Treatment of acute lymphoblastic leukaemia.

In acute lymphoblastic leukaemia the combination prednisone-vincristine induces more than 85% complete remissions. L-asparaginase which was used in complete remissions, seemed to increase their duration. Actually the best maintenance treatment consists in the combination of 6-mercaptopurine and methotrexate interrupted by reinductions. In other respects C.N.S. prophylaxis with intrathecal methotrexate and craniospinal irradiation is necessary. The well-known prognostic factors are: age, leucocytosis, tumoral syndrome, and cytological type: 216 cases of long remission have been observed. One group of these patients was treated by old methods: this represents 0.8 to 1% of the material, while 20% were treated by recent protocols with reinductions (20%).     

Quantitative analysis of the velocity characteristics of optokinetic nystagmus and optokinetic after-nystagmus

1. Velocity characteristics of optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN) induced by constant velocity full field rotation were studied in rhesus monkeys. A technique is described for estimating the dominant time constant of slow phase velocity curves and of monotonically changing data. Time constants obtained by this technique were used in formulating a model of the mechanism responsible for producing OKN and OKAN.2. Slow phase velocity of optokinetic nystagmus in response to steps in stimulus velocity was shown to be composed of two components, a rapid rise, followed by a slower rise to a steady-state value. Peak values of OKN slow phase velocity increased linearly with increases in stimulus velocity to 180 degrees /sec. Maximum slow phase eye velocities in the monkey are 2-3 times as great as in humans.3. At the onset of OKAN, slow phase velocity falls by about 10-20%, followed by a slower decline to zero. Peak OKAN slow phase velocities were linearly related to optokinetic stimulus velocities up to 90-120 degrees /sec. Above 120 degrees /sec OKAN slow phase velocity saturated although OKN slow phase velocity continued to increase.4. The charge and discharge characteristics of OKAN were studied. The OKAN mechanism charged in 5-10 sec and discharged over 20-60 sec in darkness. The time constants of decay in OKAN slow phase velocity decreased as stimulus velocities increased. They also decreased on repeated testing. In several monkeys there was a consistent difference in the rate of decay of OKAN slow phase velocity to the right and left.5. Extended visual fixation discharged the activity responsible for producing OKAN. Short fixation times caused only a partial discharge of the OKAN mechanism. Following brief periods of fixation, OKAN resumed but with depressed slow phase velocities.6. A model based on a state realisation of a peak detector was formulated which approximately reproduces the salient characteristics of OKN and OKAN. This model predicts the three dominant characteristics of OKAN: (1) charge over 5-7 sec, (2) slow discharge in darkness, and (3) rapid discharge with visual fixation. With the addition of direct fast forward pathways, it also correctly predicts the rapid and slow rise in OKN. We postulate that OKAN is produced by a central integrator which is also active during OKN. Presumably this integrator acts to maximize velocities during OKN and to smooth and stabilize ocular following during movement of the visual surround.     

Seasonal variation of mixed and pure episodes of bipolar disorder

BACKGROUND: Although seasonal patterns of manic episodes have been reported, the seasonal variation of mixed states of bipolar disorder has received little attention. In the current report we address that concern as well as the overall seasonality of manic episodes. METHODS: The seasonal pattern of 304 psychiatric hospital admissions for treatment of mixed or manic bipolar episodes over a 3-year period were analyzed employing two definitions of mixed manic states: DSM-III-R and an ROC derived definition. RESULTS: The frequency of all manic episodes combined peaked in early spring, with a nadir in late fall. Pure manic admissions showed a similar pattern. Mixed manic admissions had a significantly different pattern, with a peak in late summer and a nadir in November. The differences between pure and mixed manic admissions were demonstrated with the use of the ROC definition for mixed states. LIMITATIONS: Effects of medications and medication non-compliance may dampen natural seasonal patterns of episodes. CONCLUSIONS: The different seasonal pattern of mixed and pure manic episodes support the separation of mixed episodes as a distinct clinical subtype.     

Impact of a patient education program on adherence to HIV medication: a randomized clinical trial

Patients' knowledge of their HIV condition and its treatment, which has been recognized as a factor that influences adherence to antiretroviral therapy, can be improved through educational programs. This prospective, randomized, controlled trial compared an experimental group that participated in an educational program and a control group with standard care. The study evaluated the impact of an educational intervention on adherence to antiretroviral therapy, patients' knowledge, quality of life, and therapeutic response in patients treated with highly active antiretroviral therapy. Three hundred twenty-six patients were analyzed at inclusion. A higher level of adherence was associated with patients who were older, had higher incomes, and did not smoke. CD4 cell count and plasma viral load were correlated with adherence at entry. The educational intervention had an impact on adherence and knowledge in the experimental group at 6 months, which was maintained at 12 and 18 months. A delayed increase in adherence was observed in the control group at 12 months. No significant impact on quality of life was observed over time. The patients' health status improved in 56% of the experimental group subjects and 50% of the control subjects. However, no significant impact was shown on CD4 cell count and plasma viral load. This study shows that an educational intervention improves adherence to antiretroviral regimens and health status and suggests that it should be initiated early in therapy.     

Linkage analysis of two Canadian families segregating for X linked spondyloepiphyseal dysplasia.

X linked spondyloepiphyseal dysplasia (SED) is caused by a growth defect of the vertebral bodies leading to characteristic changes in the vertebral bodies and a short trunk. The gene responsible for this disorder has previously been mapped to Xp22, with a maximum likelihood location between markers DXS16 and DXS92. We present linkage data using microsatellite markers on two Canadian X linked SED families, one of Norwegian descent and the other from Great Britain. In the Xp22 region, three recombination events have occurred in these families, two between markers DXS996 and DXS1043 and one between DXS999 and DXS989. One family shows a maximal lod score of 3.0 at theta = 0 with marker DXS1043 and the other family has a maximal lod score of 1.2 at theta = 0 with markers DXS1224 and DXS418. Both families therefore support the previously reported gene localisation.     

Inhibition of Phagocytosis-Associated Chemiluminescence by Superoxide Dismutase

During the process of phagocytosis, human leukocytes emit a burst of luminescence which can be measured in a liquid scintillation spectrometer. The enzyme superoxide dismutase, which removes superoxide anions (O(2.)), inhibited this chemiluminescence by 70% at a concentration of 100 mug/ml. The enzyme did not inhibit phagocytosis. These results support other studies indicating that O(2.) is elaborated by phagocytizing leukocytes. They also indicate that O(2.) plays a major role in phagocytosis-associated chemiluminescence, though not necessarily as the luminescing agent. Catalase and benzoate inhibited the chemiluminescence of phagocytosis to a slight extent, suggesting that hydrogen peroxide and hydroxyl radical, respectively, might also be involved in this phenomenon. The relationship between the mediators of chemiluminescence and those responsible for phagocytic bactericidal activity remains to be defined.     

Tomo-anatomie hépatique. Introduction à l'écho-anatomie du foie normal

Résumé Ce travail tente de définir une écho-anatomie du foie normal à partir de neuf plans tomographiques de référence, chacun étant caractérisé par la morphologie de la glande hépatique, par son contenu structural et par son environnement topographique.Les auteurs interprètent l'imagerie échographique directement à partir de l'observation macroscopique de coupes anatomiques correspondantes. Ils indiquent que la corrélation anatomo-échographique est satisfaisante et dégagent quelques indications spécifiques pour chacune des incidences.     

Effect of hydrostatic pressure on ADH induced osmotic water flow in toad bladder

The effect of hydrostatic pressure (HP) on antidiuretic hormone (ADH) stimulated osmotic water flow (Jv) across the toad urinary bladder was evaluated. Jv for ADH-stimulated bladders was significantly reduced by an elevation of the serosal HP gradient to 1 cm H₂O. Subsequent elimination of the HP gradient resulted in a recovery of Jv. Serosal HP also caused a reversible increase in sucrose permeability (P sucrose). For ADH-treated bladders fixed with glutaraldehyde during serosal HP exposure, subsequent exposure to a mucosal or serosal HP gradient caused acceleration or inhibition of Jv, respectively. The reduction in ADH-associated Jv with serosal HP was apparently caused by a back-flux of water through a paracellular pathway. Jv and P sucrose were not affected by mucosal HP during ADH stimulation. The results suggest a specific sensitivity of a paracellular pathway to a small serosal HP gradient in bladders with ADH-stimulated water flow. The reversibility of this effect on P sucrose suggests that the elements comprising the apical junctions are dynamic structures capable of recovering at least some of their permeability properties.     

Synthesis and characterization of α-hydroxy, α-thiol and α-chloroformyl oligomers of poly(butylene terephthalate)

α-Hydroxy and α-chloroformyl oligomers of poly(butylene terephthalate) (PBT) were prepared in 1,1,2,2-tetrachloroethane by condensing terephthaloyl chloride and 1,4-butanediol and using benzoyl chloride and 4-hydroxybutyl benzoate as chain limitator. The average molecular weight was determined by ¹H NMR analysis, and thermal properties were assessed by differential scanning calorimetry (DSC). Preparation of α-thiol oligomers of PBT was also investigated by esterification of α-hydroxy oligomers with thioglycolic acid and using p-toluenesulfonic acid as catalyst. The DSC and TGA analyses pointed out that the introduction of a thiol group by esterification has no influence on the thermal properties of the PBT oligomers.     

A gene knockout approach in mice to identify glucose sensors controlling glucose homeostasis

A key aspect of glucose homeostasis is the constant monitoring of blood glucose concentrations by specific glucose sensing units. These sensors, via stimulation of hormone secretion and activation of the autonomic nervous system (ANS), regulate tissue glucose uptake, utilization or production. The best described glucose detection system is that of the pancreatic beta-cells which controls insulin secretion. Secretion of other hormones, in particular glucagon, and activation of the ANS, are regulated by glucose through sensing mechanisms which are much less well characterized. Here I review some of the studies we have performed over the recent years on a mouse model of impaired glucose sensing generated by inactivation of the gene for the glucose transporter GLUT2. This transporter catalyzes glucose uptake by pancreatic beta-cells, the first step in the signaling cascade leading to glucose-stimulated insulin secretion. Inactivation of its gene leads to a loss of glucose sensing and impaired insulin secretion. Transgenic reexpression of the transporter in GLUT2/beta-cells restores their normal secretory function and rescues the mice from early death. As GLUT2 is also expressed in other tissues, these mice were then studied for the presence of other physiological defects due to absence of this transporter. These studies led to the identification of extra-pancreatic, GLUT2-dependent, glucose sensors controlling glucagon secretion and glucose utilization by peripheral tissues, in part through a control of the autonomic nervous system.