the aortic arch, macroscopic visualization of these two arteries alone in the Rhesus macaques initially assured us that clipping both arteries was sufficient to produce TGI. During the course of one TGI operation, however, we detected 3 arterial branches arising from the aortic arch, which prompted us to subsequently search for 3 branches in succeeding TGI surgeries. In addition, we performed post-mortem examination of the heart to confirm the number of arterial branches in the aortic arch. Finally, in order to reveal the pathological effect of the aortic arch anomaly, we compared the hippocampal cell loss between animals found to have 3 arterial branches but had all or only two branches clipped during TGI operation. Post-mortem examination revealed that eight NHPs had the typical two arterial aortic branches, but three NHPs displayed an extra arterial aortic branch, indicating that about 30% of Rhesus macaques had 3 arterial branches arising from the aorta. Histological analyses using Nissl staining showed that in NHPs with the aortic arch anomaly clipping only two of three arterial branches led to a partial cell loss and minimal alteration in number of cell layers in the hippocampal region when compared with clipping all three branches, with the hippocampal cell death in the latter resembling the pathological outcome achieved by clipping the two arterial branches in NHPs displaying the typical two-artery aortic arch. The finding that 3 of 11 NHPs exhibited an extra arterial aortic branch recognizes this aortic arch anomaly in Rhesus macaques that warrants a critical surgical maneuver in order to successfully produce consistent TGI-induced hippocampal cell loss.

Evaluation of nano-technology-modified zirconia oral implants: a study in rabbits.

OBJECTIVE: The objective of this study was to screen candidate nano-technology-modified, micro-structured zirconia implant surfaces relative to local bone formation and osseointegration. MATERIALS AND METHODS: Proprietary nano-technology surface-modified (calcium phosphate: CaP) micro-structured zirconia implants (A and C), control micro-structured zirconia implants (ZiUnite), and titanium porous oxide implants (TiUnite) were implanted into the femoral condyle in 40 adult male New Zealand White rabbits. Each animal received one implant in each hind leg; thus, 20 animals received A and C implants and 20 animals received ZiUnite and TiUnite implants in contralateral hind legs. Ten animals/group were euthanized at weeks 3 and 6 when biopsies of the implant sites were processed for histometric analysis using digital photomicrographs produced using backscatter scanning electron microscopy. RESULTS: The TiUnite surface demonstrated significantly greater bone-implant contact (BIC) (77.6+/-2.6%) compared with the A (64.6+/-3.6%) and C (62.2+/-3.1%) surfaces at 3 weeks (p<0.05). Numerical differences between ZiUnite (70.5+/-3.1%) and A and C surfaces did not reach statistical significance (p>0.05). Similarly, there were non-significant differences between the TiUnite and the ZiUnite surfaces (p>0.05). At 6 weeks, there were no significant differences in BIC between the TiUnite (67.1+/-4.2%), ZiUnite (69.7+/-5.7%), A (68.6+/-1.9%), and C (64.5+/-4.1%) surfaces (p>0.05). CONCLUSION: TiUnite and ZiUnite implant surfaces exhibit high levels of osseointegration that, in this model, confirm their advanced osteoconductive properties. Addition of CaP nano-technology to the ZiUnite surface does not enhance the already advanced osteoconductivity displayed by the TiUnite and ZiUnite implant surfaces.

Hippocampal CA1 cell loss in a non-human primate model of transient global ischemia: a pilot study.

We exposed adult Rhesus (Macaca mulatta) to a transient global ischemia, which was induced by clipping the innominate and subclavian arteries that originated from the aortic arch. NHP1 received 20-min, while NHP2 and NHP3, were exposed to a 15-min transient global ischemia and were euthanized at day 1 (NHP1), day 5 (NHP2) or day 30 (NHP3) after ischemia, respectively. NHP1 displayed severe paralysis and rigidity, and intermittent convulsions over the next 24 h. Although histological examination of the brain revealed no detectable gross brain damage (i.e., swelling) and only minimal cell loss in the hippocampus, the acute survival time after surgery likely prevented the cerebral ischemia to fully develop and to be morphologically manifested. Nonetheless, the 20-min ischemia might have been too severe and caused a systemic multiple organ collapse that produced the abnormal behavioral symptoms. On the other hand, NHP2 and NHP3 which received 15-min ischemia only exhibited minor hindlimb paralysis. Indeed, by 48 h after ischemia, both animals appeared fully recovered with only fine motor deficits. Immunohistochemical examination revealed that NHP2 and 3, but not NHP1, had a marked neuronal cell loss in the hippocampal region, specifically the cornu Ammonis (CA1) region. The cell loss in these two ischemic NHP hippocampi was further confirmed by direct comparison with a normal Rhesus brain. These findings replicate the brain pathology seen in Japanese macaques exposed to the same ischemia model [T. Tsukada, M. Watanabe, T. Yamashima, Implications of CAD and DNase II in ischemic neuronal necrosis specific for the primate hippocampus, J. Neurochem. 79 (2001) 1196-1206; T. Yamashima, Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates, Prog. Neurobiol. 62 (2000) 273-295; T. Yamashima, Y. Kohda, K. Tsuchiya, T. Ueno, J. Yamashita, T. Yoshioka, E. Kominami, Inhibition of ischemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: a novel strategy for neuroprotection based on calpain-cathepsin hypothesis, Eur. J. Neurosci. 10 (1998) 1723-1733; T. Yamashima, T.C. Saido, M. Takita, A. Miyazawa, J. Yamano, A. Miyakawa, H. Nishijyo, J. Yamashita, S. Kawashima, T. Ono, T. Yoshioka, Transient brain ischemia provokes Ca2+, PIP2 and calpain responses prior to delayed neuronal death in monkeys, Eur. J. Neurosci. 8 (1996) 1932-1944; T. Yamashima, A.B. Tonchey, T. Tsukada, T.C. Saido, S. Imajoh-Ohmi, T. Momoi, E. Kominami, Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates, Hippocampus 13 (2003) 791-800]. The present minimally invasive transient global ischemia model using Rhesus shows many histopathological symptoms seen in human patients who experienced global ischemia, and should allow translational validation of experimental therapeutics for ischemic injury. Additional studies are warranted to reveal behavioral deficits associated with this ischemia model.

Efficacy and safety of stored and newly prepared tribromoethanol in ICR mice.

This study, performed in conjunction with an in vitro evaluation of tribromoethanol (TBE), consisted of three trials with three objectives. The first objective was to compare anesthetic efficacy and short-term pathologic findings of TBE, ketamine-xylazine (K-X), and sodium pentobarbital (NaP). The second objective was to evaluate how changes of TBE that occur during the perceived most favorable and least favorable storage conditions (8 weeks at 5 degrees C in the dark [5D] and 25 degrees C with exposure to light [25L], respectively) affect anesthetic efficacy and short-term pathology when compared to newly prepared TBE. The third objective was to perform a 6-week clinical assessment of animals that received newly prepared TBE. All animals that received TBE (400 mg/kg) and 14 of 15 that received K-X (K, 120 mg/kg; X, 16 mg/kg) were anesthetized, as defined by loss of pedal reflex. In comparison, only 8 of 15 animals administered NaP (60 mg/kg) were anesthetized. Anesthetic duration for animals that received K-X was 31.7 min, which was significantly (P = 0.0085) longer than animals that received TBE (18.5 min). Recovery times for TBE and K-X were not significantly different (26.5 and 27.5 min, respectively). Pathologic lesions associated with TBE administration were significantly (P = 0.001) greater than those associated with K-X. NaP was not associated with any pathologic lesions. The pH of newly prepared and 5D TBE was 6.5 to 7.0, whereas that for 25L TBE was 3.0. Anesthetic induction, duration, recovery times, and pathologic lesions were not significantly different, regardless of the pH or storage condition of the solution. It was noted, however, that the average anesthetic duration for animals administered newly prepared TBE in the second trial was longer (37.7 min) than the first trial that used newly prepared TBE. For the third trial (long-term clinical assessment), the average anesthetic duration for TBE was 46.5 min, significantly (P < 0.025) longer when compared to the first trial that used newly prepared TBE. During the third trial, 10 animals were found dead or moribund. All animals that were found moribund were necropsied and found to exhibit a marked ileus. Because of the variability in anesthetic effectiveness, pathology, and morbidity and mortality associated with the use of TBE, we do not recommend the use of this anesthetic agent in ICR mice.

Sharing the science on human milk feedings with mothers of very-low-birth-weight infants.

Mother's milk provides protection from serious and costly morbidity for very-low-birth-weight infants (<1500 g), including enteral feeding intolerance, nosocomial infection, and necrotizing enterocolitis. However, NICU and maternity nurses may be hesitant to encourage mothers to initiate lactation because of a reluctance to make mothers feel guilty or coerced. This article reviews the evidence for the health outcomes of mothers' milk feeding in very-low-birth-weight infants and provides examples of ways to share this science with mothers so that they can make an informed feeding decision.

A randomized study to decrease the use of potentially inappropriate medications among community-dwelling older adults in a southeastern managed care organization.

BACKGROUND: Despite progress in describing the problem of potentially inappropriate medication (PIM) use, there have been few prospective studies demonstrating that interventions with specific medication criteria can make a difference in decreasing the use of problematic drugs in older adults. OBJECTIVE: To design an intervention study to change physician behavior regarding PIM prescribing to older patients. STUDY DESIGN AND METHODS: A prospective randomized block design was used during an 18-month period from January 2001 to June 2002. The study population was primary care physicians (n = 355) in the Medicare + Choice product line of a southeastern managed care organization and their patients 65 years and older. There were 170 physicians in the treatment group and 185 in the control group. Physicians were assigned to the treatment or usual-care, groups using a randomization table, and each group included physicians who had and had not prescribed a PIM. RESULTS: Approximately 71% (84/118) of the physicians in the intervention group who prescribed a PIM completed and faxed back at least 1 potentially inappropriate medication form to the managed care organization. On 15.4% (260/1692) of the medication forms, physicians made some change regarding PIM use. CONCLUSIONS: Although many studies have addressed medication use among older adults, intervention studies aimed at influencing physician prescribing in this population are limited. This study describes a low-cost, replicable method to contact and educate physicians on drug therapy issues in older adults.

Lacrimal gland myoepithelioma in a rhesus macaque (Macaca mulatta).

An 18-year-old rhesus macaque (Macaca mulatta) developed ptosis of the left upper eyelid due to a mass that had first been observed 10 years previously. The 11 x 7 x 7-mm mass was surgically excised, and the ptosis resolved after 5 days. Histologic examination of the mass revealed two confluent cell populations. Most cells were spindle-shaped and were arranged in loose fascicles. Smaller numbers of cells had squamous differentiation. The spindle-shaped cells expressed smooth muscle actin. Cells with squamous differentiation did not express smooth muscle actin, but did, along with around half of the spindle-shaped cells, express pan-cytokeratin. On the basis of histologic and immunohistochemical findings, the mass was diagnosed as myoepithelioma. The neoplasm most likely originated from the palpebral lobe of the lacrimal gland, although accessory lacrimal gland origin could not be excluded. Recurrence of the neoplasm has not been observed 6 months after surgery.