Steroids in Duchenne muscular dystrophy--deflazacort trial

We conducted a double blind controlled trial in 28 Duchenne muscular dystrophy (DMD) patients with Deflazacort (DF), an oxazoline derivative of prednisolone which reduces its side-effects. Myometric muscle strength measurements, Scott Score and timed tests showed statistically significant improvement for the treated group (P less than 0.05). Side-effects after 9 months of treatment included mild cushingoid appearance in four patients (28%) and moderate in only one (7%), increased appetite in seven (50%), increased body hair in four (28%), irritability and hyperactivity in three (21%). Increased body weight was not prominent and was controlled with dietary measures. No patient had to be withdrawn from medication. More research and long-term follow-up are needed in order to establish the mechanism of improvement and the consequences of long-term steroid administration in DMD. In this regard DF appears as an alternative to prednisone preserving its benefits but with fewer side-effects.     

Adrenal steroids and the physiopathology of a subset of depressive disorders.

Patients suffering from Cushing's disorders (syndrome and disease) are significantly affected by psychological disturbances that overlap with depressive disorders. In turn, a subset of patients with affective disorders present with hypercortisolemia, and non-suppression in the Dexamethasone Suppression Test (DST). We have shown that long-term potentiation (LTP), a putative memory mechanism, is significantly affected by steroids when tested on the hippocampus, a crucial structure for memory processes. We propose that an imbalance of adrenal steroids and their metabolites, interacting at the level of the hippocampus, play a fundamental role in the psychophysiopathology of Cushing's and depressive disorders. By biasing memory mechanisms, the imbalance of these hormones sets both distorted mood, and hence memory contents, and distorted cognition based on recollection and present experiences.     

Duchenne muscular dystrophy and myotonic dystrophy in the same patient

We report on the first patient identified with myotonic dystrophy and Duchenne muscular dystrophy (DMD). The family of the propositus had a strong history of myotonic dystrophy, and there was an intrafamilial pathological expansion of the responsible CTG repeat between the mildly affected mother (160 repeats; normal 27 repeats) and her more severely affected son (650 repeats), and his sister (650 repeats). The propositus was an isolated case of Duchenne muscular dystrophy with marked dystrophin deficiency in muscle biopsy. The patient was still ambulatory post age 16. Myotonic dystrophy could interfere to some extent with the progression of Duchenne dystrophy. However, other interpretations are possible. Twelve percent of dystrophin revertant fibers as observed by immunohistochemistry could be sufficient to ameliorate typical DMD clinical severity, or the patient may present a somatic mosaic. The pathophysiological interactions of these two unlinked disorders are discussed at the clinical and histopathological levels. © 1995 Wiley-Liss, Inc.     

Ovarian tissue grafting: Lessons learnt from our experience with 55 grafts

Purpose

Uncertainties remain regarding the clinical efficacy of ovarian tissue cryopreservation and grafting. We report a retrospective analysis of reproductive outcomes and lessons learnt following 55 ovarian tissue transplant procedures at our center from 2006 to 2019.

Methods

We analyzed variables related to graft success such as tissue volume, follicular density, total follicular volume, and age on the duration of graft function.

Results

Follicular density and total follicular volume correlate positively with duration of graft function. All clinical pregnancies in our cohort occurred in women who were aged 35 or less at the time of ovarian tissue cryopreservation.

Conclusion

Graft success, as determined by eventual pregnancy and the longevity of graft function, may be impacted by factors including age at cryopreservation, follicular density, and total follicular volume.

     

The Diagnosis of Concussion in Pediatric Emergency Departments: A Prospective Multicenter Study

Background

The accurate identification of children with a concussion by emergency physicians is important to initiate appropriate anticipatory guidance and management.

The specificity of stress responses to different nocuous stimuli: neurosteroids and depression

The role that adrenal cortex and neurosteroid hormones may have in the etiology and/or maintenance of depressive diseases is discussed. Selye's concept of stress as the summation of unspecific body responses of the autonomic central nervous system (CNS) and hypothalamic pituitary adrenal axis (HPAA) as the main characteristic of it is contrasted with Mason's view of stress responses as being specific for different stimuli, i.e., the neuroendocrine system responds with the production of a hormonal profile individualized and characteristic for the various stimuli applied. The data reviewed provides support for Mason's interpretation of stress as fundamentally a behavioral response. In turn, the high relevance of emotional factors in the determination of stress responses led to a reconsideration of cognitive-affective interactions in nervous systems. Recent results revealed that improvement in depression treated with antidepressants (ADs) is associated with an increase in the neurosteroid 3alpha 5alpha tetrahydroprogesterone, both in the blood and cerebrospinal fluid of recovered patients. The increase occurs with both selective serotonin reuptake inhibitors and tricyclic ADs. An evaluation of the possible and putative roles for neurosteroids in the CNS is presented and suggestions for enhancing the type of supporting data from the laboratory diagnosis of depressions are advanced.     

Cytogenetic analysis of the spontaneous murine B-cell leukemia (BCL1

Cytogenetic studies were carried out on the spontaneous transplantable murine B cell leukemia (BCL₁) of BALB/c mice, a recently discovered model of chronic lympholytic leukemia. BCL₁ tumor cells appear as medium to large size mature lymphocytes located predominantly in the blood (up to 500,000/mm³) and in the x50 enlarged spleen. BCL₁ cells obtained from the spleen show a certain degree of spontaneous proliferation unlike peripheral blood lymphocytes (PBL), but both show a good in vitro response to the B-cell mitogen lipopolysaccharide (LPS). Out of 213 spontaneously dividing spleen cells and LPS stimulated PBL studied, the majority (75.5%) showed a rather stable and complex female karyotype consisting of 36 chromosomes. No normal representative of chromosome Nos. 6, 8, 12 and 15 was present and only one normal representative was found for chromosome Nos. 4, 5, 9, 14 and X. Two deleted chromosomes and seven characteristic marker chromosomes, originating from complex chromosomal rearrangements could be identified in each cell. Of special interest was the t(12:15) translocation, which had been found in several murine plasmacytomas. No direct correlation between the chromosomal changes and the phenotypic characteristics of BCL₁ tumor cells could be made. However, the highly specific karyotype may serve as a useful marker in identifying single BCL₁ tumor cells.     

Steroids, neuroactive steroids and neurosteroids in psychopathology

The term "neurosteroid" (NS) was introduced by Baulieu in 1981 to name a steroid hormone, dehydroepiandrosterone sulfate (DHEAS), that was found at high levels in the brain long after gonadectomy and adrenalectomy, and shown later to be synthetized by the brain. Later, androstenedione, pregnenolone and their sulfates and lipid derivatives as well as tetrahydrometabolites of progesterone (P) and deoxycorticosterone (DOC) were identified as neurosteroids. The term "neuroactive steroid" (NAS) refers to steroids which, independent of their origin, are capable of modifying neural activities. NASs bind and modulate different types of membrane receptors. The GABA and sigma receptor complexes have been the most extensively studied, while glycine-activated chloride channels, nicotinic acetylcholine receptors, voltage-activated calcium channels, although less explored, are also modulated by NASs. Within the glutamate receptor family, N-methyl-d-aspartate (NMDA) receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and kainate receptors have also been demonstrated to be a target for steroid modulation. Besides their membrane effects, once inside the neuron oxidation of Ring A reduced pregnanes, THP and THDOC, bind to the progesterone intracellular receptor and regulate gene expression through this path. The involvement of NASs on depression syndromes, anxiety disorders, stress responses to different stress stimuli, memory processes and related phenomena such as long-term potentiation are reviewed and critically evaluated. The importance of context for the interpretation of behavioral effects of hormones as well as for hormonal levels in body fluids is emphasized. Some suggestions for further research are given.     

Ovarian response to gonadotropin stimulation in repeated IVF cycles after unilateral salpingectomy

Purpose : This study aimed to examine ovarian response to gonadotrpoin stimulation after repeated IVF treatment cycles in patients who underwent previous unilateral salpingectomy for tubal pregnancy. Methods : The study group included 26 patients who underwent unilateral salpingectomy for tubal pregnancy 1–9 years prior to starting IVF treatment. A control group of 52 patients with anatomically intact pelvis was treated during the same time period by ICSI. The two groups were matched for age, number of gonadotropin ampules, and length of stimulation. End point measurements included number of follicles, oocytes, and cleaved embryos in consecutive treatment cycles of each group. Results : There were 98 cycles in the study group and 154 cycles in the control group. The mean number of follicles, retrieved oocytes, and cleaved embryos were not different in the two groups, and no reductions in these parameters were noted up to 10 cycles of treatment. The mean number of follicles ipsilateral to the operated side was similar to the number of follicles of the contralateral ovary and was not different whether salpingectomy was by laparoscopy or laparotomy. Conclusions : Unilateral salpingectomy does not affect ipsilateral ovarian response to gonadotropin stimulation even after repeated IVF treatment cycles.