GROWTH HORMONE SECRETION IN PRIMARY DEGENERATIVE DEMENTIA: CORRELATIONS WITH COGNITIVE IMPAIRMENT

Changes in brain peptides and neurotransmitters are thought to elicit alterations of growth hormone (GH) secretion in dementia. Baseline GH levels and hormone responses to GH-releasing hormone (GHRH)—administered alone or after pyridostigmine pretreatment—were evaluated in 17 patients, aged 52–83, with primary degenerative dementia quantified by the Clinical Dementia Rating (CDR) Scale and the Mini-Mental State Examination (MMSE) with a view to detecting correlations between neuroendocrine and clinical data. Basal GH levels were not statistically different in patients and in age-matched controls. However, when patients were split into the three CDR groups of disease severity, basal GH levels were significantly higher in those with more severe dementia than in all other patients and in controls. GH responses to GHRH, evaluated both in terms of peaks attained after simulation and of secretion areas under the curve (AUC), were significantly higher in patients than in controls after pyridostigmine pretreatment, but not after the infusion of GHRH alone. Patients with mild to moderate dementia had GH peaks after GHRH higher than more severe patients. Pyridostigmine did not potentiate GHRH effects in the more severe cases. The scores on Rey's 15-word test for memory function were directly correlated with GH peaks after GHRH. No correlations were found between GH data, age, body weight, disease duration and scores at other psychometric assessments such as MMSE, Raven's matrices, verbal fluency or WAIS tests.     

KIDNEYS DERIVED FROM MICE TRANSGENIC FOR HUMAN COMPLEMENT BLOCKERS ARE PROTECTED IN AN IN VIVO MODEL OF HYPERACUTE REJECTION

Purpose

The major obstacle to successful discordant kidney xenotransplantation is hyperacute rejection (HAR). Complement plays a key role in the induction of HRA, defined by endothelial cell activation, loss of vascular integrity, hemorrhage and thrombosis. The activation of complement is tightly controlled by a number of species-specific regulatory proteins which inhibit, at different points, the cascade of events leading to the formation of the membrane attack complex (MAC). We have tested the hypothesis that kidneys derived from transgenic mice expressing two human complement inhibitors, Decay Accelerating Factor (hDAF) and Membrane Cofactor Protein (MCP), could be protected from human complement-mediated damage.

Materials and Methods

Control and transgenic mice were perfused with human plasma by cannulation of the right jugular vein, at a perfusion rate of 10 micro L./min. for two hours. Complement C3 deposition was detected on kidney sections by immunohistochemistry using specific FITC antibody. Complement-induced tissue damage was evaluated by histopathological examination.

Results

Heavy deposition of complement C3 was observed on kidneys derived from perfused control mice. This was associated with a characteristic HAR pathology of severe interstitial hemorrhage, inflammatory reaction, loss of glomerula and tubuli structure. Kidneys derived from mice transgenic for hDAF or hMCP were partially protected from both complement C3 deposition and tissue damage. The expression of both dDAF and hMCP in double transgenic mice significantly increases the protection from human complement-mediated damage.

Conclusions

A novel model of in vivo perfusion with human plasma has been adopted to recreate the initial event of HAR. Our data show that this murine model could be very valuable to determine the effect of transgenic human molecules in protecting vascularized organs from human complement attack.     

Atrial Septal Pacing:

Atrial pacing may prevent the onset of atrial fibrillation (AF) because of: (1) prevention of the relative bradycardia that triggers paroxysmal AF; (2) prevention of the bradycardia induced dispersion of refractoriness; (3)suppression or reduction of premature atrial contractions that initiate reentry and predispose to AF; (4) preservation of AV synchrony, which might prevent switch induced changes in atrial repolarization predisposing to AF. Atrial pacing locations that decrease atrial activation and dispersion of refractoriness may be preferable in patients with a history of AF. Two different interatrial septum sites have been proposed: the Bachmann's bundle and the coronary sinus ostium. The results of two prospective randomized studies indicate that septal pacing, when compared to the traditional right atrial appendage pacing, significantly reduces : (1) paroxysmal AF recurrences and burden; and (2) progression to chronic AF. (PACE 2004; 27[Pt. II]:850–854)     

Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study

Summary. Background: There is not enough clinical evidence to make a strong recommendation on the optimal duration of thromboprophylaxis using low‐molecular weight heparins (LMWH) in patients undergoing major cancer surgery. Patients and methods: CANBESURE is a randomized, double‐blind study which enrolled patients admitted for abdominal or pelvic surgery for cancer. They received 3500 IU of bemiparin subcutaneously once daily for 8 days and were then randomized to receive either bemiparin or placebo for 20 additional days. Bilateral venography was performed after 20 days and evaluated blinded. The primary efficacy outcome was the composite of deep vein thrombosis (DVT), non‐fatal pulmonary embolism (PE) and all‐cause mortality at the end of double‐blind period. Major venous thromboembolism (proximal deep‐vein thrombosis, non‐fatal pulmonary embolism and venous thromboembolism‐related deaths) was also evaluated. The primary safety outcome was major bleeding. Results: Six hundred and twenty‐five and 488 patients were included in the safety and main efficacy analyzes, respectively. The primary efficacy outcome occurred in 25 out of 248 patients (10.1%) in the bemiparin group and 32 out of 240 (13.3%) in the placebo group (relative risk reduction 24.4%; 95% CI: ?23.7–53.8%; P = 0.26). At the end of double‐blind period, major venous thromboembolism occurred in 2 (0.8%) and 11 (4.6%) patients, respectively (relative risk reduction 82.4%; 95% CI: 21.5–96.1%; P = 0.010). No significant difference was found in major bleedings. Conclusions: Four weeks compared with 1 week of prophylaxis with bemiparin after abdominal or pelvic cancer surgery did not significantly reduce the primary efficacy outcome, but decreased major venous thromboembolism (VTE) without increasing hemorrhagic complications.     

Absorption pharmacokinetics of clonidine nasal drops in children

Background:  The α2 agonist clonidine has become a popular drug for premedication in children. Effects and pharmacokinetics after oral, rectal, and intravenous administration are well known. The aim of this study was to investigate the absorption pharmacokinetics of clonidine nasal drops in children.
Methods:  Thirteen ASA I pediatric patients received after induction of anesthesia 4 mcg·kg⁻¹ of clonidine by the nasal route. Blood samples were taken during a 12-h period and plasma levels of clonidine were analyzed by liquid chromatography–mass spectrometry. Data were calculated by a computer-aided curve-fitting program.
Results:  Plasma pharmacokinetics following administration of clonidine nasal drops showed a considerable interindividual variability and absorption was delayed and limited. A total of 95% confidence intervals for maximum plasma concentration and time to achieve maximum plasma concentration were 0.4–0.6 ng·ml⁻¹ and 1.4–3.0 h, respectively.
Conclusions:  Clonidine nasal drops are erratically absorbed from the nasal mucosa and, thus, this mode of drug administration is not recommended for premedication purposes.     

Image Integration-Guided Catheter Ablation of Atrial Fibrillation: A Prospective Randomized Study

Background: Several studies have provided details of left atrial anatomy by means of the image integration techniques, particularly focusing on the atypical patterns of the pulmonary veins.
Objective: To compare, in a prospective, randomized fashion, the conventional method of pulmonary vein disconnection and the image integration-guided approach.
Methods: Two hundred and ninety consecutive patients (290 patients, mean age 55 ± 11 years) with drug-refractory paroxysmal or persistent atrial fibrillation were enrolled in the study and were divided into two treatment groups: group 1 (145 patients) undergoing an imaging integration-guided (CartoMerge TM) ablation; group 2 (145 patients) treated by a conventional radiofrequency catheter ablation procedure. The arrhythmia was refractory to at least two antiarrhythmic drugs (IC, amiodarone).
Results: Electrical disconnection of all identified pulmonary veins was obtained in all patients of both groups. Bidirectional block of the cavotricuspid isthmus was achieved in 34 group 1 patients and in 40 group 2 patients. Left mitral isthmus ablation was attempted in 52 group 1 patients and in 56 group 2 patients. At a mean follow-up of 14 ± 12 months, the atrial fibrillation-free survival rate was significantly higher in group 1 patients compared with group 2 patients (88% vs 69%, P = 0.017). The analysis for the subset of patients with previously ineffective ablation (98 patients: 52 group 1 patients and 46 group 2 patients) showed a significantly lower recurrence rate in group 1 versus group 2 (19% vs 48%, P < 0.01).
Conclusions: Our data indicate a superior efficacy of the image-integration guided catheter ablation of atrial fibrillation over the long term.     

Septo‐optic dysplasia in childhood: the neurological,cognitive and neuro‐ophthalmological perspective

Aim We set out to describe 17 patients with septo‐optic dysplasia (SOD), focusing on the little‐explored neurological, cognitive, and neuro‐ophthalmological components. A further aim was to identify possible clinical correlations and phenotypic characteristics within the diagnostic spectrum. Method We collected clinical‐instrumental data (from the history, general and neurological examination, developmental assessment, and neuro‐ophthalmological, neuroradiological, neurophysiological, and endocrinological evaluations) on nine males and eight females (mean age 34.4mo, SD 31.6; range 4mo‐9y 6mo) diagnosed with SOD who were referred to our Centre of Child Neuro‐ophthalmology between 1999 and 2010. Results We observed a heterogeneous clinical spectrum characterized by nervous system, visual, and endocrine dysfunctions; optic nerve involvement was present in all 17 children, midline brain defects in 14, and cortical developmental malformations in seven. Developmental/cognitive delay and relational and communication difficulties were observed in eight and seven children, respectively, and reduced visual acuity and oculomotor dysfunction were observed in all. Pituitary hormone deficiencies were present in nine children. Interpretation Nervous system involvement emerged as a key feature of SOD. As part of a holistic approach to the disease, particular attention should be paid to this aspect. The emergence of new clinical correlations and correlations between clinical features and three SOD subtypes opens the way for better clarification of this disease and, therefore, more targeted diagnosis, follow‐up, and care of affected children.