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James J Grady

Publications and source records attributed to James J Grady.

6 recordsLinked to original sources

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↗

Two variables that can be used as pain indices in experimental animal models of arthritis.

Since pain is an important symptom in arthritis, useful behavioral indices for pain in experimental arthritis animal models are important tools for investigative work on arthritis. The purpose of this study was to develop simple and quantifiable behavioral tests, which would represent the level of arthritic pain that develops after induction of inflammation in the knee. Two models of knee joint arthritis were produced: (1) KC model-injection of kaolin and carrageenan into the synovial cavity of the knee, and (2) CFA model-injection of complete Freund's adjuvant into the synovial cavity of the knee. The following three variables were measured before and at various times after the induction of arthritis. As an estimate of the degree of edema, the circumference of the knee was measured. As pain indices, (1) the vocalization threshold of compression force applied to the knee joint was measured to represent tenderness of the joint, and (2) the struggle threshold of the knee extension angle was measured to represent a reduction in range of motion in the arthritic joint. A time course study showed that behavioral changes last for at least 1 week for the KC model and at least 2 weeks for the CFA model. Correlation studies showed that all three variables significantly correlated with each other in both the KC and CFA arthritic models. Systemically injected morphine produced a partial reversal of these indices with the expected time course and dose response of a morphine-induced analgesic. It is concluded that two variables, the struggle threshold for knee extension and the vocalization threshold for knee compression, could be used as simple and useful pain indices in experimental models of arthritis.

Analgesics, Opioid↗

A longitudinal study of hymenal development from 3 to 9 years of age.

PURPOSE: To document hymenal characteristics associated with normal development in girls between 3 and 9 years of age. STUDY DESIGN: The hymens of 93 children without a history of sexual abuse were examined and photographed at 3 and 5 years of age; 80 children were reexamined at 7 and 61 at 9 years of age. Hymenal features recorded included periurethral and vestibular bands, notches, transections, longitudinal intravaginal ridges, external ridges, mounds, and tags. Transhymenal diameters were measured as well as the tissue at 3, 6, and 9 o'clock positions. Changes in hymenal measurements over time were analyzed using the general estimating equation approach to repeated measures. RESULTS: Crescentic configuration became more common as the children aged (P <.01). The number of mounds and intravaginal ridges observed per child as well as the size of the transhymenal diameter increased as the sample aged. The mean amount of tissue at the 6 o'clock position significantly changed over time (P <.01). However, no significant changes were observed in the number of tags, periurethral or vestibular bands, notches, external ridges, or amount of tissue present at the 3 or 9 o'clock position. CONCLUSIONS: Few changes occur in the morphologic features of the hymen between 3 and 9 years of age.

Anthropometry↗

Placental and fetal growth and development in late rat gestation is dependent on adrenomedullin.

Adrenomedullin is a potent, endogenous vasodilator peptide synthesized and secreted by diverse locations such as adrenal glands, lungs, kidneys, vascular smooth muscle, and endothelium. Homozygous deletion of the adrenomedullin gene is embryonic lethal. We hypothesized that adrenomedullin has an important role in placental and fetal growth and development in rat pregnancy. The current study evaluated maternal systolic blood pressure, litter size, placental and pup weight, pup mortality, and placental pathology in pregnant rats following continuous in utero exposure to an adrenomedullin antagonist. Osmotic minipumps were inserted on Gestational Day 14 to continuously deliver either adrenomedullin, adrenomedullin antagonist, or vehicle control. Systolic blood pressure was recorded daily. Pregnant rats were killed on Gestational Day 15-18, 20, and/or 22 to evaluate placental development and fetal growth. The placentas were graded for the presence of necrosis in the decidua and fetal labyrinth as well as fetal vessel development in the labyrinth. A trend toward increased systolic blood pressure was noted between Gestational Days 17 and 20 in mothers treated with adrenomedullin antagonist, but the difference was not statistically significant. Antagonism of adrenomedullin function during rat pregnancy caused fetal growth restriction, decreased placental size, gross necrosis of placental margins and amniotic membranes, histologically deficient fetal vessel development in the labyrinth, and fetal edema. Adrenomedullin contributes to angiogenesis, functions as a growth factor, and helps regulate vascular tone during rat gestation.

Adrenomedullin↗

Hydroxyapatite prosthesis extrusion.

OBJECTIVE: To examine the mechanism of prosthesis extrusion and evaluate preoperative and postoperative variables associated with extrusion of hydroxyapatite prostheses for ossicular reconstruction. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral, university medical center. PATIENTS: Patients undergoing ossiculoplasty with a hydroxyapatite prosthesis and having at least six months follow-up. MAIN OUTCOME MEASURE: Prosthesis extrusion, defined as loss of the tympanic membrane resulting in exposure of the prosthesis. Extrusion is further classified into early (< 2 months) and late (> 6 months). RESULTS: Early extrusion or tympanoplasty graft failure occurred in 15/195 cases (8%). Late extrusion was seen in 17/125 cases (14%). Cases exhibiting late extrusion had a significantly greater incidence of postoperative atelectasis (p < 0.0001), recurrent otitis media (p < 0.0001), and myringitis (p = 0.003) than those with retention of the prosthesis. Regression analysis found an abnormal contralateral ear increased the risk of postoperative recurrent otitis media, while staged surgery reduced the risk, odds ratios of 3.56 (95% confidence interval 2.20-9.37) and 6.84 (95% CI 4.24-17.76) respectively. There were no preoperative variables that predicted postoperative atelectasis or myringitis. CONCLUSIONS: Recurrent otitis media, myringitis, and atelectasis developing after ossiculoplasty are associated with a greater risk of prosthesis extrusion. Predicting postoperative complications from preoperative and intraoperative findings proved difficult. Measures to prevent atelectasis, such as covering the prosthesis with cartilage, are recommended at the time of ossiculoplasty.

Cartilage↗

Use of hymenal measurements in the diagnosis of previous penetration.

OBJECTIVE: To determine the usefulness of measurements of the vaginal opening and amount of hymenal tissue present inferiorly and laterally in the diagnosis of vaginal penetration. METHODS: The transhymenal diameters and the amount of tissue present between the hymenal edge and vestibule inferiorly at 6 o'clock and laterally at 3 o'clock and 9 o'clock were measured from photographs of 189 prepubertal children with a validated history of digital or penile penetration and 197 children who denied previous sexual abuse. Statistical analyses were conducted to compare the mean values and hymenal symmetry between groups as well as to determine the sensitivity and specificity of various cutoff points. RESULTS: Comparison of the mean diameters demonstrated that children with a penetration history had a significantly larger transverse opening than nonabused children when examined in the knee-chest position (5.6 vs 4.6 mm). However, there was extensive overlap in measurements between the 2 groups. No significant differences were noted between groups in the size of the vertical diameter, the amount of tissue present inferiorly or laterally, or the symmetry of the hymen in either position. Children with previous penetration were more likely than nonabused children to have a horizontal opening measuring >6.5 mm in the knee-chest position, but the sensitivity and specificity of this test were low (29% and 86%, respectively). Higher values had better specificity but very low sensitivity. Less than 1.0 mm of hymenal tissue was detected at 6 o'clock only in those with a history of penetration (100% specificity), but the sensitivity was low (1%-2%). CONCLUSION: Most hymenal measurements lack adequate sensitivity or specificity to be used to confirm previous penetration. Less than 1.0 mm of hymenal tissue at 6 o'clock was detected only in victims of abuse, but the usefulness of this test is limited by the rarity of this finding.

Child↗