E. Bermejo

Epidemiological and clinical analysis of a consecutive series of conjoined twins in Spain.

PURPOSEnThe aim of the study was to analyze the frequency and certain epidemiological characteristics of a consecutive series of conjoined twins born in Spain.nnnMATERIAL AND METHODSnWe used data from the Spanish Collaborative Study of Congenital Malformations for the period April 1976 to 2006. Because the Spanish law permitting voluntary termination of pregnancies (TOP) when the fetus presented malformations was effective by the end of 1985, we analyzed the data in 4 periods, 2 before 1986 and 2 after. During the first period (1976-1979) only live births were recorded, whereas both still and live births were included in the other three (1980-1985, 1986-1995, and 1996-2006). In the present study, the cases were classified as symmetrical (16 pairs) and asymmetrical (1 pair) conjoined twins. Each pair of conjoined twins was considered as only one case for calculations, regardless of the type of union.nnnRESULTSnAmong a total of 2,281,604 consecutive births between 1980 and 2006, there were a total of 15 cases of symmetrical conjoined twins giving a frequency of 0.70 per 100,000 (1/152,107), whereas there was only 1 stillborn asymmetrical conjoined twin pair (0.04/100,000). Among the 13,418 consecutive stillborns surveyed, 6 cases of conjoined twins were identified (either symmetrical or asymmetrical) giving a frequency of 44.72 per 100,000, and 11 pairs were identified among the 2,425,583 total live births surveyed during the first period 1976 to 1979, a frequency of 0.45 per 100,000. Thus, the frequency among stillborn infants is 99.34 times higher than that observed among live births. However, the frequency for the total births (3 last periods) showed a decreasing trend from 1.47 per 100,000 birth in the first period (1980-1985) when TOP was illegal, to a value of 0.09 per 100,000 in the last period, more than 16-fold lower, probably because of the TOP of affected fetuses. Therefore, we consider that the frequencies observed in the period 1980 to 1985 are the basal values in our population. The most frequent type observed was thoracopagus, with an overall prevalence at birth of 0.44 per 100,000 (1/228,160) from 1980 to 2006, representing 58.82% of the total population of symmetric conjoined twin pairs. Diprosopus pairs were the next most common group (11.76%). Most of the cases were females (4 males/11 females), and although this appeared to be mainly because of the thoracopagus pairs (males-females, 2:8), in such a small number of cases, it is not possible to determine the ratios for the other groups. Gestational age was significantly shorter than in control twins for each type studied.nnnCONCLUSIONSnWe conclude that it is incorrect to consider that all types of conjoined twins have the same epidemiological characteristics, such as the frequency at birth. The differences observed may be related with the distinct embryo-fetal mortality of each type of conjoined twins in different populations, and the sex ratio, among others.

Review of the recently defined molecular mechanisms underlying thanatophoric dysplasia and their potential therapeutic implications for achondroplasia.

Achondroplasia (ACH), thanatophoric dysplasia (TD) types I and II, hypochondroplasia (HCH), and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) are all due to activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We review the clinical, epidemiological, radiological, molecular aspects, and signaling pathways involved in these conditions. It is known that FGFR3 signaling is essential to regulate bone growth. The signal transducers and activators of transcription (STAT1) pathway is involved in the inhibition of chondrocyte proliferation, and the mitogen‐activated protein kinase (MAPK) pathways are involved in chondrocyte differentiation. Hence, FGFR3 signaling is pivotal in chondrocyte differentiation and proliferation through these two different active pathways. Recent studies on the molecular mechanisms involved in chondrocyte differentiation and proliferation, demonstrated that Snail1 participates in the control of longitudinal bone growth and appears to be essential to transduce FGFR3 signaling during chondrogenesis. This result was confirmed in a newborn infant with TD, and suggests new non‐surgical therapeutic approaches, that is, Snail1 as a new encouraging therapeutic target.

Electrochemical determination of carbaryl oxidation in natural water and soil samples

An electrochemical method for the determination of carbaryl, after prior oxidation to 1,4-naphthoquinone in natural water and soils is reported. The coulometric oxidation of carbaryl at a platinum electrode was studied using 0.024 mol/L Britton-Robinson buffer (pH 7.0). The reduction of the oxidation product 1,4-naphthoquinone at a dropping mercury electrode was used for the indirect determination of carbaryl after separation on C18 Sep-pak cartridges by differential pulse polarography (detection limits: 0.41 mg L−1 of water and 0.47 mg kg−1 of soil) and directly without separation by adsorptive stripping voltammetry (detection limits: 5 μg L−1 of water and 7 μg kg−1 of soil, for 75 s preconcentration time). Relative errors were lower than 3.7% and relative standard deviations smaller than 4.5%.

Ephedrine Determination in Human Urine Using a Carbon Paste Electrode Modified with C18 Bonded Silica Gel

Abstract An electrochemical method by adsorptive stripping voltammetry with a modified carbon paste electrode with C18 bonded silica gel is described for the determination of ephedrine in human urine samples. The preconcentration step is performed at open circuit and constant stirring (1000 rpm) in 5×10−4 M sodium hydroxide and the measurement step in ammonia-ammonium chloride buffer (pH=10.0; 0.2 M) by linear scan voltammetry to 150 mVs−1 between 0.20 and 1.10 V. With the proposed method, ephedrine can be directly determined in urine, a relative standard deviation of 3.4% (n=12) and a detection limit of 270 μgmL−1 for a 2 minute preconcentration time, were obtained.

Determination of ephedrine in human urine using a glassy carbon electrode

Abstract The electrochemical behaviour of ephedrine at a glassy carbon electrode was studied using linear-sweep and differential-pulse voltammetry at a stationary electrode and a rotating disc electrode. The studies were performed using 0.04 M Britton-Robinson buffer (pH 10.0), which allowed the evaluation of the diffusion constant, the charge-transfer coefficient and the conditional charge-transfer rate constant. A method was also devised for the electrochemical determination of ephedrine in human urine samples using differential- pulse voltammetry with prior drug separation. If this separation method is applied, either calibration graphs or standard additions can be used to determine ephedrine at concentrations between 7 and 20 g ml −1 , with relative errors lower than 6.0% and relative standard deviations lower than 5.8%. The presence of norephedrine at levels 20% lower than those of ephedrine has no influence on ephedrine determination.

Determination of phenylephrine with a modified carbon paste electrode

An anodic stripping voltammetric method for determination of phenylephrine with a modified carbon paste electrode is developed. The modified carbon paste electrode was prepared with carbon paste mixed with a cation exchange resin containing the functional group CO 2 Na. Linear scan voltammetry was used for the electrochemical measurements. The experimental conditions for preconcentration and measurement steps have been optimized in order to attain the optimum analytical signal. In 0.1 M hydrochloric acid the drug shows a well defined oxidation peak at 1.07 V (vs. Ag/AgCl/3 M KCl). A procedure for determining phenylephrine in urine is also described

Electrochemical studies of ethamivan at glassy-carbon and platinum electrodes and its determination in urine by differential pulse voltammetry

Abstract The electrochemical oxidation of ethamivan (N,N-diethyl-4-hydroxy-3-methoxy-benzamide) was investigated using cyclic, linear scan and differential pulse voltammetry at glassy-carbon and platinum stationary electrodes, and rotating disk voltammetry. The values of pKa, 8.98 and 9.03, were determinated by potentiometric and spectrophotometric methods. The compound showed an electrochemically reversible two electrons oxidation peak followed by an irreversible chemical reaction, and produced a new redox couple. The best defined peaks were obtained in 0.05 M sulphuric acid or 0.1 M hydrochloric acid at 0.87, 0.55 and 0.61 V (vs. Ag/AgCl/3 M KCl). The peak currents in cyclic voltammetry and the limiting current at a rotating disk electrode are diffusion-controlled. Using rotating disk voltammetry the mass-transport rate constant was 5.26 × 10−3cms−1 for a rotation frequency of 20.34 Hz, the diffusion coefficient was 6.5 × 10−6 cm2 s−1, the charge-transfer conditional rate constant was 1.2 × 10−3cm s−1 and the charge transfer coefficient (β) was 0.91. By linear scan voltammetry calibration plots were linear in the range 7.0 × 10−5−8.0 × 10−4M at the Pt electrode and in the range 4.0 × 10−5 − 1.0 × 10−3M at the GCE in 0.05 M sulphuric acid at 50 mV s−1. A method was also developed for the electrochemical determination of ethamivan in human urine using differential pulse voltammetry with prior drug separation with C18 cartridges (Sep-Pak, Waters). The mean recovery was 92 ± 6% (n = 8). The standard addition method was applied. The relative standard deviation was lower than 9% (samples of 15 μg ml−1 ethamivan). The detection limit was 4 μg per milliliter of urine.

Application of adsorptive stripping voltammetry to the determination of the psychoactive drug temazepam in urine

SummaryThe influence of various operational parameters on the stripping response for temazepam is discussed. Interfacial and redox behaviour was also studied. 205 Å2 was the average surface area per adsorbed molecule.The determination of temazepam in urine can be performed by using adsorption as a preconcentration step previous to its measurement at the hanging mercury drop electrode by differential pulse voltammetry in 0.01 mol/l Britton-Robinson buffer at pH 3.0 with a −0.50 V accumulation potential. The detection limit was 17 ng temazepam per ml of urine (15 s accumulation time) and the relative standard deviation was lower than 6.0% for 500 ng ml−1 samples (10 s). The effects of various urine components on the voltammetric response have also been studied.

Voltammetric Studies of Psychotropic Drugs with Nitro-Groups Determination of Clonazepam in Urine by Adsorptive Stripping Voltammetry

Abstract The interfacial and redox behaviour of clonazepam was studied by adsorptive stripping voltammetry at a hanging mercury drop electrode (HMDE). The results obtained by linear scan mode indicate that the electron transfer is preceded by adsorption, a Frumkin-type adsorption process being established. Determination of clonazepam can be performed at nanomolar levels using differential pulse mode. The best conditions were obtained in 0.025 M carbonate buffer of pH 10.0, with an accumulation potential of -0.30 V. The influence of urine components on the voltammetric response was also studied. Albumin and uric acid were found to interfere to a significant degree, making a preliminary separation of the drug by extraction a necessity. The proposed method is appropiate for determation of clonazepam in urine UP to 550 ng mHof urine, with a 10 ng ml-betection limit at 60 s of accumulation t i eand a relative standard deviation lower than 2.9%

Voltammetric studies on the interactions between camazepam metabolic series and human serum albumin. Determination of oxazepam using adsorptive stripping voltammetry

Abstract The behaviour of oxazepam in adsorptive stripping voltammetry was studied taking into account those conditions which have an influence on the accumulation step (electrolyte, pH, time, potential, drop size and stirring rate), rest time and stripping step (pulse amplitude and scan rate). Oxazepam can be determined at a hanging mercury drop electrode by differential-pulse voltammetry in 0.008 M Britton-Robinson buffer at pH 2.0 with a −0.50 V accumulation potential. Its detection limit was found to be 3.6 × 10 −10 M (30-s accumulation) and the relative standard deviation for oxazepam concentrations in the range 2.8 × 10 − 8−4.0 × 10 −7 M is lower than 2.8% (80-s accumulation). In addition, a procedure using adsorptive stripping voltammetry was developed to study the interactions occurring between human albumin and the camazepam metabolic series (camazepam, temazepam and oxazepam). The interactions decreased in the order temazepam ⪢ oxazepam ⪢ camazepam and the groups and structural modifications favouring interaction were determined.