tretinoin and Central-Nervous-System-Diseases

Extramedullary relapse occurs infrequently in acute promyelocytic leukaemia (APL) but has been increasingly reported after the advent of all-trans retinoic acid (ATRA) treatment, probably as a consequence of improved patient survival. We describe our single centre experience of six APL patients who had disease localization in the central nervous system (CNS). In three patients, clinical symptoms (headache and/or nausea) that presented during follow-up led to the performance of a lumbar puncture and detection of overt CNS infiltration. Two of these patients had simultaneous haematological relapse and one was in molecular remission when CNS leukaemia was documented. One patient with no local symptoms showed CNS infiltration at the time of molecular relapse. Following the introduction of routine lumbar puncture, carried out after front-line induction in all newly diagnosed patients with white blood cell count (WBC) greater than 10 x 109/l, two additional patients in molecular remission with no local symptoms were found to have initial APL localization in the CNS. Presenting features included in 6/6 patients an elevated WBC count (> 10 x 109/l) and a predominance of the PML/RAR bcr3 type (5/6 patients) and of microgranular morphology (5/6 patients). Our findings highlight the importance of carrying out lumbar puncture in APL patients presenting with high-risk features.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Diseases; Female; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Leukemic Infiltration; Leukocyte Count; Male; Meninges; Middle Aged; Recurrence; Spinal Puncture; Tretinoin

We found the expression of neurofilament was very low in undifferentiated human adult bone marrow mesenchymal stem cells (hMSCs), but its expression could be significantly induced after treatment with combination of growth factors. Approximately 16% of hMSCs differentiated into cells expressing neurofilament after treatment with a combination of FGF and RA, retinoic acid. We also examined the effect of five different cell culture substrates on the expression of neurofilament. One specific combination that was particularly effective in provoking pre-neuronal differentiation was culturing hMSCs on fibronectin-coated dishes and stimulating them with FGF and RA; 40% of cells expressed neurofilament. These results suggest that growth factors and substrates, in combination, can effectively initiate differentiation of hMSCs along a neuronal pathway.

Topics: Adult; Bone Marrow Cells; Bone Marrow Transplantation; Cell Culture Techniques; Cell Differentiation; Cell Division; Cell Lineage; Cell Size; Cells, Cultured; Central Nervous System Diseases; Colforsin; Culture Media; Cyclic AMP; Drug Combinations; Epidermal Growth Factor; Fibroblast Growth Factors; Fibronectins; Growth Substances; Humans; Male; Mesoderm; Neurofilament Proteins; Neurons; RNA, Messenger; Stem Cells; Thionucleotides; Tretinoin

In some neurological diseases, injury to neurones reflects an over-stimulation of their receptors for excitatory amino acids. This response may disturb the Ca(2+)-homeostasis and lead to a pronounced and sustained increase in the intracellular concentration of this ion. On the basis of data derived from correlative studies, calcium-binding proteins have been postulated to play a protective role in these pathologies. We tested, directly, the capacity of the three calcium-binding proteins calretinin (CR), calbindin D-28k (CB) and parvalbumin (PV) to buffer [Ca(2+)], and to protect cells against excitotoxic death. We used P19 murine embryonic carcinoma cells, which can be specifically induced (by retinoic acid) to transform into nerve-like ones. The differentiated cells express functional glutamate-receptors and are susceptible to excitotoxic shock. Undifferentiated P19-cells were stably transfected with the cDNA for CR, CB or PV, induced to differentiate, and then exposed to NMDA, a glutamate-receptor agonist. The survival rates of clones expressing CR, CB or PV were compared with those of untransfected P19-cells using the lactate-dehydrogenase assay. CR- and CB-expressing cells were protected from death during the first 2 h of exposure to NMDA. This protection was, however, transient, and did not suffice to rescue P19-cells after prolonged stimulation. Two of the three PV-transfected clones raised were vulnerable to NMDA-induced excitotoxicity; the third, which expressed the lowest level of PV, was protected to a similar degree as that found for the CR- and CB-transfected clones. Our results indicate that in the P19-cell model, CR and CB can help to delay the onset of cell death after excitotoxic stimulation.

Topics: Animals; Calbindin 2; Calbindins; Calcium; Calcium-Binding Proteins; Cell Death; Cell Differentiation; Cell Size; Central Nervous System; Central Nervous System Diseases; Excitatory Amino Acid Agonists; Excitatory Amino Acids; Glycine; Immunohistochemistry; L-Lactate Dehydrogenase; Membrane Potentials; Mice; N-Methylaspartate; Neoplastic Stem Cells; Neurons; Neuroprotective Agents; Neurotoxins; Parvalbumins; Receptors, N-Methyl-D-Aspartate; S100 Calcium Binding Protein G; Tretinoin

Topics: Adult; Antibiotics, Antineoplastic; Central Nervous System Diseases; Cerebral Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Male; Recurrence; Tretinoin

Topics: Adult; Calcinosis; Central Nervous System Diseases; Fatal Outcome; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Male; Recurrence; Tretinoin

Topics: Administration, Topical; Central Nervous System Diseases; Humans; Tretinoin

A 13-month-old child with lamellar ichthyosis and numerous cutaneous and systemic infections died following an abrupt episode of severe hypotension. Postmortem examination revealed white matter vacuolation in the brain stem tegmentum and cerebellar hemispheres similar to that seen in toxicity from hexachlorophene, to which our patient was not exposed. The patient had been treated with many commonly used medications, including 13-cis-retinoic acid, a relatively new drug with apparent therapeutic benefit in hyperkeratotic dermatoses. This had been given systemically during the patient's last week of life. Possible relationships between the white matter lesions and extrinsic toxic agents are discussed.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Brain Stem; Central Nervous System Diseases; Cerebral Ventricles; Drug Therapy, Combination; Female; Humans; Ichthyosis; Infant; Isotretinoin; Mycoses; Myelin Sheath; Skin Diseases, Infectious; Tretinoin; Vacuoles

Topics: Acanthosis Nigricans; Administration, Topical; Adolescent; Central Nervous System Diseases; Diverticulum; Female; Gastrointestinal Diseases; Humans; Skin; Sural Nerve; Tretinoin; Vitamin A; Vitamin A Deficiency