Infraclavicular Catheter in MELAS Syndrome for Analgesic Purposes.

MELAS syndrome is defined as mitochondrial myopathy accompanied by encephalopathy, lactic acidosis, myoclonus, stroke-like episodes. It has a progressive course, multi-systemic effects and severe complications. Myoclonic contractions are unresponsive to many anti-epileptic drugs; these contractions and spasms may lead to severe pain. Systemic analgesic drugs are not sufficient to control pain. Therefore, continuous brachial plexus blockage may be preferred. Infraclavicular brachial plexus catheter is placed in our case. Local anesthetic injections through this catheter may be effective in pain management and results are to be discussed here.

An eight-case 1q21 region series: novel aberrations and clinical variability with new features.

BACKGROUND: Rearrangement of the 1q21 region of chromosome 1 manifests as multiple phenotypes, including microcephaly, intellectual disability, dysmorphic facial features, eye abnormalities, cardiac defects, genitourinary anomalies, autism spectrum disorder, psychiatric conditions and seizures. Herein, we describe eight patients with 1q21 deletion and duplication syndromes, and novel deletions and findings. METHODS: Chromosomal microarray analysis was performed to identify the existence of copy number variation. Quantitative polymerase chain reaction was applied using specific primers for the control and 1q21 region of chromosome 1. Mutational analysis was performed in case 5 using direct genomic sequencing for exons 1-6 in RBM8A. RESULTS: Copy number variation analysis identified seven deletions and one duplication of the 1q21 region in the eight patients. In addition, four variations were de novo, and two deletions are reported here for the first time. One of the cases (case 7) presents moderate intellectual disability and dysmorphic facial findings, whereas chromosomal microarray analysis showed that case 7 had an 889-kb deletion in the 1q21 proximal region (GPR89A, PDZK1, CD160, POLR3C and NBPF12). CONCLUSION: Although the deletion in case 5 did not include the thrombocytopenia-absent radius syndrome critical region or the RBM8A gene, he had pectoral muscle hypoplasia, radius and humerus hypoplasia and short curved ribs, which are indicative of a potential thrombocytopenia-absent radius region modifier. The findings in case 7 suggest that the proximal part of the 1q21 microdeletion syndrome region might be very important for the onset of clinical manifestations. Some novel findings were observed in the presented cases, such as radius and humerus hypoplasia and brain stem hypoplasia. The presented findings expand the spectrum of 1q21 aberrations and provide evidence of genotype-phenotype correlations for this region.

OCULOECTODERMAL SYNDROME: A NEW CASE WITH GIANT CELL GRANULOMAS AND NON-OSSIFYING FIBROMAS.

Oculoectodermal syndrome (OES) is a very rare disorder with an unknown etiology and characterized by aplasia cutis congenita, epibulbar dermoid and hyperpigmentation areas on the skin. To the best of our knowledge, two cases of OES have been reported to date with recurrent giant cell granuloma in the jaw and one of them also had a non-ossified fibroma in the long bones. Herein, we report the second case with aplasia cutis congenita, epibulbar dermoid, hyperpigmentation along Blaschko lines and also giant cell granuloma in the jaw and non-ossified fibromas in the bones.

Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis.

Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor-like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole-genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES being a mosaic RASopathy and confirm the common etiology of OES and ECCL. KRAS codon 146 mutations, as well as the previously reported OES-associated alterations, are known oncogenic KRAS mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype.

Remifentanil without muscle relaxants for intubation in microlaryngoscopy: a double blind randomised clinical trial.

OBJECTIVES: We aimed to compare the effect of remifentanil without muscle relaxant with succinylcholine for intubation in microlaryngoscopy. PATIENTS AND METHODS: Eighty patients were randomly divided into two groups: Group R (n=40) and S (n=40) received remifentanil 4 µg/kg intravenously or 1 µg/kg respectively. Anesthesia was induced with 2 mg/kg propofol in both groups. Intubation was performed after bolus administration of 10 ml saline as a placebo or 1 mg/kg of succinylcholine in Group R and S respectively. Remifentanil infusion was initiated at 0.025 µg/kg in each groups. RESULTS: Intubation conditions were similar in both groups. The mean arterial pressure (MAP) values at post-induction period were significantly lower in the Group S than in the Group R (p = 0.001). The requirement for ephedrine in Group R was found to be significantly lower than Group S (p = 0.023). Recovery times were significantly shorter (p = 0.001) and recovery scores were significantly higher (p = 0.021) in Group R. Time to patient could respond to commands was significantly longer in the Group S (p = 0.001). The surgeon's satisfaction score was significantly higher in Group R (p = 0.001). CONCLUSIONS: It was concluded that remifentanil without muscle relaxants provides similar intubating conditions as that provided by succinylcholine, and remifentanil is superior to succinylcholine with regard to haemodynamic stability and recovery duration.

The evaluation of long-term effects of ionizing radiation through measurement of current sister chromatid exchange (SCE) rates in radiology technologists, compared with previous SCE values.

Ionizing radiation is a strong physical mutagen, causing breakage of phosphodiester bonds in DNA at any stage of the mitotic cycle. Analysis of sister chromatid exchange (SCE) has come into use as a sensitive DNA-damage indicator. We investigated the SCE rates in radiology technologists who are occupationally and chronically exposed to ionizing radiation. The study included 39 radiology technologists and 35 sex- and age-matched healthy controls. There was a statistically significant difference in the SCE frequency between radiology technologists and controls (p<0.0001). Additionally, previous SCE data of 10 radiology technologists were compared with current results regarding radiation exposure time. There was statistically significant difference between previous and current SCE values (p=0.005). The significant increase in the frequency of SCE in radiology technologists emphasizes the importance of radiation-protection procedures in order to minimize radiation exposure and avoid possible genotoxic effects. Comparison of two studies that measured SCE values of radiology technologists after 8 years also suggests that the genotoxic effect is reversible. In conclusion, radiation is still an important mutagenic agent despite improvements in daily working hours and conditions.

Sevoflurane alone and propofol with or without remifentanil for electroconvulsive therapy-a randomised, crossover study.

We compared the effectiveness of three anaesthetic regimens (propofol alone, propofol with remifentanil and sevoflurane alone), with respect to seizure duration and seizure quality in patients undergoing electroconvulsive therapy. Thirty-nine patients underwent a total of 234 electroconvulsive therapy treatments in this prospective, observer blinded, crossover study. Each patient received either propofol 1 mg/kg alone (Group P), propofol 0.5 mg/kg and remifentanil 1 µg/kg (Group R), or sevoflurane alone 6% (Group S) for their initial electroconvulsive therapy session. The patients subsequently received an alternative regimen in their next session, such as from propofol 1 mg/kg alone to propofol 0.5 mg/kg and remifentanil 1 µg/kg, from propofol 0.5 mg/kg and remifentanil 1 µg/kg to sevoflurane alone 6%, or from sevoflurane alone 6% to a continuing alternation between drugs at each session, until their sixth session. Muscle paralysis was achieved with 1 mg/kg succinylcholine. Seizure duration, postictal suppression index, early and midictal amplitude were recorded. The mean motor and electroencephalogram seizure durations were significantly longer in Groups P and R compared to Group S (P <0.001). The postictal suppression index and early and midictal amplitude values were not significantly different among the groups. These findings indicate that the three anaesthetic regimens had similar effects on seizure quality parameters, although sevoflurane was associated with shorter seizure durations than propofol or propofol-remifentanil.

Ketofol (mixture of ketamine and propofol) administration in electroconvulsive therapy.

The aim of this study was to evaluate the effect of a ketamine:propofol combination ('ketofol') for electroconvulsive therapy on seizure activity, haemodynamic response and recovery parameters, and to compare with these with the effects of propofol alone. Twenty-four patients underwent a total of 144 electroconvulsive therapy sessions, allocated in this prospective, double-blind, crossover study. Patients were randomly assigned to receive 1 mg/kg ketofol (0.5 mg/kg propofol plus 0.5 mg/kg ketamine) or 1 mg/kg propofol 1% for anaesthesia induction. Seizure duration and quality, haemodynamic data, recovery parameters and side-effects were recorded and analysed between groups. Both motor and electroencephalography seizure durations in the ketofol group (29 ± 17 and 41 ± 17 seconds, respectively) were similar to that in the propofol group (28 ± 13 and 38 ± 16 seconds, respectively). Postictal suppression index was higher in the ketofol group (89.63 ± 7.88) than in the propofol group (79.74 ± 14.6) (P <0.05). In the ketofol group, heart rate after the seizure ended and mean arterial pressures, recorded at 0 and 5 minutes after the seizure ended, were higher than in the propofol group. Time to obeying commands was longer in the ketofol group (P <0.05). There were no untoward psychological reactions following ketofol. Although no superiority to propofol in terms of seizure duration, haemodynamic or recovery parameters was found, the ketofol mixture selected in our study provided better seizure quality than propofol. We conclude that ketofol can be an alternative strategy to enhance the seizure quality and clinical efficiency of electroconvulsive therapy.

Tetraamine-derived bifunctional chelators for technetium-99m labelling: synthesis, bioconjugation and evaluation as targeted SPECT imaging probes for GRP-receptor-positive tumours.

Owing to its optimal nuclear properties, ready availability, low cost and favourable dosimetry, (99m)Tc continues to be the ideal radioisotope for medical-imaging applications. Bifunctional chelators based on a tetraamine framework exhibit facile complexation with Tc(V)O(2) to form monocationic species with high in vivo stability and significant hydrophilicity, which leads to favourable pharmacokinetics. The synthesis of a series of 1,4,8,11-tetraazaundecane derivatives (01-06) containing different functional groups at the 6-position for the conjugation of biomolecules and subsequent labelling with (99m)Tc is described herein. The chelator 01 was used as a starting material for the facile synthesis of chelators functionalised with OH (02), N(3) (04) and O-succinyl ester (05) groups. A straightforward and easy synthesis of carboxyl-functionalised tetraamine-based chelator 06 was achieved by using inexpensive and commercially available starting materials. Conjugation of 06 to a potent bombesin-antagonist peptide and subsequent labelling with (99m)Tc afforded the radiotracer (99m)Tc-N4-BB-ANT, with radiolabelling yields of >97% at a specific activity of 37 GBq micromol(-1). An IC(50) value of (3.7+/-1.3) nM was obtained, which confirmed the high affinity of the conjugate to the gastrin-releasing-peptide receptor (GRPr). Immunofluorescence and calcium mobilisation assays confirmed the strong antagonist properties of the conjugate. In vivo pharmacokinetic studies of (99m)Tc-N4-BB-ANT showed high and specific uptake in PC3 xenografts and in other GRPr-positive organs. The tumour uptake was (22.5+/-2.6)% injected activity per gram (% IA g(-1)) at 1 h post injection (p.i.). and increased to (29.9+/-4.0)% IA g(-1) at 4 h p.i. The SPECT/computed tomography (CT) images showed high tumour uptake, clear background and negligible radioactivity in the abdomen. The promising preclinical results of (99m)Tc-N4-BB-ANT warrant its potential candidature for clinical translation.

Orally bioavailable competitive CCR5 antagonists.

The chemokine receptor CCR5 plays an important role in inflammatory and autoimmune disorders as well as in transplant rejection by affecting the trafficking of effector T cells and monocytes to diseased tissues. Antagonists of CCR5 are believed to be of potential therapeutic value for the disorders mentioned above and HIV infection. Here we report on the structure-activity relationship of a new series of highly potent and selective competitive CCR5 antagonists. While all compounds tested were inactive on rodent CCR5, this series includes compounds that cross-react with the cynomolgus monkey (cyno) receptor. One of these compounds, i.e., 26n, has good PK properties in cynos, and its overall favorable profile makes it a promising candidate for in vivo profiling in transplantation and other disease models.

Synthesis and conformational investigation of cyclic dipeptides: 7-membered rings containing alpha- and beta-amino acids.

The synthesis of heterocyclic compounds containing the 7-membered ring system [1,4]diazepane-2,5-dione is described. The aim of this study was to elaborate the solid phase and solution synthesis of eight representatives of the cyclic scaffold and to investigate their chemical stability and their conformational properties. The solid phase synthesis was performed on aminomethyl polystyrene resin using 5-(4-formyl-3,5-dimethoxyphenoxy)valeric acid as a backbone linker system (BAL-linker). After attachment of the alpha- and beta-amino acid and deprotection of the amino function, the dipeptide ester was obtained. The molecule was cyclized on the solid support by treatment with NaOMe in MeOH/NMP. The product was cleaved from the resin by TFA. For the solution pathway the linear dipeptides were synthesized by coupling of the BOC-protected L-alpha-amino acid with the beta2-amino acid ester (EDC/HOBT). After N- and C-terminal deprotection of the dipeptide, the linear species was cyclized with EDC/HOBT at a concentration of 3 mM in DMF. The products showed high chemical stability after storage in DMSO at room temperature for weeks. The x-ray and two dimensional NMR investigations were performed to investigate the conformation of the molecules. Three types of configuration could be distinguished by NMR, depending on the substitution pattern of the cyclic compounds. The x-ray results confirmed the NMR observations. In general the 7-membered rings showed rigidity, thus they could represent optimal scaffolds for new receptor ligands.