Search

Cavernous malformations (CMs) are congenital vascular malformations of the brain, which often present with drug-resistant epilepsy. Microsurgical excision remains the preferred approach for cortical-subcortical epileptogenic CMs that are not located in functional cortex. For patients presenting with seizures arising from eloquent cortex surrounding the lesion, radiosurgery appears to be a suitable alternative. We evaluated the effectiveness of Gamma Knife (GK) surgery in the management of drug-resistant seizures associated with CMs in a retrospective multicenter study. Forty-nine patients with cortical or subcortical CMs with severe long-term drug-resistant epilepsy underwent radiosurgery. The mean duration of epilepsy before these GK procedures was 7.5 (±9.3) years. The mean frequency of seizures was 6.9/month (±14). The mean marginal radiation dose was 19.17 Gy. At the last follow-up examination, 53% were seizure free. A highly significant decrease in the number of seizures was achieved for another 20%. The remaining 26% of patients showed little or no improvement. The morbidity was low. Radiosurgery is a promising management modality for epilepsy associated with CMs. The determination of the extent of the epileptogenic zone in CMs and dose selection are the critical steps towards successful radiosurgical outcome. Further prospective work is necessary to validate our data., (Copyright © 2013 S. Karger AG, Basel.)

Nowadays, recombinant proteins are used with great success for the treatment of a variety of medical conditions, such as cancer, autoimmune, and infectious diseases. Several expression systems have been developed to produce human proteins, but one of their most critical limitations is the addition of truncated or nonhuman glycans to the recombinant molecules. The presence of such glycans can be deleterious as they may alter the protein physicochemical properties (e.g., solubility, aggregation), its half-life, and its immunogenicity due to the unmasking of epitopes.The baculovirus expression system has long been used to produce recombinant proteins for research. Thanks to recent methodological advances, this cost-effective technology is now considered a very promising alternative for the production of recombinant therapeutics, especially vaccines. Studies on the lepidopteran cell metabolism have shown that these cells can perform most of the posttranslational modifications, including N- and O-glycosylation. However, these glycan structures are shorter compared to those present in mammalian proteins. Lepidopteran N-glycans are essentially of the oligomannose and paucimannose type with no complex glycan identified in both infected and uninfected cells. The presence of short N-glycan structures is explained by the low level of N-acetylglucosaminyltransferase I (GNT-I) activity and the absence of several other glycosyltransferases, such as GNT-II and β1,4-galactosyltransferase I (β1,4GalTI), and of sialyltransferases.In this chapter, we show that the glycosylation pathway of a lepidopteran cell line can be modified via infection with an engineered baculovirus to "humanize" the glycosylation pattern of a recombinant protein. This engineering has been performed by introducing in the baculovirus genome the cDNAs that encode three mammalian glycosyltransferases (GNT-I, GNT-II, and β1,4GalTI). The efficiency of this approach is illustrated with the construction of a recombinant virus that can produce a galactosylated antibody.

Pro-inflammatory cytokines like macrophage migration inhibitory factor (MIF), IL-1β and TNF-α predominate in inflammatory bowel diseases (IBD) and TNBS colitis. Increased levels of serine proteases activating protease-activated receptor 2 (PAR-2) are found in the lumen and colonic tissue of IBD patients. PAR-2 activity and pro-inflammatory cytokines impair epithelial barrier, facilitating the uptake of luminal aggressors that perpetuate inflammation and visceral pain. Soy extracts contain phytoestrogens (isoflavones) and serine protease inhibitors namely Bowman-Birk Inhibitors (BBI). Since estrogens exhibit anti-inflammatory and epithelial barrier enhancing properties, and that a BBI concentrate improves ulcerative colitis, we aimed to evaluate if a fermented soy germ extract (FSG) with standardized isoflavone profile and stable BBI content exert cumulative or synergistic protection based on protease inhibition and estrogen receptor (ER)-ligand activity in colitic rats. Female rats received orally for 15 d either vehicle or FSG with or without an ER antagonist ICI 182.780 before TNBS intracolonic instillation. Macroscopic and microscopic damages, myeloperoxidase activity, cytokine levels, intestinal paracellular permeability, visceral sensitivity, faecal proteolytic activity and PAR-2 expression were assessed 24 h, 3 d and 5 d post-TNBS. FSG treatment improved the severity of colitis, by decreasing the TNBS-induced rise in gut permeability, visceral sensitivity, faecal proteolytic activity and PAR-2 expression at all post-TNBS points. All FSG effects were reversed by the ICI 182.780 except the decrease in faecal proteolytic activity and PAR-2 expression. In conclusion, the anti-inflammatory properties of FSG treatment result from two distinct but synergic pathways i.e an ER-ligand and a PAR-2 mediated pathway, providing rationale for potential use as adjuvant therapy in IBD.

Distal choroidal artery aneurysms stemming from the lateral wall of the ventricles are rare and are mostly associated with moyamoya disease. The treatment of these aneurysms is difficult because of their deep location. The authors report the case of a 50-year-old woman followed for moyamoya disease presenting with 2 intraventricular hemorrhages. Cerebral angiography showed an aneurysm located on the left distal choroidal artery. Magnetic resonance imaging also demonstrated that the lesion protruded from the lateral wall of the trigone of the left lateral ventricle. Using MR imaging-guided stereotactic localization, the aneurysm was accurately reached endoscopically and successfully resected from the parent artery. The patient was discharged neurologically intact. To the best of the authors' knowledge, this is the first report of a successfully endoscopically treated distal anterior choroidal artery aneurysm. Endoscopic surgery may be added to the armamentarium of procedures used to treat intraventricular aneurysms.

Purpose: Although Gamma Knife radiosurgery (GKR) is widely recognized as an effective and minimally invasive treatment for intractable trigeminal neuralgia, its role in glossopharyngeal neuralgia (GPN) has not yet been determined., Methods: Between January 2002 and February 2009, 7 patients with medically intractable GPN were treated using GKR. Indication for GKR was the presence of medically intractable GPN, patient's refusal for open surgery or contraindication to microvascular decompression. Patients underwent preoperative investigation and were evaluated postoperatively with periodic assessment of pain relief and neurological function. Seven patients, 5 males and 2 females, with mean age 62 (range 36-83) presented with symptoms for an average of 28 months (range 8-72). Four patients had a neurovascular conflict. Patients were treated with a dose ranging from 60 to 80 Gy, targeted on the cisternal segment (n=2) or glossopharyngeal meatus (GPM) (n=5)., Results: Outcome was favorable with cure of GPN in 5 of 7 patients (71%) in the short-term (3 months post GKR) and 4 of 7 (57%) patients in the long term (> 7 months, mean 16 months). One patient required 2 treatments because of a recurrence of symptoms and was treated with a maximum doses of 60 and 70 Gy, respectively. There were no neurological complications., Conclusions: All patients with GPM as a target that received a dose greater than 75 Gy were cured at long-term follow-up. The 2 patients with cisternal segment as the target and received a dose lower than 70 Gy were not cured of their GPN. There were no neurological deficits involving the lower cranial nerves. It will be necessary to investigate the optimal radiation dose and target of GKR for GPN in order to achieve long-term pain relief.

Mitochondrial DNA (mtDNA) mutations have been implicated in non-syndromic hearing loss either as primary or as predisposing factors. As only a part of the mitochondrial genome is usually explored in deafness, its prevalence is probably under-estimated. Among 1350 families with non-syndromic sensorineural hearing loss collected through a French collaborative network, we selected 29 large families with a clear maternal lineage and screened them for known mtDNA mutations in 12S rRNA, tRNASer(UCN) and tRNALeu(UUR) genes. When no mutation could be identified, a whole mitochondrial genome screening was performed, using a microarray resequencing chip: the MitoChip version 2.0 developed by Affymetrix Inc. Known mtDNA mutations was found in nine of the 29 families, which are described in the article: five with A1555G, two with the T7511C, one with 7472insC and one with A3243G mutation. In the remaining 20 families, the resequencing Mitochip detected 258 mitochondrial homoplasmic variants and 107 potentially heteroplasmic variants. Controls were made by direct sequencing on selected fragments and showed a high sensibility of the MitoChip but a low specificity, especially for heteroplasmic variations. An original analysis on the basis of species conservation, frequency and phylogenetic investigation was performed to select the more probably pathogenic variants. The entire genome analysis allowed us to identify five additional families with a putatively pathogenic mitochondrial variant: T669C, C1537T, G8078A, G12236A and G15077A. These results indicate that the new MitoChip platform is a rapid and valuable tool for identification of new mtDNA mutations in deafness.

Objectives: This article reports the creation of a Universal Newborn Hearing Screening (UNHS) program in a French region, Champagne-Ardenne, and the results of its first 27 months., Materials and Methods: We introduced a UNHS program in all the Champagne-Ardenne maternities in order to screen all newborns in the region. We used a two-step strategy. The first test consists of automated transiently evoked otoacoustic emissions (TEOAE) and is performed before discharge by a nurse or a midwife. If TEOAE are absent in both ears (positive screening test), the baby is referred to the second test, which could be either TEOAE or automated auditory brainstem response (aABR) 15 days after discharge, by a physician in an outpatient clinic. If the retest is positive in both ears, the baby is referred to diagnostic tests in a reference centre. This procedure also applies to newborns in neonatal intensive care units but, in those cases, the first test procedure is aABR because of the higher incidence of auditory neuropathies in those units. UNHS data are recorded with the other neonatal screening tests in the Regional Neonatal Screening Center, which facilitates the follow-up of newborns., Results: A total of 33 873 newborns were screened, which represents a coverage rate of 92.42%. In those babies, 33 431 had a negative first test and 429 were retested. There were 34 positive retests. Among those 34 children, 27 were actually deaf (0.08%). The median age at diagnosis was shortened from 17 months to 10 weeks., Conclusion: Those 27-month results demonstrate the validity of our UNHS program, which relies on the cooperation with maternities, an easy protocol and a strong follow-up procedure.

Background: Cancer screening requires identification of individuals at high risk for cancer, mainly through an adequate family history, and documentation of dates and results of past screening examinations. By asking general practitioners (GPs) to audit their charts, we sought to encourage them to enhance chart quality and their involvement in colorectal, breast and cervical cancer screening., Methods: Chart audit of data on family cancer history and past screening examinations. Volunteer GPs, working in groups, self-audited the completeness of their charts of 20 (10 women, 10 men) consecutive patients not seen for the first time and aged 40-74 years for colorectal, breast and cervix cancer., Results: In all, 37 GPs participated, analyzing 736 charts. Family history of cancer was documented in half the charts. A fecal occult blood test was mentioned in 51.2%, with a date in 40.2%. Mammograms were mentioned in 62.7% of women's charts, but only 27.9% contained complete information (family history, date and result of mammogram documented). Similarly, 44.2% of women's charts mentioned pap smears but only 25.9% contained complete information. The rates of complete charts ranged from 0 to 100% and varied with cancer and GP., Conclusion: Quality of charts in primary care is globally poor but very heterogeneous, ranging from bad to excellent according to GP. The collection of updated information on family history and past screening examinations must be improved in primary care.

The construction of a recombinant antibody directed against the cellular epitope R7V acquired by HIV during the viral budding has been realized. The c-DNAs encoding the variable regions of the anti-R7V antibody have been cloned from B lymphocytes of a non-progressor patient. Two transfer vectors containing complete coding sequences for heavy and light chains of this antibody were constructed and a recombinant baculovirus was generated by a double recombination between baculovirus DNA and the two transfer vectors. Insect cells infected with this baculovirus produced a complete human anti-R7V immunoglobulin. This recombinant antibody, specific to the R7V peptide, recognizes and neutralizes all clades of HIV1 including resistant viruses, opening new perspectives in anti-HIV therapy.

On the basis of 18 cases of recurrent parotiditis in the child, the authors offer the current review of this condition: clinical features, radiological features, bacteriological features, course. They emphasize the importance of precise technique during sialography, which must include straight and lateral films. The progress of this condition is characterised by recurrences. These may be avoided by prolonged and appropriate antibiotic therapy. The improvement which takes place at puberty is of etiopathogenic significance. Bucco-dental septis, constantly present, is one of the causes favourising infectious parotiditis in child.

The choice of different types of anaesthesia in ophthalmologic surgery is reviewed in 2,150 cases. Data analysis shows a real increase of anaesthetic activity in ophthalmology and a trend towards local anaesthesia especially in cataract. (45% of all operations in ophthalmology).

A study of variations in intraocular pressure during anaesthetic induction with propofol was carried out in 20 patients. There were compared with the effects caused by thiopentone. The intraocular pressure fell by 50%; this was very significant. Besides, a more important fall in blood pressure was seen with propofol (congruent to 15%) than with thiopentone (less than 10%). Complete recovery was faster after an anaesthesia with propofol. This drug seemed to be particularly interesting in ophthalmologic anaesthesia in elderly people.