Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13

The extraocular fibrosis syndromes are congenital ocular-motility disorders that arise from dysfunction of the oculomotor, trochlear, and abducens nerves and/or the muscles that they innervate. Each is marked by a specific form of restrictive paralytic ophthalmoplegia with or without ptosis. Individuals with the classic form of congenital fibrosis of the extraocular muscles (CFEOM1) are born with bilateral ptosis and a restrictive infraductive external ophthalmoplegia. We previously demonstrated that CFEOM1 is caused by an autosomal dominant locus on chromosome 12 and results from a developmental absence of the superior division of the oculomotor nerve. We now have mapped a variant of CFEOM, exotropic strabismus fixus ("CFEOM2"). Affected individuals are born with bilateral ptosis and restrictive ophthalmoplegia with the globes "frozen" in extreme abduction. This autosomal recessive disorder is present in members of three consanguineous Saudi Arabian families. Genetic analysis of 70 individuals (20 affected individuals) reveals linkage to markers on chromosome 11q13, with a combined LOD score of 12.3 at the single nonrecombinant marker, D11S1314. The 2.5-cM CFEOM2 critical region is flanked by D11S4196/D11S4162 and D11S4184/1369. Two of the three families share a common disease-associated haplotype, suggesting a founder effect for CFEOM2. We hypothesize that CFEOM2 results from an analogous developmental defect to CFEOM1, one that affects both the superior and inferior divisions of the oculomotor nerve and their corresponding alpha motoneurons and extraocular muscles.     

Eucapnic voluntary hyperventilation as a bronchoprovocation technique: development of a standarized dosing schedule in asthmatics

A variety of dosing schedules have been reported for the hyperventilation method of broncho-provocation testing. To evaluate the effect of challenge technique on the bronchoconstrictive response, we had 16 subjects perform eucapnic voluntary hyperventilation (EVH) with dry, room temperature gas using four different dosing schedules. The hyperventilation challenge dosages included the following: (1) a target minute ventilation (VE) of 20 x FEV1 for 6 min; (2) a target VE of 15 x FEV1 for 12 min; (3) an interrupted challenge with a target VE of 30 x FEV1 for 2 min repeated 3 times; and (4) a target VE of 30 x FEV1 for 6 min. Challenges 2, 3, and 4 gave identical absolute ventilatory challenges (identical factor FEV1 x minutes) but at different VE dosages or time. Challenges 1 and 4 were of identical length, but different target VE. The mean postchallenge fall in FEV1 was 16.6 +/- 10.9%, 11.0 +/- 8.1%, 19.6 +/- 9.9%, and 26.7 +/- 11.3% for challenges 1, 2, 3, and 4, respectively. The response to an identical EVH challenge (FEV1 x 30 for 6 min) was reproducible when performed on separate days. We conclude that the challenge technique used for hyperventilation testing will have a significant impact on the bronchoconstrictive response and must be taken into account when interpreting study results. Tests may be quantitatively comparable over a narrow range of challenge time and VE. We recommend that a 6-min uninterrupted EVH challenge using dry, room temperature gas at a target VE of 30 x FEV1 be adopted as the "standard" challenge.     

Evolution of carbohydrate metabolic pathways

Current studies of hyperthermophilic archaea and bacteria, the phylogenetically deepest-rooted and slowest-evolving extant organisms known, are allowing new insights into the nature of presumably ancient metabolic pathways. The apparent common occurrence of modified non-phosphorylated Entner-Doudoroff (ED) pathways among saccharolytic archaea and the absence of the conventional Embden-Meyerhof-Parnas (EMP) mode of glycolysis indicate that the ED pathway is the older route of carbohydrate dissimilation. However, gluconeogenesis via the "reversed" EMP route has been found in archaea. Thus, the EMP pathway was probably an anabolic pathway to begin with; its catabolic role came later, with the evolution of fructose phosphate kinases, using ATP, ADP or pyrophosphate as phosphate donors. Similarly, the presence of reductive reactions of the citric acid cycle in anaerobic archaea and the most deeply rooted bacteria, including autotrophs, indicates that the citric acid cycle was originally a reductive biosynthetic pathway.     

Effect of sinus denervation and vagotomy on c-fos expression in the nucleus tractus solitarius after exposure to CO2

Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14-16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50- "mu"m section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.     

Severe facial clefting, limbic dermoid, hypoplasia of the corpus callosum, and multiple skin appendages: severe frontofacionasal "dysplasia" or newly recognised syndrome?

We report on a child with severe midline facial cleft, bilateral cleft lip and palate, telecanthus, S-shaped palpebral fissures, limbic dermoid, midface hypoplasia, hypoplastic corpus callosum, and multiple skin appendages. This case may be an example of severe frontofacionasal "dysplasia" or a newly recognised syndrome.     

Ambulatory urodynamics: extramural testing of the lower and upper urinary tract by Holter monitoring of cystometrogram, uroflowmetry, and renal pelvic pressures

This article elucidates the clinical applicability and state of the art of ambulatory urodynamics. Ambulatory urodynamics have evolved into practical investigations like EAC, HFM, and EAC combined with renal pelvimetry. EAC has been shown to be the method of preference if detrusor overactivity is involved. Conventional filling cystometry has proved to be an unreliable way to exclude detrusor instability. De novo instability after suspension surgery often indicates that an existing detrusor overactivity was not identified preoperatively. EAC including flowmetry has shown considerable variance in obstructive and contractility parameters in males with LUTS indicative for BPH. This raises doubt whether the clinical flow analysis is the suitable "gold standard" as advocated by the ICS. For a real break through of EAC, less complex automatic analysis is necessary. HFM is a newer method within the range of ambulatory urodynamic tests. It has not yet been completely evaluated. But, because the technique is analogous to the office flowmetry, noninvasive and very well accepted by the patients, it is expected to be widely used. This expectation is strengthened by the fact that HFM seems to show individual therapeutic efficacy of drugs, such as alpha-blockers. As a research tool to evaluate efficacy, it is far more powerful than conventional methods because of the reduction of within-patient standard deviation to about 10%. Finally, EAC combined with pelvimetry offers a promising method for the clinical evaluation of a combined dysfunction of upper and lower urinary tract.     

Impact assessment of odours emitted by a wastewater treatment plant

Complaints from the Domingos Martins population about sewage odours in the city made the district attorney order an impact assessment of the odours emitted by the city wastewater treatment plant (WWTP). This study comprised various techniques, models and population surveys. In 2007, an odour emission model proved that the main hydrogen sulphide emitter was the aeration tank of the WWTP (13.5 g h(-1)) and such emissions, according to CALPUFF model, should be perceived in the whole Domingos Martins city centre area. In this area, 58% of those interviewed were annoyed by the WWTP odours. However, in 2009, the odour monitoring panel recorded few odour occurrences. A second population survey showed that hereafter only 20% of those interviewed were annoyed by the WWTP emissions. Odour emission and dispersion models run with 2010 data proved a drastic reduction of the WWTP aeration tank emissions and consequently the city centre was not bothered by WWTP emissions anymore. The odour emission reduction was due to the modification of the WWTP aeration tank system. Despite the odour emission reduction, houses located southeast of the WWTP were still annoyed by sewage odours. However, in this part of the town, other sources of sewage odours have been found.     

Differential binding of tropane-based photoaffinity ligands on the dopamine transporter

Benztropine and its analogs are tropane ring-containing dopamine uptake inhibitors that produce behavioral effects markedly different from cocaine and other dopamine transporter blockers. We investigated the benztropine binding site on dopamine transporters by covalently attaching a benztropine-based photoaffinity ligand, [125I]N-[n-butyl-4-(4"'-azido-3"'-iodophenyl)]-4', 4"-difluoro-3alpha-(diphenylmethoxy)tropane ([125I]GA II 34), to the protein, followed by proteolytic and immunological peptide mapping. The maps were compared with those obtained for dopamine transporters photoaffinity labeled with a GBR 12935 analog, [125I]1-[2-(diphenylmethoxy)ethyl]-4-[2-(4-azido-3-iodophenyl)ethy l]p iperazine ([125I]DEEP), and a cocaine analog, [125I]3beta-(p-chlorophenyl)tropane-2beta-carboxylic acid, 4'-azido-3'-iodophenylethyl ester ([125I]RTI 82), which have been shown previously to interact with different regions of the primary sequence of the protein. [125I]GA II 34 became incorporated in a membrane-bound, 14 kDa fragment predicted to contain transmembrane domains 1 and 2. This is the same region of the protein that binds [125I]DEEP, whereas the binding site for [125I]RTI 82 occurs closer to the C terminal in a domain containing transmembrane helices 4-7. Thus, although benztropine and cocaine both contain tropane rings, their binding sites are distinct, suggesting that dopamine transport inhibition may occur by different mechanisms. These results support previously derived structure-activity relationships suggesting that benztropine and cocaine analogs bind to different domains on the dopamine transporter. These differing molecular interactions may lead to the distinctive behavioral profiles of these compounds in animal models of drug abuse and indicate promise for the development of benztropine-based molecules for cocaine substitution therapies.     

3D reconstruction of tomographic images applied to largely spaced slices

This paper presents a full reconstruction process of magnetic resonance images. The first step is to bring the acquired data from the frequency domain, using a Fast Fourier Transform algorithm. A Tomographic Image Interpolation is then used to transform a sequence of tomographic slices in an isotropic volume data set, a process also called 3D Reconstruction. This work describes an automatic method whose interpolation stage is based on a previous matching stage using Delaunay Triangulation. The reconstruction approach uses an extrapolation procedure that permits appropriate treatment of the boundaries of the object under analysis.