[Implantation of an Artificial Iris in 11 Patients]. / Rekonstruktive Irischirurgie bei 11 Patienten mit einem künstlichen Irisdiaphragma.

Background. Iris defects are mostly acquired after injury, or may be iatrogenic after surgical excision of iris tumours or the result of collateral trauma after anterior segment surgery. They cause severe visual disability, e.g. glare, loss of contrast sensitivity, and loss of best corrected visual acuity. The foldable Koch iris prosthesis has a customised iris design and may be used to reconstruct the anterior segment in patients with partial or complete aniridia. History and Signs. We present the surgical management and clinical course of 6 patients with traumatic iris defects, together with 3 patients with partial aniridia after cataract surgery. Cataract surgery and implantation of an artificial iris were performed in 2 female patients (3 eyes) with congenital aniridia syndrome. Therapy and Outcome. No patient exhibited complications in the postoperative course, with the exception of various intraocular pressure peaks due to secondary glaucoma, that were all corrected by medication to lower topical pressure. Conclusions. In patients with major iris defects, the artificial iris allows functionally and aesthetically satisfactory reconstruction of the anterior segment.

Gender-related sensitivity of development and growth to real microgravity in Xenopus laevis.

Exposure of organisms to microgravity can induce morphological, physiological, and behavioral modifications which normalize after re-entry in 1g-condition within hours to few weeks. Development of Xenopus laevis tadpoles, their metamorphosis, and adults' growth were monitored for 3 years after their flight on the 12-day Soyuz mission TMA13 to the International Space Station. At onset of microgravity, tadpoles had just developed the hind limb (stage 47) or forelimb bud (stage 50). Recordings during the first 4 days after landing revealed no differences of developmental progresses and growth between flight and ground tadpoles. Further development and growth were strongly retarded in all animals; nevertheless, significant differences appeared between flight and ground groups during this postflight period. They include (1) acceleration of development in stage 47 but not stage 50 flight tadpoles; (2) earlier metamorphosis of stage 47 flight tadpoles compared to their 1g-ground controls while stage 50 flight tadpoles metamorphosed later than their ground controls; (3) maintenance of a tail during the juvenile stage exclusively in some stage 47 flight animals, and (4) accelerated growth of stage 47 male flight toads but retarded growth of stage 50 flight males compared to the respective 1g-ground control males. No difference of growth was detected between flight and ground females after metamorphosis. All differences between flight and ground animals disappeared 1 year after landing. We conclude (1) that limited spatial and nutritional conditions during the mission period caused developmental retardation, and (2) that the thyroid gland of Xenopus is susceptible to spatial environment, in particular, during the period of beginning activation.

The vestibuloocular reflex of tadpoles (Xenopus laevis) after knock-down of the isthmus-related transcription factor XTcf-4.

Development of the amphibian vestibular organ is regulated by molecular and neuronal mechanisms and by environmental input. The molecular component includes inductive signals derived from neural tissue of the hindbrain and from the surrounding mesoderm. The integrity of hindbrain patterning, on the other hand, depends on instructive signals from the isthmus organizer of the midbrain, including the transcription factor XTcf-4. If the development of the vestibular system depends on the integrity of the isthmus as the organizing centre, suppression of isthmus maintenance should modify vestibular morphology and function. We tested this hypothesis by downregulation of the transcription factor XTcf-4. 10 pmol l(-1) XTcf-4-specific antisense morpholino oligonucleotide was injected in one blastomere of two-cell-stage embryos of Xenopus laevis. For reconstitution experiments, 500 pg mRNA of the repressing XTcf-4A isoform or the activating XTcf-4C isoform were co-injected. Overexpression experiments were included using the same isoforms. Otoconia formation and vestibular controlled behaviour such as the roll-induced vestibuloocular reflex (rVOR) and swimming were recorded two weeks later. In 50% of tadpoles, downregulation of XTcf-4 induced (1) a depression of otoconia formation accompanied by a reduction of the rVOR, (2) abnormal tail development and (3) loop swimming behaviour. (4) All effects were rescued by co-injection of XTcf-4C but not, or only partially, by XTcf-4A. (5) Overexpression of XTcf-4A caused similar morphological and rVOR modifications as XTcf-4 depletion, while overexpression of XTcf-4C had no effect. Because XTcf-4C has been described as an essential factor for isthmus development, we postulate that the isthmus is strongly involved in vestibular development.

The sensitivity of an immature vestibular system to altered gravity.

Stimulus deprivation or stimulus augmentation can induce long-lasting modifications to sensory and motor systems. If deprivation is effective only during a limited period of life this phase is called "critical period." A critical period was described for the development of the roll-induced vestibuloocular reflex (rVOR) of Xenopus laevis using spaceflights. Spaceflight durations and basic conditions of Xenopus' development did not make it possible to answer the question whether exposure of the immature vestibular organ to weightlessness affects rVOR development. The embryonic development of Pleurodeles waltl is slow enough to solve this problem because the rVOR cannot be induced before 15 dpf. Stage 20-21 embryos (4 dpf) were exposed to microgravity during a 10-day spaceflight, or to 3g hypergravity following the same time schedule. After termination of altered gravity, the rVOR was recorded twice in most animals. The main observations were as follows: (1) after the first rVOR appearance at stage 37 (16 dpf), both rVOR gain and amplitude increased steadily up to saturation levels of 0.22 and 20°, respectively. (2) Three days after termination of microgravity, flight and ground larvae showed no rVOR; 1 day later, the rVOR could be induced only in ground larvae. Differences disappeared after 3 weeks. (3) For 10 days after 3g exposure, rVOR development was similar to that of 1g-controls but 3 weeks later, 3g-larvae showed a larger rVOR than 1g-controls. These observations indicate that the immature vestibular system is transiently sensitive to microgravity exposure and that exposure of the immature vestibular system to hypergravity leads to a slowly growing vestibular sensitization.

Gravity-related critical periods in vestibular and tail development of Xenopus laevis.

Sensory systems are characterized by developmental periods during which they are susceptible to environmental modifications, in particular to sensory deprivation. The experiment, XENOPUS, on Soyuz in 2008 was the fourth space flight experiment since 1993 to explore whether tail and vestibular development of Xenopus laevis has a gravity-related critical period. During this flight, tadpoles were used that had developed either the early hindlimb (stage 47) or forelimb bud (stage 50) at launch of the spacecraft. The results revealed (1) no impact of microgravity on the development of the roll-induced vestibuloocular reflex (rVOR) in both stages and (2) a stage-related sensitivity of tail development to microgravity exposure. These results were combined and compared with observations from space flights on other orbital platforms. The combined data revealed (1) a narrow gravity-related critical period for rVOR development close to the period of the first appearance of the reflex and (2) a longer one for tail development lasting from the early tail bud to the early forelimb bud stage.

NER and HR pathways act sequentially to promote UV-C-induced germ cell apoptosis in Caenorhabditis elegans.

Ultraviolet (UV) radiation-induced DNA damage evokes a complex network of molecular responses, which culminate in DNA repair, cell cycle arrest and apoptosis. Here, we provide an in-depth characterization of the molecular pathway that mediates UV-C-induced apoptosis of meiotic germ cells in the nematode Caenorhabditis elegans. We show that UV-C-induced DNA lesions are not directly pro-apoptotic. Rather, they must first be recognized and processed by the nucleotide excision repair (NER) pathway. Our data suggest that NER pathway activity transforms some of these lesions into other types of DNA damage, which in turn are recognized and acted upon by the homologous recombination (HR) pathway. HR pathway activity is in turn required for the recruitment of the C. elegans homolog of the yeast Rad9-Hus1-Rad1 (9-1-1) complex and activation of downstream checkpoint kinases. Blocking either the NER or HR pathway abrogates checkpoint pathway activation and UV-C-induced apoptosis. Our results show that, following UV-C, multiple DNA repair pathways can cooperate to signal to the apoptotic machinery to eliminate potentially hazardous cells.

Microgravity-induced modifications of the vestibuloocular reflex in Xenopus laevis tadpoles are related to development and the occurrence of tail lordosis.

UNLABELLED: During space flights, tadpoles of the clawed toad Xenopus laevis occasionally develop upward bended tails (tail lordosis). The tail lordosis disappears after re-entry to 1g within a couple of days. The mechanisms responsible for the induction of the tail lordosis are unknown; physical conditions such as weight de-loading or physiological factors such as decreased vestibular activity in microgravity might contribute. Microgravity (microg) also exerts significant effects on the roll-induced vestibuloocular reflex (rVOR). The rVOR was used to clarify whether tail lordosis is caused by physiological factors, by correlating the occurrence of microg-induced tail lordosis with the extent of microg-induced rVOR modifications. Post-flight recordings from three space flights (D-2 Spacelab mission, STS-55 in 1993; Shuttle-to-Mir mission SMM-06, STS-84 in 1997; French Soyuz taxi flight Andromède to ISS in 2001) were analyzed in these experiments. At onset of microgravity, tadpoles were at stages 25-28, 33-36 or 45. Parameters tested were rVOR gain (ratio between the angular eye movement and the lateral 30 degrees roll) and rVOR amplitude (maximal angular postural change of the eyes during a 360 degrees lateral roll). A ratio of 22-84% of tadpoles developed lordotic tails, depending on the space flight. The overall observation was that the rVOR of tadpoles with normal tails was either not affected by microgravity, or it was enhanced. In contrast, the rVOR of lordotic animals always revealed a depression. In particular, during post-flight days 1-11, tadpoles with lordotic tails from all three groups (25-28, 33-36 and 45) showed a lower rVOR gain and amplitude than the 1g-controls. The rVOR gain and amplitude of tadpoles from the groups 25-28 and 33-36 that developed normal tails was not affected by microgravity while the rVOR of microg-tadpoles from the stage-45 group with normal tails revealed a significant rVOR augmentation. IN CONCLUSION: (1) the vestibular system of tadpoles with lordotic tails is developmentally retarded by microgravity; (2) after a critical status of vestibular maturation obtained during the appearance of first swimming, microgravity activates an adaptation mechanism that causes a sensitization of the vestibular system.

The development of gravity sensory systems during periods of altered gravity dependent sensory input.

Gravity related behavior and the underlying neuronal networks are the most suitable model systems to study basic effects of altered gravitational input on the development of neuronal systems. A feature of sensory and motor systems is their susceptibility to modifications of their adequate physical and/or chemical stimuli during development. This discovery led to the formulation about critical periods, which defines the period of susceptibility during post-embryonal development. Critical periods can be determined by long-lasting modifications of the stimulus input for the gravity sensory system (GSS). Techniques include: (1) destruction of the gravity sense organ so that the gravity cannot be detected any longer and the central neuronal network of the GSS is deprived of gravity related information, (2) loading or deloading of parts of the body by weights or counterweights, respectively, which compensates for the gravitational pull, and (3) absence or augmentation of the gravitational environment per se by the exposure of organisms to microgravity during spaceflights or to hypergravity by centrifugation. Most data came from studies on compensatory eye or head movements in the clawed toad Xenopus laevis, the cichlid fish Oreochromis mossambicus, and crickets (Acheta domesticus, Gryllus bimaculatus). The responses are induced by a roll or pitch stimulation of the gravity sense organs, but are also affected by sensory inputs from proprioreceptors and eyes. The development of these compensatory eye and head responses reveals species-specific time courses. Based on experiments using spaceflights, centrifugation, lesion and loading or deloading, all species revealed a significant susceptibility to modifications of the gravity sensory input during development. Behavioral responses were depressed (Xenopus) or augmented (Xenopus, Oreochronis) by microgravity, and depressed by hypergravity except in crickets. In Acheta, however, the sensitivity of its position sensitive neuron PSI was reduced by microgravity. After termination of the period of modified gravity sensory input, all behavioral and physiological modifications disappeared, in some preparations such as the PSI of Acheta or the eye response in Xenopus, however, delayed after exposure to hypergravity. Irreversible modifications were rare; one example were malformations of the body of Xenopus tadpoles caused by lesion induced deprivation. Several periods of life such as the period of hatching or first appearance of gravity related reflexes revealed a specific sensitivity to altered gravity. Although all studies gave clear evidences for a basic sensitivity of developing GSSs to long-lasting modifications of the gravity sensory input, clear arguments for the existence of a critical period in the development of the sense of gravity are still missing. It has to take into consideration that during long-term exposures, adaptation processes take place which are guided by central physiological and genetically determined set points. The International Space Station (ISS) is the necessary platform of excellence if biological research is focussed on the analysis of long-term space effects on organisms.

Effects of the specific bradycardic agent zatebradine on hemodynamic variables and myocardial blood flow during the early postresuscitation phase in pigs.

Cardiopulmonary resuscitation (CPR) leads to an excessive stimulation of the sympathetic nervous system that may result in tachycardia and malignant arrhythmias in the postresuscitation phase. The attenuation of this reaction by a specific bradycardic agent has not been compared to beta-blockade and placebo. After 4 min of ventricular fibrillation, and 3 min of CPR, 21 pigs were randomized to receive 45 microg/kg epinephrine in combination with either a specific bradycardic agent (0.5 mg/kg zatebradine; n = 7), or a beta-blocker (1 mg/kg esmolol; n = 7), or placebo (normal saline; n = 7). Two minutes after drug administration, defibrillation was performed to restore spontaneous circulation (ROSC). Hemodynamic variables, left ventricular contractility, right ventricular function, and myocardial blood flow were studied at prearrest, and for 3 h after ROSC. In comparison with esmolol and placebo, zatebradine resulted in a significant reduction in heart rate during the postresuscitation period, and reduced the number of premature ventricular contractions in the first 5 min after ROSC. This reduction in heart rate was associated with a significantly higher right ventricular ejection fraction, stroke volume, and endocardial/epicardial perfusion ratio at 5 min after ROSC. In comparison with placebo, esmolol administration decreased heart rate only moderately, but significantly reduced right ventricular stroke volume and cardiac output at 5 min after ROSC. Although only one dose and only one administration pattern of zatebradine has been investigated, we conclude that zatebradine administration during CPR effectively reduced heart rate without compromising myocardial contractility during the postresuscitation phase in pigs.

[Long-term outcome after surgical treatment of gastroesophageal reflux in infancy and childhood]. / Langzeiterfolg nach operiertem gastro-oesophagealem Reflux im Säuglings- und Kindesalter.

In this series 99 out of 131 children have been operated upon gastroeosophageal reflux at an age of 2.5 years. They were reevaluated 4.5 years later for their longterm results in 1997. All patients have been primary free of reflux postoperatively. By questionnaire, x-ray studies and 24 h/ph-metry signs of reflux could not be found in 88/99 children. 4 patients proved to suffer from a recurrant reflux and 3 out of these had to be reoperated. Another 7 showed a mild, not pathological reflux without needing medical treatment. Looking at the recurrencies especially preoperative peptic oesophagitis and stenoses as well as brachyoesophagus after oesophageal atresia turned out to be a problem in respect to prognosis. Control studies for longterm results should be done at least 1 year postoperatively.

Electrificación básica de hogares rurales. Experiencia de la GTZ en la difusión de pequeños sistemas fotovoltaicos: una guía para tomadores de decisiones, planificadores y proveedores.

Durante los últimos años, el uso de la tecnología fotovoltaiza (FV) para el suministro mínimo de electricidad, para hogares rurales en áreas de población dispersa en el Tercer Mundo, se ha convertido en una alternativa real al suministro tradicional de electricidad.

Glycosidases induced in Aspergillus tamarii. Mycelial alpha-D-galactosidases.

Two alpha-D-galactosidases (alpha-D-galactoside galactohydrolase, EC 3.2.1.22) produced by Aspergillus tamarii were purified from the mycelial extract by a procedure including chromatography on hydroxyapatite, DEAE-cellulose and ECTEOLA-cellulose. Each of these enzymes showed a single protein band corresponding to the alpha-D-galactosidase activity when examined by polyacrylamide-gel electrophoresis. They catalysed the hydrolysis of o-nitrophenyl alpha-D-galactoside, melibiose, raffinose and stachyose, but did not attack the galactomannans. Their Mr values were respectively 265000 +/- 5000 and 254000 +/- 5000 by the method of Hedrick & Smith [(1968) Arch. Biochem. Biophys. 126, 155-164]. Polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate in each case showed a single protein band, with Mr 88000 and 77500 respectively. The purified enzymes contained carbohydrate, consisting of N-acetylglucosamine, mannose, glucose and galactose in the estimated molar proportions of 1:9:5:8 in alpha-galactosidase I.

Glycosidases induced in Aspergillus tamarii. Secreted alpha-D-galactosidase and beta-D-mannanase.

An alpha-D-galactosidase (EC 3.2.1.22) and a beta-D-mannanase (EC 3.2.1.78), which were secreted into the growth medium when Aspergillus tamarii was cultivated in the presence of galactomannan, were purified by a procedure including chromatography on hydroxyapatite and DEAE-cellulose columns. Each of these enzymes showed a single protein band, corresponding to their respective activities, on polyacrylamide-gel electrophoresis. Both enzymes were shown to be glycoproteins containing N-acetylglucosamine, mannose and galactose, with molar proportions of 1:6:1.5 for alpha-D-galactosidase and 1:13:8 for beta-D-mannanase. Mr values as determined by polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate and by the electrophoretic method of Hedrick & Smith [(1968) Arch. Biochem. Biophys. 126, 155-164] were 56000 and 53000 respectively. The alpha-D-galactosidase differed markedly from the mycelial forms I and II studied in the preceding paper [Civas, Eberhard, Le Dizet & Petek (1984) Biochem. J. 219, 849-855] with regard to both its kinetic and structural properties.

Multivariate data analysis based on a computerized patient monitoring system.

Multivariate time series data in post-operative patients (respiratory and cardiovascular) are compared to reference groups. Using this technique under the program control of a computerized patient monitoring system (IBM 1800) various classes in the respiratory and cardiovascular spectrum can define the co-ordinate system in hyperspace. The patient in crisis is recognised by his deviation from normal rates of change of the variable set, as well as by the time trajectories of recovery in the hyperspace.