Duration of spinal anaesthesia is determined by the partition coefficient of local anaesthetic

We have compared the duration of motor block produced by four local anaesthetics administered into a chronically implanted subarachnoid catheter in rabbits. Each group (n = 6) received four different doses of amethocaine, bupivacaine, lignocaine or procaine, and the duration of the resulting motor block was assessed. Dose-response curves were plotted for each drug. As a measure of activity of the anaesthetics, we used the dose of each drug required to produce block of 60-min duration (D60 min) and the correlation between D60 min and different drug properties was examined. An inverse linear correlation (r = 0.995; P < 0.01) was observed between log D60 min and the log of the partition coefficient of the local anaesthetics. No correlation was found between the effect and degree of protein binding, pKa or molecular weight. These results suggest that, in spinal anaesthesia, the partition coefficient could be used as a predictor of the duration of anaesthetic action.     

High-Frequency Variations in the Rotation of the Earth

We report here observational results demonstrating that a three-station network of properly distributed VLBI observatories can routinely determine UT1 with a formal standard error of ±0.05 ms of time, in an observing period of 24 h. We also report the results of a three-month series of daily observing sessions of only 1-h duration with a single interferometer, which produced estimates of UT1 with standard errors of ±0.1 ms. The UT1 values obtained from the 1-h observing sessions track smoothly between the points of the 24-h time series, and the combined time series shows that it is not unusual for UT1 to vary by 1-2 ms in periods of several days. Preliminary results of reprocessing the 24-h observing sessions in 2-h segments suggest that variations of 0.4 ms may occur on time scales of only 6-8 h.     

Inefficiency of lactation in primiparous rats: the costs of first reproduction

To investigate the energetic costs of lactation in a female mammal in relation to previous reproductive history, we compared the performance of adult female Long-Evans rats that had previously bred (multiparous) with young females that had not previously given birth (primiparous). All litters were standardized to 10 +/- 1 young. We compared maternal production (growth of pups), body mass, and energy intake (food consumption) of mothers, as well as their energy expenditure (resting oxygen consumption). The mass of litters at birth and the growth of pups during lactation did not differ according to reproductive history of the mothers. The body mass of primiparous mothers was less than that of multiparous mothers, and primiparous mothers showed an increase in mass during early lactation. To accomplish the essentially identical production of offspring under these circumstances, the primiparous mothers consumed and expended more energy than the multiparous mothers. This remarkable performance of first-time mothers results in an overall efficiency of energy allocation to reproduction amounting to only 25%, compared with 38% in multiparous mothers. The energetic inefficiency of primiparous female lactation results largely from the excessive expenditures associated with physiological and behavioral performances of first-time reproduction, together with a small component of additional expenditure due to further growth by the primiparous mothers. We suggest that this inefficiency probably contributes to the observed low reproductive success of novice breeders; furthermore, active restraint of fecundity may be an evolutionary response to the constraints of the energetic inefficiency of primiparous breeding by female mammals.     

Mechanisms of virus assembly probed by Raman spectroscopy: the icosahedral bacteriophage P22

A microdialysis flow cell has been developed for time-resolved Raman spectroscopy of biological macromolecules and their assemblies. The flow cell permits collection of Raman spectra concurrent with the efflux of small solute molecules into a solution of macromolecules and facilitates real-time spectroscopic detection of structural transitions induced by the effluent. Additionally, the flow cell is well suited to the investigation of hydrogen-isotope exchange phenomena that can be exploited as dynamic probes of viral protein folding and solvent accessibility along the assembly pathway. Here, we describe the application of the Raman dynamic probe to the maturation of the icosahedral capsid of bacteriophage P22, a double-stranded DNA virus. The P22 virion is constructed from a capsid precursor (procapsid) consisting of 420 coat subunits (gp5) in an outer shell and a few hundred scaffolding subunits (gp8) within. Capsid maturation involves expulsion of scaffolding subunits coupled with shell expansion at the time of DNA packaging. Raman static and dynamic probes reveal that the scaffolding subunit is highly alpha-helical and highly thermolabile, and lacks a typical hydrophobic core. When bound within the procapsid, the alpha-helical fold of gp8 is thermostabilized; however, this stabilization confers no apparent protection against peptide NH-->ND exchange. A molten globule model is proposed for the native scaffolding subunit that functions in procapsid assembly. Accompanying capsid expansion, a small conformational change (alpha-helix-->beta-strand) is also observed in the coat subunit. Domain movement mediated by hinge bending is proposed as the mechanism of capsid expansion. On the basis of these results, a molecular model is proposed for assembly of the P22 procapsid.     

Bone SPECT of the jaws after fracture, onlay osteoplasty of insertion of implants

AIM: The aim of this study was early differentiation between uncomplicated and complicated processes of healing in the jaw using bone SPECT. METHODS: Investigations were performed in 40 mandibular fractures and 26 jaws after onlay osteoplasty as well as secondary insertion of implants. Bone SPECT was carried out within 1-2 months and after approximately 4-5 months. The uptake in the jaw was assessed semi-quantitatively using ROI analysis. RESULTS: Fractures with uncomplicated healing showed a decrease of uptake in follow-up, whereas fractures with an infection in the later course showed an increase, resulting in a significantly higher uptake at the follow-up investigation for the latter group. 1-2 months after onlay osteoplasty significantly lower uptake was found in regions with later occurrence of sequestration. In regions with implants in which osseointegration failed, there was significant reduction of uptake initially and significant elevation at the follow-up investigation. CONCLUSION: These results indicate a prognostic relevance of bone SPECT in the evaluation of processes of healing in the jaw.     

Phasic alerting of neglect patients overcomes their spatial deficit in visual awareness

Patients with extensive damage to the right hemisphere of their brain often exhibit unilateral neglect of the left side of space. The spatial attention of these patients is strongly biased towards the right, so their awareness of visual events on the left is impaired. Extensive right-hemisphere lesions also impair tonic alertness (the ability to maintain arousal). This nonspatial deficit in alertness is often considered to be a different problem from spatial neglect, but the two impairments may be linked. If so, then phasically increasing the patients' alertness should temporarily ameliorate their spatial bias in awareness. Here we provide evidence to support this theory. Right-hemisphere-neglect patients judged whether a visual event on the left preceded or followed a comparable event on the right. They became aware of left events half a second later than right events on average. This spatial imbalance in the time course of visual awareness was corrected when a warning sound alerted the patients phasically. Even a warning sound on the right accelerated the perception of left visual events in this way. Nonspatial phasic alerting can thus overcome disabling spatial biases in perceptual awareness after brain injury.     

Pharmacology of ATP-sensitive potassium channel (KATP) openers in models of myocardial ischemia and reperfusion

Cancer cells release various antigens, some of which appear in the urine. Oral autourotherapy is suggested as a new treatment modality for cancer patients. It will provide the intestinal lymphatic system with the many tumor antigens against which antibodies may be produced. These antibodies may be pierced through the blood stream and attack the tumor and its cells.