Bioavailability of oestradiol and oestriol administered orally to oophorectomized women

A bioavailability study was performed on ten oophorectomized women in a randomized cross-over design. The absorption of tablets containing 2 mg of micronized oestradiol and 1 mg of micronized oestriol (Estrofem®) was compared to the absorption of the same micronized hormones administered in an aqueous suspension. Serum concentration values of oestradiol, oestriol and oestrone were measured by radioimmunoassay. The data obtained were analyzed both by univariate and multivariate analyses, and neither the serum concentrations at the various sample times, the maximum concentrations, the times for the maximum concentrations, nor the areas under the serum concentration curves disclosed any significant differences between the tablet and suspension administrations at the 5% level. The serum concentration values achieved by giving 2 mg of oestradiol and 1 mg of oestriol were of the same magnitude or higher than those of the normal menstrual cycle.     

Pharmacology in vivo of the phenylindan derivative,lu 19-005, a new potent inhibitor of dopamine,noradrenaline and 5-hydroxytryptamine uptake in rat brain

Summary Behavioural effects on dopaminergic transmission of a phenylindane derivative, Lu 19-005 [(±)-trans-3-(3,4-dichlorophenyl)-N-methyl-l-indanamine, HCl], with potent inhibitory effect on dopamine (DA), noradrenaline (NA) and serotonin (5-HT) uptake in rats and the effect on DA, NA and 5-HT activity in mice have been studied and compared with those of other known DA, NA and 5-HT uptake inhibitors with different selectivity ratios.Lu 19-005 induced stereotyped behaviour after parenteral and oral administration with a duration of action of more than 24 h. The stereotyped licking and biting induced by Lu 19-005 was antagonized by reserpine and cis(Z)-flupentixol, but not affected by prazosin, p-chlorophenylalanine and -methyl-p-tyrosine pretreatments. Metergoline slightly facilitated the onset of stereotypy. Lower doses of Lu 19-005 induced ipsilateral circling in unilaterally 6-hydroxy-DA-lesioned rats. Finally, Lu 19-005 antagonized the catalepsy induced by perphenazine. In mice, Lu 19-005 potentiated the apomorphine-induced gnawing, reversed tetrabenazine-induced ptosis and potentiated the behavioural effects of 5-HTP within a similar dose range.The effects of Lu 19-005 were compared with those of other reference compounds. Nomifensine had qualitatively similar effects in rats although of much shorter duration. In mice, nomifensine selectively reversed tetrabenazine-induced ptosis. Weaker effects in all test models were found with bupropion, LR 5182 and GBR 13.069, compounds with inhibitory effect on DA and NA uptake. The DA-, NA-and 5-HT-uptake inhibitor diclofensine, however, had no effect in rats except in the 6-hydroxy-DA-circling test and had low potency in mice. The specific 5-HT-and NA-uptake inhibitors citalopram and talsupram, respectively, were ineffective in all rat models. They selectively potentiated 5-HTP or reversed tetrabenazine0induced ptosis in mice, respectively, as expected according to their in vitro profile. These results indicate that effect on DA mechanisms are responsible for the behavioural activity of the test compounds in the rat models and that the circling model is the most sensitive. Since DA may be involved in some depressive states Lu 19-005 could be an attaactive new antidepressant as it combines the pharmacological profile of established antidepressants (effect on NA and/or 5-HT uptake) with equipotent activity on DA uptake.     

Plasma secretin in response to pure bile salts and endogenous bile in man

The effect of exogenous bile salts on plasma concentrations of secretin was studied by infusion of chenodeoxycholate, cholate, glycocholate, and taurocholate into the duodenum of normal subjects. The effect of endogenous bile on plasma secretin was studied by ingestion of a liquid test meal, by reinfusion of postprandial duodenal aspirates with known contents of bile salts, and by stimulation of gallbladder contraction by cholecystokinin. Each experiment was performed in groups of seven subjects. The relative secretin-releasing potencies of glycocholate, cholate, taurocholate and chenodeoxycholate (2.25 mmol) were 1.01.31.93.2. Hydrochloric acid (0.5 mmol) was, on a molar basis, approximately ten times more potent than sodium cholate. The effect of taurocholate was diminished when a liquid meal was used as vehicle instead of saline. Endogenous bile did, in no circumstance, elicit release of secretin. It is concluded that although bile salts have the ability to stimulate secretin release, endogenous secretin release is of minor, if any, importance for secretin release when physiological conditions are approached.This study was supported by grants from the Danish Hospital Foundation for Medical Research, Region of Copenhagen, The Faroe Islands and Greenland (J.nr. 78/45 and 79/48) and Borgen Legatet.     

EEG-Monitored ECT: A Comparison of Seizure Duration under Anesthesia with Etomidate and Thiopentone

Electroencephalogram-monitored electroconvulsive therapy (ECT) was carried out in 20 depressed inpatients. Before treatment, patients were randomly allocated to treatment using etomidate (Hypnomidat) (n = 10) or thiopentone (n = 10) for anesthesia. The groups were matched for sex, age, weight, and type and severity of depression. The seizure duration (seconds) was measured by electroencephalography (EEG), and the electrical energy (Joules, J) was determined for each treatment. A ratio of seizure duration:electrical energy (s/J) was computed. Both seizure duration and seizure duration:electrical energy were greater in the etomidate group than in the thiopentone group, whereas electrical energy did not differ significantly. The number of treatments in the etomidate group did not differ from that in the thiopentone group, as may be expected, perhaps because of the small size.     

“Handedness” of spiral fractures of the tibia

Handedness is a basic property of spirals. In many cases it is possible to determine whether spiral fractures are right or left handed by analysis of radiographs. Spiral fractures of the tibia show striking bilateral symmetry, with right-handed spirals predominating on the left side of the body, and left-handed spirals on the right.     

A Systematic Review of Job Loss Prevention Interventions for Persons with Inflammatory Arthritis

Journal of Occupational Rehabilitation - Purpose To present an overview of the evidence of the effect of job loss prevention interventions, aiming to improve work ability and decrease absenteeism...     

Direct versus indirect transfer for traumatic brain injury to James Cook University Hospital: a retrospective study

IntroductionPatients with traumatic brain injury are referred to the neurosurgical unit at James Cook University Hospital, Middlesbrough, either from local accident and emergency departments (direct transfer from the scene) or from other hospitals (indirect transfer). This study looked at the outcome in both groups.Material and methodsThis was a retrospective observational study using trauma audit research network data for patients treated for traumatic brain injury at the neurosurgery department at the neurosurgical unit at James Cook University Hospital.ResultsA total of 356 patients with traumatic brain injury were admitted under the care of neurosurgeons; 143 (40%) of these patients had a neurosurgical procedure. Of the patients undergoing a neurological procedure, 111 patients were transferred directly while 32 were indirect transfers; 213 patients were managed conservatively. Of those managed conservatively, 165 were transferred directly while 48 were indirect transfers.We compared the length of hospital stay and Glasgow Outcome Scale score for the patients based on whether they were conservatively managed or required surgery in the direct and indirect transfer groups. The difference in the length of stay in the surgical and conservative groups following direct and indirect transfer was insignificant (p = 0.07). The time to the operation in direct and indirect transfer was also not statistically significant (p = 0.06).ConclusionPatients are as safe, if not safer, by reaching the nearest trauma unit with facilities for resuscitation and imaging.     

Characterization of Salmonella enterica serovar gallinarum biovars gallinarum and pullorum by plasmid profiling and biochemical analysis

One-hundred-and-five strains of Salmonella enterica serovar gallinarum, biovar pullorum and 43 strains of biovar gallinarum were characterized by biochemical reactions, and 95 strains of biovar pullorum and 32 strains of biovar gallinarum were examined for plasmid content. Twenty-one (66%) of the strains classified as biovar gallinarum contained a 85-kb virulence plasmid. Six of these strains also contained a 2.5-kb plasmid. Ten strains (31%) were without plasmids. Ninety-three strains (98%) belonging to biovar pullorum contained the virulence plasmid and, in addition, these strains contained from one to four small plasmids. Two strains did not contain plasmids. Restriction enzyme digestions of the virulence plasmid showed three different profiles, two of which were common for biovars gallinarum and pullorum. It is suggested that the phenotypic diversity of biovars gallinarum and pullorum, as well as the diversity of plasmid profiles of biovar pullorum, could be used as epidemiological markers. Differences in phenotypic characters were not related to plasmids demonstrated in biovars of S. enterica serovar gallinarum.     

Indications for thyroxine therapy after surgery for nontoxic benign goitre

Of 287 consecutive patients, surgically treated at our department for benign, nontoxic goitre during a six-year period, 261 could be followed up, on average, 8.0 years postoperatively. Unilateral surgical procedures had been used in 199 patients, subtotal thyroidectomy in 62. 29 patients were treated with thyroxine (T4) immediately postoperatively ("recurrence prophylaxis"); in the other patients thyroxine was only given in cases of hypothyroidism (significant increase of s-TSH). 26 patients had a goitre recurrence 0.5-10 years after surgery; of these 3 had got T4 as "recurrence prophylaxis" and 23 had not. There was no significant difference between patients with and without T4 postoperatively regarding the rate of recurrence. Of 55 patients treated with subtotal thyroidectomy, 33 had postoperative latent (n = 26) or manifest (n = 7) hypothyroidism. Only 13 of 177 patients operated on unilaterally developed hypothyroidism; two of these had Hashimoto's thyroiditis. All cases of hypothyreosis except 4 were detected within the first 12 months of follow-up. This study indicates that routine use of thyroxine as prophylaxis against recurrence after surgery for benign nontoxic goitre can be strongly questioned and that the risk of hypothyroidism is high after subtotal thyroidectomy.     

Continuous blockade of the lumbar plexus after knee surgery: a comparison of the plasma concentrations and analgesic effect of bupivacaine 0.250% and 0.125%

In 20 patients a continuous block of the lumbar plexus was administered after knee-joint surgery, and the analgesic effect of two different concentrations of bupivacaine was compared. The same volume of bupivacaine was given to both groups of patients: a bolus dose of 0.4 ml/kg, 0.5% or 0.25%, followed by infusion of 0.14 ml/kg/h, 0.25% or 0.125%, respectively, via a catheter placed in the neurovascular fascial sheath of the femoral nerve according to the "3-in-1 block" technique. The median morphine consumption during the first 16 h postoperatively was 6.0 mg when bupivacaine 0.5/0.25% was used and 9.5 mg when 0.25/0.125% was used. This difference is not significant. The visual analogue pain scores were also similar in the two groups (P greater than 0.05). All plasma concentrations were below 4 micrograms/ml, the highest concentration measured being 3.6 micrograms/ml. It is concluded that when used for a continuous block of the lumbar plexus after knee-joint surgery, bupivacaine in a concentration of 0.125% offers the same pain relief as a concentration of 0.25%, and the risk of toxic reactions is reduced.