Durante mucho tiempo no había principios uniformes para la Atribución de nombres a los antibióticos https://antibioticos-wiki.es . Más a menudo se les llama por el nombre genérico o especie del producto, con menos frecuencia-de acuerdo con la estructura química. Algunos antibióticos se nombran de acuerdo con el lugar donde se asignó el producto.
Haematologica-thj.org
short report Haematologica 1996; 81:152-154 ALL-TRANS-RETINOIC ACID AND PSEUDOTUMOR CEREBRI IN A YOUNG ADULT WITH ACUTE PROMYELOCYTIC LEUKEMIA: A POSSIBLE DISEASE ASSOCIATION Giuseppe Visani,* Giovanni Bontempo,° Silvia Manfroi,* Alberto Pazzaglia,# Roberto D'Alessandro,° Sante Tura* *Institute of Hematology “L. & A. Seragnoli”, University of Bologna; °Servizio di Neurologia, Policlinico S.Orsola-Malpighi,Bologna; #Clinica Oculistica I, University of Bologna, ItalyABSTRACT Pseudotumor cerebri or idiopathic intracranial hypertension is a neurological syndrome charac- terized by signs and symptoms of intracranial hypertension without clinical or radiological evi- dence of infective or space occupying lesions. Iatrogenic factors are frequent; in particular, cases of pseudotumor cerebri associated with all-trans-retinoic acid treatment in acute promyelocytic leukemia (APL) have been frequently described in pediatric patients. We report on a case observed in an older patient (young adult age) and give diagnostic and therapeutic guidelines. Key words: pseudotumor cerebri, all-trans-retinoic acid, acute promyelocytic leukemia, therapy, retinoids
All-trans-retinoic acid (ATRA) is able to µg/mL. Bone marrow biopsy, karyotype exami-
nation and molecular biology were compatible
with a diagnosis of APL.4 The patient was treat-
than 80% of cases both in adults and in chil-
ed with ATRA 45 mg/m2 p.o. (80 mg/day, total
dren.1-3 ATRA is considered a safe agent.
dose) plus daunorubicin 100 mg/day for three
Nevertheless, adverse reactions have been
observed to affect various organs and districts
Thirty-one days after beginning treatment the
(skin, liver, lung, blood, metabolism, heart and
patient started complaining of headache, diplop-
vascular system, central nervous system).1-3
ia and tinnitus. WBC count was 5.8ϫ109/L and
Some of these have been described only in sub-
platelets were 197ϫ109/L; bone marrow biopsy
jects affected by APL, whereas others, such as
and karyotype confirmed achievement of com-
pseudotumor cerebri (PTC), are possible in
plete remission. Neurological examination was
other conditions. In this context, we describe a
negative. Ophthalmological examination docu-
case of PTC occurring in a young adult patient
mented a visual acuity of 9/10 in both eyes.
Pupillary reactions were normal and slitlampexamination results were normal. Fundus oculiexamination showed that both optic disks were
Case Report
blurred and elevated; in addition, we observed
R.S., a 16-year-old male presented in January
venous engorgement, tortuous vessels and scat-
1994 with bleeding, macrohematuria and fever
tered, flame-shaped peripapillary hemorrhages.
(38.5°C). Blood tests showed: hemoglobin 8.6
Golman perimetry revealed bilateral enlarge-
g/dL; platelets 23ϫ109/L; WBC 1.09ϫ109/L, dif-
ment of the blind spot and a concentric contrac-
ferential count: 60% blast cells (promyelocytes
tion of the peripheral field. Visual evoked poten-
with Auer rods), 6% neutrophils, 34% lympho-
tials (pattern reversal) were normal.5 A cerebral
computed tomography (CT) examination per-
Correspondence: Giuseppe Visani, MD, Institute of Hematology “Seràgnoli”, University of Bologna, Policlinico S. Orsola, via Massarenti 9, 40138Bologna, Italy. Acknowledgments: supported in part by MURST 40%-60%. Received September 13, 1995; accepted February 7, 1996.ATRA and pseudotumor cerebri
formed the same day and 15 days later failed to
detect the presence of space occupying lesions or
(NMR) is not considered a mainstay for the
ventricular space enlargement. Diagnosis of PTC
diagnosis of PTC since the shape of ventricular
was therefore made. ATRA was stopped on the
enlargement is adequately described by CT.
day of onset of intracranial hypertension symp-
Lumbar puncture could be helpful to confirm
toms and the patient was treated with acetazo-
diagnosis. The case described here is a typical
lamide. Because of a scarce response to the phar-
example of PTC arising in a young adult (16
macological treatment, a lumbar puncture was
years old) following treatment with ATRA,
performed after 15 days. It showed a strong ele-
without the simultaneous use of other drugs
vation of cerebrospinal fluid (CSF) pressure (310
with a potential risk of inducing PTC; further-
mm of water), and the fluid was clear and color-
more, clinical and instrumental documentation
less in appearance. Cytochemical and microbio-
satisfied all accepted criteria for a diagnosis of
logical evaluation was negative. A total amount
of 28 cc of CSF were removed, leaving final CSF
The pathogenesis of ATRA-induced PTC still
pressure of 150 mm of water. This procedure was
remains to be established. It could be seen as a
followed by prompt clinical improvement. No
manifestation of vitamin A overdose; high doses
recurrence of symptoms was noted and no other
of ATRA induce an over stimulation of RAR-␣
ATRA-related side effects were observed. The
(retinoic acid receptor), which proves to be help-
patient has been in continuous complete remis-
ful in gaining control over the leukemic myeloid
sion for 17 months; he completed the chemo-
clone (in which the receptor is expressed in an
therapy protocol, including autologous bone
aberrant form) but which is frankly pathological
marrow transplantation, without any neurologic
in other tissues, including the central nervous
system. In fact, the existence of retinoid recep-
tors and related cytoplasmic binding proteinshas been demonstrated in the nervous system.7,8
Discussion
The retinoids seem to have a fundamental mor-
PTC is a diagnosis of exclusion and a con-
phological action in the nervous system.9 In par-
firmed diagnosis requires the following widely
ticular, ATRA is involved in fundamental aspects
of the development of the central nervous sys-
1. signs and symptoms of intracranial hyper-
tem.9 A change in the metabolic pathways related
to retinoids after embryonic development, or an
action exerted by retinoids not at the level of the
3. lack of focal neurological signs except for
nerve cells – neurons and glial cells – but on the
those referable to intracranial hypertension
structures of the blood-brain barrier or on the
and those lacking in locational value, such as
drainage of cerebrospinal fluid (choroid plexuses
4. normally-sized and shaped cerebral ventri-
and arachnoid villi, respectively) could be postu-
cles and absence of space occupying lesions
small ventricles and of empty sella is, howev-
previously described in ten pediatric patients
treated for APL with ATRA at doses ranging
5. documented elevation of cerebrospinal fluid
from 45 to 80 mg/m2/day.10-12 PTC was also
pressure (200 mm of water in non obese and
reported in children treated with ATRA for neo-
plasms other than APL, whereas clinical trials
6. normal composition of cerebrospinal fluid;
performed on young adults or adults treated
7. no other identifiable causes of intracranial
with higher dosages (up to 150 mg/m2/day) for
pathologies other than APL did not show any
A correct diagnostic approach consists of
evidence of toxicity on the central nervous sys-
physical examination and computerized tomo-
tem. At present, the appropriate management
G. Visani et al.
2. Degos L, Chomienne C, Daniel MT, et al. Treatment of first
of patients who experience this syndrome is still
relapse in acute promyelocytic leukemia with all-trans
unclear. Major analgesic drugs, such as codeine
retinoic acid. Lancet 1990; 336:1440-1.
or morphine sulphate, or temporary ATRA dis-
3. Castaigne S, Chomienne C, Daniel MT, et al. All-trans
retinoic acid as a differentiation therapy for acute promyelo-
continuation in non responding cases may help
cytic leukemia. I. Clinical results. Blood 1990; 76:1704-9.
in reducing the severe headache, nausea and
4. Diverio D, Riccioni R, Mandelli F, Lo Coco F. The PML/RAR␣
vomiting; acetazolamide or furosemide is rec-
fusion gene in the diagnosis and monitoring of acutepromyelocytic leukemia. Haematologica 1995, 80:155-60.
ommended to reduce CSF pressure, as is lum-
5. Spoor TC, Ramocki JM, Madion MP, Wilkinson MJ.
bar puncture with removal of CSF in order to
Treatment of pseudotumor cerebri by primary and secondaryoptic nerve sheath decompression. Am J Ophtalmol 1991;
maintain a final CSF pressure of no more than
6. Radhakrishnan K, Ahlskog JE, Cross SA, Kurland LT,
O’Fallon WM. Idiopathic intracranial hypertension -Descriptive epidemiology in Rochester, Minn, 1976 to 1990,
retinoid stimulation in the central nervous sys-
tem, or a progressive age-related reduction of
7. Maden M, Ong DE, Chytil F. Retinoid-binding protein dis-
RAR expression in the central nervous system
tribution in the developing mammalian nervous system. Development 1990; 109:75-80.
could be postulated. However, the case described
8. Ruberte E, Friederich V, Chambon P, Morris-Kay G. Retinoic
highlights the possibility of a diagnosis of PTC in
acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse ner-
APL patients no longer in the pediatric age, sug-
vous system development. Development 1993; 118:267-82.
gesting that PTC should be considered at all ages
Maden M, Holder N. The involvement of retinoic acid in the
in the diagnostic procedure for APL patients
development of the vertebrate central nervous system,Development 1991; 11(Suppl. 2):87-94.
10. Smith MA, Adamson PC, Balis FM, et al. Phase I and phar-
macokinetic evaluation of all-trans-retinoic acid in pediatricpatients with cancer, J Clin Oncol 1992; 10:1666-73.
11. Warrell RP, Frankel SR, Miller WH. Jr, et al. Differentiation
References
therapy of acute promyelocytic leukemia with tretinoin (all-
trans-retinoic acid). N Engl J Med 1991; 324:1385-93.
1. Huang ME, Ye YC, Chen SR. et al. Use of all-trans retinoic
12. Mahmoud HH, Hurwitz CA, Roberts WM, Santana VM,
acid in the treatment of acute promyelocytic leukemia. Blood
Ribeiro RC, Krance RA. Tretinoin toxicity in children with
acute promyelocytic leukaemia. Lancet 1993; 342:1394-5.
Batteries Explained CHOOSING THE RIGHT BATTERY Rechargable batteries have come a long way in the past decade or two and whereas early model ers had only one choice - the humble nicad, today there is a vast array of different types on the market. Unfortunately, al this choice can leave model ers confused as to which is the best battery to use and how to take care of them. Get a good charger
THE VALHEIL WORLD SEBASTIAN HAYES SchoolPlay Productions Ltd 15 Inglis Road, Colchester, Essex CO3 3HU www.schoolplayproductions.co.uk This play is fully protected by copyright. It is an infringement of the copyright to give any public performance or reading of this play in its entirety or in the form of excerpts without the prior consent in writing No part of this publication m