Why we prefer the thin layer technique to conventional Pap smears. A double-blind study of 473 specimens

The study evaluated the feasibility of a thinlayer technique on a routine basis for cervical smears and compared 473 ThinPrep preparations to the matched conventional Papsmears. The interpretation was double-blind and performed according to the Bethesda system. A consensus was established in discordant cases. The technique was easily mastered by gynecologists and technicians. Main advantages of the thinlayer technique were: a low number (1%) of unsatisfactory samples; a constant quality; homogeneity of cell distribution; the disappearance of problems of interpretation due to fixation or smear artifacts, red cells, polymorphs; a more precise interpretation, a firmer diagnosis; less visual fatigue; a shorter time of interpretation; the possibility of preparing more slides and performing special techniques on the same specimen. Main disadvantages were a higher cost and a necessary period of learning for cytologists.     

Cerebellar involvement in the coordination control of the oculo-manual tracking system: effects of cerebellar dentate nucleus lesion

Summary When the hand of the observer is used as a visual target, oculomotor performance evaluated in terms of tracking accuracy, delay and maximal ocular velocity is higher than when the subject tracks a visual target presented on a screen. The coordination control exerted by the motor system of the arm on the oculomotor system has two sources: the transfer of kinaesthetic information originating in the arm which increases the mutual coupling between the arm and the eyes and information from the arm movement efferent copy which synchronizes the motor activities of both subsystems (Gauthier et al. 1988; Gauthier and Mussa-Ivaldi 1988). We investigated the involvement of the cerebellum in coordination control during a visuo-oculo-manual tracking task. Experiments were conducted on baboons trained to track visual targets with the eyes and/or the hand. The role of the cerebellum was determined by comparing tracking performance defined in terms of delay, accuracy (position or velocity tracking errors) and maximal velocity, before and after lesioning the cerebellar dentate nucleus. Results showed that in the intact animal, ocular tracking was more saccadic when the monkey followed an external target than when it moved the target with its hand. After lesioning, eye-alone tracking of a visual target as well as eye-and-hand-tracking with the hand contralateral to the lesion was little if at all affected. Conversely, ocular tracking of the hand ipsilateral to the lesion side became more saccadic and the correlation between eye and hand movement decreased considerably while the delay between target and eyes increased. In normal animals, the delay between the eyes and the hand was close to zero, and maximal smooth pursuit velocity was around 100 degrees per second with close to unity gain; in eye-alone tracking the delay and maximal smooth pursuit velocity were 200 ms and 50 deg per second, respectively. After lesioning, delay and maximum velocity were respecttively around 210 ms and 40 deg per second, that is close to the values measured in eye-alone tracking. Thus, after dentate lesioning, the oculomotor system was unable to use information from the motor system of the arm to enhance its performance. We conclude that the cerebellum is involved in the coordination control between the oculomotor and manual motor systems in visuo-oculo-manual tracking tasks.     

An immunochemical approach to investigating the mechanism of inhibition of cysteine proteinases by members of the cystatin superfamily.

Antibodies were raised against a synthetic dodecameric peptide KGAGQVVAGPWK (K12K), encompassing sequences thought to be important for the function of the cysteine proteinase inhibitors of the cystatin superfamily. These antibodies specifically recognized molecules of family 3, i.e., kininogens, in the serum of seven mammalian species tested in this study. The only notable exception was that of rat thiostatin (T kininogen) which is structurally related to the kininogen family. The antibodies also discriminated between family 2 (cystatins) and family 3 (kininogens) of the cystatin superfamily, since neither chicken cystatin nor human and rat cystatins C and S, which all belong to family 2 were recognized. The cystatin-like inhibitory domains resulting from fragmentation of human low molecular weight kininogen by bovine trypsin, were still recognized by antibodies, indicating that discrimination does not require two neighbouring inhibitory sites on the kininogen heavy chain. The antibodies blocked the capacity of kininogens to inhibit papain, suggesting that they recognize a conformational epitope at or near the kininogen inhibitory sites. The inhibitory properties of family 2 cystatins remained unchanged, confirming that members of this family do not interact with anti K12K antibodies. These antibodies are thus a new tool able to discriminate functionally and structurally between the members of the cystatin superfamily.     

Neurologic crises in hereditary tyrosinemia

Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconi's syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.     

Shunt surgery for treatment of portal hypertension in children

Shunt surgery in children suffering from portal hypertension (PH) is considered as an immediate and definite mode of prevention of recurrent gastrointestinal hemorrhage. Certain conditions must be met: (a) normal liver; (b) normal veins available within the portal system; (c) a sufficient portosystemic gradient of pressure; and (d) a surgical team with experience in portal venous surgery. In patients in whom PH is an epiphenomenon of severe liver disease, other means of hemostasis for bleeding esophageal varices should be sought. The difficult decision is in the child with specific liver alterations without major hepatocellular dysfunction but in whom the prognosis cannot be precisely foreseen. A few more years will be needed before one can tell if shunt surgery is the best choice for this category of patient.

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Resumen La cirugía derivativa (shunts portosistémicos) en los niños que sufren de hipertensión portal es considerada como una forma inmediata y definitiva de prevenir la hemorragia gastrointestinal recurrente. Ciertas condiciones deben existir para su realization: (a) hígado normal; (b) venas disponibles dentro del sistema porta; (c) suficiente gradiente en las presiones portosistémicas; y (d) disponibilidad de un equipo quirúrgico con experiencia en cirugía venosa portal. Otros medios de hemostasis de las várices esofágicas sangrantes deben ser utilizados en aquellos pacientes en quienes la hipertensión portal es un epifenómeno de enfermedad hepática severa. La decisión más difícil se presenta en el niño con alteraciones hepáticas específicas pero sin mayor disfunción hepatocelular en quien no se puede determinar con precisión el pronóstico. Todavía serán necesarios unos años más antes de poder afirmar que la cirugía derivativa representa la mejor escogencia para esta categoría de pacientes.

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Résumé La dérivation portale chez les enfants atteints d'hypertension portale constitue une méthode immédiate et définitive de prévention des hémorragies digestives récidivantes. Les conditions les plus favorables sont les suivantes: a) foie normal; b) veines disponibles dans le secteur porte pour l'anastomose; c) gradient de pression suffisant entre le système porte et le système cave et d) équipe entraînée à la chirurgie portale. Lorsque l'hypertension portale est un épiphénomène au cours d'une affection hépatique sévère, d'autres méthodes d'hémostase des varices oesophagiennes rompues doivent être envisagées. La décision du choix thérapeutique à adopter est difficile lorsqu'il existe une atteinte hépatique, sans altération hépatocellulaire majeure, mais de pronostic incertain à long terme. Quelques années encore seront nécessaires avant de pouvoir affirmer que la dérivation représente la meilleure opération pour traiter ce type d'hypertension portale.

     

Distinct immunopathological mechanisms of EBV-positive and EBV-negative posttransplant lymphoproliferative disorders

EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4⁺<300 cells/mm³, p <  .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm³) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.