Carotid and femoral B-mode ultrasound intima-media thickness measurements in adult post-coarctectomy patients.

AIM: Cardiovascular and cerebrovascular morbidity and mortality in adult post-coarctectomy patients is increased even after successful surgical repair of the aorta. B-mode ultrasound intima-media thickness (IMT), a validated marker for atherosclerosis and vascular disease risk, was used to measure pre-coarctatial carotid and post-coarctatial femoral arterial wall changes in these patients. METHODS: Measurements were done in 131 patients (mean age 31.6 y [SD 11.3 y]; 78 were normotensive, 53 were hypertensive) and in 26 controls (30.9 y [SD 9.4 y]). RESULTS: Age, serum lipids and smoking history were similar in patients and controls. Overall, IMT in patients and controls were similar (0.59 mm [SD 0.14 mm] and 0.59 mm [SD 0.08 mm]. In patients, carotid IMT was increased (0.67 mm [SD 0.12 mm] vs 0.61 mm [SD 0.08 mm] in controls: p=0.01); femoral IMT was decreased (0.48 mm [SD 0.09 mm] vs 0.57 mm [SD 0.07 mm]: p=0.001). In normotensive patients carotid IMT was not increased (0.64 mm [SD 0.12 mm] vs 0.61 mm [SD 0.08 mm]: p=0.2), but patients showed a higher SD. Carotid IMT in hypertensive patients was increased (0.72 mm [SD 0.12 mm] vs 0.64 mm [SD 0.11 mm] in normotensive patients: p<0.001). The femoral IMT in normo- and hypertensives patients were similar (0.48 mm [SD 0.09 mm] and 0.49 mm [SD 0.10 mm]: p=0.12). Carotid IMT in patients with aortic coarction and age at surgery were associated (r=0.36, p<0.0001), where femoral IMT is not. CONCLUSION: Early peripheral arterial wall damage is prominent in hypertensive post-coarctatial patients and is limited to pre-coarctatial conduits. The decreased femoral IMT in all patients may indicate a relatively low post-coarctatial blood pressure if pressure control is guided according to pre-coarctatial RR. Pre-coarctatial arterial wall change is less apparent in post-coarctectomy patients who have a controlled blood pressure and who had early surgical repair.     

Pharmacogenetics of antipsychotic adverse effects: Case studies and a literature review for clinicians

There is a growing body of literature supporting the contribution of genetic variability to the mechanisms responsible for the adverse effects of antipsychotic medications particularly movement disorders and weight gain. Despite the current gap between research studies and the practical tools available to the clinician to identify such risks, it is hoped that in the foreseeable future, pharmacogenetics will become a critical aid to guide the development of personalized therapeutic regimes with fewer adverse effects. We provide a summary of two cases that are examples of using cytochrome P450 pharmacogenetics in an attempt to guide treatment in the context of recent literature concerning the role of pharmacogenetics in the manifestation of adverse effects of antipsychotic therapies. These examples and the review of recent literature on pharmacogenetics of antipsychotic adverse effects illustrate the potential for applying the principles of predictive, preventive, and personalized medicine to the therapy of psychotic disorders.     

Evaluation of a Commercial PCR Kit for Diagnosis of Cytomegalovirus Infection of the Central Nervous System

We evaluated the AMPLICOR cytomegalovirus (CMV) PCR kit for the diagnosis of neurologic CMV infections on 43 positive and 112 negative archived cerebrospinal fluid specimens originally tested by an in-house PCR method. The AMPLICOR kit showed sensitivity and specificity of 95 and 100%, respectively, versus the home-grown assay, indicating its utility in this clinical setting.     

Early ultrastructural effects of gentamicin cochleotoxicity

Ultrastructural changes in the cochlear hair cells during the early stages of gentamicin intoxication were investigated after tri-aldehyde primary fixation and OSO4/K4Ru(CN)6 post-fixation. In cochleas treated for 5, 10 and 15 days with gentamicin the individual outer hair cells (OHC1, OHC2 and OHC3) were randomly affected. Degeneration of the inner hair cells was not observed at this stage. Ultrastructurally, the earliest identifiable changes were an increase in lysosomes, proliferation of the endoplasmic reticulum, and formation of Hensen's bodies. This was followed by dilatation of the endoplasmic reticulum and the nuclear envelope, giving rise to extensive cytoplasmic vacuolation. These results demonstrate that gentamicin-induced changes primarily involve the cell's synthetic apparatus. All further intracellular changes occur at a much later stage and are therefore to be considered secondary events.     

Anticipatory control of head posture.

OBJECTIVE: We tested a hypothesis on two patterns of anticipatory postural adjustments (APAs) in neck muscles, reciprocal and co-activation, that may be used in a task-specific way. We also explored possible relation of APAs in leg and trunk muscles to head stabilization. METHODS: Load perturbations (loading and unloading) were applied to the head, trunk, and head and trunk simultaneously using similar hand actions by standing persons. Electromyographic signals (EMGs) from 10 muscles were recorded. Shifts of the center of pressure and EMG indices were computed over typical time intervals for APA. RESULTS: Time-shifted (reciprocal) activation of neck flexor and extensor muscles during APAs was seen when perturbations were applied directly to the head. Simultaneous activation dominated when the perturbations were applied to the trunk. Minimal APAs were seen in the leg/trunk muscles during head perturbation tests. APAs during trunk perturbation were not different from those during trunk and head perturbation. CONCLUSIONS: The results confirm the existence of two different patterns of APAs in neck muscles. A time-shifted (reciprocal) pattern is more likely to be used in anticipation of a perturbation acting directly on the head. A simultaneous activation (co-activation) pattern is used when direction of head perturbation cannot be predicted with certainty. Leg/trunk APAs are unlikely to help stabilize head posture. SIGNIFICANCE: These results are important for better understanding of feed-forward mechanisms of the control of head posture with possible implications for neurological patients who suffer from impaired feed-forward postural control.     

Freeze-drying polymeric colloidal suspensions: nanocapsules, nanospheres and nanodispersion. A comparative study.

Different polymeric nanoparticles were freeze-dried and the powders compared to determine the influence of the lipophilic core (Miglyol 810) or benzyl benzoate) and polymeric material (poly(epsilon-caprolactone) or Eudragit S90) on their drug content and morphology. Diclofenac, a non-steroidal anti-inflammatory drug, was used as a model. To characterize the products, a biological experiment based on the evaluation of the mucosal toxicity of diclofenac was conducted. Nanocapsule and nanosphere suspensions were prepared by nanoprecipitation and freeze-dried after the addition of colloidal silicon dioxide. The powders were examined under scanning electron microscopy (SEM) and gastrointestinal tolerance of products was evaluated in rats. Powders presented drug contents between 90.2+/-5.5 and 101.1+/-1.9% (HPLC). SEM analyzes showed non-spherical microparticles and, at higher magnifications, the micro-powder surface presented a homogeneous nanocovering. Regarding the gastrointestinal tolerance, with the exception of benzyl benzoate-loaded formulations, powders presented lesional indexes lower than the diclofenac salt solution. In contrast to the literature, nanocapsules can be dried by freeze-drying without leakage of drug or breaking the capsule wall.     

Up-Regulation of TH2 feto-placental levels could be involved in the protective effect of low-molecular-weight heparin treatment on spontaneous abortion in mice

The cytokines that predominate at the healthy maternal fetal interface are compatible with those produced by Th2/3 cells. Th1 and Th2 type immunity are mutually inhibitory and cytokine profiles are regulated in part by maternal sex steroids. The immune and endocrine equilibrium required for pregnancy success may be modified by external factors including stress, infection and altered maternal nutrition. The latter has received surprisingly little attention particularly as the effects of nutrition on immunity per se are widely documented. We have used animal models to investigate the effects of altered maternal diet on both immune and endocrine mechanisms important for pregnancy success. In rodents, maternal deficiencies in iron and vitamin A have been shown to negatively alter the expression of placental cytokines and in the case of vitamin A, increase placental apoptosis. In a highly controlled sheep model, overfeeding young growing females carrying singleton pregnancies restricts placental growth resulting in the premature delivery of low birth weight lambs. This is associated with reduced maternal concentrations of progesterone, placental lactogen, PSPB, GH and increased insulin, IGF-1, leptin and thyroid hormones (Wallace et al. Reprod 2001; 122:347–357). At day 80 of gestation (term=145) the placentae of overfed dams exhibit reduced expression of proliferation markers, predominantly in the fetal trophectoderm, and increased expression of the pro-apoptotic protein bax. These data indicate an altered balance between placental proliferation and apoptosis, possibly linked to maternal endocrine status. We conclude that maternal diet has considerable impact on immuno-endocrine mechanisms critical for pregnancy success.     

The product of the imprinted H19 gene is an oncofetal RNA.

AIMS/BACKGROUND: The H19 gene is an imprinted, maternally expressed gene in humans. It is tightly linked and coregulated with the imprinted, paternally expressed gene of insulin-like growth factor 2. The H19 gene product is not translated into protein and functions as an RNA molecule. Although its role has been investigated for more than a decade, its biological function is still not understood fully. H19 is abundantly expressed in many tissues from early stages of embryogenesis through fetal life, and is down regulated postnatally. It is also expressed in certain childhood and adult tumours. This study was designed to screen the expression of H19 in human cancer and its relation to the expression of H19 in the fetus. METHODS: Using in situ hybridisation with a [35S] labelled probe, H19 mRNA was detected in paraffin wax sections of fetal tissues from the first and second trimesters of pregnancy and of a large array of human adult and childhood tumours arising from these tissues. RESULTS: The H19 gene is expressed in tumours arising from tissues which express this gene in fetal life. Its expression in the fetus and in cancer is closely linked with tissue differentiation. CONCLUSIONS: Based on these and previous data, H19 is neither a tumour suppressor gene nor an oncogene. Its product is an oncofetal RNA. The potential use of this RNA as a tumour marker should be evaluated.