[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.

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.

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.

Randomized clinical trial of the effect of pneumoperitoneum on cardiac function and haemodynamics during laparoscopic cholecystectomy.

BACKGROUND: Conventional laparoscopic cholecystectomy (CLC) with carbon dioxide pneumoperitoneum may cause major cardiovascular changes. The aim of this study was to evaluate the effect of carbon dioxide pneumoperitoneum and positional changes on haemodynamics and cardiac function in patients assigned randomly to CLC or gasless laparoscopic cholecystectomy (GLC). METHODS: Fifty patients with American Society of Anesthesiologists physical status I and II were randomly allocated to CLC (28 patients) or GLC (22). Left ventricular end-diastolic and end-systolic diameters, fractional shortening and cardiac output were determined by transoesophageal echocardiography. Measurements were performed before (phase 1) and 10 and 30 min (phases 2 and 3 respectively) after pneumoperitoneum or abdominal wall traction, and after desufflation or release of abdominal wall traction (phase 4) in supine, Trendelenburg and reverse Trendelenburg positions. RESULTS: Mean diastolic diameter, systolic diameter, mean arterial pressure and heart rate were significantly higher, and fractional shortening was significantly lower, with carbon dioxide pneumoperitoneum than with the gasless procedure during phases 2 and 3. There were no significant differences in cardiac output between the two groups. CONCLUSION: Carbon dioxide pneumoperitoneum was associated with increased preload and afterload in patients undergoing laparoscopic cholecystecomy. It also decreased heart performance (fractional shortening), but did not affect cardiac output.

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.

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.

Randomized study of coagulation and fibrinolysis during and after gasless and conventional laparoscopic cholecystectomy.

BACKGROUND: Carbon dioxide pneumoperitoneum may be an important pathophysiological factor stimulating the coagulation system during conventional laparoscopic cholecystectomy. The aim of this study was to test the hypothesis that gasless laparoscopy produces smaller changes in the coagulation and fibrinolytic system than carbon dioxide pneumoperitoneum in patients undergoing laparoscopic cholecystectomy. METHODS: Fifty patients were allocated randomly to conventional (n = 26) or gasless (n = 24) laparoscopic cholecystectomy. Blood samples were obtained on admission, after induction of anaesthesia, after insufflation or traction, 30 min after introduction of the laparoscope, 10 min after exsufflation of carbon dioxide or traction, 4 h after extubation and 24 h after operation. RESULTS: The two groups were comparable with respect to age, sex, body mass index and duration of operation. Plasma levels of prothrombin fragment 1 and 2 (F1 + 2), soluble fibrin and D-dimer did not differ between the two groups. F1 + 2 levels varied significantly in both groups during and after operation (P < 0.001). Soluble fibrin and D-dimer levels did not change during operation in either group, but after operation the levels increased significantly in both groups (P < 0.001). CONCLUSION: Carbon dioxide pneumoperitoneum does not enhance the activation of coagulation and fibrinolysis associated with laparoscopic cholecystectomy. The coagulation and fibrinolytic systems are activated during and after gasless as well as conventional laparoscopic cholecystectomy.

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.

Enhancement of central nervous system pathology in early simian immunodeficiency virus infection by dopaminergic drugs.

Human immunodeficiency virus infection (HIV) at late stages of the disease is accompanied by neurological complications, including motor, behavioral and cognitive impairment. Using simian immunodeficiency virus (SIV)-infected rhesus monkeys, an animal model of HIV infection, we found that during the asymptomatic SIV infection dopamine (DA) deficits are early components of central nervous system (CNS) dysfunction. To investigate the role of the DA system in SIV infection and to restore the DA deficiency, we administered selegiline, an agent with DAergic and neuroprotective properties, to SIV-infected monkeys. Selegiline increased DA availability but induced CNS vacuolization, SIV encephalitic lesions, and enhanced CNS viral replication during early SIV infection. The pathological changes seem to be mediated by DA, as treatment with L-DOPA, the precursor of DA, had similar effects. We propose that any natural or induced DAergic dysregulation which results in increased DA availability may potentiate HIV-associated neurological disease (ND). Our findings raise new questions regarding the pathogenesis of HIV-ND and generate concerns about the safety of dopaminergic drugs in the clinical management of HIV-infected patients.

Expression, but not activity, of neuronal nitric oxide synthase is regionally increased in the alcoholic brain.

The regional distribution of nitric oxide synthase (NOS) was investigated in alcoholic post-mortem brains compared with brains of non-alcoholic control individuals. Total enzyme activity in 28 brain regions was determined using the [(3)H]l-citrulline formation assay, whereas Western blot analyses were used for semi-quantitative measurement of the neuronal isoform of NOS (nNOS). In the alcoholic brain, nNOS protein expression was increased in the following regions: frontal cortex (85%), the cingulate gyrus (294%), the nucleus accumbens (54%), the entorhinal cortex (85%) and the thalamus (51%). These increases were, however, not associated with higher total NOS activity. Interestingly, nNOS protein content was increased in the frontal cortex and the nucleus accumbens, brain regions which are suggested to be involved in the dopaminergic mesolimbic reward system. It is concluded that upregulation of signal transduction pathways, such as the adenosine 3',5'-monophosphate and the protein kinase C-dependent pathway, due to stimulation of G-protein-coupled neurotransmitter receptor regulation, as a form of functional tolerance, could be responsible for increased nNOS protein expression, and downregulation of NOS enzyme activity in these brain regions.

Winchester syndrome.

Winchester syndrome was first described in 1969 and since then nine patients have been reported in the literature. The syndrome is characterized by short stature, coarse face, corneal opacities, generalized osteolysis and progressive painful arthropathy with joint stiffness and contractures of distal phalanges in combination with skin changes. The etiology is unknown. Parental consanguinity supports autosomal inheritance. The diagnosis is based on clinical and radiological manifestations. We describe a case in a 7-year-old Pakistani boy.

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.

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.

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.

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.

Single-dose pharmacokinetics of citalopram in patients with moderate renal insufficiency or hepatic cirrhosis compared with healthy subjects.

OBJECTIVE: To compare the pharmacokinetics of the antidepressant citalopram and its metabolites demethylcitalopram and didemethylcitalopram in subjects with moderate renal insufficiency and subjects with hepatic cirrhosis with that in healthy subjects. METHODS: Pharmacokinetic parameters from three individual, open-label, phase I trials were derived following single oral or intravenous citalopram dose (40 mg) to healthy subjects and a single oral dose (20 mg) to patients. Serum and urine concentrations of citalopram and metabolites were determined using a validated HPLC method. RESULTS: The absolute bioavailability of citalopram tablets in healthy subjects was 80%. The renal clearance was a minor component (<20%) of the total elimination of citalopram. Serum Cmax and t(max) for citalopram were essentially unaffected by the occurrence of renal or hepatic disease. In comparison with healthy subjects, renal impairment was associated with a significant reduction in the renal elimination of citalopram and its two metabolites and a slight prolongation of serum citalopram t1/2 (49.5 h vs 36.8 h in healthy subjects). Cirrhosis resulted in significant decrease in citalopram CLoral (0.21 vs 0.331 x h(-1) x kg(-1) in healthy subjects) and increase in Vz x f(-1) with an approximately twofold increase in t1/2 (83.4 h vs 36.8 h in healthy subjects). Indices of renal (creatinine or 51Cr-EDTA clearances) and hepatic (galactose elimination capacity or Child-Pugh score) function were poor predictors of the changes in the pharmacokinetics of citalopram and its metabolites in these populations. CONCLUSION: No reduction of citalopram dosage is warranted in patients with moderately impaired renal function. However, that may not apply for patients with severe renal failure. In patients with impaired hepatic function, prescription of a lower dosage of citalopram may be appropriate.

Weight, length and head circumference standards based on a population of Danish newborn boys and girls in gestational weeks 25 to 43.

Growth standards of birth weight, birth length and birth head circumference were constructed based on a population of Danish newborn boys and girls in gestational weeks twenty-five to forty-three. Study populations were residents of the municipality of Odense for later gestational ages and residents of the county of Funen for early gestational ages. Strict selection criteria were employed.