Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy

The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy.     

Measurement of 5-HIAA levels in ventricular CSF (by LCEC) and in striatum (byin vivo voltammetry) during pharmacological modifications of serotonin metabolism in the rat

Summary The relationship between the concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the CSF and in the striatum has been evaluated in the rat by measuring the levels of this metabolite in ventricular CSF (by liquid chromatography coupled with electrochemical detection) and in the striatal extracellular fluid (byin vivo voltammetry) after administration of inhibitors of serotonin synthesis or degradation. Pargyline, NSD 1015 and-propyldopacetamide all caused an exponential decline of 5-HIAA in both CSF and striatum. For a given drug, the rate constants for 5-HIAA disappearance were identical in the CSF and in the striatal extracellular fluid. These results confirm the view that CSF 5-HIAA may serve as a good index of brain serotonin turnover.     

Synovial cysts of unusual localization. 2 cases and review of the literature

Two patients with true synovial cysts in atypical sites (internal compartment of knee and inguinal hollow) were investigated by radioarthrography, ultrasound and computed tomography imaging. The cyst in the hip region originated from a dilated serous bursa of the iliopsoas muscle that did not communicate or was no longer in communication with the joint. In contrast, the cyst of the knee appeared to be a lateral synovial capsule hernia. Positive diagnosis in both cases was dependent on combined ultrasound-CT scan imaging, this eliminating a tumor (sarcoma) of soft tissues. However, affirmation of the synovial origin (mesothelial covering of the wall) of the lesion was obtained by histology only, this allowing differentiation from a "capsular" (fibrous wall) cyst, which probably provokes similar ultrasound and CT scan images.     

The origin of human B and T cells from multipotent stem cells: a study of the Tn syndrome

The Tn (or polyagglutinability) syndrome corresponds to a human nonmalignant acquired condition which results from a somatic mutation occurring at the level of bone marrow stem cells. This model offers therefore a unique opportunity to study the contribution of multipotential stem cells to the maintenance of cells from the lymphoid lineage. We found that the Tn mutation is expressed by both myeloid and lymphoid mature blood cells. Whereas a large proportion of surface IgM-bearing B cells carry the Tn mutation, only a small percentage of T cells and IgA- or IgG-bearing B cells are defective, showing that under physiological conditions the penetration of stem cells into the various myeloid and lymphoid compartments is variable.     

Effect of brain and spinal cord injuries on motor imagery

Summary The timing of mentally executed movements was measured in ten patients with hemiplegia, tetraplegia and paraplegia. In hemiplegic patients a significant difference in mental duration times was found between the paralysed and the normal represented limb. The paralysed limb was mentally much slower than the healthy one. In contrast, movement times in tetraplegic and paraplegic patients did not differ from those in normal subjects. All patients reported a sensation of subjective effort accompanying the execution of the mental tasks. These observations are compatible with an outflow processing underlying motor imagery.     

Endoscopic cordectomy. a proposal for a classification by the Working Committee, European Laryngological Society

The European Laryngological Society is proposing a classification of different laryngeal endoscopic cordectomies in order to ensure better definitions of postoperative results. We chose to keep the word “cordectomy” even for partial resections because it is the term most often used in the surgical literature. The classification comprises eight types of cordectomies: a subepithelial cordectomy (type I), which is resection of the epithelium; a subligamental cordectomy (type II), which is a resection of the epithelium, Reinke’s space and vocal ligament; transmuscular cordectomy (type III), which proceeds through the vocalis muscle; total cordectomy (type IV); extended cordectomy, which encompasses the contralateral vocal fold and the anterior commissure (type Va); extended cordectomy, which includes the arytenoid (type Vb); extended cordectomy, which encompasses the subglottis (type Vc); and extended cordectomy, which includes the ventricle (type Vd). Indications for performing those cordectomies may vary from surgeon to surgeon. The operations are classified according to the surgical approach used and the degree of resection in order to facilitate use of the classification in daily practice. Each surgical procedure ensures that a specimen is available for histopathological examination. Received: 29 December 1998 / Accepted: 2 July 1999     

Study of the Complex Between the Contrast Agent lobitridol (Xenetix®) and Elastase (PPE): A Model for Hydrophobic Site Protection in Drug-Protein Interactions

Purpose. The concept of Hydrophilic Sphere Stabilization, or Hydrophobic Shielding, has been postulated in the synthesis of biocompatible contrast agents in vascular imaging. To improve the safety of these polyiodinated agents, interactions with protein hydrophobic sites in biomacromolecules should be kept as low as possible. In order to evaluate the level of interactions with proteins, we have selected the serine proteinase Elastase, in presence of Iobitridol (Xenetix^®), as a model. Methods. The complex between Iobitridol and Pancreatic Porcine Elastase was investigated by X-ray diffraction techniques, on saturated monocrystals, using the synchrotron radiation at 0.98. Results. In contrast to Iohexol, which displays several interactions including one in the active site, Iobitridol is unable to interact directly with elastase. Only one partially occupied site is found in between two molecules of the crystal packing. Conclusions. The validation of the 'hydrophobic shielding' concept, which was at the origin of the design of the Iobitridol molecule, has been proven to be an essential feature in minimizing in vivo protein interactions.     

Mucoadhesion of Latexes. I. Analytical Methods and Kinetic Studies

A Fourier transform infrared spectroscopy/attenuated total reflection technique for direct quantification of adsorbed poly(styrene) latexes on rat intestinal mucosa was developed for deposited latex amounts up to 1.5 g/m². The method agreed well with another dosage assay of adsorbed particles by turbidimetry after denaturation of the mucus. Adsorption kinetics were made under static conditions at latex concentrations of 4 g/L in physiological saline. Ninety percent of equilibrium was reached after 10 min for a particle size of 230 nm, 20 min for a size of 320 nm, and 30 min for a size of 670 nm. The plateaus were between 0.6 and 0.9 g/m² (adsorbed mass per apparent surface of mucosa). The first phase of the kinetics was theoretically approached by a diffusion model in the suspension medium. Mucosa from rat jejunum and ileum could be considered as a homogeneous biological model for latex adsorption.     

Results and indications of lateral ileostomy functionally terminated in colorectal surgery

Loop ileostomy (LI) ensures fecal diversion to protect an anastomosis or anatomic colorectal or ano-perineal damage. The aim of this retrospective study was to evaluate loop ileostomy morbidity in emergency and planned colorectal surgery. PATIENTS AND METHODS: From 1991 to 1996, 145 loop ileostomies were performed in 139 patients, 77 men and 62 women with a mean age of 48.7 years (15-82). The etiology was a rectal tumor (cancer or large villous tumor n = 47), inflammatory bowel disease (n = 47, ulcerative colitis = 37 and Crohn's disease = 10) Familial Adenomatous Polyposis (n = 13) and other diseases (n = 32). 80% LI (n = 116) protected ileo-anal anastomoses (n = 46) colo-anal anastomoses (n = 45, 26 with colonic pouch), ileo-rectal anastomoses (n = 11) and other anastomoses (n = 15). 20% LI (n = 29) dysfunctional ano-perineal lesions (n = 8), anastomosis leak (n = 4) or distal bowel without intestinal resection (n = 17). RESULTS: 7 deaths were not stoma-related. 91% LI were closed after a mean diversion time of 3.6 months. LI closure was performed by a parastomal (n = 128) or laparotomy procedure (n = 4). Morbidity during LI diversion was observed in 24 patients (16.5%) 12 of whom (8.3%) were operated for small bowel obstruction (n = 6; 4.2%) stoma revision (n = 5; 3.5%) and prolapse (n = 1; 0.7%). 2 patients had peristomal skin excoriations, and 5 patients required readmission for dehydration due to high LI output. Morbidity after LI closure was observed in 12 patients (8.6%) 5 of whom were operated for anastomotic leak (n = 4) or small bowel obstruction (n = 1). Low morbidity and defunctioning efficiency confirm the indications for LI. LI is our first-line stoma in planned or emergency colorectal surgery.     

EEG and cardiac activation during periodic leg movements in sleep: support for a hierarchy of arousal responses

OBJECTIVE: To investigate other physiologic changes that occur with periodic leg movements during sleep (PLMS) that might be considered to be more sensitive indices of sleep fragmentation. BACKGROUND: Although PLMS are associated with recurrent microarousals (MA), the frequency of PLMS with MA does not correlate with objective daytime sleepiness. It is postulated that the lack of correlation results from the low sensitivity of the standard criteria used to score MA. METHODS: Ten drug-free patients with a polygraphic and clinical diagnosis of restless legs syndrome (RLS) and PLMS were examined. The EEG correlates of PLMS were analyzed by visual scoring and spectral analysis during PLMS that ended in a visible microarousal (PLMS with MA) or not (PLMS without MA). The R-R interval in the EKG signal was also examined. RESULTS: A total of 34% of PLMS were associated with MA lasting >3 seconds, and 3% of PLMS were associated with MA lasting <3 seconds. Although PLMS with MA were associated with an increase in alpha activity, for PLMS without MA a significant increase in delta and theta activity was present. Both types of PLMS induced a shortening of the R-R interval; this was particularly more marked for PLMS with MA. CONCLUSIONS: First, visual scoring of MA that include a duration of less than 3 seconds has little effect on the detection of PLMS with MA. Second, EEG activation and tachycardia are present during both types of PLMS. Third, a hierarchy in the arousal response is present-going from autonomic activation to bursts of delta activity to alpha activity to a full awakening.