Striatal and mesolimbic dopaminergic contribution to 3,4-dihydroxyphenylacetic acid sulfate in rat plasma

Free and sulfated 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in rat plasma after bilateral 6-hydroxydopamine lesions of striatum or mesolimbic tissue (nucleus accumbens + olfactory tubercle). Both lesions selectively reduced plasma DOPAC sulfate levels without altering free DOPAC or catecholamine levels in plasma, sympathetic ganglia or adrenal medulla. The present work confirms our previous findings and suggests that DOPAC sulfate functional state of striatal and mesolimbic dopaminergic neurons.     

Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur

A retrospective multi-institutional study of 227 patients with osteosarcoma of the distal end of the femur was done to compare rates of local recurrence, metastasis, and survival. Three cohorts of patients who had had either a limb-sparing procedure, an above-the-knee amputation, or disarticulation of the hip were compared. The results revealed prevalences of eight of seventy-three, nine of 115, and zero of thirty-nine as to local recurrence; forty-three of seventy-three, sixty-five of 115, and twenty-one of thirty-nine as to metastasis; and thirty-three of seventy-three, forty-eight of 115, and eighteen of thirty-nine as to death. Of the seventeen patients who had a local recurrence, sixteen died. In the limb-salvage group, eighteen patients required amputation, because of local recurrence in eight and other local complications in ten. The Kaplan-Meier estimates of the percentage of patients who survived and the percentage of patients without recurrent disease showed no difference among the three surgical groups (Mantel-Cox test statistic: p = 0.8) after a median length of follow-up of five and one-half years. Various covariant adjusted estimates yielded similar results. For the entire group of patients, the rate of continuously disease-free survival was 42 per cent, and the over-all rate of survival was 55 per cent at five years. It appears that, compared with above-the-knee amputation or disarticulation of the hip, the use of a limb-salvage procedure for osteosarcoma of the distal end of the femur did not shorten the disease-free interval or compromise long-term survival.     

Role of delayed enhancement MRI in patients with acute coronary syndrome and unobstructed coronary arteries: reply

We thank Coceani and L'Abbate for their comments on our paper.We concur that ‘pathophysiology cannot be inferred fromcoronary lumenography alone’, and this was one of thekey motivations in conducting the present study.     

Genetics of epilepsy: epilepsy research foundation workshop report.

The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defi ned phenotypes, robust statistical data handling, and follow-up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.     

Intracellular messengers and the control of protein synthesis

The molecular events responsible for controlling cell growth and development, as well as their coordinate interaction is only beginning to be revealed. At the basis of these controlling events are hormones, growth factors and mitogens which, through transmembrane signalling trigger an array of cellular responses, initiated by receptor-associated tyrosine kinases, which in turn either directly or indirectly mediate their effects through serine/threonine protein kinases. Utilizing the obligatory response of activation of protein synthesis in cell growth and development, we describe efforts to work backwards along the regulatory pathway to the receptor, identifying those molecular components involved in modulating the rate of translation. We begin by describing the components and steps of protein synthesis and then discuss in detail the regulatory pathways involved in the mitogenic response of eukaryotic cells and during meiotic maturation of oocytes. Finally we discuss possible future work which will further our understanding of these systems.     

Lung injury in acute pancreatitis: primary inhibition of pulmonary phospholipid synthesis

Alterations in the pulmonary surfactant system are partly responsible for the respiratory insufficiency seen with acute pancreatitis. In this model of cerulein-induced pancreatitis in rats, we utilized a new stable isotope metabolic tracer technique to examine one aspect of the pulmonary surfactant system and its relationship to associated lung injury. We have demonstrated primary, early depression of lung phospholipid synthesis reflected in both lung tissue and alveolar washings. We suggest that this quantitative change in pulmonary surfactant synthetic rate may partly explain the occurrence of respiratory failure with acute pancreatitis.     

The 2006 Henry N. Wagner Lecture: Of mice and men (and positrons)--advances in PET imaging technology.

There have been major advances in PET technology that cumulatively have helped improve image quality, increased the range of applications for PET, and contributed to the more widespread use of PET. Examples of these technologic advances include whole-body imaging, 3-dimensional imaging, new scintillator materials, iterative reconstruction algorithms, combined PET/CT, and preclinical PET. New advances on the immediate horizon include the reintroduction of time-of-flight PET, which takes advantage of the favorable timing properties of newer scintillators; the integration of PET and MRI scanners into a dual-modality imaging system; and the possibility of further significant improvements in spatial resolution in preclinical PET systems. Sensitivity remains a limiting factor in many PET studies. Although, conceptually, huge gains in sensitivity are still possible, realizing these gains is thwarted largely by economic rather than scientific concerns. Predicting the future is fraught with difficulty; nonetheless, it is apparent that ample opportunities remain for new development and innovation in PET technology that will be driven by the demands of molecular medicine, notably sensitive and specific molecular diagnostic tools and the ability to quantitatively monitor therapeutic entities that include small molecules, peptides, antibodies, nanoparticles, DNA/RNA, and cells.     

Precision grip function after free toe transfer in children with hypoplastic digits.

Although toe-to-hand transfer has a defined role in the management of congenital hand deformities, it remains unclear how well children integrate the transferred digits into physiological grasping. We analysed fingertip forces in the precision grip of 13 patients when lifting a test object more than three years after free toe transfer for absent or hypoplastic digits. Clinically, most patients showed normal sensibility of transferred digits, but active motion and pinch strength were limited as compared to the normal hand. For the control of fingertip forces, two key features of the normal two-digit opposition grip were seen in all operated hands: adaptation of grip force to object weight and parallel coordination of lift and grip forces. These physiological grasping strategies developed independently of the patients' age at the time of operation, which ranged from one to 13 years. In four patients, we observed increased tangential load forces with the operated hand due to misalignments in the application of fingertips on the grasp surfaces. Such forces lead to increased grip force requirements on both fingers that may overload transferred digits with limited motor function. The need for optimal alignment of the grip axis during toe-transfer surgery is emphasised.     

Zur anatomie des xanthoma palpebrarum

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