Cervical spine fractures in the elderly: factors influencing survival in 65 cases

To evaluate whether a cervical spine fracture increases the death risk in elderly patients, and to define risk factors, we studied the survival of 65 patients (26 women) with a mean age of 77 (66-99) years. 8 of the patients were tetraparetic. In 35 patients, the upper cervical spine was fractured. 7 patients suffered from ankylosing spondylitis. Severe co-morbidity was present in 16. Survival status and the date of death were retrieved from the government official personal registry. The expected survival was calculated from data retrieved from the Swedish National Board of Health and Welfare. Variables having a possible relation with survival (i.e., a p-value < 0.10 when entered into a Kaplan-Meier survival analysis) were used in a Cox multiple regression survival analysis. 53 (24-105) months after injury, 25 of the 65 patients had died. The survival was significantly lower than the expected values. Severe co-morbidity (risk ratio: 5,6), neurological injury (6,4), high age (1,1), and ankylosing spondylitis (5,5) proved to be significant risk factors for death. Thus, a cervical spine fracture may lead to earlier death in a patient with a severe co-morbidity. A neurological complication constitutes a risk also for a previously healthy individual. Patients having ankylosing spondylitis (with increased death risk) run a higher than normal risk of sustaining a cervical spine fracture.     

Relationships among patient and therapist ratings of therapeutic alliance and patient assessments of therapeutic process: a study of cognitive therapy with long-term mentally ill patients.

The therapeutic alliance as rated by therapists and patients was assessed every 5 weeks throughout the treatment period in an in-patient treatment program for schizophrenic and other long-term mentally ill patients. The patients (N = 26) also assessed perceived curative factors (Curative Factors Questionnaire) and made therapy session evaluations (Session Evaluation Questionnaire). The most important patient rated factors showing a relationship with therapist-rated alliance were in the initial phase of treatment depth in the therapy sessions, in the working phase the experience of involvement in the treatment, and in the discharge phase perceived helpfulness of encouragement and reassurance. The investigation of curative factors, session evaluations, and alliance as rated by patients showed a relationship in the initial phase between alliance and encouragement, reassurance and awareness, in the working phase between alliance and depth in sessions and "talking to someone who understands," and in the discharge phase between alliance and self-understanding and problem solution.     

Clusterin upregulation following rubrospinal tract lesion in the adult rat

We have examined the expression of the multifunctional protein clusterin in the axotomized red nucleus, at the lesion site in the lateral funiculus of C3, as well as along the Wallerian degeneration in the lateral funiculus of T1. There was a marked increase in clusterin-immunoreactivity (IR) and clusterin mRNA in red nucleus nerve cell bodies. An early, transient occurrence of large, heavily clusterin-IR globules were found in axons in the spinal cord at the lesion site in C3 as well as a marked upregulation of mRNA for clusterin, presumably associated with reactive astrocytes and oligodendrocytes from 1 to 4 weeks postoperatively. Clusterin-IR and its mRNA were markedly increased in the zone of Wallerian degeneration at T1, where some strongly expressing cells were identified as oligodendrocytes. Taken together with previous changes in clusterin expression following peripheral nerve and dorsal root injury, we suggest that this protein is involved in regenerative as well as degenerative neural responses.     

Antipsychotic-like effect of the AMPA receptor antagonist LY326325 as indicated by suppression of conditioned avoidance response in the rat

The effect of LY326325, a novel AMPA receptor antagonist, on the conditioned avoidance response and catalepsy was investigated in the rat. The conditioned avoidance response is a behavioral methodology which is regarded to predict potential antipsychotic efficacy of experimental drugs. Catalepsy ratings were utilized to assess the putative propensity of LY325326 to induce extrapyramidal side effects. Systemic administration of LY326325, 18 mg/kg subcutaneously, caused a selective suppression of conditioned avoidance response, without effect on escape behavior or intertrial crosses. In addition, no catalepsy was observed. Our present and previous results support an antipsychotic effect of AMPA receptor antagonists with a low liability for extrapyramidal side effects, i.e. pharmacological effects consonant with an atypical antipsychotic profile.     

Short-lasting conditioned stimulus applied to the middle cerebellar peduncle elicits delayed conditioned eye blink responses in the decerebrate ferret

In delay eye blink conditioning, the conditioned stimulus (CS) ends at the time of the unconditioned stimulus (US). If the CS duration is decreased, there will be a 'trace' period with no ongoing CS before the onset of the US. During this period some neural activity has to continue after the CS offset to: (i) permit association between the CS and the US; and (ii) elicit a conditioned response appearing after the CS offset. In this study we test the role of the cerebellum in maintaining CS activity required for eliciting a conditioned response after the CS offset. Decerebrate ferrets were trained in a delay conditioning paradigm with an electrical stimulation of the forelimb as CS and of the periorbital area as US. The conditioned responses in the upper eyelid were monitored with electromyographical techniques. In well-trained animals, test CSs of short duration down to 0.2 ms were applied to the forelimb or the middle cerebellar peduncle, while the interstimulus interval between CS onset and US onset was kept constant at 300 ms. Test CSs of short duration applied to the forelimb elicited conditioned responses. More importantly, also a short-lasting CS to the middle cerebellar peduncle could elicit conditioned responses. The results indicate that precerebellar CS pathways are not required for maintaining the neural activity that elicits conditioned responses after the CS offset. It is suggested that neurons maintaining such activity are located in the cerebellum, either the cortex alone or the cortex and the deep nuclei.     

Screening for mutations in candidate genes for hypospadias

Hypospadias, a condition with a frontally placed urethral orifice on the penis, is the most common malformation in males. During fetal development several components are necessary for normal male genital development. Testosterone and dihydrotestosterone act via the androgen receptor but a defective receptor function results in different degrees of genital malformations. Testosterone-5α-reductase converts testosterone to dihydrotestosterone, which is crucial for normal differentiation, and a total lack of this enzyme results, in syndromes with hypospadias. The Wilms' tumour 1 (WT1) gene is expressed in the fetal gonad and genital malformations can occur due to WT1 gene mutations. These genes are therefore strong candidate genes for hypospadias. We have analysed 35 boys with hypopadias and one girl diagnosed as with complete androgen insensitivity syndrome, using exon by exon polymerace chain reaction (PCR) amplification of the AR, WT1 and 5α-reductase genes and screened for point mutations and performed subsequent DNA sequencing. No mutations in any of these genes were found in the 26 patients with isolated hypospadias. Two patients with severe hypospadias with cryptorchidism were found to carry mutations in the androgen receptor gene. Also the girl with clinically diagnosed complete androgen insensitivity was found to be homozygous for a splice mutation in the 5α-reductase gene. In summary, mutations in the WT1, AR and 5α-reductase genes are not common causes of isolated hypospadias. Received: 1 October 1997 / Accepted: 4 May 1998     

Naloxone reverses disinhibitory/aggressive behavior in 5,7-DHT-lesioned rats; involvement of GABA(A) receptor blockade?

Effective medical treatment for impulsive aggression and several impulse control disorders is needed. Disinhibited, impulsive behavior of e.g. murderers, arsonists, suicidal patients, and patients suffering from antisocial personality or substance abuse disorders has been associated with signs of a deficiency in brain serotonin (5-HT) systems. Depletion of brain 5-HT consistently produces disinhibition and aggression also in experimental animals. The present series of experiments using a modified Vogel’s conflict test indicates that the disinhibitory behavior of 5-HT-lesioned rats can be reversed by the commonly used opiate receptor antagonist naloxone at doses (0.1–5.0 mg/kg, s.c.) that do not significantly affect behavior in sham-lesioned controls. Moreover, this effect of naloxone, which resembles that previously observed after administration of negative modulators of γ-aminobutyric acid_A (GABA_A)/benzodiazepine receptor complexes, was reversed by a low inert dose (2.0 mg/kg, i.p.) of amobarbital. Furthermore, both naloxone (5.0 mg/kg, s.c.) and Ro 15-4513 (1.0 mg/kg, p.o.; a partial inverse agonist at benzodiazepine receptors) significantly decreased the number of attacks and the time spent in aggressive acts in 5,7-DHT-lesioned male residents. These results taken together with previous behavioral and neurochemical data suggest that the behavioral effects of naloxone observed here may involve an antagonistic action at brain γ-aminobutyric acid_A (GABA_A)/benzodiazepine receptor complexes. Thus, naloxone, its stable analogue naltrexone or other weak negative modulators of brain GABA_A/benzodiazepine receptor complexes may represent a new pharmacological principle for the treatment of impulse control disorders.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Storage of specimens at 4 degrees C or addition of sodium fluoride (1%) prevents formation of ethanol in urine inoculated with Candida albicans.

The microbial synthesis of ethanol was investigated in urine specimens containing 0.5% or 1.0% (w/v) glucose and inoculated with the yeast Candida albicans (100 cfu/mL). Aliquots (10 mL) of urine were dispensed into plastic tubes containing enough sodium fluoride to give final concentrations of 0.1%, 0.25%, 0.5%, 0.75%, 1%, and 2% (w/v), and C. albicans was added. The tubes were tightly stoppered and allowed to stand either at room temperature (22 degrees C) or in a refrigerator (4 degrees C) for up to 34 days before concentrations of ethanol were determined by headspace gas chromatography. Urine samples stored at 22 degrees C without sodium fluoride produced 0.25 g/L ethanol after two days, and the concentration increased to 2.10 g/L and 4.50 g/L after eight days for specimens containing 0.5% (w/v) and 1% (w/v) glucose, respectively. The ratio of the serotonin metabolites 5-hydroxytryptophol/5-hydroxyindoleacetic acid (5HTOL/5HIAA) in urine remained within the reference range (< 15 pmol/nmol) despite high concentrations of ethanol being produced. Urine samples kept at 4 degrees C did not produce any ethanol (< 0.01 g/L) even without sodium fluoride present as a preservative. The production of ethanol by C. albicans was stopped completely by adding 1% or 2% (w/v) sodium fluoride but not by concentrations of 0.75% (w/v) or less. The microbial synthesis of ethanol in urine samples initially stored at room temperature without sodium fluoride was slowed down considerably by moving them into a refrigerator at 4 degrees C. In conclusion, the production of ethanol in urine by C. albicans can be prevented by storage of samples in a refrigerator at 4 degrees C or by adding sodium fluoride > or = 1% (w/v). Measuring the ratio of 5HTOL/5HIAA can help to distinguish postsampling production of ethanol from metabolism and excretion processes.