Chronic antiepileptic monotherapy,bone metabolism,and body composition in non‐institutionalized children

Aim The aim of this study was to determine the influence of chronic monotherapy with antiepileptic drugs (AEDs) on vitamin D levels, bone metabolism, and body composition. Method Eighty‐five children (38 males, 47 females; mean age 12y 5mo, SD 3y 4mo) were treated with valproate and 40 children (28 males, 12 females; mean age 11y 10mo, SD 3y) were treated with other AEDs (lamotrigine, sulthiame, or oxcarbazepine), comprising the non‐valproate group. Forty‐one healthy children (29 males 12 females; mean age 12y 1mo, SD 3y 5mo) served as a comparison group. Height, weight, body impedance analysis, 25‐hydroxyvitamin D, calcium, phosphate, two bone resorption markers (receptor activator of nuclear factor κB ligand [RANKL] and tartrate‐resistant acid phosphatase 5b [TRAP5b]), osteoprotegerin, and leptin were measured. Results No child was vitamin D deficient as defined by a 25‐hydroxyvitamin D (25OHD) level of less than 25nmol/l (<10ng/ml). Leptin, body fat, weight standard deviation score (SDS), and body mass index (BMI) SDS were all significantly higher (each p<0.001) in valproate‐treated children than in the non‐valproate group, as were calcium (p=0.027) and RANKL (p=0.007) concentrations. Similarly, leptin was significantly higher in the valproate group than in control participants (p<0.001), as were body fat (p=0.023), weight SDS (p=0.046), BMI SDS (p=0.047), calcium (p<0.001), and RANKL (p<0.001), whereas TRAP5b concentrations were significantly lower in the valproate‐treated group (p=0.002). Furthermore, calcium and RANKL levels were significantly higher in the non‐valproate group than in comparison participants (p<0.001 and p=0.016 respectively). Interpretation Non‐enzyme‐inducing or minimal enzyme‐inducing AED monotherapy does not cause vitamin D deficiency in otherwise healthy children with epilepsy. Valproate therapy is associated with increases in weight, body fat, and leptin concentration, as well as with a bone metabolic profile that resembles slightly increased parathyroid hormone action.     

Pulsed Dye Laser Treatment is Effective in the Treatment of Recalcitrant Viral Warts

BACKGROUND Verrucae vulgaris can be removed in a variety of ways but a specific therapy of choice has not yet been developed. Doctors are faced with a challenge, especially in the treatment of recalcitrant warts. It has been suggested that the success of pulsed dye laser treatment lies in the fact that warts contain an increased number of dilated blood vessels.
METHODS Seventy-three patients (42 female, 31 male) with verrucae vulgaris on their hands or feet (1:1.5) were given a maximum of 12 treatments with a flashlamp-pumped pulsed dye laser every 2 weeks over a period of 24 weeks until complete clearance had been achieved. A laser energy density of 8 to 12 J/cm² with a spot size of 5 mm and a pulse duration of 450 μsec were used. The minimum follow-up period was 6 months.
RESULTS A total of 15.1% patients achieved complete clearance after 1 session and 47.9% after 2 to 5 sessions, resulting in a remission of 63.0% patients after a maximum of 5 treatment sessions. A remission of 23.3% patients was seen after 6 to 9 treatments and a total of 89.0% of patients showed remission after a maximum of 10 sessions. Only three patients (4.1%) failed and five patients (6.9%) stopped the treatment on account of pain/noncompliance. Only one patient, from a group of patients treated between January 2003 and April 2004, has relapsed.
CONCLUSION Pulsed dye laser treatment is effective and safe in the treatment of recalcitrant viral warts.     

Rate and Time Dependent Effects of D-Sotalol on the Monophasic Action Potential After Sudden Increase of the Heart Rate

Experimental and clinical data suggests that almost all Class III antiarrhythmic agents diminish their ability to prolong cardiac repolarization at fast heart rates. However, only limited data exists about the time course of efficacy decay of Class III agents after sudden increase of the heart rate. In the present study, we assessed both rate and time dependent changes of the efficacy of d-sotalol in higher stimulation frequencies following an abrupt increase in heart rate. This might imitate the situation seen in the development of paroxysmal tachycardias. Monophasic action potentials were recorded from the right ventricular apex during sinus rhythm and constant stimulation with the paced cycle length (PCL) of 550 ms, 400 ms, and 330 ms in the baseline and 20 minutes after intravenous administration of d-sotalol (2.5 mg/kg) in seven patients with documented life-threatening ventricular tachyarrhythmias. D-sotalol significantly prolonged monophasic action potential duration at different steady-state heart rates (sinus rhythm: 21.1%± 3.6%; PCL 550 ms: 16.6%± 4.3%, 400 ms: 11.2%± 2.7%, 330 ms: 5.8%± 2.1%). The prolongation is significantly shorter in higher steady-state pacing, confirming a pronounced reverse-use dependent decrease of the efficacy of d-sotalol at faster stimulation frequencies. After the abrupt increase in heart rate, the beat-to-beat adaptation of the postdrug action potential prolongation exhibits only slight reverse-use dependent shortening. The decrease of the efficacy of d-sotalol is insignificant for the first 20 consecutive beats at the stimulation frequency of the PCL of 400 msec (from 16.6% at PCL of 550 ms to 14.6% at the 20th beat of the PCL of 400 ms), and for the first ten consecutive beats at the stimulation frequency of the PCL of 330 ms (from 16.8% at PCL of 550 ms to 12.3% at the 10th beat of the PCL of 330 ms). This slow decay of action potential prolongation after an abrupt increase in heart rate might contribute to the antiarrhythmic action of d-sotalol in cardiac tachyarrhythmias.     

Discrimination of Actinic Keratoses from Normal Skin with Reflectance Mode Confocal Microscopy

BACKGROUND Recently, a wide range of new noninvasive therapies has been introduced for the treatment of actinic keratoses. As these treatment options do not provide tissue for histopathologic examination, in vivo confocal laser scanning microscopy may become an important method for obtaining a reliable diagnosis.
OBJECTIVE The objective was to validate the diagnostic confocal examination of actinic keratoses.
METHODS Thirty actinic keratoses and skin fields from the contralateral sides of the patients were consecutively sampled and examined using a confocal microscope. Stored images were rated by four independent observers.
RESULTS Distinct diagnostic morphologic features could be visualized. Overall, sensitivity of 93.34% and specificity of 88.34% could be achieved by two clinical dermatooncologists (positive predictive value 88.94%, negative predictive value 93.15%). Assessment of distinct confocal microscopy features showed a moderate interobserver correlation (κ= 0.4–0.6 in five of seven criteria). Classification and regression tree analysis yielded a one-step algorithm based on only one criterion (irregular keratinocyte cell borders), facilitating a correct classification in 86.67% of actinic keratoses and 85% of normal skin.
LIMITATIONS Hyperkeratotic actinic keratoses were excluded from the study set.
CONCLUSIONS This study provides a set of morphologic confocal microscopy criteria showing promise as a noninvasive monitoring tool in the treatment of actinic keratoses.     

Synthesis and biological characterisation of a series of iberiotoxin analogues

We report here the synthesis of iberiotoxin (IbTX), a 37-amino acid peptide containing three disulfide bridges, and a series of mono-looped analogues. All syntheses were conducted using Fmoc chemistry. Synthesis of IbTX gave a product which was indistinguishable from a reference sample in both its physicochemical properties and its biological activity. A series of three mono-looped analogues, in which four of the six cysteines were replaced by alanine, were synthesised to give [Ala^7,13,28,33]-IbTX, [Ala^13,17,33,35]-IbTX and [Ala^7,17,28,35]-IbTX. Oxidation of the linear form of [Ala^7,17,28,35]-IbTX to form the Cys¹³ to Cys³³ disulfide bridge proceeded more slowly than that of the other two analogues. None of these analogues was biologically active, indicating that no single loop is the mediator of channel blocking activity.     

Comparative Nephrotoxicity of a Novel Platinum Compound, Cisplatin, and Carboplatin in Male Wistar Rats

The nephrotoxicity of three platinum-containing antitumor agentswas compared at doses that approximate the LDIO (cisplatin)or the LD5O (CI-973, carboplatin) doses. Male Wistar rats wereadministered single iv doses of 45 mg/kg CI-973, 6.5 mg/kg cisplatin,or 65 mg/kg carboplatin and observed for 4 days. Cisplatin treatmentincreased blood urea nitrogen (4X), creatinine (3x), glucose,and fractional electrolyte excretions, and decreased creatinineclearance by Day 4. These parameters were not significantlyaltered in CI-973- and carhoplatin-treated animals. Cisplatinincreased urinary excretion of LDH (six fold), GGT (twofold),and NAG (twofold); CI-973 and carbo platin increased GGT excretion(approximately twofold). Cis platin induced the following functionalchanges as a conse quence of direct nephrotoxicity: decreasesin GFR (84%), ERPF (97%), ERBF (96%), and ERTS (95%), and increasesin FF (fivefold). Functional changes, attributed to prerenaleffects of CI-973, included a decrease in ERPF (35%) and anincrease in FF (48%). No changes were seen following carboplatintreat ment. All cisplatin-treated rats had proximal tubularnecrosis in the outer stripe of the outer medulla, extendingmultifocally into inner cortical medullary rays. No renal lesionswere de tected by light or electron microscopy in the controlor Cl-973- or carboplatin-treated rats. Cisplatin produced markednephro toxicity as determined by biochemical, functional, andhisto pathologic endpoints. CI-973 and carboplatin were significantlyless nephrotoxic than cisplatin.     

Anatomical compartments of the parasellar region: adipose tissue bodies represent intracranial continuations of extracranial spaces

The cavernous sinus is traditionally described as a single anatomical compartment that contains cranial nerves, blood vessels, and connective tissue. A detailed analysis of 45 infant and 4 fetal parasellar regions shows that this view must be modified. The spatial arrangement, the topographic relations, and the expansion of the adipose and connective tissue spaces were analysed and reconstructed 3-dimensionally on a computer. It is shown that 3 different anatomical compartments, which are strictly demarcated by connective tissue, compose the parasellar region of infants. Two represent intracranial continuations of extracranial tissue spaces. The 3rd compartment corresponds to the so-called 'cavernous sinus' of the adult. Each of the 3 compartments contains characteristic adipose tissue bodies. Because the cavernous sinus represents only one compartment of the area, we propose to use the term 'parasellar region' to designate the entire anatomical region on either side of the sella turcica.