Development of a mild prenatal stress rat model to study long term effects on neural function and survival

Early development of the brain’s neural circuitry has been shown to be vulnerable to high levels of circulating steroid hormones such as corticosterone. These steroid hormones are lipophylic and can cross the placental barrier especially during the last week of gestation leading to disturbances in the formation of neural circuits that contain amongst others dopaminergic and serotonergic neurons. The effects of this disruption of neuronal circuit formation during gestation has been shown to manifest in adult offspring as behavioural abnormalities such as anxiety and an abnormal hypothalamic-pituitary-adrenal (HPA) axis. Models of prenatal stress include food deprivation and a model that involves exposure of the pregnant rats to different stressors, commonly referred to as a mild stress model. The objective of this study was to create a mild stress model that did not manifest as anxiety in adult offspring. In the last week of gestation, the pregnant dams were divided into three groups; (1) non-stressed (2) 50% food-deprived and (3) mildly stressed rats that we will refer to as the mildly stressed rats. Following birth, all pups were cross-fostered onto non-stressed dams and on postnatal day 60 (P60), behaviour in the elevated plus maze and the open field box was tested. On P66 the rats were exposed to an acute restraint stress following which trunk blood was collected for HPA axis analysis. The adrenal glands were also dissected and weighed. Results show that the mildly stressed rat model of prenatal stress is even milder than models described in the literature, since we did not find differences in time spent in the open arms of the elevated plus maze or adrenal gland size. In the open field, our model displayed slightly less locomotor activity and also had a slightly blunted adrenocorticotropic hormone (ACTH) response to restraint stress even though the corticosterone response was similar to controls.     

Penetrating keratoplasty for keratoconus: long-term results

PURPOSE: To study central corneal endothelial cell density and morphology and corneal topography in transplanted corneas for keratoconus 10 to 17 years postoperatively. METHODS: Retrospective, noncomparative case series including all keratoconus patients who underwent penetrating keratoplasty by one surgeon, at the same center, between January 1986 and December 1994. Seventeen patients (22 eyes) met the criteria. Four patients (5 eyes) with unchanged visual acuity during the follow-up period did not agree to return for the last follow-up examination, 1 patient (1 eye) had graft failure, and 3 patients (4 eyes) were lost to follow-up. We reviewed the charts of 9 patients (12 eyes), and collected data including manifest refraction, best corrected visual acuity (BCVA), endothelial cell density, cell morphology, and corneal topography. RESULTS: The mean follow-up period for all eyes evaluated was 13.3 +/- 2.4 years (range 10-17 years). At the last follow-up, 91.7% of eyes achieved BCVA of 20/40 or better, and mean endothelial cell density was 695 +/- 113.6 cells/mm(2). Pleomorphism was detected in 5 eyes. Keratoconus pattern, by corneal topography, was not detected in any eye at the final examination. CONCLUSION: Endothelial cell count 10-17 years post-PKP for keratoconus is very low with pleomorphism and viable grafts, indicating continued endothelial instability.     

The use of the QNST-II as a measure for the identification of children with perceptual-motor deficits

This study aimed to examine the ability of the Quick Neurological Screening Test QNST II) (Mutti et al., 1998) to discriminate between children with and without perceptual-motor deficits and to further clarify its psychometric characteristics. Ninety-four children aged six to seven years were tested on the QNST-II. Out of this pool of subjects, 63 children had perceptual-motor deficits and 31 were typical controls. The children with perceptual-motor deficits scored significantly lower than the control children on the total score and on each of the subtest' s scores of the QNST II. Inter-rater reliability indicated a high degree of correlation between both evaluators' total scores of the QNST II. In terms of the test' s sensitivity and specificity, QNST II scores correctly classified 97% of the children with perceptual-motor deficits and 84% of the children from the control group. The findings of this study support the capability of the QNST II to discriminate between children with perceptual-motor deficits and typical children; thereby suggesting its usefulness as a screening measure to identify children at risk for difficulties in school performance.     

In vitro bioactivity and degradation behavior of silica xerogels intended as controlled release materials

Room temperature-processed silica-based sol-gel, termed silica xerogel, is a novel type of controlled release material. As shown previously, these materials are porous, degradable and can release biologically functional molecules in a controlled manner. It was also demonstrated that these materials are biocompatible in vivo. Herein we report on the ability of silica-based xerogels to form a bioactive, apatite-like (AP) surface and the effect of AP surface on the xerogel stability in vitro. Formation of a crystalline, carbonated AP (c-AP) was found on all silica xerogels studied, with or without Ca- and P-oxides. Calcium and phosphate (Ca-P) free xerogels showed long times to Ca-P precipitation and to formation of a detectable AP-layer (up to 2 weeks). In contrast, the times to precipitation were reduced by 2-3 orders of magnitude, and the c-AP layer was formed within 24 h on all Ca-P containing xerogels. Mechanisms of the c-AP formation on these xerogels were similar to those typical for Ca-P based ceramics: dissolution of calcium and phosphate ions, solution oversaturation with respect to AP and subsequent precipitation of bone-like minerals. The presence of the c-AP surface film produced a remarkable surface stabilizing effect: the rates and the amounts of Si release were significantly reduced in comparison to those for xerogels without the film. This evidence of in vitro bioactivity and controlled degradation, combined with previous in vitro and in vivo reports, suggests that silica xerogel is a promising controlled release material.     

In vivo tissue response to resorbable silica xerogels as controlled-release materials

Biodegradable, controlled-release carrier materials with non-toxic degradation products are valuable for local delivery of biologically active molecules. Previously, it was shown that room-temperature processed silica sol-gels (or xerogels) are porous, resorbable materials that can release molecules of various sizes in a controlled, time dependent manner. Previous in vitro studies also demonstrated benefits of silica xerogels as controlled-release materials for the treatment of bone infections. Herein the tissue and cell response to xerogels is documented using a subacute implantation procedure. The tissue response was correlated to composition, surface properties, resorption rate and incorporation of the antibiotic vancomycin. Ca- and P-free and Ca- and P-containing xerogels, with and without apatite (AP) surface, were used. Xerogels were implanted either as discs in a subcutaneous site, or as granules in the iliac crest of New Zealand white rabbits. The samples with surrounding tissue were retrieved after 2 and 4 weeks of implantation. Silica xerogels implanted either as discs subcutaneously or as granules in the iliac crest showed a favorable tissue response. The granules, either with or without Ca and P content, gradually resorbed over time. The resorption was accompanied by extensive trabecular bone growth and a minimal inflammatory response. Ca- and P-containing granules with an AP-surface layer showed a slower resorption rate and more extensive new bone growth than those without AP layer. Among AP-coated granules, those with incorporated vancomycin showed the most favorable tissue response. The present in vivo data together with prior in vitro data suggest that these xerogels have potential as controlled-release materials for the treatment of bone infections and as carrier materials for a variety of other applications.     

Relationship between late potentials and the predischarge electrocardiographic pattern in patients with acute anterior wall myocardial infarction

Hypothesis: The presence of late potentials on the signalaveraged electrocardiogram (SAECG) identifies patients at high risk for development of ventricular tachyarrhythmias after myocardial infarction (MI). Methods: The electrocardiogram and left ventricular function in 65 patients recovering from a first acute anterior wall MI were analyzed. We compared the pattern of the ST segment (isoelectric or elevated) and of the T wave (positive or negative) with the SAECG using an orthogonal bipolar lead configuration (X, Y, Z) with bidirectional Butterworth filtering (Simson's method). Results: Abnormal SAECG was found in 17 (26%) patients; 11 of 18 patients with ST elevation had abnormal SAECG, and only 6 of 47 patients with isoelectric ST segment developed abnormal SAECG (p<0.0001, odds ratio = 10.74). Of 19 patients with positive T waves, 10 had abnormal SAECG, and abnormal SAECG was found in 7 of 46 patients with negative T waves (p<0.003, odds ratio = 5.27). When both parameters were considered together, 9 of 12 patients with ST elevation and positive T wave developed abnormal SAECG, and 35 of 40 patients with isoelectric ST and negative T wave had normal SAECG (p<0.0002). Left ventricular ejection fraction was similar in patients with abnormal SAECG (43 ± 14%) and normal SAECG (46 ± 11 %). Conclusion: These findings suggest that patients with anterior wall MI and a predischarge pattern of ST elevation and positive T wave have a higher incidence of abnormal SAECG and therefore may have a worse prognosis, especially related to the subsequent development of ventricular arrhythmias.     

The anteroposterior pericardial sac diameter measured by echocardiography correlates with the volume of pericardial effusion and with effort dyspnea.

AIMS: To examine the value of the anteroposterior pericardial sac diameter (APD) for prediction of the volume of pericardial effusion. METHODS AND RESULTS: We measured the APD by echocardiography before 52 pericardiocentesis procedures and correlated it with the aspirate volume, etiology, symptoms, and clinical outcome. The volume of the aspirate ranged from 60 to 2300 ml (median 650 ml). The APD (range 8.0 cm-15.9 cm, median 12 cm) correlated well with the cubic root of the volume of the effusion [volume=(0.8APD-0.6)3, r2=0.533, p<0.01]. An APD>or=12 cm had a positive predictive value of 88% and a negative predictive value of 83% for effusion volume above the sample median (>or=650 ml) and a positive predictive value of 100% for effusion in the middle or upper aspirate volume tertiles. Effort dyspnea was more common among patients with APD>or=12.0 cm (n=13) than in those with APD<12.0 cm (n=11) (p=0.007). One-year survival after pericardiocentesis was closely related to the severity of the underlying etiology and was not influenced by the volume of the effusion before aspiration. CONCLUSIONS: The APD is a simple, valuable method for non-invasive prediction of pericardial fluid volume. A greater APD is associated with, and may explain, effort dyspnea.     

Discharge-ready patients who remain hospitalized: A re-emerging problem for mental health services

There is evidence that mentally ill patients nationwide are retained in state hospitals in spite of the fact that they are discharge-ready. New Jersey provided a unique opportunity to study this phenomenon, since it had been using specific procedures to identify discharge-ready patients in state hospitals. An analysis of New Jersey state hospital data found that about 45% of the state hospital patients were designated by either the legal or the clinical system, or both, as discharge-ready. Although a substantial number of these patients were, disabled, they were assessed as being able to manage in the community with appropriate support. Characteristics and service needs of these patients are described, and the differences between those designated as discharge-ready and those who were not are examined. Recommendations are made for future research addressing the legal, clinical and social processes that affect discharge readiness.