Biomedical subjects

James J Grady

Publications and source records attributed to James J Grady.

At least 19 recordsLinked to original sources

PubMed2007

Human fetal neural stem cells grafted into contusion-injured rat spinal cords improve behavior.

Grafted human neural stem cells (hNSCs) may help to alleviate functional deficits resulting from spinal cord injury by bridging gaps, replacing lost neurons or oligodendrocytes, and providing neurotrophic factors. Previously, we showed that primed hNSCs differentiated into cholinergic neurons in an intact spinal cord. In this study, we tested the fate of hNSCs transplanted into a spinal cord T10 contusion injury model. When grafted into injured spinal cords of adult male rats on either the same day or 3 or 9 days after a moderate contusion injury, both primed and unprimed hNSCs survived for 3 months postengraftment only in animals that received grafts at 9 days postinjury. Histological analyses revealed that primed hNSCs tended to survive better and differentiated at higher rates into neurons and oligodendrocytes than did unprimed counterparts. Furthermore, only primed cells gave rise to cholinergic neurons. Animals receiving primed hNSC grafts on the ninth day postcontusion improved trunk stability, as determined by rearing activity measurements 3 months after grafting. This study indicates that human neural stem cell fate determination in vivo is influenced by the predifferentiation stage of stem cells prior to grafting. Furthermore, stem cell-mediated facilitation of functional improvement depends on the timing of transplantation after injury, the grafting sites, and the survival of newly differentiated neurons and oligodendrocytes.

Animals↗

PubMed2007

Demographic correlates of body size changes in children undergoing treatment for acute lymphoblastic leukemia.

INTRODUCTION: While it is known that leukemia therapy is associated with obesity in survivorship, limited information is available on its time-related pattern of development and its variation across patient subgroups. The goal of the present study was to examine demographic correlates of body mass index (BMI) changes over time from diagnosis through chemotherapy for children with B-precursor acute lymphoblastic leukemia (ALL). METHODS: The study cohort consisted of 307 pediatric patients diagnosed with ALL who were treated at four South Texas pediatric oncology centers between 1990 and 2002. To minimize treatment-related variability, we excluded patients who received cranial irradiation as part of their treatment. Variation in age- and gender-standardized BMI z-scores according to age at diagnosis, gender, and ethnicity were assessed. RESULTS: The overall study cohort exhibited an increase in age- and gender-adjusted BMI z-scores for the first 24 months of chemotherapy followed by a slight decrease in BMI at 30 months (end of therapy). A repeated measures analysis indicated a statistically significant difference in the time-related pattern of BMI changes for age at diagnosis (P = 0.001) but no significant effect for gender (P = 0.32) or Hispanic versus non-Hispanic ethnicity (P = 0.89). DISCUSSION: In our cohort of ALL patients, BMI was elevated at diagnosis (mean standardized BMI z-score = 0.22, standard deviation = 1.4) then increased and remained elevated for the entire duration of chemotherapy. Children who were 2-9 years of age at diagnosis began therapy with a substantially lower BMI and remained lower over the course of chemotherapy than patients aged 10-18 years at diagnosis. It will be important for future investigations to explore the biological and behavioral factors that may underlie such differential patterns of BMI change over time.

Adolescent↗

PubMed2006

Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx.

BACKGROUND: Allergic airway diseases are more common in females than in males during early adulthood. A relationship between female hormones and asthma prevalence and severity has been suggested, but the cellular and molecular mechanisms are not understood. OBJECTIVE: To elucidate the mechanism(s) by which estrogens enhance the synthesis and release of mediators of acute hypersensitivity. METHODS: Two mast cell/basophil cell lines (RBL-2H3 and HMC-1) and primary cultures of bone marrow derived mast cells, all of which naturally express estrogen receptor-alpha, were examined. Cells were incubated with physiological concentrations of 17-beta-estradiol with and without IgE and allergens. Intracellular Ca(2+) concentrations and the release of beta-hexosaminidase and leukotriene C(4) were quantified. RESULTS: Estradiol alone induced partial release of the preformed, granular protein beta-hexosaminidase from RBL-2H3, BMMC and HMC-1, but not from BMMC derived from estrogen receptor-alpha knock-out mice. The newly synthesized LTC(4) was also released from RBL-2H3. Estradiol also enhanced IgE-induced degranulation and potentiated LTC(4) production. Intracellular Ca(2+) concentration increased prior to and in parallel with mediator release. Estrogen receptor antagonists or Ca(2+) chelation inhibited these estrogenic effects. CONCLUSION: Binding of physiological concentrations of estradiol to a membrane estrogen receptor-alpha initiates a rapid onset and progressive influx of extracellular Ca(2+), which supports the synthesis and release of allergic mediators. Estradiol also enhances IgE-dependent mast cell activation, resulting in a shift of the allergen dose response.

Allergens↗

PubMed2006

A strong association between body fat mass and protein profiles in nipple aspirate fluid of healthy premenopausal non-lactating women.

Fluid can be aspirated from the nipples of most non-lactating women. This nipple aspirate fluid (NAF) is a potential source for the discovery of new breast cancer biomarkers. NAF has two distinct protein profiles. Type I NAF is similar to the fluid associated with cystic disease of the breast, whereas type II NAF is enriched in milk-associated proteins. The prevalence of these two profiles differs in healthy women and in breast cancer patients. This study investigated the relationship of these two NAF profiles to reproductive history, body composition, diet, and levels of lipids, steroids and thyroid hormones in healthy premenopausal women (age 30-40 years) who had regular menstrual cycles and normal mammograms and were not taking contraceptive medications. On average, women with the type I NAF profile were older, had more years since last childbirth, were less likely to have breastfed their babies and had higher dietary saturated fat intake, body mass index, body fat mass, and levels of plasma low density lipoproteins than women with the type II profile (P <0.05). Using multiple logistic regression, type I NAF was predicted independently (P <0.05) by higher body fat mass [Odds Ratio (OR) = 3.0; 95% Confidence Interval (CI): 1.5-6.1], more years since last childbirth (OR = 2.6; 95% CI: 1.3-5.2) and a higher percentage of calories from saturated fat (OR = 4.1; 95% CI: 1.1-14.6). These results suggest that protein profiles of NAF might be influenced by amounts or types of dietary and body fat, but further study of the relationship of the two profiles to breast cancer risk is needed.

Adipose Tissue↗

PubMed2006

Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury.

Traumatic brain injury (TBI) often produces cognitive impairments by primary or secondary neuronal loss. Stem cells are a potential tool to treat TBI. However, most previous studies using rodent stem or progenitor cells failed to correlate cell grafting and cognitive improvement. Furthermore, the efficacy of fetal human neural stem cells (hNSCs) for ameliorating TBI cognitive dysfunction is undetermined. This study therefore characterized phenotypic differentiation, neurotrophic factor expression and release and functional outcome of grafting hNSCs into TBI rat brains. Adult Sprague-Dawley rats underwent a moderate parasagittal fluid percussion TBI followed by ipsilateral hippocampal transplantation of hNSCs or vehicle 1 day post-injury. Prior to grafting, hNSCs were treated in vitro for 7 days with our previously developed priming procedure. Significant spatial learning and memory improvements were detected by the Morris water maze (MWM) test in rats 10 days after receiving hNSC grafts. Morphological analyses revealed that hNSCs survived and differentiated mainly into neurons in the injured hippocampus at 2 weeks after grafting. Furthermore, hNSCs expressed and released glial-cell-line-derived neurotrophic factor (GDNF) in vitro and when grafted in vivo, as detected by RT-PCR, immunostaining, microdialysis and ELISA. This is the first direct demonstration of the release of a neurotrophic factor in conjunction with stem cell grafting. In conclusion, human fetal neural stem cell grafts improved cognitive function of rats with acute TBI. Grafted cells survived and differentiated into neurons and expressed and released GNDF in vivo, which may help protect host cells from secondary damage and aid host regeneration.

Animals↗

PubMed2006

Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability.

Insulin promotes muscle anabolism, but it is still unclear whether it stimulates muscle protein synthesis in humans. We hypothesized that insulin can increase muscle protein synthesis only if it increases muscle amino acid availability. We measured muscle protein and amino acid metabolism using stable-isotope methodologies in 19 young healthy subjects at baseline and during insulin infusion in one leg at low (LD, 0.05), intermediate (ID, 0.15), or high (HD, 0.30 mUxmin(-1)x100 ml(-1)) doses. Insulin was infused locally to induce muscle hyperinsulinemia within the physiological range while minimizing the systemic effects. Protein and amino acid kinetics across the leg were assessed using stable isotopes and muscle biopsies. The LD did not affect phenylalanine delivery to the muscle (-9 +/- 18% change over baseline), muscle protein synthesis (16 +/- 26%), breakdown, or net balance. The ID increased (P < 0.05) phenylalanine delivery (+63 +/- 38%), muscle protein synthesis (+157 +/- 54%), and net protein balance, with no change in breakdown. The HD did not change phenylalanine delivery (+12 +/- 11%) or muscle protein synthesis (+9 +/- 19%), and reduced muscle protein breakdown (-17 +/- 15%), thus improving net muscle protein balance but to a lesser degree than the ID. Changes in muscle protein synthesis were strongly associated with changes in muscle blood flow and phenylalanine delivery and availability. In conclusion, physiological hyperinsulinemia promotes muscle protein synthesis as long as it concomitantly increases muscle blood flow, amino acid delivery and availability.

Adult↗

PubMed2006

Effect of pneumococcal conjugate vaccine on nasopharyngeal bacterial colonization during acute otitis media.

The heptavalent pneumococcal conjugate vaccine (PCV7) has been shown to reduce the incidence of acute otitis media (AOM) caused by Streptococcus pneumoniae by 34% and reduces the overall incidence of AOM by 6% to 8%. More recent studies have shown increases in the proportion of Haemophilus influenzae and Moraxella catarrhalis in the middle-ear fluid of PCV7-immunized children. There has been no report on the effect of PCV7 on all 3 bacterial pathogens combined, either in the middle-ear fluid or nasopharynx of individual children with AOM. We investigated the impact of PCV7 on nasopharyngeal colonization with bacterial pathogens during AOM in the pre-PCV7 and post-PCV7 vaccination eras. Four hundred seventeen children (6 months to 4 years of age) were enrolled onto AOM studies between September 1995 and December 2004. Of these, 200 were enrolled before the vaccine use (historical controls), and 217 were enrolled after the initiation of PCV7 vaccination (101 were underimmunized, and 116 were immunized). Although the nasopharyngeal colonization rate for S pneumoniae was not different between the 3 groups, a significantly higher proportion of PCV7-immunized children with AOM were colonized with M catarrhalis. Overall, the mean number of pathogenic bacteria types isolated from immunized children (1.7) was significantly higher than in controls (1.4). The increase in bacterial colonization of the nasopharynx during AOM could be associated with an increase in AOM pathogens and theoretically can predispose PCV7-immunized children with AOM to a higher rate of antibiotic treatment failure or recurrent AOM.

Acute Disease↗

PubMed2005

Patterns and perceptions of ecstasy use among young, low-income women.

A significant number of young, low-income women experiment with ecstasy outside of club or rave settings. The current study examined patterns and risk factors of ecstasy use among this group of women. A cross-sectional survey was conducted among 696 women aged 18 to 31 who sought gynecological care from two university clinics in southeast Texas between December 1, 2001, and May 30, 2003. Fifteen percent of participants reported ever using ecstasy. Of those, over 90% used it at a friend's home. Compared with women who used only marijuana or other illicit drugs, ecstasy users were more likely to be white, use a larger number of other drugs, be willing to use drugs in the future, and have more friends who used drugs. Fewer ecstasy users strongly disapproved of adult drug use than users of other illicit drugs. Future interventional efforts should target young, low-income women to prevent future experimentation with illicit drugs.

Adolescent↗

PubMed2005

Decreased circulating levels of tumor necrosis factor-alpha in postmenopausal women during consumption of soy-containing isoflavones.

CONTEXT: TNF-alpha is a key mediator of inflammatory responses and may play a pivotal role in the development of cancer and in bone resorption. OBJECTIVE: This study determined the effect of soy rich in isoflavones on levels of TNF-alpha. DESIGN: Twelve postmenopausal women ingested a 36-oz portion of soymilk containing isoflavones daily for 16 wk and provided fasting blood samples multiple times before, during, and after soy consumption for the analyses of cytokines and monocyte content. RESULTS: Compared with prediet levels (36.3 +/- 14.0 pg/ml), serum levels of TNF-alpha decreased by 25.1% (27.2 +/- 10.3 pg/ml; P < 0.01) as early as 2 wk after soy consumption and by 66.7% (11.6 +/- 5.3 pg/ml; P < 0.01) 10 wk after soy consumption and recovered to the prediet levels 4 wk after the termination of soy consumption (38.6 +/- 19.6 pg/ml; P = 0.66). A similar decrease of up to 56.6 and 14.4% was found for serum IL-1alpha and the mean percentage of blood monocytes during soy consumption, respectively, but not for IL-6. In cultures of monocytes or whole blood from postmenopausal women, soy isoflavones (genistein and daidzein, 10-1000 nm), tamoxifen (10-1000 nm), or 17beta-estradiol (0.1-10 nm) inhibited lipopolysaccharide (1 microg/ml)-induced TNF-alpha production by up to 55.8%. CONCLUSIONS: Isoflavones may be the active components in soy responsible for the decrease of TNF-alpha found in postmenopausal women during a soy diet. This antiinflammatory effect of the isoflavones may be important in immune modulation and the prevention of bone loss and cancer.

Aged↗

PubMed2005

Therapy-related changes in body size in Hispanic children with acute lymphoblastic leukemia.

BACKGROUND: The objective of this study was to examine changes over time in body mass index (BMI) from diagnosis through chemotherapy for pediatric patients with B-precursor acute lymphoblastic leukemia (ALL). METHODS: The study cohort consisted of 141 white Hispanic pediatric patients who were diagnosed with ALL and were treated at 2 South Texas pediatric oncology centers between 1993 and 2002. Changes in age-standardized and gender-standardized BMI scores were assessed. RESULTS: The study cohort exhibited a steady increase in age-adjusted and gender-adjusted BMI scores for the first 12 months of therapy, a modest increase in BMI scores during the 18-23 month and 24-29 month periods, followed by a slight decrease in BMI scores at 30 months (end of therapy). A repeated-measures analysis indicated significant effects for time (P = 0.019) and time by baseline BMI category interaction (P = 0.0001) but no significant interaction effect between time and gender (P = 0.65). CONCLUSIONS: Although it is known that leukemia therapy is associated with prevalent obesity in survivorship, its pattern of development during therapy has not been elucidated. In the current cohort of Hispanic children with ALL, BMI scores were elevated at diagnosis (mean +/- standard deviation standardized BMI Z score, 0.33 +/- 1.4), then increased, and remained elevated for the entire duration of chemotherapy. Patients who were classified as normal weight exhibited an increase in BMI over time; patients who were classified as overweight at diagnosis exhibited BMI patterns that were relatively stable; and patients who were classified as obese exhibited a very slight decline over time. These findings suggest that the risk for chemotherapy-related weight gain applies predominantly to children who begin ALL therapy within a normal weight range.

Adolescent↗

PubMed2005

Human papillomavirus infection and P53 codon 72 genotypes in a Hispanic population at high-risk for cervical cancer.

Cervical cancer mortality is high in Texas, especially among Hispanic women living in south Texas and adjacent Mexico. Though human papillomavirus (HPV) infection has a causal role in the development of cervical cancer, there are no published data on the prevalence of HPV genotypes in this underscreened region. We studied 398 Hispanic women on both sides of the border along the lower Rio Grande River to determine the prevalence of HPV genotypes and risk factors for cervical cancer. Using a nested PCR system HPV was detected in 62% of cervical specimens, including all the known high-risk HPV genotypes, with HPV16 and HPV18 the most frequent (30.6% and 23.0%, respectively). Multiple infections were common (29.4% of the infected specimens), and where this occurred we were more likely to find high-risk HPV genotypes. We examined host p53 codon 72 genotype frequencies and found that patients with cervical abnormalities and women with HPV16 and HPV18 infections had a lower genotype frequency of the homozygous (AA) previously reported to be associated with cervical cancer, than uninfected women with no abnormalities. In this US/Mexico border population high rates of potentially oncogenic HPV viruses and multiple infections are consistent with observed elevated cervical cancer rates. These data are further evidence that in this underserved population HPV infections are associated with high rates of malignancy, but that host p53 genotypic variations are unlikely to be primary factors in oncogenesis.

Adolescent↗

PubMed2005

Pelvic Organ Support Study (POSST) and bowel symptoms: straining at stool is associated with perineal and anterior vaginal descent in a general gynecologic population.

OBJECTIVE: The purpose of this study was to evaluate the association of constipation symptoms and anal incontinence with vaginal wall and pelvic organ descent in a general gynecologic population. STUDY DESIGN: In this multicenter, cross-sectional study, 1004 women attending routine gynecologic healthcare underwent pelvic organ prolapse quantification (POPQ) measurements, and were surveyed regarding anal incontinence, digitation, < 2 bowel movements (BMs)/week, and > 25% frequency of: straining, hard/lumpy stools, and incomplete emptying. Constipation scores reflected the sum of positive responses. Associations between POPQ measurements (Ba, C, Bp, gh+pb), constipation scores, and anal incontinence were evaluated using multivariable regression. RESULTS: Of 119 women with Bp > or = -1.00, 47% reported no constipation symptoms. Hard/lumpy stools (26%), incomplete emptying (24%), and straining (24%) were more prevalent; fewer women reported < 2 BMs/week (15%) or digitation (7%). Constipation scores were weakly correlated with Bp, gh+pb (both r < .1, P < .02). Women reporting > or = 2 symptoms had greater gh+pb measurements than women reporting 0 or 1 symptom (P = .03). Women with anal incontinence had greater gh+pb and gh values than women without anal incontinence (P < .01). POPQ measurements were regressed separately onto (1) total constipation scores, (2) dichotomized scores, and (3) individual symptoms, with BMI, age, number of vaginal deliveries (NVD), weight of largest vaginal delivery (WLVD), race, hysterectomy, study site, and income included as covariates. Total constipation scores and dichotomized scores were nonsignificant in all models. With regard to individual symptoms, straining at stool was significant in the models for Ba and gh+pb, with greater Ba and gh+pb measurements among strainers relative to nonstrainers. CONCLUSION: Most associations between bowel symptoms and vaginal or pelvic organ descent were weak. After controlling for important covariates, straining at stool remained associated with anterior vaginal wall and perineal descent.

Adult↗

PubMed2005

Effect of a soymilk supplement containing isoflavones on urinary F2 isoprostane levels in premenopausal women.

Epidemiological studies have associated soy diets with reduced risk of breast and some other cancers, and oxidative cellular damage may contribute to the development of these and other diseases. We tested the effect of a soymilk supplement rich in isoflavones on a measure of cellular lipid peroxidation in a controlled feeding study. Eight premenopausal women consumed a constant diet that included soymilk containing 113-207 mg/day total isoflavones and 4 mo later a constant soy diet low (<5 mg/day) in isoflavones, both for a complete menstrual cycle. The average daily urinary excretions of daidzein and genistein were 24.6 +/- 10.1 and 9.2 +/- 6.1 mg/day, respectively, during the high-isoflavone soy diet and were below the detection limit during the low-isoflavone diet. F2 isoprostane 8-iso-PGF-2alpha excretion varied widely within and between subjects, and the group mean was not significantly different during the high- and low-isoflavone soy diet (7.67 +/- 1.13 and 8.65 +/- 1.18 nmol/12 h, mean +/- SD, respectively). However, individual changes in 8-iso-PGF-2alpha between the two soymilk drinks were significantly associated with age (r = -0.87; P = 0.006) and several measures of isoflavone exposure, namely, daidzein dose (r = 0.81; P = 0.015), combined daidzein and genistein dose (r = 0.77; P = 0.03), and total urinary excretion of isoflavones (daidzein, genistein, and equol) (r = 0.71; P = 0.05). The findings suggest that soy isoflavones may reduce lipid peroxidation in an age-dependent manner, with greater effects in older women, and with lower doses of isoflavones.

Adult↗

PubMed2004

Pro-nociceptive role of peripheral galanin in inflammatory pain.

We investigated the peripheral function of galanin (GAL) in capsaicin (CAP)-induced inflammatory pain. Intraplantar GAL (0.1 ng/microl) alone does not produce nociceptive behaviors. However, ipsilateral but not contralateral GAL at low doses (0.1 ng/microl) significantly increases CAP-evoked nociceptive behaviors approximately twofold. This effect is attributed to activation of peripheral GAL receptor 2 (GalR2) because a selective GalR2 agonist (AR-M1896) mimics the pro-nociceptive actions of GAL. Recording from nociceptors confirms that GAL does not modify activity of nociceptors but markedly enhances CAP-induced excitation of these fibers. CAP produces a discharge rate of 0.15+/-0.05 impulses/s which increases to 0.54+/-0.17 impulses/s following CAP+GAL. Immunohistochemical studies indicate GalR2 are highly expressed (65.8%) in L5 dorsal root ganglion (DRG) cells. Also, 44.5% GalR2-positive DRG neurons label for the capsaicin receptor (vanilloid receptor 1, VR1) while 61.7% of VR1-positive DRG neurons label for GalR2; 28.1% of total DRG neurons are double-labeled supporting the hypothesis that GAL-induced effects are mediated by GalR2 on capsaicin-sensitive primary afferents. Furthermore, 68.0% unmyelinated and 23.1% myelinated digital nerve axons label for GalR2, indicating the receptor is transported out to the periphery. Immunostaining for GAL peptide in digital nerves labels 46.4% unmyelinated and 27.1% myelinated axons, suggesting that afferents are a major source of ligand for peripheral GalR2. These results suggest that peripheral GAL has an excitatory role in inflammatory pain, likely mediated by peripheral GalR2 and that GAL can modulate VR1 function.

Action Potentials↗

PubMed2004

Effects of different catecholamines on the dynamics of volume expansion of crystalloid infusion.

BACKGROUND: The authors studied the influence of alpha, beta, and dopaminergic catecholamines on blood volume expansion in conscious normovolemic sheep before, during, and after a bolus infusion of a crystalloid. METHODS: A 0.9% NaCl bolus (24 ml/kg in 20 min) was infused in four paired experiments each: no drug, dopamine infusion (50 microg . kg . min), isoproterenol infusion (0.1 microg . kg . min), and phenylephrine infusion (3 microg . kg . min). Blood volume expansion was calculated by the dilution of blood hemoglobin concentration. RESULTS: Dopamine had little effect on peak blood volume expansion (12.7 +/- 0.9 ml/kg) compared with 0.9% NaCl (13.0 +/- 2.7 ml/kg); in contrast, isoproterenol augmented blood volume expansion (18.5 +/- 1.8 ml/kg), and phenylephrine reduced blood volume expansion (8.9 +/- 1.4 ml/kg). Two hours after the 0.9% NaCl bolus, sustained blood volume expansion was greatest in the isoproterenol protocol (12.2 ml/kg), whereas the dopamine protocol (6.8 ml/kg) remained similar to the control protocol (4.1 ml/kg), and the phenylephrine protocol had a net volume loss (-1.9 ml/kg). Some blood volume expansion differences were attributed to changes in renal function as phenylephrine infusion increased urinary output, whereas isoproterenol was associated with antidiuresis. However, dopamine caused diuresis and sustained augmentation of blood volume. CONCLUSION: Catecholamines can alter the intravascular volume expansion of fluid therapy. beta-Receptor (isoproterenol) stimulation augmented blood volume expansion, whereas alpha (phenylephrine) stimulation reduced blood volume expansion. Combined dopaminergic, beta, and possibly alpha stimulation with dopamine augmented blood volume expansion and cardiac output while inducing diuresis.

Adrenergic alpha-Agonists↗

PubMed2004

Effects of hormonal contraception on bone mineral density after 24 months of use.

OBJECTIVE: To measure the effect of 24 months of depot medroxyprogesterone acetate use on bone mineral density compared with oral contraception (pills) and nonhormonal contraception. METHODS: Women aged 18-33 years self-selected oral contraception, depot medroxyprogesterone acetate, or nonhormonal contraception (controls). Those selecting pills were randomized to formulations containing either 35 microg ethinyl estradiol and norethindrone or 30 microg ethinyl estradiol and desogestrel. Controls were frequency matched on age and race/ethnicity to hormonal contraception users. Dual-energy X-ray absorptiometry of the lumbar spine (L1-L4) was performed at baseline, 12 months, and 24 months. Percent change in bone mineral density was analyzed by using analysis of covariance, adjusting for age, race/ethnicity, weight-bearing exercise, calcium intake, smoking status, and body mass index. RESULTS: Of the 191 women making up the final sample, 86 used pills, 47 used depot medroxyprogesterone acetate, and 58 used nonhormonal contraception. Women using depot medroxyprogesterone acetate for 24 months experienced, on average, a 5.7% loss in bone mineral density, with a 3.2% loss occurring between months 12 and 24. On average, users of desogestrel pills experienced a 2.6% loss in bone mineral density after 24 months. Bonferroni-adjusted pairwise comparisons demonstrated that bone mineral density changes from baseline to 24 months among depot medroxyprogesterone acetate users differed significantly from changes experienced by either of the pill groups or the control group. Changes in bone mineral density among users of either pill did not significantly differ from each other or from controls. CONCLUSION: Loss of bone mineral density associated with depot medroxyprogesterone acetate use appears to be linear during the first 2 years of use. Shifts in bone mineral density among pill users were not significant when compared with controls.

Adolescent↗

PubMed2004

Hypotensive resuscitation of multiple hemorrhages using crystalloid and colloids.

Hypotensive resuscitation has been advocated as a better means to perform field resuscitation of penetrating trauma. Our hypothesis is that hypotensive resuscitation using either crystalloid or colloid provides equivalent or improved metabolic function while reducing the overall fluid requirement for resuscitation of hemorrhage. We compared hypotensive and normotensive resuscitation of hemorrhage using lactated Ringer's (LR) with hypotensive resuscitation using Hextend (Hex), 6% hetastarch in isotonic buffered saline. Instrumented conscious sheep were hemorrhaged in three separate bleeds, 25 mL/kg at T0 and 5 mL/kg at both T50 and T70. Resuscitation was started at T30 and continued until T180. Hypotensive resuscitation to a mean arterial pressure (MAP) of 65 mmHg was performed with LR or Hex using a closed-loop resuscitation (CLR) system for a LR-65 and Hex-65 treatment protocol. A control treatment protocol was resuscitation with LR to a MAP target of 90 mmHg, LR-90. All treatment protocols were successfully resuscitated to near target levels. Two animals in the hypotensive treatment protocols died during the second and third bleedings, one in the LR-65 and one in the Hex-65 treatment protocol. Mean infused volumes were 61.4 +/- 11.3, 18.0 +/- 5.9, and 11.6 +/- 1.9 mL/kg in the LR-90, LR-65, and Hex-65 treatments, respectively (*P < 0.05 versus LR-90). Mean minimum base excess (BE) values were +1.9 +/- 1.4, -5.8 +/- 4.3, and -5.9 +/- 4.0 mEq/L in the LR-90, LR-65, and Hex-65 treatments, respectively. Hypotensive resuscitation with LR greatly reduced volume requirements as compared with normotensive resuscitation, and Hex achieved additional volume sparing. However, trends toward lower BE values and the occurrence of deaths only in the hypotensive treatment protocols suggest that resuscitation to a target MAP of 65 mmHg may be too low for optimal outcomes.

Animals↗

PubMed2003

Adrenomedullin requires an intact nitric oxide system to function as an endogenous vasodilator in rat gestation.

OBJECTIVE: We hypothesize that administration of adrenomedullin (AM), an endogenous vasodilator, will ameliorate the hypertension and growth restriction associated with chronic nitric oxide inhibition induced by L-omega nitro-L-arginine methyl ester (L-NAME) infusion in pregnant rats. METHODS: Osmotic minipumps were inserted on day 14 of gestation to deliver continuously either AM, L-NAME, AM+L-NAME, or vehicle control. Systolic blood pressure was recorded daily in pregnant rats. Pregnant rats were either sacrificed on gestational days 15, 16, 17, 18, or 22, or they were allowed to deliver at term. The placentas from all of the treated groups were fixed for 24 hr in Bouin solution, sectioned, processed, embedded in paraffin, and stained with hematoxylin and eosin. The placentas were graded for the quality of fetal vessel development in the labyrinth. RESULTS: Systolic blood pressure was increased in AM+L-NAME-treated rats. The animals that delivered in the AM+L-NAME group exhibited decreased pup weight (L-NAME and AM+L-NAME, 5.2+/-0.1 compared with 6.4+/-0.1 g for both AM and controls, p<0.001) and increased pup mortality (AM+L-NAME, 44.4% compared with 16.7% in L-NAME, 0% in AM and 3.1% in controls, p<0.001 AM+L-NAME compared with controls). Increased decidual necrosis, necrosis in the labyrinth, and deficient fetal vessel development in the labyrinth was identified in the placentas treated with AM+L-NAME. CONCLUSIONS: Addition of the endogenous vasodilator AM to an L-NAME-induced state of chronic NO inhibition did not ameliorate hypertension and growth restriction.

Adrenomedullin↗