Contribution of intrinsic neuronal factors in the generation of cortically driven electrographic seizures

Some electrographic seizures are generated intracortically. The cellular and ionic bases of cortically generated spontaneous seizures are not fully understood. Here we investigated spontaneously occurring seizures consisting of spike-wave complexes intermingled with fast runs in ketamine-xylazine anesthetized cats, using dual intracellular recordings in which one pipette contained a control solution and another pipette contained blockers of K(+), Na(+), or Ca(2+) currents. We show that closely located neocortical neurons display virtually identical fluctuations of the membrane potential during electrographic seizures, thus directly demonstrating a high degree of focal synchrony during paroxysmal activity. In addition to synaptic drives, the persistent Na(+) current [I(Na(p))] and probably the high-threshold Ca(2+) current contributed to the generation of paroxysmal depolarizing shifts (PDSs) during cortically driven seizures. Ca(2+)-activated K(+) current [I(K(Ca))] took also part in the control of the amplitude and duration of PDSs. The hyperpolarizing components of seizures largely depended on Cs(+)-sensitive K(+) currents. I(K(Ca)) played a significant, while not exclusive, role in the mediation of hyperpolarizing potentials related to EEG "waves" during spike-wave seizures. We conclude that intrinsic cellular factors have significant role in the generation of depolarizing and hyperpolarizing components of seizures.     

Percutaneous Microwave Ablation of Renal Angiomyolipomas

Purpose

To evaluate the safety and efficacy of US-guided percutaneous microwave (MW) ablation in the treatment of renal angiomyolipoma (AML).

Materials and Methods

From January 2011 to April 2014, seven patients (5 females and 2 males; mean age 51.4) with 11 renal AMLs (9 sporadic type and 2 tuberous sclerosis associated) with a mean size of 3.4 ± 0.7 cm (range 2.4–4.9 cm) were treated with high-powered, gas-cooled percutaneous MW ablation under US guidance. Tumoral diameter, volume, and CT/MR enhancement were measured on pre-treatment, immediate post-ablation, and delayed post-ablation imaging. Clinical symptoms and creatinine were assessed on follow-up visits.

Results

All ablations were technically successful and no major complications were encountered. Mean ablation parameters were ablation power of 65 W (range 60–70 W), using 456 mL of hydrodissection fluid per patient, over 4.7 min (range 3–8 min). Immediate post-ablation imaging demonstrated mean tumor diameter and volume decreases of 1.8 % (3.4–3.3 cm) and 1.7 % (27.5–26.3 cm³), respectively. Delayed imaging follow-up obtained at a mean interval of 23.1 months (median 17.6; range 9–47) demonstrated mean tumor diameter and volume decreases of 29 % (3.4–2.4 cm) and 47 % (27.5–12.1 cm³), respectively. Tumoral enhancement decreased on immediate post-procedure and delayed imaging by CT/MR parameters, indicating decreased tumor vascularity. No patients required additional intervention and no patients experienced spontaneous bleeding post-ablation.

Conclusion

Our early experience with high-powered, gas-cooled percutaneous MW ablation demonstrates it to be a safe and effective modality to devascularize and decrease the size of renal AMLs.

     

The Frequency Of Arterial Hypertension Versus Orthostatic Hypotension In Diabetic Patients

Aim: The aim of this study was to assess the relationship between supine high blood pressure and orthostatic hypotension both in Type 1 (T1DM) and Type 2 (T2DM) diabetic patients. Patients and Methods: Our study included 321 T2DM patients (153 M/168 F; mean age 62.3 (14.2 yr; duration of disease 12.1 (7.6 yr) and 116 T1DM patients (65 M/51 F; mean age 39.7 (9.2 yr; duration of diabetes 11.9 (8.1 yr). Patients with orthostatic hypotension were divided into 3 groups: A – without symptoms; B – mild/moderate symptoms (short and tolerable dizziness when standing); C – severe symptoms (persistent and disabling dizziness or even fainting in upright position). Results: Arterial hypertension was registered in 67.6% of T2DM patients (217 from 321 cases) and in 50.0% of T1DM patients (58 from 116 cases). Orthostatic hypotension (defined as a decrease in systolic blood pressure (30 mm Hg)) was encountered in 64.5% in T2DM patients (207 out of 321 cases) and in 60.3% of T1DM patients (70 out of 116 cases). From 207 T2DM patients with orthostatic hypotension, 105 were in Group A (50.7%), 89 in Group B (42.99%) and 13 in Group C (6.28%), while from 70 T1DM patients with orthostatic hypotension 14 were in Group A (20.0%), 51 in Group B (72.8%) and 5 in Group C (7.14%). An association of supine arterial hypertension with orthostatic hypotension was registered in 96 (29.9%) T2DM patients (68 of them receiving antihypertensive treatment) and in 25 (21.5%) T1DM patients (19 of which were on antihypertensive treatment). From the 18 patients with severe orthostatic hypotension (13 T2DM and 5 T1DM), supine arterial hypertension was registered in 5 cases (3 T2DM and 2 T1DM). In 4 of these 5 cases, patients were receiving antihypertensive treatment. Discontinuation of this treatment led to a decrease in the intensity of clinical signs of orthostatic hypotension in 4 out of 5 cases. An improvement of clinical symptoms of orthostatic hypotension was recorded in about 1/3 of hypertensive patients after discontinuation or just lowering of the dose of antihypertensive drugs (26 out of 87 cases). Conclusion: An association between hypertension and orthostatic hypotension is frequent both in T1DM and in T2DM, rising in difficulties for treatment. The treatment of hypertension in diabetic patients should take into account the possible orthostatic hypotension induced by some of the antihypertensive drugs.     

Comparative studies of rat IgG to further delineate the Fc : FcRn interaction site

Recent data have indicated that the MHC class I-related receptor, FcRn, regulates the half-lives of serum IgG in addition to its known role in transferring IgG from mother to young. In the current study, the activity of rat IgG (rIgG) isotypes in FcRn-mediated functions has been analyzed. The serum half-life and maternofetal transfer in mice decreased in the order rIgG2a > rIgG1 > rIgG2c > rIgG2b. This decrease in activity correlates well with reduced binding affinity for soluble mouse FcRn, and site-directed mutagenesis of a recombinant Fc-hinge fragment has been used to investigate the molecular basis for the differences in activities of the rIgG. Analysis of the serum half-lives of the mutated Fc-hinge fragments demonstrated that, in addition to Ile253, His310, His435 and His436 that were identified in earlier studies, amino acids at positions 257, 307 and 309 play a role in building the FcRn interaction site of IgG. The study also excludes the involvement of amino acids in a fourth loop located at the CH2-CH3 domain interface that encompasses residues 386 – 387 in FcRn binding. Sequence differences at positions 257, 307 and 309 between rIgG most likely account for the reduced affinity of rIgG2b and IgG2c relative to rIgG1 and rIgG2a for binding to FcRn.     

Synthesis and characterization of poly(azomethine)s with rotaxane architecture

Poly(azomethine)s with rotaxane architecture were synthesized by means of solution polycondensation of terephthalaldehyde with 1,6-hexamethylenediamine/α- and ß-cyclodextrin adducts, and blocking of the chain ends with a bulky aromatic amine, i.e., p-aminophenyltriphenylmethane. As compared with the polymer obtained in the absence of cyclodextrin, these polymers are more hygroscopic and soluble in polar solvents while their IR, NMR and DSC data support the presence of cyclodextrins in the polymer chain.     

Multipolar maps in patients with postinfarction heart failure

Purpose

The aim of this study was to assess the changes in body surface maps in patients with postinfarction heart failure (PIHF).

Materials and Methods

Body surface mapping was performed in 22 patients with PIHF and 20 age-matched healthy controls, using a 64-electrode vest. A card index was made for every patient and person of the control group, containing isopotential and isointegral maps. The number and absolute value of maxima and minima were assessed for every map.

Results

Only bipolar maps were recorded in the healthy control group, and multipolar maps were found in 55% of the patients with PIHF. All patients with multipolar isointegral QRST maps had also multipolar isopotential ST maps (J + 110 milliseconds); 67%, multipolar isopotential QRS peak maps; 33%, multipolar isointegral Q40 maps; 17%, multipolar isointegral QRS maps; 67%, multipolar isointegral STT maps; and 50%, multipolar isointegral ST maps. Significant differences were noticed in maxima and minima in patients with PIHF compared with healthy controls and in patients with multipolar isointegral maps (QRST and Q40) compared with those with bipolar maps. Multiple regression analysis revealed that multipolar QRST maps were significantly associated (P < .001) with maxima and minima of the isointegral maps. Isointegral multipolar QRST maps were significantly associated (P < .001) with multipolar isopotential ST maps, multipolar isointegral QRS maps, multipolar isointegral STT maps, and multipolar isointegral ST maps.

Conclusion

Postinfarction heart failure increases the prevalence of multipolar maps and significantly changes maxima and minima. Multipolar QRST isointegral maps are significantly associated with maxima and minima of the QRS, ST, STT, and QRST maps and with other types of multipolar maps: isointegral QRS, STT, ST and isopotential ST (J + 110 milliseconds), and QRS peak maps.