Is homozygous α-thalassaemia a lethal condition in the 1990s?

Two cases of homozygous α-thalassaemia who received active treatment in accordance with parental wishes are reported. One infant survived and the other, although successfully weaned off mechanical respiratory support, unexpectedly developed portal vein thrombosis and died. Homozygous a-thalassaemia, a condition previously considered to be universally fatal, and an indication for therapeutic abortion, is now potentially curable with advances in diagnostic technology and treatment. However, active management of these cases raises serious ethical questions and has major financial implications on the health-care system. Invasive prenatal and intensive postnatal interventions should remain experimental and cannot be recommended as routine clinical practice until the questions of long-term neurodevelopmental outcome, and the morbidity and mortality associated with bone-marrow transplantation have been fully addressed. As a result of advances in information technology, more and more parents of affected foetuses are likely to request active treatment.     

Magnetic resonance imaging of prosthetic heart valves

To evaluate the safety of magnetic resonance (MR) imaging of prosthetic heart valves, nine different synthetic and tissue valves were studied ex vivo. Deflection was measured in 0.35-tesla (T) and 1.5-T superconducting magnets and at the edge of the bore of a 2.35-T electromagnet in field gradients of 5, 1.1, and 6.3 mT/cm, respectively. No valve deflected in the 0.35-T magnet; six synthetic valves deflected 0.25 degrees-3 degrees in the 1.5-T magnet; all valves deflected 1 degree-27 degrees at the edge of the 2.35-T magnet. Each valve was then submerged in a vial of water and the temperature was measured immediately before and after each of two spin-echo imaging sequences in the two superconducting magnets. No significant temperature rise followed exposure in either magnet. Image distortion varied from negligible to severe in both imagers; magnitude of distortion paralleled magnitude of deflection. These data suggest that patients with present-day prosthetic heart valves can be safely imaged in present-day MR imagers and that prosthesis-induced artifacts will not interfere with interpretation in most instances.     

Hydroxypropyl-beta-cyclodextrin can modulate the activity of spinally administered sufentanil.

Hydroxypropyl-beta-cyclodextrin increased the effectiveness of sufentanil after epidural and intrathecal administration in rats, both in terms of a longer duration of analgesia after a fixed dose of sufentanil, and in a reduction of the lowest ED50s to produce analgesia. There was also an increase in specificity, as indicated by the greater dissociation between the ED50s for analgesia and for supra-spinal side-effects. Maximal activity was measured after inclusion complexation of sufentanil in 10% hydroxypropyl-beta-cyclodextrin. At higher concentrations of hydroxypropyl-beta-cyclodextrin, both the activity and the specificity were attenuated. The increased safety of sufentanil in 10% hydroxypropyl-beta-cyclodextrin after spinal administration was also confirmed in terms of opioid-induced deviations in arterial PO2, PCO2 and oxygen saturation. At a dose of twice the ED50 for deep surgical analgesia, the sufentanil/hydroxypropyl-beta-cyclodextrin complex produced no changes in these parameters. With sufentanil alone at comparable analgesic doses, significant shifts in all three parameters were present immediately after drug administration. At higher concentrations of sufentanil in hydroxypropyl-beta-cyclodextrin changes in the three blood gases were present but the deviations were always smaller than those observed with comparable doses of plain sufentanil. These results support the notion that after complexation sufentanil is present longer at the spinal level after spinal administration. As a consequence, there is less free sufentanil available for redistribution into lipid tissue and into the circulatory system, producing less systemic side-effects.     

Pharmacotherapy of opioids: present and future developments

The clinically available opiolds have different physicochemical properties, resulting in differences in clinical profile with regard to potency, onset, and duration of activity. However, they all have comparable side-effects after acute systemic application. Several approaches can be used to overcome these side-effects. The following approaches, with special emphasis on the perioperative use of the opioids, are discussed: (1) the use of alternative routes of administration, such as via the spine (epidurally and intrathecally); (2) optimization of opioid delivery by means of slow-release preparations, chronic infusions with indwelling catheters, and transdermal delivery systems; (3) use of additional agents to potentiate the analgesic properties of the oploids so that the dose of oploid can be reduced; and (4) searching for new analgesics on the basis of knowledge of the pain-transmission system and the different opioid receptors with their functional interactions.     

Young adults with α1antitrypsin deficiency identified neonatally: their health, knowledge about and adaptation to the high-risk condition

The psychological and psychosocial consequences of screening for α₁-antitrypsin deficiency (α₁ ATD) were investigated when the subjects were 5–7 years old. The present study was conducted when the subjects were 18–20 years old, the foci of interest being their health, psychosomatic problems, knowledge about α₁ATD and the potential effect of that knowledge on their lives and future family planning. Samples of 61 PiZ and 61 demographically matched control subjects, 18–20 years old, were asked to participate. Written, structured questionnaires covered the following items: basic familial characteristics, psychosomatic symptoms, opinions on medical check-ups, information and views on future α₁ATD screening, whether the knowledge about α₁ATD had affected the life and family planning of α₁ATD individuals. Items concerning the “α₁ATD matter” were excluded in the questionnaires given to the controls. Questionnaire data were obtained from 50 α₁ ATD and 48 control individuals, 41 of each being matched α₁ATD-control pairs. No significant differences were found in demographic or educational backgrounds, psychosomatic complaints such as headache, sleep difficulties, stomach ache, tiredness or anxiety. Lung symptoms occurred more frequently in α₁ATD subjects (p= 0.05). Six per cent of the α₁ATD individuals planned working careers with a high risk of air pollution. The majority (86%) of the α₁ATD subjects perceived the contact with the medical services as positive; 14% as both positive and negative. The information concerning α₁ATD was assessed as satisfactory by 73%, as both good and bad by 17% and as unsatisfactory by 10%. All α₁ATD subjects advocated general screening for α₁ATD, the neonatal period being chosen as optimal by 94%. Half of the α₁ATD individuals thought that the knowledge of their high-risk condition had affected their lives, particularly their awareness of the dangers of smoking and environmental pollution. The majority, 88%, knew that they should avoid smoking to protect their lungs. In conclusion, no negative psychosocial consequences of the neonatal α₁AT-screening were found in early adulthood. The α₁ATD individuals were aware of the dangers of smoking and were of the opinion that α₁ AT-screening should be recommended.     

Quantification of tremor sensitivity and inhibition of exploratory behaviour during alcohol withdrawal in rats

Rats given a 10% (v/v) alcohol liquid diet over two weeks reached high blood alcohol levels of around 200mg/dl. Discontinuation of the alcohol intake resulted within 6h in several withdrawal reactions including a tremorogenic activity and a reduction in exploratory behaviour in novel environments. The tremorogenic activity of the alcohol withdrawal could be quantified, using a piezo-film technique, in terms of a supersensitivity to both an inactive and a moderately active dose of the tremorogenic compound harmine. As compared to controls, the rats in alcohol withdrawal revealed more frequent tremor after both 5 and 10mg/kg harmine. The supersensitivity to harmine-induced tremor started within 6h after alcohol withdrawal and remained present with 10mg/kg harmine for up to 48h. The supersensitivity was independent of the length of the tremor bursts used to quantify harmine-induced tremor. Alcohol withdrawal also resulted in an inhibition of exploratory behaviour in a neutral two-chamber box. Both in terms of the number of transits into the open field as well as the time spent in the open area, rats in alcohol withdrawal were significantly less active than control animals. The reduced exploration started within 6h after withdrawal and remained present for up to 24h after the last alcohol intake. These results indicate that both alcohol withdrawal-induced sensitivity to tremorogenic agents and inhibition of exploratory behaviour can be quantified over time, allowing the pharmacological mechanisms involved to be studied.     

Ritanserin overcomes exploratory inhibition induced by cocaine withdrawal

Rats given a subchronic cocaine treatment for 10 days display an inhibition of exploratory behaviour 24h after the last cocaine treatment in the open field test. As compared to the vehicle controls, the exploratory inhibition could be measured in terms of a longer latency to enter the open area, a reduction in the time spent in the open field and a decrease in the number of transits from the small dark compartment into the open area. The serotonin (5-HT(2/1C)) antagonist ritanserin, given subcutaneously 1h prior to testing, overcame this behavioural inhibition. At doses between 0.04mg/kg and 10.0mg/kg ritanserin, a complete normalization of exploratory activity was obtained. In chronic vehicle treated rats, ritanserin did not increase exploration. Therefore the effects of ritanserin cannot be attributed to a general activation. The results are discussed with regard to withdrawal anxiety and a possible therapeutic role of ritanserin in drug addicts.