Dynamic needle tip positioning - ultrasound guidance for peripheral vascular access. A randomized, controlled and blinded study in phantoms performed by ultrasound novices.

PURPOSE: The application of ultrasound-guidance for peripheral venous access is gaining popularity. It is possible to produce a short axis or a long axis sonographic view of the target vessel and apply an out-of-plane or in-plane needle tip approach. Our aim was to present the dynamic needle tip positioning technique and to estimate which approach is the most accurate for inserting the needle tip into the center of the target vessel. MATERIALS AND METHODS: Fiftynine novices in ultrasound-guided peripheral vascular access participated. (A) a short axis view combined with an out-of-plane needle tip approach using dynamic needle tip positioning was compared to (B) a long axis view combined with an in-plane needle tip approach to a target vessel embedded in a gelatine phantom. RESULTS: The success rate of method (A) was significantly higher than method (B) (97 % versus 81 %). The distance between the center of the target vessel and the final needle tip position was significantly shorter for method (A) compared to method (B). CONCLUSION: The combined short axis and out-of-plane technique using dynamic needle tip positioning had a higher success rate and a shorter distance between the center of the target vessel and the needle tip compared to the combined long axis and in-plane technique.

Electrical amygdala kindling in alcohol-withdrawal kindled rats.

Repeated alcohol withdrawal has been shown to kindle seizure activity. The purpose of the present investigation was to study electrical amygdala kindling in rats previously exposed to alcohol-withdrawal kindling. In three independent experiments, male Wistar rats were subjected to multiple episodes each consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. In the first experiment, the alcohol-withdrawal kindled animals were divided into two groups depending on whether spontaneous alcohol-withdrawal seizures were observed in episodes 10-13. In the second and third experiments, the alcohol-withdrawal kindled animals were compared to a group in which alcohol-withdrawal kindling was prevented by diazepam treatment during the withdrawal reactions in order to discriminate between the effect of withdrawal and intoxication. Electrical kindling was initiated 28-35 days after the last alcohol dose by exposing the animals to daily electrical stimulations of the right amygdala. The results showed that amygdala kindling was facilitated in alcohol-withdrawal kindled animals which showed spontaneous withdrawal seizure activity, compared with animals exposed to multiple episodes of alcohol withdrawal which did not develop withdrawal seizures or with animals exposed to a single episode of alcohol intoxication. When compared to the control group, the alcohol-withdrawal kindled group with seizures also kindled at a faster rate, but the difference did not reach statistical significance and therefore the results must be regarded as preliminary at present.

Relapse prevention by means of paroxetine in ECT-treated patients with major depression: a comparison with imipramine and placebo in medium-term continuation therapy.

In-patients with severe major depression were treated in the acute phase with electroconvulsive therapy (ECT) in combination with antidepressants. The drug treatment consisted of two randomized trials which were both extended into the post-ECT continuation phase. Patients with electrocardiological impairment were randomized to either 30 mg paroxetine daily or placebo under blind conditions. Patients without electrocardiological impairment were randomized to either 30 mg paroxetine daily or 150 mg imipramine daily. There was a high level of agreement between the Hamilton Depression Scale and the Melancholia Scale, demonstrating that the patients treated with ECT plus imipramine in the acute phase showed greater symptom reduction than those treated with ECT plus paroxetine. However, in the post-ECT phase paroxetine was superior to both imipramine and placebo in preventing relapse. Thus in the post-ECT phase 65% of the placebo-treated patients relapsed, compared to 30% of the imipramine-treated patients and 10% of the paroxetine-treated patients. The psychometric analysis of the Melancholia Scale in the continuation or post-ECT phase showed that relapsing patients displayed a pattern with lack of interests, impaired concentration, depressed mood and anxiety among the less severe symptoms (first-compartment symptoms). In other words, these symptoms represent the gate to full-blown depression (second-compartment symptoms). Serotonin-selective antidepressants such as paroxetine appear to be more effective in controlling the first-compartment symptoms.

A definite and a semidefinite questionnaire version of the Hamilton/melancholia (HDS/MES) scale.

A definite (anchored) and a semidefinite (semi-anchored) questionnaire version of the Hamilton Depression Rating Scale (HDS) and the Bech-Rafaelsen Melancholia Scale (MES) were compared with the HDS/MES by observer-rating and self-rating of 24 patients fulfilling the DSM-3R criteria for major depressive disorder. Both types of questionnaire showed substantial agreement with the observer scale from which they were derived. The sum scores were for the definite questionnaires and the corresponding observer scales closely similar whereas the sum scores of the semidefinite questionnaires were significantly higher than the sum scores of the corresponding observer scales. These results indicate that patients' 'halo' effect may be avoided by using definite scaling criteria for self-rating. Thus, of the two versions of questionnaires the definite versions are recommended.

Combined treatment with imipramine and mianserin. A controlled pilot study.

The effect of imipramine plus mianserin and imipramine plus a placebo was compared in 40 depressed patients with a median age of 60 years. The imipramine dosage was flexible to give a plasma concentration around 200 nmol/l and mianserin was given at a fixed dosage of 30 mg daily. After six weeks of treatment the results showed that the scores on the Hamilton Depression Scale as well as on the Melancholia Scale were significantly more improved in the imipramine-plus-minaserin group than in the group of patients receiving imipramine alone (P less than 0.01). In terms of percentage of improvement (a reduction of baseline rating scores of 50% or more) 77% of the imipramine-plus-mianserin group had improved, compared with 27% of the imipramine group. The combination of imipramine and mianserin was well tolerated both as regards clinical side-effects and laboratory tests.

Convulsive behaviour during alcohol dependence: discrimination between the role of intoxication and withdrawal.

Male Wistar rats were subjected to repeated weekly episodes of 2 days severe alcohol intoxication (intragastric intubation) and 5 days of withdrawal. In half of the animals the withdrawal reaction was attenuated during the first nine weekly episodes by intragastric intubations with phenobarbital. During episodes 10-14 both phenobarbital treated and phenobarbital untreated animals were allowed to develop a withdrawal reaction; all animals were video-recorded during withdrawal and the records were rated blindly for the occurrence of convulsive seizures. The results were analyzed by step-wise logistic analysis of regression including phenobarbital treatment, alcohol dose and intoxication score as explanatory variables for the occurrence of convulsive seizures. The animals that had been in withdrawal during all episodes developed significantly more convulsive seizures compared with animals that had their first nine withdrawal episodes attenuated by phenobarbital. The development of withdrawal seizures depended on repeated episodes of withdrawal, whereas repeated alcohol intoxication per se did not explain the development of seizures. There were no differences between the groups in the severity of the non-convulsive signs of alcohol withdrawal. Thus the development of seizures and the non-convulsive signs of alcohol withdrawal may result from two pathogenetically different mechanisms: 1) seizures from a cumulative kindling-like effect over long time periods and 2) physical signs of alcohol withdrawal may reflect the degree of physical dependence during the most recent drinking bout.

Acidic phospholipids in synaptosomal plasma membranes during repeated episodes of physical ethanol dependence in the rat.

The effects of repeated episodes of ethanol intoxication and the hyperexcitable state of withdrawal on the synaptosomal concentration of acidic phospholipids were studied in rats. There was no indication that cumulative changes in the synaptosomal acidic phospholipid composition in general occurred during multiple episodes of ethanol intoxication and withdrawal. There was, however, a statistically significant decrease in acidic phospholipid concentration (phosphatidylinositol; PI) in synaptosomal membranes from animals revealing spontaneous convulsive behaviour during ethanol withdrawal. Hypothetically this may reflect an inability to increase acidic phospholipid membrane content and thus to adaptively increase the seizure threshold during withdrawal.

The use of case vignettes in studies of interrater reliability of psychiatric target syndromes and diagnoses. A comparison of ICD-8, ICD-10 and DSM-III.

This study is part of the ICD-10 field trials in which the use of case vignettes for interrater agreement has been examined. From our electronic database of 880 consecutively admitted inpatients we selected 24 cases that were transcribed to vignettes covering the first 5 ICD-10 target syndrome of dementia, substance use disorders, schizophrenia, mood and anxiety disorders. ICD-10 was compared with ICD-8 and DSM-III. The results showed that all 3 standard classification systems obtained an acceptable interrater agreement. Among the diagnoses, depressive disorders gave rise to most disagreement between the raters. Discrepancies between the methods of measuring interrater agreement were found when intraclass reliability was compared with consensus calculations for the individual patient.

Cerebral blood flow during delirium tremens and related clinical states studied with xenon-133 inhalation tomography.

The regional cerebral blood flow of 12 patients with severe alcohol withdrawal reactions (delirium tremens or impending delirium tremens) was measured during the acute state before treatment and after recovery. Greater cerebral blood flow was significantly correlated with visual hallucinations and agitation during the acute withdrawal reaction. The results suggest that delirium tremens and related clinical states represent a type of acute brain syndrome mainly characterized by CNS hyperexcitability.

Local cerebral glucose consumption during ethanol withdrawal in the rat: effects of single and multiple episodes and previous convulsive seizures.

Local cerebral glucose consumption (l-CMRgl) was studied using [14C]2-deoxyglucose autoradiography in minimally restrained rats during acute (12 or 18 h postwithdrawal (p.w.] and late (14 days p.w.) ethanol withdrawal, as well after 10 previous, weekly withdrawal episodes as after a similar period of isocalorical feeding. A period of two days of intoxication was established by gastric intubation. Spontaneous incomplete convulsive seizures were observed during the 8th to 10th withdrawal episode. Audiogenic seizures occurred following stimulation during the 6th and 10th withdrawal episode. Animals with previous spontaneous or audiogenic seizure were distributed randomly and evenly among the groups. l-CMRgl values were adjusted to a temperature of 38 degrees C. During acute withdrawal, l-CMRgl was significantly reduced by 18-32% in cortical and most limbic regions, but unchanged in cerebellum and subcortical structures as compared with the neutral state (late withdrawal and control groups). l-CMRgl was relatively more lowered in the amygdala in animals with previous spontaneous withdrawal seizures and in structures belonging to the auditory system in animals with previous audiogenic seizures. l-CMRgl did not differ among neutral groups. The lowered l-CMRgl in cortical and limbic regions during withdrawal contrasts to the results of previous studies. This difference may be attributed to the minimal restraint of animals in this study. The pattern of l-CMRgl in acute and late withdrawal animals with previous spontaneous withdrawal seizures is consistent with a mechanism comparable to electrical amygdala kindling contributing to seizure genesis.

Anticholinergic side-effects of antidepressants: studies of the inhibition of salivation.

Studies of the peripheral anticholinergic effects of antidepressants initiated by Ole J. Rafaelsen are reviewed. They were all cross-over trials, either in patients who received continuous medication or in which continuous medication was temporarily discontinued, or in volunteers given single doses. Anticholinergic effects were evaluated from the inhibition of salivation rate measured by a tampon method. In essence, the studies revealed that 1) the method was sufficiently reliable and sensitive, 2) inhibition of salivation by tricyclic antidepressants persisted during long-term treatment, and 3) the newer antidepressants Nomifensine, Zimeldine, Mianserin, Citalopram, and Femoxetine were less potent as to anticholinergic effects than tricyclic antidepressants. The results of the studies reviewed have generally been in good agreement with similar studies of other centers and with clinical between-group studies. Other authors have found a sufficient specificity of salivation rate measurements for anticholinergic effects, but other methods, for instance based on heart rate measurements, may prove to be more specific.

The GABA/benzodiazepine receptor chloride channel complex during repeated episodes of physical ethanol dependence in the rat.

The GABA/benzodiazepine (BZ) receptor chloride channel complex was investigated during repeated episodes of ethanol intoxication and withdrawal in the rat; the intragastric intoxication technique was applied and the severity of intoxication, withdrawal and number of seizures were recorded. The following groups were studied after decapitation during withdrawal 10-16 h after the last ethanol feeding: A) isocalorically fed controls not receiving ethanol; B) isocalorical controls subjected to a single ethanol intoxication period; C) animals subjected to 15 intoxication-withdrawal episodes (spontaneous seizures); D) same as C, but without developing seizures. A radio receptor technique was applied in the characterization of the receptor complex comprising specific binding to the BZ-receptor, the chloride channel and the GABA receptor by 3H-diazepam, 35S-TBPS and 3H-muscimol, respectively. The allosteric couplings among the components of the receptor complex were studied by 3H-diazepam and 35S-TBPS binding enhancement tests involving muscimol, ZK 93423 and DMCM. Cortex, hippocampus and cerebellum were the brain regions studied. Except for a reduced specific binding of 3H-diazepam in cerebellum, there were no indications of changes in specific binding to any part of the receptor complex. The allosteric coupling of BZ and GABA receptors as well as chloride channel-BZ receptors were unchanged in all groups. It is notable that no changes at all could be related to number of intoxication-withdrawal episodes or to the development of seizures. Thus, the present study gave no indication that the GABA/benzodiazepine receptor chloride channel complex is directly involved in the augmentation of cerebral nervous system excitability (seizures) during repeated episodes of physical ethanol dependence.

Lithium: long-term effects on the kidney. III. Prospective study.

Renal function in 32 patients treated with lithium for an average period of 10 years was reexamined 2 years after the first examination. A markedly influenced tubular function leading to increased urine volume (average 3 litres/24 h) and decreased renal concentrating capacity was still found, whereas glomerular function remained unimpaired in nearly all of the patients. No statistically significant changes in renal functions were observed at the follow-up examination. The results were compared with the same renal functional tests obtained from a control group consisting of 53 patients with affective disorders never treated with lithium. The control group had a significantly lower urine output (average 2 litres/24 h), but lithium-treated patients on a one-dose schedule had an average urine volume of only 500 ml/24 h more than the controls. In conclusion, this prospective study found no evidence of a progressive impairment of glomerular or tubular function in lithium-treated patients reexamined after 2 years. Patients with affective disorders never treated with lithium had normal renal concentrating capacity.

Lithium: long-term effects on the kidney--II. Structural changes.

Forty-six patients treated with lithium for an average of 8 yr participated in a follow-up study involving a kidney biopsy. The results were compared with renal biopsy specimens from an age-matched group of controls never treated with lithium. The average number of totally scelerotic glomeruli and atrophic tubuli was higher in lithium-treated patients. The histopathological changes showed significant correlations with lithium dosage schedule. Both the proportions of sclerotic glomeruli, atrophic tubuli and focally distributed interstitial fibrosis were higher in patients receiving their lithium two or three times a day than when lithium was given in a single daily dose.

Brain marker protein changes after short- and long-term ethanol intoxication and withdrawal in the rat.

The brain marker proteins, D1, D2, and D3, localised to neuronal membranes, and mitochondrial and cytoplasmic marker proteins (MM and CM), were studied during 1-6 days (short term) intragastrically-induced severe ethanol intoxication and during 1 month (long-term) ethanol intoxication established by a liquid diet regimen. The concentrations of the same brain proteins were also measured during withdrawal from the ethanol intoxication periods. Three categories of effect were encountered: decreased concentration of brain marker proteins during severe short-term intoxication the effect being most marked for D3, possibly indicating degradation of mature synapses; increased concentration of proteins D2 and MM during withdrawal, the D2 changes possibly indicating formation of new synapses; increased concentration of D1 protein and MM during long-term intoxication. We suggest that the changes in brain marker proteins reflect dynamic changes of subcellular neuronal structures which may form a part of the basis of functional tolerance to and physical dependence upon ethanol or the reversion of these states after withdrawal of ethanol.

The effect of phenobarbital and carbamazepine on the ethanol withdrawal reaction in the rat.

The effects of phenobarbital (PB) and carbamazepine (CZ) on the ethanol withdrawal reaction in the rat were investigated in a blind study including an untreated control group. Physical ethanol dependence was established by intragastric intubation during a 4-day period. Both the degree of intoxication and the withdrawal reaction were assessed by standardised assessment instruments. Treatment with PB (40-60 mg/kg) and CZ (80-120 mg/kg) was initiated 10 h after the last ethanol dose and continued during the first 24 h of withdrawal. Serum concentrations of the drugs were measured. Both PB and CZ significantly reduced the ethanol withdrawal reaction compared to controls, and PB was significantly more effective than CZ. The degree of drug intoxication signs assessed by the same rating scale as the degree of ethanol intoxication indicated that maximum tolerable drug doses were used. PB probably exerts its treatment effect through the mechanism of cross dependence with ethanol, while CZ may exert a more specific effect on limbic structures responsible for central nervous system excitability.

Convulsive and non-convulsive ethanol withdrawal behaviour in rats with lesions of the noradrenergic locus coeruleus system.

The ascending noradrenergic pathways from the locus coeruleus were lesioned bilaterally in 10 rats by intracerebral 6-hydroxydopamine injections. Ten rats were sham-operated. All animals were subjected to a 4-day ethanol intoxication period using intragastric intubation. Intoxication and withdrawal assessments were performed blindly. The 6-hydroxydopamine lesions did not appear to affect tolerance to ethanol. During withdrawal, however, lesioned animals showed minor, but statistically significant changes in scores of certain non-convulsive withdrawal signs, but incidence and intensity of spontaneous and audiogenic convulsive seizures were not different between the groups.

Physical dependence on ethanol during multiple intoxication and withdrawal episodes in the rat: evidence of a potentiation.

An animal model of repeated alcohol intoxication-withdrawal episodes consisting in a 2-day period of intoxication followed by 5 days abstinence in a 17 week period of study is presented. Gastric intubation was used. As a group the animals presented a statistically significant increase of convulsive withdrawal phenomena which during the 10th and 17th episode was comparable to the withdrawal reaction in abstinent 4-day alcohol-intoxicated animals. It is suggested that the present model may represent a paradigm for the study of effects of multiple ethanol withdrawal episodes.

Salivation after single-doses of the new antidepressants femoxetine, mianserin and citalopram. A cross-over study.

Twelve healthy volunteers were given oral single doses of a reference drug (nortriptyline), test drugs, and placebo on a randomised single-blind basis at weekly intervals. The doses corresponded to average daily patient medication. Spontaneous whole mouth salivation was measured before (at 10 p.m.) and 10 hours after drug administration (at 8 a.m.). Drug plasma levels were determined after 4 and 10 hours. When analysing the salivations 10 hours after drug administration adjusted for the effects of the pre-treatment salivations, statistically significant inhibition of salivation was found after nortriptyline (56%), femoxetine (34%), and mianserin (29%) when compared with placebo, while for citalopram and cis- and trans-flupenthixol no significant inhibition of salivation was demonstrated (Fig. 1, Table 5). From the estimated log linear regression coefficients, relating adjusted salivation rates and drug plasma levels 10 hours after drug administration (Table 6), and reported average steady-state plasma drug levels (Table 7), semiquantitative predictions of the average level of anticholinergic activity during long-term treatment may be made: For femoxetine and mianserin, moderate anticholinergic activity, less pronounced than with nortriptyline, are predicted, while for citalopram no such activity can be predicted (Table 7).