[Uroliths of cats in Switzerland from 2002 to 2009]. / Urolithen bei Katzen in der Schweiz von 2002 bis 2009.

INTRODUCTION: In this study data on composition of uroliths collected from cats and epidemiologic data of affected cats in Switzerland from 2002 to 2009 are summarised. Of 884 stones analysed 50% (n=441) were composed of calcium oxalate, 45% (n=398) of struvite, 3% (n=18) of ammonium urate, 1% (n=12) were mixed stones, 1% (n=9) were composed of silica, 3 stones were solidified blood, 2 consisted of cystine and 1of xanthine. 40% of the ureteral stones were composed of struvite. Domestic cats had significantly less calcium oxalate stones compared to British Shorthair or Persian cats. Cats with calcium oxalate stones were older and cats with struvite stones were younger than other affected cats. Female and male cats were equally affected with stones. Compared to studies from other countries, in Switzerland silica stones occurred more often and ureteral stones were more often composed of Struvite. The present study shows that occurrence and prevalence of urinary calculi of cats from Switzerland exhibited only slight differences to studies from other countries.

INTRODUCTION: Dans le présent travail, on résume les données relatives à la composition des calculs urinaires chez les chats en Suisse ainsi que les données épidémiologiques de ces animaux entre 2002 et 2009. Parmi les 884 calculs analysés, 50% (n=441) étaient composés d'oxalate de calcium, 45% (n=398) de struvite, 3% (n=18) d'urate d'ammonium, 1% (n=12) étaient des calculs mixtes 1% (n=9) se composaient de silicate, 3 calculs étaient formé de sang aggloméré, 2 étaient composés de cystine et un de xanthine. 40% des calculs urétraux se composaient de struvite. Les chats de maison avaient significativement moins de calculs d'oxalate de calcium que les British Shorthair ou les Persans. Les chats présentant des calculs d'oxalate de calcium étaient plus âgés et ceux présentant des struvites plus jeunes que tous les autres chats atteints. Les femelles et les mâles souffraient de calculs de façon équivalente. En comparaison avec des études menées dans d'autres pays, les calculs de silicate étaient plus fréquents en Suisse et les calculs urétraux se composaient plus souvent de struvite. Cette étude démontre que la survenue et la fréquence de calculs urinaires chez les chats en Suisse ne présente que peu de différence avec les études faites dans d'autres pays.

[Uroliths of dogs in Switzerland from 2003 to 2009]. / Urolithen von Hunden in der Schweiz von 2003 bis 2009.

Information on composition of uroliths collected between 2003 and 2009 from dogs in Switzerland and epidemiologic data of affected dogs are summarised in this paper. Of 490 stones analysed 44% were composed of calcium oxalate, 330% of struvite, 80% of silica, 7% of urate, 3% of cystine, 3% were mixed stones and 1% each were calcium phosphate and xanthine stones. Compared to other dogs, Norwich Terriers, Norfolk Terriers, Miniature Schnauzers, Miniature Pinscher and Yorkshire Terriers had a significantly increased risk to suffer from calcium oxalate stones, Dalmatians and Continental Bulldogs from urate stones and English Bulldogs from cystine stones. No breed had an increased risk of struvite or silica stones. Stones composed of silica were more prevalent in Switzerland compared to other countries and were more common in the eastern part than in the western part of Switzerland. This study shows that there are differences in occurrence and prevalence of uroliths between Switzerland and surveys of other countries.

Targeting expression to megakaryocytes and platelets by lineage-specific lentiviral vectors.

Essentials Platelet phenotypes can be modified by lentiviral transduction of hematopoietic stem cells. Megakaryocyte-specific lentiviral vectors were tested in vitro and in vivo for restricted expression. The glycoprotein 6 vector expressed almost exclusively in megakaryocytes. The platelet factor 4 vector was the strongest but with activity in hematopoietic stem cells. SUMMARY: Background Lentiviral transduction and transplantation of hematopoietic stem cells (HSCs) can be utilized to modify the phenotype of megakaryocytes and platelets. As the genetic modification in HSCs is transmitted onto all hematopoietic progenies, transgene expression from the vector should be restricted to megakaryocytes to avoid un-physiologic effects by ectopic transgene expression. This can be achieved by lentiviral vectors that control expression by lineage-specific promoters. Methods In this study, we introduced promoters of megakaryocyte/platelet-specific genes, namely human glycoprotein 6 (hGP6) and hGP9, into third generation lentiviral vectors and analyzed their functionality in vitro and in vivo in bone marrow transplantation assays. Their specificity and efficiency of expression was compared with lentiviral vectors utilizing the promoters of murine platelet factor 4 (mPf4) and hGP1BA, both with strong activity in megakaryocytes (MKs) used in earlier studies, and the ubiquitously expressing phosphoglycerate kinase (hPGK) and spleen focus forming virus (SFFV) enhancer/promoters. Results Expression from the mPf4 vector in MKs and platelets was the strongest similar to expression from the viral SFFV promoter, however, the mPf4 vector, also exhibited considerable off-target expression in hematopoietic stem and progenitor cells. In contrast, the newly generated hGP6 vector was highly specific to megakaryocytes and platelets. The specificity was also retained when reducing the promoter size to 350 bp, making it a valuable new tool for lentiviral expression in MKs/platelets. Conclusion MK-specific vectors express preferentially in the megakaryocyte lineage. These vectors can be applied to develop murine models to study megakaryocyte and platelet function, or for gene therapy targeting proteins to platelets.

Anxiety modulates cognitive deficits in a perinatal glutathione deficit animal model of schizophrenia.

In this study, we investigated long-term repercussion of early glutathione deficit by l-buthionine-(S,R)-sulfoximine (BSO) injections as a rat model of schizophrenia. BSO rats were tested through various behavioral tasks requiring animals to take into account previously delivered information. We showed that relative to controls, BSO rats (1) were less active and more anxious in an Elevated Plus Maze test, allowing us to split them into two subgroups with high and low anxiety levels; (2) demonstrated normal abilities of behavioral flexibility tested with a rat-adapted version of the Wisconsin Card Sorting Test (WCST), with even higher abilities in anxious BSO rats suggesting reduced interference of previously acquired rules; (3) did not forage normally in radial arm mazes and mainly used clockwise strategies; (4) exhibited a lack of habituation during a startle response task; and (5) showed a normal prepulse inhibition of the startle response (PPI) and a normal conditioned taste aversion (CTA). All these results indicate that early glutathione deficit provokes persistent changes in adulthood and improves the validity of this animal model of schizophrenia. They further suggest difficulties binding temporally separated events (WCST), except when the salience of this information is very strong (CTA). We propose that the transient glutathione deficit during cerebral development could alter a "cognitive binding" process in interaction with the emotional state that could possibly account for the disruption of integrative function that characterizes schizophrenia.

Ibotenate Lesions of Hippocampus and/or Subiculum: Dissociating Components of Allocentric Spatial Learning.

This study examined the effects of ibotenic acid-induced lesions of the hippocampus, subiculum and hippocampus +/- subiculum upon the capacity of rats to learn and perform a series of allocentric spatial learning tasks in an open-field water maze. The lesions were made by infusing small volumes of the neurotoxin at a total of 26 (hippocampus) or 20 (subiculum) sites intended to achieve complete target cell loss but minimal extratarget damage. The regional extent and axon-sparing nature of these lesions was evaluated using both cresyl violet and Fink - Heimer stained sections. The behavioural findings indicated that both the hippocampus and subiculum lesions caused impairment to the initial postoperative acquisition of place navigation but did not prevent eventual learning to levels of performance almost as effective as those of controls. However, overtraining of the hippocampus + subiculum lesioned rats did not result in significant place learning. Qualitative observations of the paths taken to find a hidden escape platform indicated that different strategies were deployed by hippocampal and subiculum lesioned groups. Subsequent training on a delayed matching to place task revealed a deficit in all lesioned groups across a range of sample choice intervals, but the subiculum lesioned group was less impaired than the group with the hippocampal lesion. Finally, unoperated control rats given both the initial training and overtraining were later given either a hippocampal lesion or sham surgery. The hippocampal lesioned rats were impaired during a subsequent retention/relearning phase. Together, these findings suggest that total hippocampal cell loss may cause a dual deficit: a slower rate of place learning and a separate navigational impairment. The prospect of unravelling dissociable components of allocentric spatial learning is discussed.

The place preference task: a new tool for studying the relation between behavior and place cell activity in rats.

This study describes a task that combines random searching with goal directed navigation. The testing was conducted on a circular elevated open field (80 cm in diameter), with an unmarked target area (20 cm in diameter) in the center of 1 of the 4 quadrants. Whenever the rat entered the target area, the computerized tracking system released a pellet to a random point on the open field. Rats were able to learn the task under light and in total darkness, and on a stable or a rotating arena. Visual information was important in light, but idiothetic information became crucial in darkness. Learning of a new position was quicker under light than in total darkness on a rotating arena. The place preference task should make it possible to study place cells (PCs) when the rats use an allothetic (room frame) or idiothetic (arena frame) representation of space and to compare the behavioral response with the PCs' activity.

Absence of snapshot memory of the target view interferes with place navigation learning by rats in the water maze.

Contribution of visual and nonvisual mechanisms to spatial behavior of rats in the Morris water maze was studied with a computerized infrared tracking system, which switched off the room lights when the subject entered the inner circular area of the pool with an escape platform. Naive rats trained under light-dark conditions (L-D) found the escape platform more slowly than rats trained in permanent light (L). After group members were swapped, the L-pretrained rats found under L-D conditions the same target faster and eventually approached latencies attained during L navigation. Performance of L-D-trained rats deteriorated in permanent darkness (D) but improved with continued D training. Thus L-D navigation improves gradually by procedural learning (extrapolation of the start-target azimuth into the zero-visibility zone) but remains impaired by lack of immediate visual feedback rather than by absence of the snapshot memory of the target view.

Adenosine mediates tubuloglomerular feedback response: an element of metabolic control of kidney function.

Numerous studies have shown during the past 10 years that adenosine is present in the normoxic kidney and accumulates when ATP hydrolysis prevails over ATP synthesis. Local generation of adenosine by the macula densa cells and its release into the interstitium of the juxtaglomerular apparatus (JGA) is considered to be the link between the enhanced NaCl concentration in the tubular fluid and the subsequent responses including preglomerular vasoconstriction and reduction of renin release by the juxtaglomerular cells. Micropuncture and microperfusion experiments using specific adenosine agonists and antagonists support the concept that adenosine functions as a mediator in the signal transmission of the JGA.

A homing procedure for studying spatial memory in immature and adult rodents.

In this procedure, subjects learn the spatial position of one hole out of many, that allows them to escape from a large open-field into their home cage. The arena is circular and can be rotated between trials so that no proximal landmark is permanently associated with the target hole. This task is thus similar to the Morris water maze procedure, since subjects must remember the position of the escape hole relative to extra-arena cues only. In addition it allows studying the importance of olfactory cues such as scent marks in or around a hole. Since the motivation is to reach home and the motor requirement is low, this task provides a useful alternative to the Morris place navigation task for studying spatial orientation in weanling or senescent rats. Examples are given showing that various behavioural parameters provide a good estimation as how subjects learn this task.

Auditory cues support place navigation in rats when associated with a visual cue.

Rats, like other crepuscular animals, have excellent auditory capacities and they discriminate well between different sounds [Heffner HE, Heffner RS, Hearing in two cricetid rodents: wood rats (Neotoma floridana) and grasshopper mouse (Onychomys leucogaster). J Comp Psychol 1985;99(3):275-88]. However, most experimental literature concerning spatial orientation almost exclusively emphasizes the use of visual landmarks [Cressant A, Muller RU, Poucet B. Failure of centrally placed objects to control the firing fields of hippocampal place cells. J Neurosci 1997;17(7):2531-42; and Goodridge JP, Taube JS. Preferential use of the landmark navigational system by head direction cells in rats. Behav Neurosci 1995;109(1):49-61]. To address the important issue of whether rats are able to achieve a place navigation task relative to auditory beacons, we designed a place learning task in the water maze. We controlled cue availability by conducting the experiment in total darkness. Three auditory cues did not allow place navigation whereas three visual cues in the same positions did support place navigation. One auditory beacon directly associated with the goal location did not support taxon navigation (a beacon strategy allowing the animal to find the goal just by swimming toward the cue). Replacing the auditory beacons by one single visual beacon did support taxon navigation. A multimodal configuration of two auditory cues and one visual cue allowed correct place navigation. The deletion of the two auditory or of the one visual cue did disrupt the spatial performance. Thus rats can combine information from different sensory modalities to achieve a place navigation task. In particular, auditory cues support place navigation when associated with a visual one.

Postnatal intracerebroventricular administrations of NGF alter spatial memory in adulthood.

The present work assessed the effects of intracerebroventricular injections (2x5 mg/2.5 ml) of recombined human nerve growth factor (rhNGF) at postnatal days 2 and 3 upon the development of spatial learning capacities in rats. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and reducing attention to the distant spatial cues. At the age of 2 months all the rats were retrained in the same task. Treatment effects were found in both immature and adult rats. The injection of NGF induced a slight alteration of the immature rats' performance. In contrast, a marked impairment of spatial abilities was shown in the 2-month-old rats. The most consistent effects were a significant increase in the escape latency and a decrease bias towards the training platform area during probe trials. The reduction of spatial memory was particularly marked if the subjects had been trained in a cued condition. Taken together, these experiments reveal that an acute pharmacological treatment that leads to transient modifications during early development might induce a behavioural change long after treatment. Thus, the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures that could be altered by precocious NGF administrations.

Molecular and prognostic classification of advanced melanoma: a multi-marker microcontamination assay of peripheral blood stem cells.

The presence or absence of melanoma cells in human peripheral blood has recently been shown to be associated with disease prognosis, including overall survival. The detection of tyrosinase mRNA-positive circulating melanoma cells by reverse transcription-polymerase chain reaction (RT-PCR) has been limited to disseminated tumours expressing measurable amounts of this melanocyte-specific enzyme. To biologically classify both melanotic and amelanotic melanomas and to evaluate the clinical and prognostic relevance of tumour cell microcontamination, we examined autologous peripheral blood stem cell (PBSC) harvests from patients with advanced malignant melanoma prior to dose-escalated chemotherapy. To assay heterogeneous melanoma cell antigen expression, we developed a highly sensitive RT-PCR using four melanoma- and one tumour-associated antigen as molecular markers. Expression of the melanocyte-associated transcripts of tyrosinase, MART1/Melan-A, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) as well as the tumour-specific transcript of MAGE-3 was analysed by RT-PCR in PBSC harvests from 31 patients. Seven of the 31 PBSC harvests tested positive for one or more molecular markers: two patients for tyrosinase only, and one patient for MAGE-3 only, one patient for tyrosinase and MAGE-3, one for tyrosinase and MART1/Melan-A, and two patients for tyrosinase, MART1/Melan-A, TRP-2 and MAGE-3. mRNA-positive patients exhibited a significantly impaired overall survival (P = 0.0032), with a median survival of 3 months as opposed to 10 months in PBSC mRNA-negative patients. In conclusion, the use of this multiple-marker microcontamination assay allowed for molecular and prognostic classification of advanced malignant melanoma.

Influence of local environmental olfactory cues on place learning in rats.

The aim of the present study was to assess the influence of local environmental olfactory cues on place learning in rats. We developed a new experimental design allowing the comparison of the use of local olfactory and visual cues in spatial and discrimination learning. We compared the effect of both types of cues on the discrimination of a single food source in an open-field arena. The goal was either in a fixed or in a variable location, and could be indicated by local olfactory and/or visual cues. The local cues enhanced the discrimination of the goal dish, whether it was in a fixed or in a variable location. However, we did not observe any overshadowing of the spatial information by the local olfactory or visual cue. Rats relied primarily on distant visuospatial information to locate the goal, neglecting local information when it was in conflict with the spatial information.

[131I therapy in hyperthyroidism. Results of treatment from 1960-1974]. / 131J-Therapie der Hyperthyreose. Behandlungsergebnisse von 1960-1974

488 PATIENTS WITH Graves' disease were treated by 131Iodine between 1960 and 1974. 427 (87,5%) of these patients were reexamined several times (clinically, 131I-uptake, PB127I, T4 (CPB-A), T3-uptake, and since 1973 TRH-test). The 131I was given as an individually calculated single dose treatment, using 7 000 -- 10 000 rd before 1965 and 6 000 rd thereafter. Two thirds of the patients became euthyroid after a single 131I-dose. In 20% the treatment had to be repeated. These patients show evidently a different biological behaviour of their disease, since multiple treatments revealed a higher rate of failure (33--35%). There is no principal difference between the out-come after 131I-therapy and surgery concerning the rate of failure, respectively relapse (3--4%) and hypothyroidism. Early incidence of hypothyrodism is dose--dependent, as could be shown in patients treated with higher doses before 1965. The reduction of the irradiation dose to 6 000 rd was followed by a drop of hypothyroidism from 18% to 7%. The reasons of late incidence of hypothyroidism are discussed. The incidence of hypothroidism was calculated by three different methods (over-all incidence, incidence within the observed interval after therapy, life-table method). All three methods revealed different results. This has to be taken into account comparing results after radioiodine as well as after surgery. Radioiodine therapy for hyperthyroidism offers a true alternative to surgery.

[Not Available]. / Influence du sexe sur l'activite nocturne mesuree chez le mulot sylvestre apres un changement de milieu.

Adult male and female woodmice (Apodemus sylvaticus L.) were isolated for 4-6 days in actographs. Time spent in the nest box, eating, drinking, locomotor activity in the enclosure ,and wheel-running were automatically recorded. The individual breeding cages were also equipped with a wheel. The immediate reaction following the introduction in an actograph, at about 11.00 a.m., lasted for 30-120 min; locomotor activity and wheel-running was higher in the male than in the female group. During the first night, the mice were more active in the whole enclosure and ran less in the wheel than during the following nights. This was more evident in the female group, but both groups showed similar activity from the third day, and expressed more wheel-running than when in the breeding cage. When brought back into the breeding cage, the mice's wheel-running activity strongly decreased on the first night, and was even lower in the female group than before testing. In the actographs, increasing the accessible surface around the wheel led to a transitory drop in wheel-running for 1-2 days. Cleaning the breeding cage induced a similar but less pronounced change, On the whole, the novelty of a situation depressed wheel-running and increased locomotor activity for a few days. This reaction was more important in the female than in the male group, although the males showed a greater amount of activity as an immediate response to environmental changes.

Developpement de la locomotion chez le mulot sylvestre (Apodemus sylvaticus L.).

This longitudinal study describes the functional development of locomotion in the woodmouse, Apodemus sylvaticus . It shows that postnatal day (PND) 11 is a critical age in the acquisition of independence. Locomotion develops in successive stages before reaching the adult pattern (walking) at PND 11. Intermediate patterns are determined by the degree of coordination between the different parts of the body. Some of these patterns overlap and do not necessarily appear in every individual in our experiments. The young woodmouse respond optimally in three sensorimotor tests on PND 10 (contact righting, negative geotaxis) and on PND 11 (cliff avoidance). Immature reflexes, which may have specific functions in a short period of the early development have then disappeared. Simultaneously, there is a transition from stereotyped to oriented reactions (exploration, flight, etc.) which depend more and more on nonspecific stimulations (manipulation, etc.) rather than on specific ones (slope, cliff). These decisive changes are accomplished two days before eye opening. We can parallel them to the drastic ones that we reported elsewhere in the production of ultrasonic vocalisations. These signals elicit the retrieval of the pups by the mother, thereby compensating for the incapacity of the pup to move in an organised way. This study gives a basis for comparisons with other Rodents. In general, the woodmouse matures earlier than the rat by about two days, but later than the housemouse by two days. However, this delay might vary according to the given task. We discuss our results from a methodological point of view, and underline the advantages of measuring a continuous variable against an arbitrary criterion.

Development of place navigation in rats from weaning to puberty.

Young hooded rats were trained to escape onto a hidden platform after swimming in a pool of opaque water. Subjects 21, 28, 35, 42, and 64 days of age on the first training day were given 28 trials on 5 consecutive days. Half of the rats were required to localize the platform in relation to external room cues only ("place only" condition) and the other half were helped by the presence of a visible cue on the platform ("cue + place" condition). A deficiency in place navigation was observed in the 21- and 28-day groups; they showed slow escape and took circuitous routes more often than older rats. This deficiency was related to a poor spatial bias toward the training position when the subjects were allowed to swim for 30 s in the absence of the platform, at the end of the 28-trial training period (probe trial). The 35-day group showed adult-like learning ability in both training conditions, but failed to show searching behavior during the probe trial after having been trained in the presence of the proximal cue. Only rats older than 40 days showed typical adult behavior such as swimming directly toward the platform from any starting position and localized searching around the absent platform's position during the probe trial, no matter what the training conditions were. These results suggest that central nervous system structures responsible for place learning in the rat are functional from around 32 days of age, but fail to trigger searching behavior following cued training before the sixth week.

A course on collaboration between social workers and general practitioners during their vocational training.

The educational programme reported was an experiment in the vocational training scheme of the department of General Practice, Erasmus University, Rotterdam, Holland, and is now part of the course. The programme focused on the training in team function (co-operation) given to trainee GPs and social workers. It became clear that both groups during their professional training develop markedly different attitudes and views about patient (client) care. These differences form a fundamental handicap in any discussion about teamwork. During the programme the students were made aware of this divergence of viewpoint and were taught how to handle these resulting handicaps and, if possible, to eliminate them.