What to Do, and What Not to Do, When Diagnosing and Treating Breakthrough Cancer Pain (BTcP): Expert Opinion.

Clinical management of breakthrough cancer pain (BTcP) is still not satisfactory despite the availability of effective pharmacological agents. This is in part linked to the lack of clarity regarding certain essential aspects of BTcP, including terminology, definition, epidemiology and assessment. Other barriers to effective management include a widespread prejudice among doctors and patients concerning the use of opioids, and inadequate assessment of pain severity, resulting in the prescription of ineffective drugs or doses. This review presents an overview of the appropriate and inappropriate actions to take in the diagnosis and treatment of BTcP, as determined by a panel of experts in the field. The ultimate aim is to provide a practical contribution to the unresolved issues in the management of BTcP. Five 'things to do' and five 'things not to do' in the diagnosis and treatment of BTcP are proposed, and evidence supporting said recommendations are described. It is the duty of all healthcare workers involved in managing cancer patients to be mindful of the possibility of BTcP occurrence and not to underestimate its severity. It is vital that all the necessary steps are carried out to establish an accurate and timely diagnosis, principally by establishing effective communication with the patient, the main information source. It is crucial that BTcP is treated with an effective pharmacological regimen and drug(s), dose and administration route prescribed are designed to suit the particular type of pain and importantly the individual needs of the patient.

LaseRitz: Far-Infrared Laser Line Assignment and Prediction by the Ritz Combination Principle, with Application to Methanol and Hydrazine.

A "LaseRitz" program is described for the systematic assignment and prediction of far-infrared laser (FIRL) transitions for a given molecule, such as methanol or hydrazine, which can be generated by optical pumping with known laser lines. The input data set for the program consists of identified molecular energy levels in ground and excited vibrational states, as compiled by our Ritz assignment program from the analysis of infrared (IR) bands and the FIR ground state spectrum. The program scans the data set for appropriate IR matches with an input list of laser pump lines for CO(2), N(2)O, etc., and generates an output table of all possible FIRL lines consistent with the molecular selection rules and lying within a prescribed wavenumber range. Initial tests on CH(3)OH have led to three likely new FIRL assignments; for N(2)H(4), assignments have been found for 14 new FIRL transition systems and verified for five others. Lists have been produced (deposited as supplementary data with the JMS archive reached at www.idealibrary.com or available on request from the authors) of CH(3)OH and N(2)H(4) FIRL lines potentially accessible by optical pumping with regular, sequence-band, hot-band, and isotopic CO(2) lines, plus N(2)O lines for N(2)H(4). The systematic approach with the LaseRitz program is more global and rigorous than earlier line-by-line studies, permitting calculation of all FIRL wavenumbers to spectroscopic accuracy. Copyright 2000 Academic Press.

Millimeter-Wave Spectra and Global Torsion-Rotation Analysis for the CH(3)OD Isotopomer of Methanol.

New millimeter-wave and microwave measurements for CH(3)OD have been combined with previous literature data and with an extended body of Fourier transform far-infrared observations in a full global analysis of the first two torsional states (v(t) = 0 and 1) of the ground vibrational state. The fitted CH(3)OD data set contained 564 microwave and millimeter-wave lines and 4664 far-infrared lines, representing the most recent available information in the quantum number ranges J

Assignment and Power Series Analysis of the FIR Fourier Transform Spectrum of Cyanamide Using a Multimolecule Ritz Program.

The "Ritz" program, originally written for the analysis of the Fourier transform spectra of the methanol isotopomers and presented in previous papers, has been extended in order to analyze the spectra of other molecules. This program evaluates the term values involved in the assigned transitions by the Rydberg-Ritz combination principle, and can tackle such perturbations as Fermi-type resonances or Coriolis interactions. As a first application of the extended version, we present an investigation of the Fourier transform spectrum of cyanamide between 25 and 980 cm-1. More than 16 000 lines have been assigned. Our Ritz database now comprises a list of more than 19 000 assigned lines (including of the microwave and FIR lines available in the JPL database) and more than 3900 term values. All of the lines presented in this paper correspond to transitions within the ground and first excited inversion levels of the ground vibrational state of the small-amplitude modes. Copyright 1998 Academic Press.

Methanol Laser Line Assignments: Evidence of Four-Level Laser Systems

The "Ritz" computer program, developed for facilitating the assignment of molecular Fourier transform absorption spectra and described in a previous work, determines the energy level values involved in the assigned transitions by the Rydberg-Ritz combination principle. Combining the data obtained from the analyses of high-resolution infrared (IR) and far-infrared (FIR) spectra, it is possible to predict possible FIR laser emissions of molecules. In the present work we have applied this method to the common isotopomer methanol, 12CH3 16OH, and obtained 14 proposed assignments for previously unassigned FIR laser lines. We also predict 15 possible new FIR laser emissions. For the first time, an assignment involving a four-level laser system with collisional population transfer to a slightly higher energy level is reported. Copyright 1998 Academic Press.

High Resolution Fourier Transform Far Infrared Spectroscopy of CH3OD

The high resolution Fourier transform far infrared spectrum of the torsion rotation band of CH3OD has been recorded in the range 20-350 cm-1 at a resolution of 0.002 cm-1. The spectrum shows splitting of the lines due to strong torsional, rotational, and vibrational interactions in the molecule. Assignments were possible for rotational subbands in the ground torsional state (n = 0) for K values up to 15 and J values of up to 30, for all the symmetry species. In addition, some subbands were also identified which involve torsionally excited states. A total of 63 b-type subband origins, including 6 Q-branch origins obtained from microwave (MW) and millimeter-wave (MMW) studies, were fitted to a semiempirical model. The molecular parameters so determined were able to reproduce the subband origins almost to within experimental uncertainty. The torsional-rotational state-dependent effective molecular parameters and the asymmetry splitting parameters have also been determined. These should prove valuable in the assignment of transitions involving torsionally excited states in the ground vibrational state. Copyright 1997 Academic Press. Copyright 1997Academic Press

The electrophysiological work of Carlo Matteucci. 1964.

In 1964, Giuseppe Moruzzi (1910-1986), a prominent neurophysiologist of worldwide fame with a scholarly interest in the history of science, published an extensive and insightful analysis of the work and personality of Carlo Matteucci, a 19th century Professor of Physics at the University of Pisa who had worked on "animal electricity" in the great tradition of Galvani. By discovering fundamental phenomena such as the demarcation potential and action current in muscle and nerve, Matteucci paved the way for the development of modern electrophysiology. Being written in Italian and having appeared in a not easily available journal of history of science, Moruzzi's essay has been lost to most members of the international neuroscience community. An English translation of it is published here with two aims: first, to make known to a large audience of neuroscientists a fascinating account of the origins of electrophysiology as seen through a perceptive interpretation of the successes and failures of a brilliant scientist and passionate man; and second, to pay tribute to the memory of Giuseppe Moruzzi and his everlasting contributions to learning and science on the occasion of the 10th anniversary of his death.

An annotated interview with Giuseppe Moruzzi, 1910-1986. Interview by Louise M. Marshall.

Utilizing three modes of information exchange, this "annotated autobiography" presents in perspective a picture of an eminent neuroscientist of the 20th century. The reminiscences of Guiseppe Moruzzi, Director of the Institute of Physiology of the University of Pisa for more than thirty years, were combined with contemporary tributes, a review of his major published work, and comments of friends and associates. Such a three-dimensional view of a scientific career illustrates the possibilities of "the medium is the message."

Apomorphine pecking in the pigeon.

Pecking activity elicited by apomorphine was studied quantitatively in intact and thalamic pigeons. While apomorphine pecking is easily observed in the intact pigeon, it is absent in the acute thalamic animal. I reappears, however, in the chronic preparation simultaneously with the recovery of spontaneous pecking. Apomorphine pecking is described by satiation and increased by fasting. Reticular stimulation produces reversible blockade of both apomorphine and spontaneous pecking with the same parameters, without increase in heart rate. Apomorphine pecking can be observed only in the presence of visual contrast, and is always aimed at the contrast points or edges. A decrease in contrast produces a decrease in the number of pecks delivered to the contrast points and an increase in those missing the target, while the total number of pecks delivered in a unit time is unaffected. A lowering of the background luminance is followed by a decrease in the total number of pecks, which is mostly due to a reduction of those aimed at the contrast points. All these findings are discussed and it is concluded that: i) apomorphine exerts an excitatory action (direct or indirect) on the hypothalamic feeding centers; hence apomorphine pecking can be considered as a pharmacologically motivated behavior; ii) visual contrast exerts a dual action on apomorphine pecking, namely it acts both as triggering stimulus and goal object; iii) the decrease in apomorphine pecking induced by lowering the ambient light intensity is probably due to a decrease in the level of the general arousal.

Regulation of ribonucleic acid synthesis by polyamines. Reversal by spermine of inhibition by methylglyoxal bis(guanylhydrazone) of ribonucleic acid synthesis and histone acetylation in rabbit heart.

The relationship between polyamines and RNA synthesis was studied by considering the action of spermine on histone acetylation in perfused heart. In addition, the effect of methylglyoxal bis(guanylhydrazone), inhibitor of putrescine-activated S-adenosylmethionine decarboxylase activity, on RNA and polyamine specific radioactivity and on acetylation of histone fractions was also investigated in perfused heart. Different concentrations of spermine and/or methylglyoxas bis(guanylhydrazone) were injected into the heart, 15 min after beginning the perfusion. The results demonstrate that spermine stimulates the specific radioactivity of RNA of subcellular fractions. Acetylation of the arginine-rich histone fractions, involved in the regulation of RNA transcription, is enhanced by spermine. The perfusion with methylglyoxal bis(guanylhydrazone) causes a decrease in the specific radioactivity of polyamines and RNA, and in acetylation of histone fractions. However, spermine is able to reverse the methylglyoxal bis(guanylhydrazone) inhibition when injected simultaneously. From these results we may assume a possible role for spermine in the regulation of RNA transcription.

The effect of spermine on transcription of mammalian chromatin by mammalian deoxyribonucleic acid-dependent ribonucleic acid polymerase.

Isolated rat liver nuclei demonstrate an increased ability to synthesize RNA in the presence of either spermine or spermidine. Spermidine has more effect on the low-salt alpha-amanitin-insensitive reaction, and spermine has more effect on the high-salt alpha-amanitin-sensitive reaction. Spermine is effective at concentrations of 0.1 mM and 1 muM, showing a biphasic effect. The RNA polymerase activity associated with nuclear chromatin is increased in the presence of spermine only at a concentration of 0.1 mM. Aso the transcription of deproteinized liver DNA by liver form-B polymerase or Escherichia coli enzyme is more efficient in the presence of 0.1 mM-spermine. Only when liver chromatin is transcribed by its homologous enzyme (and not by E. coli enzyme) is spermine active at both 0.1mM and 1 muM as in purified nuclei. The lower concentration of spermine (1 muM) is able to affect chromatin transcription by increasing the affinity of chromatin for the enzyme. Our findings suggest a regulatory role of spermine at the level of genome transcription.

Polyamine and nucleoprotein correlations in hypertrophied and perfused heart.

A close relationship has been observed between polyamine, as spermine and spermidine, and nucleic acid synthesis during heart hypertrophy, induced in the rats experimentally, by physical exericse (swimming). The role of spermine on RNA synthesis has been studied by perfusion experiments of the heart. Spermine is able to stimulate myocardial RNA synthesis of all subcellular fractions. The biochemical mechanism of this phenomenon may be explained by the results of histone acetylation under the action of spermine, showing an increased radioactivity of F 2aI and F 2a2 arginine-rich histone fractions. This suggests that spermine may act modulating histone acetylation, with a consequence on the gene transcription mechanism.