Formalin-fixed and paraffin-embedded nodal non-Hodgkin's lymphomas demonstrate the same chromosome changes as those found in frozen samples: a comparative study using interphase fluorescence in situ hybridization.

Cytogenetic studies in lymphomas classically require fresh or frozen tissue, whereas in many instances only paraffin-embedded biopsies are available. We applied an interphase FISH assay on nuclei extracted from thick paraffin sections to determine accuracy of molecular cytogenetics in such samples. Twenty-three lymphoma samples and 4 reactive lymph nodes were tested with various commercially available DNA probes, and hybridization patterns were compared with those obtained on frozen nuclei counterparts. Successful hybridization with all probes tested was observed for 23/27 (85%) paraffin-embedded tissues and for all (100%) frozen samples, and cut-off levels defining positivity were superimposable for both situations. Chromosome changes were detected in the same way, without any false-positive or false-negative cases. Hybridization signals observed on dewaxed samples were either those classically expected to define the relevant chromosome change or were atypical: all atypical changes could be demonstrated also into nuclei from the frozen counterpart. Moreover, all typical and atypical chromosome changes observed on frozen nuclei were also detected in paraffin-embedded tissues. Our study shows that our interphase FISH assay performed on paraffin-embedded samples is a valuable alternate to conventional methods to ascertain diagnosis of lymphomas as to include patients into therapeutic trials.     

Steroid synthesis and metabolism in the nervous system: Trophic and protective effects

Steroids influence the activity and plasticity of neurons and glial cells during early development, and they continue to exert trophic and protective effects in the adult nervous system. Steroids are produced by the gonads and adrenal glands and reach the brain, the spinal cord and the peripheral nerves via the bloodstream. However, some of them, named neurosteroids, can also be synthesized within the nervous system. They include pregnenolone, progesterone, dehydroepiandrosterone and their reduced metabolites and sulfate esters. Little is known concerning the regulation of steroid synthesis in the nervous system, which involves interactions between different cell types. For example, the synthesis of progesterone by Schwann cells in peripheral nerves is regulated by a diffusible neuronal signal. Neurotrophic and neuroprotective effects of steroids have been documented both in cell culture and in vivo. PROG plays an important role in the neurological recovery from traumatic injury of the brain and spinal cord by mechanisms involving protection from excitotoxic cell death, lipid peroxydation and the induction of specific enzymes. After transection of the rat spinal cord, PROG increases the number of nitric oxide synthase expressing astrocytes immediately above and below the lesion. PROG also plays an important role in the formation of new myelin sheaths. This has been shown in the regenerating mouse sciatic nerve after lesion and in cocultures of sensory neurons and Schwann cells. PROG promotes myelination by activating the expression of genes coding for myelin proteins. The modulation of neurostransmitter receptors, in particular the type A -aminobutyric acid, the N-methyl-D-aspartate and the sigma 1 receptors, is involved in the psychopharmacological effects of steroids and allows to explain their anticonvulsant, anxiolytic, antidepressive and sedative effects as well as their influence on memory. Pregnenolone sulfate has been shown to reverse age-related deficits in spatial memory performance and to have protective effects on memory in different models of amnesia.     

No association between DUP25 and anxiety disorders.

Gratacos et al. [2001: Cell 106:367-379] described an interstitial duplication dup(15)q24q26 (DUP25) in patients with anxiety disorders; this duplication was found in approximately 90% of patients and in 7% of controls. In order to determine if DUP25 is present in additional individuals susceptible to panic attacks, we tested 44 patients with anxiety disorders, using probes 251c23 and 216c14 mapping in the 15q24 and 15q26 region. We have not detected any DUP25. Our results suggest that DUP25 is not common in people with anxiety disorders in the population tested here.     

Isodicentric/pseudoisodicentric chromosome 21 amplification in four cases of acute myelocytic leukemia or myelodysplasia

The bone marrow karyotypes of three patients with acute myelocytic leukemia (AML) or myelodysplastic syndrome (MDS) were studied at diagnosis and revealed, multiple copies of the same chromosomal anomaly, considered as psu idic(21)(q22) associated with other rearrangement(s). The karyotype of a fourth patient with MDS in transformation showed one copy of a dicentric marker presumably derived from a similar psu idic(21) by (tandem?) interstitial amplification of part of its structure, resembling a "homogeneous staining region", and described as der(21)psu idic(21)(q22)hsr(21)(q22). This rearrangement, previously described in isolated cases only, might be considered as recurrent in AML/MDS and associated with an unfavorable prognosis. It is most probably a secondary change, because it was never observed as sole abnormality and the main association, as for trisomy 21, was with del(5q). In the four cases, the number of partial supernumerary segmental 21pter-->21q22 copies, ranged from 2 to 10. The AML1 gene did not appear to be the common target of this amplification because this locus had been lost by the psu idic(21) in one patient     

Effect of sensory stimulus on striatal dopamine release in humans and cats: a [(11)C]raclopride PET study

BACKGROUND: Sensory stimulation of the forelimb extremities constitutes a well-established experimental model that has consistently shown to activate dopamine (DA) neurotransmission in the mammals' forebrain. OBJECTIVES: To visualize in vivo this modification of striatal DA release in healthy human volunteers using Positron Emission Tomography (PET) and [(11)C]raclopride. Experiments in humans were paralleled by experiments in anesthetized cats. Changes in endogenous DA release were assessed through its competition with [(11)C]raclopride binding (BP(raclo)), a radioligand probing DA D2-receptors. RESULTS: In humans no significant difference of BP(raclo) in caudate (with sensory stimulation: 2.0 +/- 0.3 versus without sensory stimulation: 2.2 +/- 0.3; P = 0.3) or putamen (2.6 +/- 0.3 versus 2.6 +/- 0.2; P = 0.9) ipsilateral to the stimulus was disclosed as a result of sensory stimulation. Similarly, no change of BP(raclo) was observed contralaterally to the stimulation in the caudate nucleus (with sensory stimulation: 2.0 +/- 0.4 versus without sensory stimulation: 2.1 +/- 0.2; P = 0.5) and the putamen (2.5 +/- 0.4 versus 2.6 +/- 0.2; P = 0.4). In cats the same results were obtained in the ipsilateral to stimulation striatum (with sensory stimulation: 2.5 +/- 0.03 versus without sensory stimulation: 2.4 +/- 0.05; P = 0.7). No change was also observed contralaterally to the stimulation (2.4 +/- 0.04 versus 2.5 +/- 0.06; P = 0.6). The [(11)C]raclopride binding remained unchanged by sensory stimuli in both humans and cats. CONCLUSION: This suggests that the DA release induced by sensory stimulus is mostly extrasynaptic whereas the synaptic DA release is probably small, which fits well with the absence of [(11)C]raclopride displacement. The mechanism of this extrasynaptic DA release could be related to a local action of glutamate on dopaminergic terminals via a thalamo-cortico-striatal loop. Present results also underline homology between cat and human responses to sensory stimuli and validate the use of cat brain to find physiological concepts in humans.     

Optimal donation of kidney transplants after controlled circulatory death

Controlled donation after circulatory death (cDCD) is used for “extended criteria” donors with poorer kidney transplant outcomes. The French cDCD program started in 2015 and is characterized by normothermic regional perfusion, hypothermic machine perfusion, and short cold ischemia time. We compared the outcomes of kidney transplantation from cDCD and brain-dead (DBD) donors, matching cDCD and DBD kidney transplants by propensity scoring for donor and recipient characteristics. The matching process retained 442 of 499 cDCD and 809 of 6185 DBD transplantations. The DGF rate was 20% in cDCD recipients compared with 28% in DBD recipients (adjusted relative risk [aRR], 1.43; 95% confidence interval [CI] 1.12–1.82). When DBD transplants were ranked by cold ischemia time and machine perfusion use and compared with cDCD transplants, the aRR of DGF was higher for DBD transplants without machine perfusion, regardless of the cold ischemia time (aRR with cold ischemia time <18 h, 1.57; 95% CI 1.20–2.03, vs aRR with cold ischemia time ≥18 h, 1.79; 95% CI 1.31–2.44). The 1-year graft survival rate was similar in both groups. Early outcome was better for kidney transplants from cDCD than from matched DBD transplants with this French protocol.     

Non-traumatic brain abscess

Between 1953 and 1989 eighty cases of non-traumatic brain abscess were treated in our department. We have re-examined the clinical and neuroradiological features of this pathological process and present our therapeutic approach and results. We believe that the optimal treatment for brain abscess consists of surgical removal.The prognosis for these lesions has undergone a marked improvement over the last two decades in response to neuroradiological, microbiological and surgical advances. The most influential prognostic factor seems to be preoperative clinical status.     

Directional coronary atherectomy: experience in 310 patients

This article describes the acute and long-term clinical outcomes of 310 consecutive patients who underwent directional coronary atherectomy (DCA) for treatment of coronary artery disease. An overall procedural success rate of 95% was noted with a total major complication rate of 5%. Analyses of minimal luminal diameter (MLD) were performed pre- and post-procedure for 160 patients. Clinical follow-up including treadmill testing and/or clinical symptoms was obtained on 293 patients. Results of angiographic analyses corresponded with the Kuntz model suggesting that larger MLDs are associated with lower restenosis rates. The overall target vessel revascularization rate was 27.6%, with a mean post-procedure percent diameter stenosis of 16%. These results indicate that DCA is associated with acceptable clinical restenosis rates, complications and long-term outcome.     

Turcot's syndrome: Case report and review of the classification

Summary We report a case of association of a brain tumor with multiple colorectal polyposis and offer an analysis of the relevant literature with a view to revising the classification of the syndrome in relation to familial multiple polyposis and Gardner's syndrome. Differences emerged, depending on the brain tumor type, which suggests that this association may be classified as two distinct syndromes.