Remission and Recovery in the Treatment for Adolescents With Depression Study (TADS): Acute and Long-Term Outcomes

ObjectiveWe examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS).MethodThe TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive–behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined whether residual symptoms at the end of 12 weeks of acute treatment predicted later remission.ResultsAt week 36, the estimated remission rates for intention-to-treat cases were as follows: combination, 60%; fluoxetine, 55%; cognitive–behavioral therapy, 64%; and overall, 60%. Paired comparisons reveal that, at week 24, all active treatments converge on remission outcomes. The recovery rate at week 36 was 65% for acute phase remitters and 71% for continuation phase remitters, with no significant between-treatment differences in recovery rates. Residual symptoms at the end of acute treatment predicted failure to achieve remission at weeks 18 and 36.ConclusionsMost depressed adolescents in all three treatment modalities achieved remission at the end of 9 months of treatment.     

Die Rolle der Zytokine bei Knorpeldefekten und in der Knorpeltherapie

Cytokines play a pivotal role in the pathogenesis of degenerative joint disease but also in inflammatory conditions as well as osteoarthritis (OA) and rheumatoid arthritis (RA). A key role is attributed to interleukin-1 and tumor necrosis factor-α. Certain cytokines that can inhibit the activity of catabolic cytokines have great therapeutic potential and are currently being investigated in numerous clinical studies. Available scientific findings indicate that proinflammatory cytokines stimulate cartilage breakdown and blockade of these cytokines can protect the cartilage.     

The growth of coronary artery branches in man under physiological conditions. Morphological studies of corrosion casts of the anterior interventricular branch of the coronary artery]

In corrosion casts of the left anterior descending coronary artery and its branches of higher order, the length, diameter, and number of branches were examined in 20 hearts, from 9 adults, 3 children, 4 new-born and 4 fetuses. We counted 5245 branches in total, thereof 147 branches in the corrosion casts of adult hearts were systematically analyzed, as were 46 branches of children's hearts, 55 branches of the new-born and 35 branches of the fetuses, respectively (left anterior descending coronary arteries and branches of 1st to 6th order). The length of the left coronary arteries and of their branches of 1st and 2nd order increases to almost the same degree as the linear measurements of the hearts. The left anterior descending coronary artery is about four times as long as the 1st order branches and these have twice the length of the 2nd order branches. These differences result from the divergent course of the branches. The results indicate that no significant increase in the number of the 1st to 3rd order branches of the coronary arteries occurs from birth to adulthood in human hearts. During the postnatal growth in human hearts there seems to be no remarkable neogenesis of coronary artery branches of greater diameter. Nearly all of them exist at birth and even in the late fetal period. Their length increases harmonically with the linear measurements of the heart and they become progressively separated. These findings parallel those obtained in a previous study in pigs.     

Neurotensin-like immunoreactivity in presumptive baroreceptor neurons innervating the guinea pig carotid sinus

This study was carried out to determine the ultrastructure and origin of previously described neurotensin-like immunoreactive (NT-LI) nerve fibres in the wall of the carotid sinus of the guinea pig. In our degeneration experiments, these NT-LI axons were unaffected by surgical sympathectomy but disappeared in response to transection of the carotid sinus nerve, thus suggesting a sensory origin. This assumption could be supported by combined retrograde tracing and immunohistochemistry. Primary afferent neurons of the sensory glossopharyngeal (petrosal) ganglion projecting to the carotid sinus were identified by injecting the retrograde fluorescent tracer, Fluoro-Gold, into the sinus wall, and some of these neurons displayed NT-LI. Within the carotid sinus, the terminals of these NT-LI sensory neurons exhibited ultrastructural features characteristic of baroreceptor endings, i.e. axonal swellings filled with mitochondria and closely associated to elastin. However, many endings also fulfilling the ultrastructural criteria for baroreceptors were devoid of immunolabelling. Thus, we conclude that the NT-LI terminals constitute a subgroup rather than the entire population of baroreceptor endings within the guinea pig carotid sinus. With respect to the established pharmacological effects of NT in guinea pig, we propose an involvement of NT-LI fibres in the modulation of baroreception at the peripheral level.     

Transfer of DDT used in malaria control to infants via breast milk.

The transfer of p,p'-DDT (1,1,1-tricholoro-2,2-bis(4-chlorophenyl)ethane) and its metabolites to infants via breast-feeding was studied in an area of KwaZulu, South Africa, where DDT is used to interrupt malaria transmission. Samples of whole blood were collected from 23 infants, together with samples of breast milk from their respective mothers. The mean sigma DDT (total DDT) in the whole blood was 127.03 micrograms.l-1 and that in the breast milk, 15.06 mg.kg-1 (milk fat). The % DDT (% DDT of sigma DDT) was significantly higher in the infant blood than in the breast milk (P less than 0.05). A multiplicative regression analysis indicated that sigma DDT increased significantly (P less than 0.01) in infant whole blood with infant age. Multiple regression showed that 70.0% of the variation in sigma DDT was due to the variation in parity of the mother, age of the infant, and the sigma DDT in breast milk. These variables accounted also for 76.3% of the variation in p,p'-DDE but only for 38.2% of that in p,p'-DDT. Organochlorines were therefore largely transferred to the infant from the mother, with DDT in the environment playing a secondary role.     

Ontogeny of the VIP system in the gastro-intestinal tract of the Axolotl,Ambystoma mexicanum: successive appearance of co-existing PACAP and NOS

Evidence for the presence and potential co-existence of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP) and nitric oxide synthase (NOS) in gastro-intestinal endocrine cells and/or nerve fibers is conflicting and very few results exist on development. This immunofluorescence study aims to clarify the appearance and localization of VIP, PACAP and NOS in the gastro-intestinal tract of the Axolotl, Ambystoma mexicanum, during ontogeny. VIP-immunoreactivity appeared in nerve fibers as early as on day 3 after hatching likely indicating a particular role, such as a trophic action, of VIP in very early development. PACAP-immunoreactivity was observed 3 days later within the VIP-immunoreactive (-IR) fibers. From this time on, VIP- and PACAP-immunoreactivity exhibited complete co-existence. VIP/PACAP-IR fibers were found throughout the gastro-intestinal tract. They were most prominent in the myenteric plexus and the muscle layers and less frequent in the submucosa. NOS-immunoreactivity appeared as late as at the 1st (64 days) juvenile stage in a subpopulation of the VIP/PACAP-IR fibers that contacted submucosal arteries. We found only very few VIP/PACAP-IR perikarya, indicating that part of the VIP/PACAP-IR fibers is of extrinsic origin. On day 12 and in the 1st and 2nd (104 days) juvenile stage, infrequent PACAP-IR entero-endocrine cells were noted, while neither VIP- nor NOS-immunoreactivity occurred in endocrine cells at any stage of development. The complete coexistence of neuronal PACAP- and VIP-immunoreactivities and their very early appearance in ontogeny may suggest important and coordinated roles of both peptides in the control of Axolotl gastro-intestinal activity, while the VIP/ PACAP/NOS-IR fibers may be involved in the regulation of submucosal blood flow.     

Electrophysiological transcortical diaschisis after middle cerebral artery occlusion (MCAO) in rats

Remote changes in brain function following stroke are called diaschisis. These remote effects may contribute to the neurological deficit following brain infarction; in addition they may lead to post-stroke epilepsy and affect functional recovery. In the present study we addressed the question of whether an increase in excitability can be observed contralateral to middle cerebral artery (MCA) infarction. Permanent occlusion of the middle cerebral artery (MCAO) was induced experimentally in rats with an intraluminal silicon-coated filament. Seven days later, brain excitability was tested with extracellulare recording techniques in neocortical coronal brain slices using a paired-pulse stimulus protocol. In rats with MCAO, excitability was increased in the neocortex contralateral to the infarction compared with the control group. These alterations extended through wide parts of the contralateral neocortex. The study demonstrates that MCAO causes transcallosal electrophysiological diaschisis. Together with results obtained previously with photothrombotic cortical lesions, it can be concluded that these remote effects are not due to characteristics of the individual lesion model, but are common consequences of brain lesions.     

Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioral responses of the rat

Using immunohistochemistry evidence was obtained for the coexistence of calcitonin gene-related peptide (CGRP)- and substance P (SP)-like immunoreactivity in spinal sensory neurons. Analysis of caudally directed biting and scratching (CBS) behavior was carried out after intrathecal administration of CGRP and SP alone or in combination. Thus, SP (up to 20 micrograms) alone caused CBS only for a few minutes after injection, whereas SP (10 micrograms) plus CGRP (20 micrograms) caused a response with a duration up to 40 min. CGRP (20 micrograms) alone had no effects in this model. These findings provide support for a possible interaction of the two peptides at synapses in the dorsal horn of the spinal cord.