Bimodal mesoporous silica with bottleneck pores.

Bimodal mesoporous silica consisting of two sets of well-defined mesopores is synthesized by a partial pseudomorphic transformation of an ordered mesoporous starting material (SBA-15 type). The introduction of a second set of smaller mesopores (MCM-41 type) establishes a pore system with bottlenecks that restricts the access to the core of the bimodal mesoporous silica particles. The particle size and shape of the starting material are retained, but micropores present in the starting material disappear during the transformation, leading to a true bimodal mesoporous product. A varying degree of transformation allows the adjustment of the pore volume contribution of the two mesopore domains. Information on the accessibility of the mesopores is obtained by the adsorption of fluorescence-labeled poly(amidoamine) dendrimers and imaging by confocal laser scanning microscopy. This information is correlated with nitrogen sorption data to provide insights regarding the spatial distribution of the two mesopore domains. The bimodal mesoporous materials are excellent model systems for the investigation of cavitation effects in nitrogen desorption isotherms.

Implication of neuropilin 2/semaphorin 3F in retinocollicular map formation.

Neural representations of the environment within the brain take the form of topographic maps whose formation relies on graded expression of axon guidance molecules. Retinocollicular map formation, from retinal ganglion cells (RGCs) to the superior colliculus (SC) in the midbrain, is mainly driven by Eph receptors and their ligands ephrins. However, other guidance molecules participate in the formation of this map. Here we demonstrate that the receptor Neuropilin-2 is expressed in an increasing nasal-temporal gradient in RGCs, whereas one of its ligands, Semaphorin3F, but not other Sema3 molecules, presents a graded low-rostral to high-caudal expression in the SC when mapping is underway. Neuropilin-2 and its coreceptor Plexin A1 are present on RGC growth cones. Collapse assays demonstrate that Semaphorin3F induces significant growth cone collapse of temporal, but not nasal, RGCs expressing high levels of Neuropilin-2. Our results suggest that Neuropilin-2/Semaphorin3F are new candidates involved in retinotopy formation within the SC.

Variant hepatocyte nuclear factor 1 expression in the mouse genital tract.

Variant Hepatocyte Nuclear Factor 1 (vHNF1/HNF1beta) is a homeodomain-containing transcription factor first expressed in the primitive endoderm and its derivatives, the visceral and parietal endoderm. It is subsequently expressed in epithelial cells of different organs, including the primitive gut and derivatives (liver, pancreas, lung), the kidney, and transiently, in the neural tube. We report here new data concerning vHnf1 expression in the mouse genital tract, using both RNA analyses and our vHnf1 heterozygous mutant mouse line, in which the first coding exon of the vHnf1 gene is replaced by the NLSLacZ reporter gene. Both beta-galactosidase activity and vHnf1 transcripts are detected in epididymus, vas deferens, seminal vesicle, prostate, uterus and oviduct. RNA analysis and in situ hybridization studies demonstrate that vHnf1 transcripts are restricted to the germinal cells of the testis. Unexpectedly, no beta-galactosidase activity is detected in the testis. We further show that, in addition to the somatic transcript, two more abundant vHnf1 transcript variants, which lack exons 1-4, appear in this organ after meiosis.

[Results and extraordinary complications of surgery for exostoses of the external auditory canal]. / Resultate und ausser- gewöhnliche Komplikationen der Chirurgie der Gehörgangexostosen.

We present a retrospective study on 22 operations of exostosis of the external auditory canal in 20 patients. 8 patients were passionated by water sports. The most frequent indication for surgery (13 operations) was recurrent external otitis or ceruminal obstruction. In 7 cases the need for a wider access to the middle ear indicated surgery. Surgery was usually performed as an outpatient procedure, maximum hospitalization was 3 days. The mean healing period was 6 (3-10) weeks. Mean follow up was 43 (3-110) months. There were no severe intraoperative complications such as facial paresis, lesions of the ossicles or of the inner ear. As intraoperative complications we found 2 perforations of the tympanic membrane, 2 expositions of the capsule of the mandibular joint, one of which was followed by chronic pain. As postoperative complications we found an early soft tissue stenosis of the external auditory canal and one late soft tissue stenosis which recurred after revision surgery. No recurrence of exostosis was seen. We describe an up to now unknown complication: the appearance of bilateral petrositis caused by staphylococcus epidermidis after bilateral surgery in an otherwise healthy patient. This study confirms that severe complications are rare, minor ones however relatively common. And that also minor complications may have a troublesome follow. Therefore and because of the potential of severe complications indication for surgery must be made cautiously and risks of the operation must not be underestimated.

Application of isotope-selective non-dispersive infrared spectrometry for the evaluation of the 13C-urea breath test: comparison with three concordant methods.

The aim of this work was to compare the performance of isotope-selective non-dispersive infrared spectrometry (IRIS) for the 13C-urea breath test with the combination of the 14C-urea breath test (14C-UBT), urease test and histologic examination for the diagnosis of H. pylori (HP) infection. Fifty-three duodenal ulcer patients were studied. All patients were submitted to gastroscopy to detect HP by the urease test, histologic examination and 14C-UBT. To be included in the study the results of the 3 tests had to be concordant. Within one month after admission to the study the patients were submitted to IRIS with breath samples collected before and 30 min after the ingestion of 75 mg 13C-urea dissolved in 200 ml of orange juice. The samples were mailed and analyzed 11.5 (4-21) days after collection. Data were analyzed statistically by the chi-square and Mann-Whitney test and by the Spearman correlation coefficient. Twenty-six patients were HP positive and 27 negative. There was 100% agreement between the IRIS results and the HP status determined by the other three methods. Using a cutoff value of delta-over-baseline (DOB) above 4.0 the IRIS showed a mean value of 19.38 (minimum = 4.2, maximum = 41.3, SD = 10.9) for HP-positive patients and a mean value of 0.88 (minimum = 0.10, maximum = 2.5, SD = 0.71) for negative patients. Using a cutoff value corresponding to 0.800% CO2/weight (kg), the 14C-UBT showed a mean value of 2.78 (minimum = 0.89, maximum = 5.22, SD = 1.18) in HP-positive patients. HP-negative patients showed a mean value of 0.37 (minimum = 0.13, maximum = 0.77, SD = 0.17). IRIS is a low-cost, easy to manage, highly sensitive and specific test for H. pylori detection. Storing and mailing the samples did not interfere with the performance of the test.

Application of isotope-selective non-dispersive infrared spectrometry for the evaluation of the 13C-urea breath test: comparison with three concordant methods

The aim of this work was to compare the performance of isotope-selective non-dispersive infrared spectrometry (IRIS) for the 13C-urea breath test with the combination of the 14C-urea breath test (14C-UBT), urease test and histologic examination for the diagnosis of H. pylori (HP) infection. Fifty-three duodenal ulcer patients were studied. All patients were submitted to gastroscopy to detect HP by the urease test, histologic examination and 14C-UBT. To be included in the study the results of the 3 tests had to be concordant. Within one month after admission to the study the patients were submitted to IRIS with breath samples collected before and 30 min after the ingestion of 75 mg 13C-urea dissolved in 200 ml of orange juice. The samples were mailed and analyzed 11.5 (4-21) days after collection. Data were analyzed statistically by the chi-square and Mann-Whitney test and by the Spearman correlation coefficient. Twenty-six patients were HP positive and 27 negative. There was 100 per cent agreement between the IRIS results and the HP status determined by the other three methods. Using a cutoff value of delta-over-baseline (DOB) above 4.0 the IRIS showed a mean value of 19.38 (minimum = 4.2, maximum = 41.3, SD = 10.9) for HP-positive patients and a mean value of 0.88 (minimum = 0.10, maximum = 2.5, SD = 0.71) for negative patients. Using a cutoff value corresponding to 0.800 per cent CO2/weight (kg), the 14C-UBT showed a mean value of 2.78 (minimum = 0.89, maximum = 5.22, SD = 1.18) in HP-positive patients. HP-negative patients showed a mean value of 0.37 (minimum = 0.13, maximum = 0.77, SD = 0.17). IRIS is a low-cost, easy to manage, highly sensitive and specific test for H. pylori detection. Storing and mailing the samples did not interfere with the performance of the test.

Variant hepatocyte nuclear factor 1 is required for visceral endoderm specification.

Genetic and molecular evidence indicates that visceral endoderm, an extraembryonic cell lineage, is required for gastrulation, early anterior neural patterning, cell death and specification of posterior mesodermal cell fates. We show that variant Hepatocyte Nuclear Factor 1 (vHNF1), a homeodomain-containing transcription factor first expressed in the primitive endoderm, is required for the specification of visceral endoderm. vHnf1-deficient mouse embryos develop normally to the blastocyst stage, start implantation, but die soon afterwards, with abnormal or absent extraembryonic region, poorly organised ectoderm and no discernible visceral or parietal endoderm. However, immunostaining analysis of E5.5 nullizygous mutant embryos revealed the presence of parietal endoderm-like cells lying on an abnormal basal membrane. Homozygous mutant blastocyst outgrowths or differentiated embryonic stem cells do not express early or late visceral endoderm markers. In addition, in vHnf1 null embryoid bodies there is no activation of the transcription factors HNF-4alpha1, HNF1alpha and HNF-3gamma. Aggregation of vHnf1-deficient embryonic stem cells with wild-type tetraploid embryos, which contribute exclusively to extraembryonic tissues, rescues periimplantation lethality and allows development to progress to early organogenesis. Our results place vHNF1 in a preeminent position in the regulatory network that specifies the visceral endoderm and highlight the importance of this cell lineage for proper growth and differentiation of primitive ectoderm in pregastrulating embryos.

The effect of d-amphetamine on optokinetic nystagmus in the guinea pig.

The effect of d-amphetamine oral administration in doses of 1-2.5 mg/kg on horizontal optokinetic nystagmus (OKN) and after nystagmus (OKAN) was investigated in the guinea pig. Eye movements were recorded by means of the electromagnetic search-coil technique. After amphetamine administration the range of stimulus velocities effective for eliciting OKN was 10-20 deg/s higher than before treatment. The mean values and the fluctuations of the eye velocity during slow nystagmus phases before and after treatment did not differ. Administration of amphetamine led to 2-8 s increase in OKAN duration. The OKAN prolongation did not depend on stimulation velocity. The dependency of OKAN duration on stimulation velocity was well approximated by a linear regression. The slope of the regression line was 0.160 +/- 0.022 before and 0.177 +/- 0.028 after treatment. Similarity in the coefficients indicates that amphetamine did not alter the relationship between the velocity of optokinetic stimulus and the duration of after nystagmus. Constant prolongation of OKAN over the whole range of stimulation velocities could reflect a constant shift in activity of neurons representing the velocity storage. The effects observed on OKN gain curves and the increase in OKAN duration did not display a clear dependency on the dosages of d-amphetamine used in the experiments. We assume that the effects of treatment reflected a general increase in attentiveness and motility of animals resulting from the arousal action of amphetamine.

The role of acoustic rhinometry in the pre- and postoperative evaluation of surgery for nasal obstruction.

This is a prospective study evaluating the role of acoustic rhinometry (AR) in the measurement of nasal patency before and after surgery for nasal obstruction. We examined 27 patients before and 2 to 6 months after septoplasty associated with turbinoplasty, cauterisation of the inferior turbinates, rhinoplasty or uvulopalatopharyngoplasty in some cases. Surgery was performed for subjective nasal obstruction and indication based on symptoms and clinical findings. AR was performed after indication was made. Patients were evaluated for this study by marking subjective global nasal obstruction on a visual analogue scale and by AR before and after decongestion. All patients noted an improvement of subjective nasal patency after surgery. Mean unilateral minimal cross-sectional area (MCA) of the preoperatively narrower side and total MCA both increased but showed wide ranges with also negative results. The total volume of the nasal fossae did not increase. The volume of the preoperatively narrower nasal fossa increased with surgery, but there are enormous ranges. We could not find any correlation between the MCA of the preoperatively narrower side or the total MCA and subjective nasal patency, neither before nor after surgery. The same was the case for the volume of the nasal fossae. In our opinion AR is not a valuable method for the indication or evaluation of surgery for nasal obstruction.

Neuropsychiatry of 18q- syndrome.

Our understanding of neuropsychiatric abnormalities in patients with deletions of the long arm of chromosome 18 (18q- syndrome) is based mainly on sporadic case reports. We characterized the neuropsychiatric phenotype in 27 patients across a wide age range (2-47 years) with breakpoints ranging from 18q22.3-18q21.2. Adaptive behavior scores (Vineland Composite) were significantly higher in females than in males (62 +/- 5 vs. 43 +/- 3). Intelligence ranged from borderline to severely deficient (IQ, 73- < 40), with academic achievement similarly impaired. Performance in specific neuropsychological functions, including attention, novel problem solving, memory, language, visuomotor integration, and fine motor dexterity, was consistently in the moderately-to-severely impaired range. Behavioral problems were common in both sexes, including aggressivity, hyperactivity, and temper tantrums. Contrary to the few previous reports, we found no evidence of psychosis in any patients. In a subset of patients selected on the basis of no prior knowledge of behavioral problems, 1 of 16 patients (6%) had autism, as defined by the Autistic Diagnostic Interview--Revised (ADI-R) [Lord et al., 1994: J Autism Dev Disord 24:659-685]. Thus, the prevalence of autism in 18q- syndrome is probably no greater than that in other developmental disabilities with a similar level of cognitive impairment. In contrast to what has been believed since 18q- was first described 30 years ago, we found no relationship between chromosome deletion size and any measure of cognition or behavior; nor were there any correlations between any of these measures with the presence or absence of abnormalities on MRI or somatosensory-evoked potentials.

Analysis of a splice-site mutation in the sap-precursor gene of a patient with metachromatic leukodystrophy.

Sphingolipid activator proteins (SAPs) are small, nonenzymatic glycoproteins required for the lysosomal degradation of various sphingolipids with a short oligosaccharide chain by their exohydrolases. Four of the five known activator proteins (sap-A-sap-D), also called "saposins," are derived from a common precursor by proteolytic processing. sap-B stimulates hydrolysis of sulfatides by arylsulfatase A in vivo. Its recessively inherited deficiency results in a metabolic disorder similar to classical metachromatic leukodystrophy, which is caused by a defect of arylsulfatase A. Here we report on a patient with sap-B deficiency. Reverse-transcription-PCR studies on the patient's mRNA revealed the occurrence of two distinct mutant species: one with an in-frame deletion of the first 21 bases of exon 6, the other with a complete in-frame deletion of this exon. The patient was homozygous for the underlying mutation, which was found to be a G-->T transversion within the acceptor splice site between intron e and exon 6, abolishing normal RNA splicing. Allele-specific oligonucleotide hybridization revealed that the parents and both grandfathers of the patient were carriers of this mutation. In order to analyze the fate of the mutant precursor proteins, both abnormal cDNAs were stably expressed in baby hamster kidney cells. Pulse-chase experiments showed that the deletion of 21 bp had no effect on the transport and the maturation of the encoded precursor. All sap forms except sap-B were detectable by immunochemical methods. The cDNA bearing a complete deletion of exon 6 encoded a shortened precursor of only 60 kD, and no mature SAPs were detectable. The carbohydrate chains of this polypeptide were of the high-mannose and hybrid type, indicating no transport of the mutant precursor beyond early Golgi apparatus. An endoplasmic-reticulum localization of this polypeptide was supported by indirect immunofluorescence analysis.

[The current treatment of trigeminal neuralgia. Experience in 162 thermorhizotomies]. / Die aktuelle Behandlung der Trigeminusneuralgie. Erfahrung bei 162 Thermorhizotomien.

The neuralgia of the trigeminal nerve is the most frequent neuralgia of the cranial nerves. It is mostly seen in the elderly. In younger patients it must always be suspected as a symptomatic neuralgia. The course is recurrent and progressive. Spontaneous temporary remissions are usual. Later the pain becomes more frequent, unbearable and disabling. At first the therapy is a conservative one, the drug of choice is Carbamazepin, alternatively Phenytoin and Baclofen. If the conservative therapy fails, the only possible treatment is a neurosurgical one. Nowadays all methods aim at the Gasserian ganglion. In use are several percutaneous transoval procedures or the microvascular decompression through a craniotomy. Our surgical procedure of choice is the percutaneous thermorhizotomy in the Gasserian ganglion and the nerve root, where the pain-conducting fibers are destroyed, preserving tactile sensibility. This procedure is practically without vital hazards for the patient. It is applied in local anesthesia and a short intravenous analgesia. The recurrence rate of 32% is considerable, but the procedure can be repeated. The success cannot be deduced from the recurrence rate alone but must take into account the side effects of the procedure. These are mainly a loss of sensibility to touch by too aggressive rhizotomy and anesthesia of the cornea. By the criteria explained in the text we achieved a good result in 44%, a fair one in 25%, an indifferent one in 10% and a poor result in 7%. In 14% the result is unknown.

Mental retardation.

Mental retardation is defined using two criteria: intelligence quotient and adaptive functioning. Subclassification based on IQ is helpful in predicting outcome and determining educational program. Advances continue to be made in identifying specific medical causes of intellectual deficits. As the natural history of conditions such as fragile-X becomes better understood, treatment approaches based on medical diagnosis will likely evolve. Clinicians working with mentally retarded patients should pursue vigorously medical diagnosis because of its implications for genetic counseling, family management, and full recognition of other handicapping conditions which may affect the patient. Psychopathology in the mentally retarded resembles that in nonretarded individuals, but occurs more frequently. Treatment of psychiatric disorders must be individualized. Mildly and some moderately retarded persons can benefit from psychotherapy. Behavioral approaches, particularly applied behavior analysis, are the most effective treatment for specific aberrant behaviors. Pharmacotherapy should be based on psychiatric diagnosis. Medications may be used, together with behavioral interventions, to treat specific destructive behaviors, but the scientific support for such use is new and somewhat limited.

Childhood chronic disease and family functioning: a study of phenylketonuria.

Families with young children with phenylketonuria (n = 45) were compared with matched comparison families (n = 49) with respect to parental psychologic distress, marital satisfaction, parenting stress, family cohesion and adaptability, and child behavior. Multivariate analyses failed to show significant group differences. Univariate analyses indicated lower levels of adaptability and cohesion for the families with a child with phenylketonuria and evidence of lower levels of social competence in the children with phenylketonuria than in the comparison group. Group differences with regard to parental psychologic distress, marital satisfaction, and parenting stress were not found. The study results provide implications for understanding the impact of childhood chronic disease on families.

Phenylalanine control and family functioning in early-treated phenylketonuria.

The association between effective metabolic control and patients' intelligence test performance and behavior in phenylketonuria (PKU) has been demonstrated frequently. The present study reexamined this relationship in a population of 41 young children with early-treated PKU, and added a dimension of family investigation to determine relationships between dietary phenylalanine control and patient functioning, family functioning and phenylalanine control, and family functioning and patient functioning. Significant correlations were found between concurrent phenylalanine control and patients' intelligence test scores, and lifetime phenylalanine control and patients' social competence. Parent-report measures of family psychological adjustment, stress, interaction, and socioeconomic status showed no significant association with children's dietary phenylalanine control. Family cohesion and adaptability correlated positively with patients' cognitive performance. Results support a policy of diet continuation in PKU, and suggest that family interaction patterns influence patient functioning. Longitudinal study of family factors in PKU is indicated.

Scanning electron microscopy of corpus luteum formation in the golden hamster.

SEM observations of corpus luteum formation in the golden hamster reveal considerable cellular migration occurring in both the newly forming luteal mass and the remaining surface epithelium. During the first 24 h of the 4-day cycle, cells in the luteal mass become aligned into cords which obliterate the crater-like rupture. Individual cords lose their distinct surface profiles as the luteal mass forms a mushroom-like cap, the edges of which overhang surface epithelial cells (SEC) bordering the rupture site. The luteal mass continues to be remodeled as the edges slowly recede during the next 3 days of the cycle, and the follicle assumes a more spherical shape with a slightly sunken apex as regression begins. Covering of the rupture site by the SEC is a slow process which involves two mechanisms. Most of the mass is gradually covered by finger-like columns of SEC which migrate from the collar of cells surrounding the luteal mass to slowly surround, then cover small spherical or oval regions of the slightly sunken mass. In addition, individual SEC migrate out of the collar and move up onto the mass. The entire covering process appears to be random and poorly coordinated until very late in the 4-day cycle. This is attributed to changing surface properties of the luteal mass during the cycle.