Disturbance of continuous, pump administration of cardiovascular drugs by hydrostatic pressure

Administration of highly concentrated, highly potent, and therefore highly dangerous drugs with syringe pumps is common in modern anaesthesia as well as in intensive care and emergency medicine. Because of their exact flow rates down to < 1 ml/h, these pumps are predestined for delivery of drugs with short half-lives, such as catecholamines and vasodilators. But intravenous application of drugs with syringe pumps is not without problems. While it is well known that syringes not fixed correctly into the pump can empty themselves by the influence of gravity, it seems not to be known that hydrostatic pressure can influence the flow rate of a correctly connected system even during continuous infusion. In this situation a change of height of the syringe pump in relation to the patient's position can have tremendous effects on hemodynamics due to unintended acceleration or deceleration of the flow rate. This case report demonstrates that the elevation of a connected epinephrine pump while moving a cardiac surgery patient after ACB operation from the operation table into his bed led to critical increases of heart rate, blood pressure and left atrial pressure. In order to quantify the problem we repeated the situation experimentally. It could be demonstrated that the elevation of the syringe pump by 80-100 cm delivers an additional bolus of 4-5 drops as the central venous catheter outlet. Lowering the pump consecutively leads to the opposite effect. In the case reported, the accidentally administered bolus of epinephrine was 12-15 micrograms (we use a concentration of 60 micrograms/ml epinephrine for continuous infusion with syringe pumps). From this accidental observation the following conclusion can be drawn: The change of height, in relation to the patient's position, of a running syringe pump during continuous infusion of highly concentrated cardiovascular drugs may cause considerable, even life-threatening hemodynamic disorders. Even in a closed infusion system (syringe-extension-central venous catheter), hydrostatic pressure influences infusion rate. Elevation of the pump leads to unintended bolus administration, and lowering of the pump is followed by an interruption of the infusion. In the knowledge of this phenomenon, unexpected hemodynamic reactions during transport of critically ill patients cannot always be interpreted as a result of inadequate anesthesia or volume load, but may be a consequence of incorrect handling of the syringe pumps as described in this report.     

Effects of Plasmodium berghei infection on arteether metabolism and disposition

Arteether (AE) is primarily deethylated to dihydroqinghaosu (DQHS) in rats and humans. Conversion of AE to DQHS was impaired in microsomes from rats infected with Plasmodium berghei. The Km for AE was 175.1 +/- 49.1 and 124.4 +/- 115.1 mumol/l, and Vmax was 2.24 +/- 0.45 and 1.22 +/- 0.67 nmol AE formed/mg protein/min in control and infected microsomes (p < 0.05), respectively. Calculated intrinsic clearance (CLint = initial Vmax/Km) for AE was only 4% lower in infected microsomes. Apparent pharmacokinetic parameter estimates for AE using the isolated perfused rat liver demonstrated no differences (p > 0.05) in volume of distribution, clearance, and half-life between normal and infected animals. Malaria infection resulted in decreased biliary excretion of free AE and DQHS. The majority of AE is eliminated via biliary excretion of conjugated DQHS, which is approximately 500-fold higher than free DQHS and 75-fold higher than free AE on a molar basis.     

Global folds of highly deuterated, methyl-protonated proteins by multidimensional NMR

The development of 15N, 13C, 2H multidimensional NMR spectroscopy has facilitated the assignment of backbone and side chain resonances of proteins and protein complexes with molecular masses of over 30 kDa. The success of these methods has been achieved through the production of highly deuterated proteins; replacing carbon-bound protons with deuterons significantly improves the sensitivity of many of the experiments used in chemical shift assignment. Unfortunately, uniform deuteration also radically depletes the number of interproton distance restraints available for structure determination, degrading the quality of the resulting structures. Here we describe an approach for improving the precision and accuracy of global folds determined from highly deuterated proteins through the use of deuterated, selectively methyl-protonated samples. This labeling profile maintains the efficiency of triple-resonance NMR experiments while retaining a sufficient number of protons at locations where they can be used to establish NOE-based contacts between different elements of secondary structure. We evaluate how this deuteration scheme affects the sensitivity and resolution of experiments used to assign 15N, 13C, and 1H chemical shifts and interproton NOEs. This approach is tested experimentally on a 14 kDa SH2/phosphopeptide complex, and a global protein fold is obtained from a set of methyl-methyl, methyl-NH, and NH-NH distance restraints. We demonstrate that the inclusion of methyl-NH and methyl-methyl distance restraints greatly improves the precision and accuracy of structures relative to those generated with only NH-NH distance restraints. Finally, we examine the general applicability of this approach by determining the structures of several proteins with molecular masses of up to 40 kDa from simulated distance and dihedral angle restraint tables.     

Dyspnea resulting from phrenic nerve paralysis after interscalene brachial plexus block in an obese male--a case report

While current psychiatric taxonomies recognise a classification of amphetamine dependence, derived from the notion of an alcohol dependence syndrome, little research has validated that such a condition exists for this drug. Current amphetamine users (N = 331), were interviewed using the World Health Organization operationalisation of DSM-III-R substance dependence criteria, and a measure of the psychological components of dependence. Structural analyses indicated that a unidimensional dependence syndrome as assessed by DSM-III-R and DSM-IV criteria exists for amphetamine, and that physiological, psychological and behavioural indicators were all important in accounting for the variance in responses. It was demonstrated that the concept of a dependence syndrome is applicable to amphetamine, and that the inclusion of the amphetamine dependence syndrome in DSM-III-R and DSM-IV is valid.     

Paracetamol poisoning in the north east of England: presentation, early management and outcome

1. Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning. 2. To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994. 3. There were 400 presentations (attendance rate 1.14/10(3) population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R = 0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination. 4. In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h. 5. One patient died, from arrhythmias caused by co-ingested dothiepin. 6. Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentrations, but those who do often present late and antidotal treatment may be delayed inappropriately.     

Prenatal diagnosis of an extensive fetal lymphangioma using ultrasonography, magnetic resonance imaging and cytology

An unusual case of fetal lymphangioma diagnosed before delivery is reported in a second trimester pregnant woman. The lymphangioma was suspected at 28 weeks on the basis of the ultrasound appearances and progression of the lesions with advancing gestation. MRI was used to evaluate the extent and the tissue characteristics of the lesions. Cytology of the fluid aspirated from the cystic lesions showed abundant lymphocytes and macrophages, confirming the diagnosis of a lymphangioma. The parents opted for a pregnancy termination because of the rapid growth of the lesions and the poor prognosis. It is suggested that the combination of these tests could enable the early diagnosis of these tumours at a stage when the lesion is relatively limited and accessible to therapy in utero.     

Demonstration of an ion-implanted, wavelength-shifted quantum-well laser

A technique for fabricating many different wavelength lasers on the same wafer has been developed. High energy ion implantation was used to selectively blue shift the emission wavelength of an InP-based quantum well laser structure. This structure was then processed into fully functional broad-area lasers whose current threshold was unaffected by the implantation process, indicating extremely high material quality after bandgap-shifting. This process has the potential for the integration of not only different wavelength lasers, but also other devices, such as waveguides, detectors, modulators, etc., on a single wafer.