[Gluteal compartment syndrome after immobilization following opioid abuse]. / Gluteales Kompartmentsyndrom nach Liegetrauma bei Opiatabusus.

This article reports the case of a 42-year-old male patient, who sustained a gluteal compartment syndrome after drug-induced immobilization with subsequent rhabdomyolysis and sciatic nerve palsy. Unlike compartment syndrome of the forearm or lower leg, this is a rare condition. After immediate surgical decompression and installation of negative pressure wound treatment, hemofiltration in acute renal failure could be averted using forced diuresis. The sensorimotor function of the lower extremity improved already after the first treatment and secondary wound closure was possible after 1 week. The patient was discharged 11 days after admission with complete recovery of sensorimotor and renal functions.

Glacial effects limiting mountain height.

The height of mountain ranges reflects the balance between tectonic rock uplift, crustal strength and surface denudation. Tectonic deformation and surface denudation are interdependent, however, and feedback mechanisms-in particular, the potential link to climate-are subjects of intense debate. Spatial variations in fluvial denudation rate caused by precipitation gradients are known to provide first-order controls on mountain range width, crustal deformation rates and rock uplift. Moreover, limits to crustal strength are thought to constrain the maximum elevation of large continental plateaus, such as those in Tibet and the central Andes. There are indications that the general height of mountain ranges is also directly influenced by the extent of glaciation through an efficient denudation mechanism known as the glacial buzzsaw. Here we use a global analysis of topography and show that variations in maximum mountain height correlate closely with climate-controlled gradients in snowline altitude for many high mountain ranges across orogenic ages and tectonic styles. With the aid of a numerical model, we further demonstrate how a combination of erosional destruction of topography above the snowline by glacier-sliding and commensurate isostatic landscape uplift caused by erosional unloading can explain observations of maximum mountain height by driving elevations towards an altitude window just below the snowline. The model thereby self-consistently produces the hypsometric signature of the glacial buzzsaw, and suggests that differences in the height of mountain ranges mainly reflect variations in local climate rather than tectonic forces.

Informal carers' experiences and needs when supporting patients through chemotherapy: a mixed method study.

Informal carers provide important emotional support to patients having chemotherapy and assistance in monitoring and managing side-effects. If they are inadequately supported in this, patient and carer morbidity may result. This study explored needs of informal carers supporting patients with cancer having chemotherapy. The study used a mixed methods approach. Carers of colorectal or lymphoma cancer patients at one comprehensive cancer centre participated. Questionnaire data informed semi-structured interviews conducted with a subsample of respondents. Interviews were analysed using Framework analysis. Questionnaire data were analysed descriptively. Fifty-nine informal carers were invited to participate; 48 returned the questionnaire (response rate 81%) and 13 were interviewed. Informal carers' needs for information about chemotherapy and its side-effects were largely met although a third felt completely or somewhat unprepared to deal with particular symptoms experienced by patients at home. Many carers had unmet needs regarding financial support and their own needs as carers. Assertiveness was important to many caring roles, but it appeared difficult for informal carers to adopt when they were unsupported in this and their role was unrecognised by health professionals. Future research should develop interventions to systematically prepare carers for their carer role, improve carer involvement and ultimately improve patient outcomes.

Cervical sprouting of corticospinal fibers after thoracic spinal cord injury accompanies shifts in evoked motor responses.

The adult central nervous system (CNS) of higher vertebrates displays a limited ability for self repair after traumatic injuries, leading to lasting functional deficits [1]. Small injuries can result in transient impairments, but the mechanisms of recovery are poorly understood [2]. At the cortical level, rearrangements of the sensory and motor representation maps often parallel recovery [3,4]. In the sensory system, studies have shown that cortical and subcortical mechanisms contribute to map rearrangements [5,6], but for the motor system the situation is less clear. Here we show that large-scale structural changes in the spared rostral part of the spinal cord occur simultaneously with shifts of a hind-limb motor cortex representation after traumatic spinal-cord injury. By intracortical microstimulation, we defined a cortical area that consistently and exclusively yielded hind-limb muscle responses in normal adult rats. Four weeks after a bilateral transsection of the corticospinal tract (CST) in the lower thoracic spinal cord, we again stimulated this cortical field and found forelimb, whisker, and trunk responses, thus demonstrating reorganization of the cortical motor representation. Anterograde tracing of corticospinal fibers originating from this former hind-limb area revealed that sprouting greatly increased the normally small number of collaterals that lead into the cervical spinal cord rostral to the lesion. We conclude that the corticospinal motor system has greater potential to adapt structurally to lesions than was previously believed and hypothesize that this spontaneous growth response is the basis for the observed motor representation rearrangements and contributes to functional recovery after incomplete lesions.

Inhibition of conditional avoidance response by neuroleptics upon repeated administration.

Development of tolerance to neuroleptic compounds tested in the conditional avoidance model was investigated. Since tolerance may manifest itself by a diminished potency and/or a shortened duration of effect, the complete time course of effect was registered in these experiments. Rats were pretreated approximately 2 weeks with daily oral doses of chlorprothixene (20 mg/kg), flupenthixol (10 mg/kg), fluphenazine (2.5 mg/kg), or haloperidol (10 mg/kg) or twice a week with piflutixol (0.31 mg/kg). Three days after withdrawal chlorprothixene and flupenthixon caused a slightly but significantly weaker inhibition of avoidance performance in rats pretreated with the respective compounds and compared with non-pretreated rats, the duration of effect was shortened. Six dasy after withdrawal of piflutixol the duration of effect of a dose of piflutixol causing maximum inhibition was significantly shortened, while no homologous tolerance could be demonstrated in fluphenazine-pretreated rats. Cross tolerance was found after haloperidol-pretreatment when the rats were tested with fluphenazine 6 days after withdrawal. Homologous piflutixol tolerance could be shown 4 weeks after withdrawal. These results indicate that it is possible to demonstrate a slight tolerance to the effect of neuroleptic compounds when these are tested in conditional avoidance experiments. The cause of this tolerance is discussed.

Sensitization of prepulse inhibition deficits by repeated administration of dizocilpine.

RATIONALE: Repeated administration of psychoactive drugs results in a progressive enhancement of the behavioral effects of these compounds, a phenomenon termed sensitization. OBJECTIVE: We tested whether repeated administration of the non-competitive NMDA receptor antagonist dizocilpine (MK-801) induces sensitization of the disruptive effects of this compound on prepulse inhibition (PPI) of startle. METHODS: Rats received nine daily i.p. injections of 0.1 mg/kg MK-801 in the startle cage and were tested for PPI, startle in the absence of prepulses and motor activity in the startle cage. Another group of rats received MK-801 in the home cage on 9 days without daily testing. Controls were injected with saline and tested daily, while a separate group of rats received saline in the home cage without daily testing. On day 10, all rats received saline injections and were tested. On day 11, all rats were injected with 0.1 mg/kg MK-801 and tested again. On day 12, all rats received 1 mg/kg dl-amphetamine i.p. and were tested for PPI, to assess a possible cross-sensitization. RESULTS: MK-801 had no effect on day 1 of testing but induced a PPI deficit after 6-9 days of daily treatment and testing in those rats that received the drug in the startle cage, but not in the home cage. Motor activity was increased after repeated treatment and testing. There was also a trend towards sensitization of enhancement of the startle magnitude by MK-801 in these rats. dl-Amphetamine reduced PPI in those rats that received daily MK-801 injections in the startle cage to a similar extent as saline injections. CONCLUSIONS: Since PPI is considered as a measure of sensorimotor gating, our data indicate that sensorimotor gating deficits induced by MK-801 are subject to a sensitization process. These findings may be relevant for current hypotheses relating schizophrenic symptoms to sensitization.

Small bowel fistulas treated with somatostatin: preliminary results.

Small bowel cutaneous fistula appearing after laparotomy was treated with the tetradecapeptide somatostatin in six patients to reduce the volume and enzyme content of the intestinal secretion. Continuous intravenous infusion of somatostatin diminished output from the fistula in all cases. Spontaneous fistula closure occurred after 11 to 33 days of treatment in four patients. There were no complications such as sepsis, peritonitis, or wound or skin problems from the contact with intestinal secretion. The hospital stay ranged from 19 to 50 days and bowel function was restored to normal. These preliminary results indicated that somatostatin can promote healing of small bowel fistula by inhibiting intestinal secretions.

Characterization and regional distribution of nitric oxide synthase in the human brain during normal ageing.

Nitric oxide (NO) is a highly diffusible cellular mediator generated from L-arginine by the enzyme nitric oxide synthase (NOS). As little is known about the regional distribution of NOS in the human brain, we examined the distribution pattern of nitric oxide synthase activity in 28 regions of the human brain using the [(3)H]L-citrulline formation assay. To elucidate which isoforms contribute to the total NOS activity we performed Western blot analysis of neuronal, inducible and endothelial NOS. We further determined brain levels of arginine and citrulline as a potential index of NOS activity pre mortem. NOS activity appears to remain unaltered during ageing and is independent of post mortem delay, gender or sample storage time. We identified a regional pattern of NOS distribution with highest levels of NOS activity in the substantia innominata, cerebellar cortex, nucleus accumbens and subthalamicus, whereas lowest levels were measured in the corpus callosum, thalamus, occipital cortex, and dentate nucleus. nNOS was measured throughout the brain, in contrast iNOS and eNOS were not detectable. We therefore conclude that primarily nNOS is responsible for NOS activity in the human brain. Levels of citrulline were higher than those of arginine, but did not correlate with the enzyme activity, suggesting that these parameters are unsuitable for testing NOS activity premortem. The characterization and topographical pattern of NOS in the human brain during normal ageing may assist our understanding of the physiological role of NO and its relevance in Parkinson's and Alzheimer's disease, alcoholism, schizophrenia and AIDS.

Pharmacology of a new phthalane (Lu 10-171), with specific 5-HT uptake inhibiting properties.

The pharmacological profile of a new bicyclic substance, Lu 10-171 (1-(3-(dimethylamino)propyl)-1-(p-fluorophenyl)-5-phthalancarbonitril), is described and compared with that of existing tricyclic thymoleptics. In mice and rats the compound exhibited marked 5-HT potentiating properties both in vivo and in vitro, being 5-10 times as active as chlorimipramine. The tests included 5-HT-, 5-HTP- and tryptophan-potentiation. In monoamine oxidase inhibitor treated dogs and rabbits the compound caused a marked hyperthermia. In rabbits this effect was completely blocked by pretreatment with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine. Hyperthermia induced by the central catecholamine displacing substance H 77/77 in rats was not affected by Lu 10-171, whereas the substance abolished the temperature rise induced by H 75/12. Reserpine- and tetrabenazine-induced ptosis and tetrabenazine-induced immobility in mice were antagonized by relatively low doses of existing tricyclic thymoleptics, whereas Lu 10-171 was very weak in this respect. Very weak in vitro anticholinergic and antihistaminergic properties were also registered for Lu 10-171. It is concluded that Lu 10-171 is a very potent and highly specific potentiator of 5-HT both in vivo and in vitro probably due to inhibition of 5-HT uptake. Thus this compound might be a useful agent in studying the role of 5-HT neurone systems in the control of mood. The substance does not possess the NA potentiating and anticholinergic and antihistaminergic properties characteristic of the tricyclic antidepressants.

Zuclopenthixol and haloperidol in patients with acute psychotic states. A double-blind, multi-centre study.

A double-blind, multi-centre study was carried out in 49 hospitalized patients with an acute psychosis or an exacerbation of a chronic psychosis to compare the wanted and unwanted effects of the neuroleptics, zuclopenthixol and haloperidol. Patients were allocated at random to receive treatment with one or other of the trial drugs for 8 weeks or until discharge. Five patients on zuclopenthixol and 6 on haloperidol were excluded from the efficacy analyses because they did not complete a minimum of 4-weeks' treatment. Dosage was chosen and adjusted to the individual patient's condition and response. The average daily doses in Week 4 were 33.5 mg and 10.3 mg, respectively. Clinical assessments, including CGI, BPRS and the UKU side-effect scale, were done at baseline, and after 1, 2, 4, 6 and 8 weeks of treatment or at discharge if the patient was discharged earlier than Week 8. Both treatments caused a significant reduction in scores with no between-group differences. More patients in the zuclopenthixol group were discharged early indicating slightly more rapid onset of action. Zuclopenthixol caused a significantly greater improvement in 'anxious-depression' factor score than haloperidol. The most frequent unwanted effects were extrapyramidal symptoms and there were no significant differences between the groups. The extrapyramidal symptoms tended to be transient in the zuclopenthixol group, but not in the haloperidol group. The study confirmed that both zuclopenthixol and haloperidol were effective drugs in the treatment of acute, psychotic patients. There was a trend towards a slightly more rapid onset of effect and a somewhat stronger anxiolytic-antidepressant effect by zuclopenthixol compared to haloperidol.

Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia.

Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect. This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia (TD) and less rebound aggravation after withdrawal than pure D2 antagonists. In this study the effect of zuclopenthixol (mixed D1/D2 antagonist) and haloperidol (D2 antagonist) was evaluated in chronic psychotic patients with TD. Fifteen patients completed a randomized crossover study with blind evaluation of TD and parkinsonism. The test medications, haloperidol and zuclopenthixol, caused a significant suppression of TD and a significant increase of parkinsonism. No significant differences between haloperidol and zuclopenthixol were observed. No TD aggravation was seen. The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD.

Randomized comparison of conventional and gasless laparoscopic cholecystectomy: operative technique, postoperative course, and recovery.

The positive CO2 pneumoperitoneum needed to create the working space for laparoscopic surgery induces cardiovascular, neuroendocrine, and renal changes. Concern about these pathophysiologic changes has led to the introduction of a gasless technique. Fifty consecutive patients with symptomatic gallstones were randomized to conventional (CLC) or gasless laparoscopic cholecystectomy (GLC), with special reference to overall patient satisfaction, technical difficulties, duration of surgery, postoperative pain, and recovery. The overall exposure of the operative field was extremely poor in the GLC group, whereas the duration of surgery, steps involved in the cholecystectomy technique, length of hospital stay, and postoperative pain score did not differ significantly. After discharge, the median time to complete relief of pain tended to be shorter in the gasless group (5 days [range 1 to 15]) vs. the conventional group (8 days [range 1 to 15]). The period to return to normal activity was shorter in the GLC group (6 days [range 1 to 15]) compared to the CLC group (8.5 days [range 1 to 15]) (P = 0.031). No differences were found in terms of fatigue, dizziness and nausea, and overall satisfaction with the outcome. This study demonstrates a significantly shorter convalescence after laparoscopic cholecystectomy by means of the gasless technique compared to the conventional CO2 technique. Exposure of the operative field was less than optimal using the gasless technique.

Immediate early gene expression in rat basal ganglia after destruction of the dopaminergic system.

In the present study, we performed immunocytochemical mapping of cFos and c-Jun as markers for changes in neural activity in the brains of dopamine denervated rats. We observed a prolonged c-Fos and c-Jun expression in basal ganglia motor and limbic circuits over 96 h. This might be due to alterations in transmitter balances. We conclude, that changes in neural activities are involved in the development of 'extranigral' pathology of Parkinson's disease.

The neuroprotectant properties of glutamate antagonists and antiglutamatergic drugs.

In the slowly progressive neurodegenerative disorders like Parkinson's disease and Alzheimer's disease very different neuronal populations undergo degenerative processes, although the cascades of cellular events leading to death are supposed to be similar. We suggest that the complex pattern of degeneration in Parkinson's disease depends on two processes, a 'primary neurodegeneration' that takes place in the striato-nigral dopamine neurons and a 'secondary degeneration', occurring in distant structures of the basal ganglia network. For the purpose of explaining the regionally different expression of 'primary neurodegeneration' in different diseases, we postulate that the origin of neurodegeneration is associated with the local release of a neurotransmitter. For Parkinson's disease this would mean that the metabolism of dopamine in the striatum, nucleus accumbens and presumably the pedunculopontine tegmental nucleus, together with one or more pathological factors contribute to the initial neurodegeneration. There are recent studies indicating that a transneuronal retrograde degeneration of the substantia nigra pars compacta neurons might be induced by a loss of function of dopaminergic synapses in the striatum. We have recently established an animal model of retrograde striato-nigral degeneration, where the assessment of markers for cellular stress is possible. In Parkinson's disease, several structures distal from the substantia nigra pars compacta undergo neuropathological changes, characterizing the 'secondary neurodegeneration. Our recent studies provide experimental evidence for a chronic cellular stress in these structures because of a relative or absolute glutamatergic overactivity due to the initial loss of dopaminergic innervation. Thus, a loss of dopamine transforms the basal ganglia to a 'destructive network'. Both processes, the 'primary' and 'secondary neurodegeneration', affecting each other, characterize the progress of chronic neurodegeneration. From this point of view, we would further like to develop strategies for symptomatic amendment. Excitatory amino acids seem to be involved not only in the secondary processes of neurodegeneration, but also in initiation of the 'primary degeneration' of the substantia nigra pars compacta. Therefore, a reduction of glutamatergic overactivity constitutes a promising neuroprotective strategy. Especially the new antagonists of the NMDA-receptors with high affinity to the NR2B subunit of the receptor are in focus of our interest, since they reveal a favourable profile of side effects, therefore providing a promising tool for neuroprotection.

The optimal dosing regimen for citalopram--a meta-analysis of nine placebo-controlled studies.

Optimal dosing schedules for an antidepressant drug can only be established during clinical studies in depressed patients. The benefits of antidepressant therapy are usually progressive, and thus patients must be maintained on a particular treatment for at least 3-4 weeks to assess the efficacy of different doses. Meta-analysis, a widely accepted statistical technique which allows the combination of the results of multiple studies, was used to assess the efficacy of several doses of citalopram over nine placebo-controlled clinical trials. Statistically significant differences between citalopram and placebo were found at both the 20 and 40 mg dose levels. The minimal effective dose of citalopram was shown to be 20 mg. However, analysis of patient subgroups revealed a tendency for those patients suffering from severe or recurrent depression to achieve better results with a higher dosage (40 mg), while patients experiencing their first period of depression or with less severe depression responded well to the minimally effective dose of 20 mg.

Comparison of the primary structures of acidic proteinases and of their zymogens.

From the scattered information about primary structures of aspartate proteinases the following general features appear: 1) Sequence determinations show that two catalytically active aspartic acid residues are located in highly conservative surroundings. 2) Zymogens have so far only been found for extracellular aspartate proteinases of the vertebrates. The zymogens from the gastric mucosa are converted into active enzymes by a limited proteolysis releasing 42 to 44 residues from the NH2-terminus. A common pattern of basic and apolar residues is observed in this NH2-terminal segment. 3) In the presently known structures gastric proteinases and their zymogens have about 40% of all residues in common. The sequence of penicillopepsin shows 18% of identity with the gastric proteinases.

Early experience with the farm environment and effects on later behaviour in silver Vulpes vulpes and blue foxes Alopex lagopus.

Seventy-one silver fox and 141 blue fox cubs were exposed to constant visual contact with the farm environment from the age of 2 to 8 weeks. The exposure consisted in opening a door in the nest box facing the feed gang-way. Control cubs (33 silver and 77 blue foxes) were reared in similar but closed nest boxes. All cubs were tested at the age of 12-16 weeks and again at the age of 23-28 weeks; during these tests the behavioural responses of the foxes towards a human being were recorded. Both tests showed that in the two species, the early experience with the farm environment reduced the fear responses of the foxes towards humans. The conclusion of the study was that early visual experience with the farm environment makes the foxes better adapted to captivity, including the presence of humans.

Effects of whole-year nest boxes on cortisol, circulating leucocytes, exploration and agonistic behaviour in silver foxes.

An experiment was carried out for a period of 2 years, using 50 silver fox vixens kept in cages with nest boxes, and 50 vixens kept in barren wire cages without any sort of equipment. At the end of the experiment, the animals living with access to nest boxes had lower base levels of cortisol and eosinophils, and higher base levels of lymphocytes. They also were less fearful towards humans and more active/ explorative in an open field test. It was concluded that these animals were less stressed than those living without nest boxes, a result that could have practical implications for the welfare of foxes during everyday life at the farm.

Preference for various nest box designs in farmed silver foxes (Vulpes vulpes) and blue foxes (Alopex lagopus).

Nest box choice experiments were carried out outside the breeding season on adult silver and blue fox vixens with no previous permanent nest box experience. Nest boxes were varied in height of placement, number of rooms, presence of entrance room or platform and light conditions. Only one parameter was varied in any one experiment. Both fox species clearly preferred an elevated multi-room nest box; while silver foxes showed preference for boxes supplied with a platform, blue foxes preferred boxes with an entrance room. There was no significant box preference with respect to light conditions. The possible welfare implications of the preferences are discussed.