Death of an apprentice bodybuilder following 2,4-dinitrophenol and clenbuterol intake.

We present the case of a 17-year-old man, who died after 2,4-dinitrophenol (DNP) and clenbuterol consumption, which he likely took for physical enhancement. Forensic post-mortem examination revealed a yellowish skin colour and nonspecific signs of asphyxia. Analytical confirmation of the intoxication was obtained in blood and urine, with high levels of DNP and clenbuterol. Both of these substances are used by bodybuilders as DNP enhance lipolysis and clenbuterol has anabolic properties, but their toxicity is underestimated. DNP uncouples oxidative phosphorylation, leading to thermogenesis and even relatively small doses can cause fatal hyperthermia. Clenbuterol is a ß2 agonist that causes electrolyte disturbances (hypokalemia and hyperglycemia mostly) and death have been described through coronary vasospasm. Given the circumstances in which the body was found and toxicological results, we believe the cause of death to be fatal hyperthermia from DNP intake. These substances are illegal in many countries, but easily bought online. Through this availability, the last decades have seen an increase of fatal intoxications. Websites selling them are regularly closed by French public authorities and Interpol, but unfortunately it seems insufficient.

Is the pterygopalatomaxillary suture (sutura sphenomaxillaris) a growing suture in the fetus?

The pterygopalatomaxillary suture is considered as having an important role in the posteroanterior growing of the maxilla. To determine whether this suture is a growing suture in the fetus, we performed a histological study of this suture in a fetus aged of 16 weeks of amenorrhea. Serial sections (5 microm) of the pterygopalatomaxillary suture area have been performed. Fibrous sutures are separating four pieces of ossification (maxilla, palatine bone, lateral and medial plates of the pterygoid process). A fibroblastic growing site has been observed on the dorsal aspect of the pterygopalatomaxillary suture, in contact to the anterior border of the lateral plate of the pterygoid process. The posteroanterior growing of maxilla is dependent on a growing suture located on the anterior border of the pterygoid process. The pterygoid process (via its lateral plate) makes the junction between the maxilla and both the cranial base and the condylar mandibular site of growth.

Reversible meiotic abnormalities in azoospermic men with bilateral varicocele after microsurgical correction.

Because of a possible relationship between microenvironmental disturbances and meiotic abnormalities and of a straight relationship between lower-quality semen in patient carrying a varicocele and first meiotic non-disjunction, bilateral bipolar testicular biopsies are realized according the thermic differential gradient described in varicocele. Systematic meiotic studies of multiple testicular biopsies from 65 azoospermic men with bilateral varicocele were done in a multi-centric study on microsurgical correction of bilateral varicocele with microthermic intra-operative evaluation using minimally invasive thermal microsensors (Betatherm 10K3MCD2). In the present study abnormal temperature raising, histomorphometric abnormalities (spermatocyte arrest) and meiotic abnormalities (class IIC) are strongly correlated. In the ten patients submitted to another testicular biopsy procedure six months after surgery for TESE, normal thermal differential is registered and no meiotic abnormalities recurrences are found.

High-intensity focused ultrasound in the treatment of postpartum hemorrhage: an animal model.

OBJECTIVE: To investigate the use of high-intensity focused ultrasound (HIFUS) to reduce uterine artery blood flow in ewes in the postpartum period. METHODS: HIFUS was applied to the uterine arteries of seven ewes in the postpartum period. Arterial flow velocities were measured before and after the procedure at the site of HIFUS application (target), as well as 3 cm upstream and 3 cm downstream from the target. The uterine arteries were then removed for macroscopic and histological examination. RESULTS: Maximum flow velocities in the target area increased after the procedure by 350% and those upstream from the target decreased by 65%. Macroscopically, the vessel diameter was shown to have reduced at the site of HIFUS application. Microscopically, both the endothelium and media showed thermal lesions. Tissues surrounding the arteries were macroscopically and microscopically normal. CONCLUSION: Exposure of uterine arteries to HIFUS reduces the vessel diameter and thus induces a dramatic increase in the maximum flow velocities within the target area. HIFUS may have a role in the treatment of postpartum hemorrhage.

Sequential expression of genes involved in muscular dystrophies during human development.

To elucidate the normal and pathophysiological roles of genes involved in the aetiology of muscular dystrophies, we studied the expression of dystrophin, four sarcoglycans, beta-dystroglycan and merosin during early human development. These proteins are expressed mainly in skeletal muscles while dystrophin, beta-dystroglycan, delta-sarcoglycan and merosin are in cardiac and smooth muscles. Dystrophin, beta-, delta-sarcoglycan and beta-dystroglycan are first expressed in the myotome at the 4th week of human embryogenesis, followed by gamma-sarcoglycan and merosin at the 6th week of development; alpha-sarcoglycan appears only at the level of the muscular fibre at the end of the embryonic period.

[The persistence of ontogenic characteristics in the adult masseter muscle]. / Persistance de caractères ontogéniques dans le muscle masséter adulte.

During embryonic and foetal development, the masseter is formed from two successive generations of muscle fibers in a manner which is very similar to that which has been previously described for other skeletal muscles. This phenotype is characterised by the persistence of ontogenic myosin isoforms (embryonic and foetal myosin heavy chains, embryonic light chain) and by the presence of two distinct populations of fibers: small diameter fibers which coexpress the embryonic, foetal and fast isoforms of the myosin heavy chains but never express the slow isoform; large diameter fibers which express the slow myosin heavy chain either exclusively or in variable associations with the other isoforms. These characteristics of the human masseter muscle probably correspond not only to its embryological origin and its special innervation, but also to the functional constraints to which it is submitted after birth.

Defective satellite cells in congenital myotonic dystrophy.

In this study we have developed an in vitro cell culture system which displays the majority of the defects previously described for congenital myotonic dystrophy (CDM) muscle in vivo. Human satellite cells were isolated from the quadriceps muscles of three CDM fetuses with different clinical severity. By Southern blot analysis all three cultures were found to have approximately 2300 CTG repeats. This CTG expansion was found to progressively increase in size during the proliferative life span, confirming an instability of this triplet in skeletal muscle cells. The CDM myoblasts and myotubes also showed abnormal retention of mutant RNA in nuclear foci, as well as modifications in their myogenic program. The proliferative capacity of the CDM myoblasts was reduced and a delay in fusion, differentiation and maturation was observed in the CDM cultures compared with unaffected myoblast cultures. The clinical severity and delayed maturation observed in the CDM fetuses were closely reflected by the phenotypic modifications observed in vitro. Since the culture conditions were the same, this suggests that the defects we have described are intrinsic to the program expressed by the myoblasts in the absence of any trophic factors. Altogether, our results demonstrate that satellite cells are defective in CDM and are probably implicated in the delay in maturation and muscle atrophy that has been described previously in CDM fetuses.

[Fetal development and postnatal maturation of the longus colli muscle]. / Développement foetal et maturation postnatale du muscle longus colli.

In adults, the predominant expression of a slow phenotype in the m. longus colli corresponds to its important postural function. Morphologically, there is a dispersion in fiber size predominating on the fast type 2 fibers which are significantly smaller than the slow type 1 fibers. We deemed it of interest, therefore, to analyze the metabolic differentiation of the muscle longus colli during its development. This study has been carried out on six anatomical samples, in foetuses aged between 16 and 40 weeks of pregnancy and in an 18 month-old child. The histological study combined H&E staining and immunohistochemical techniques (using antibodies specific for the slow and the fast isoforms of the myosin heavy chains). Our results indicate that the m. longus colli differentiates during the foetal period in a way which is quite comparable to that of other skeletal muscles, such as the quadriceps. In this series, a major slow predominance with a significant dispersion in fiber size was first observed in the 18 month-old child. Thus, it can be concluded that the establishment of the adult phenotype of this muscle starts during postnatal life, following the development of the mechanisms holding up the head and neck and leading to the appearance of the cervical lordosis.

[Metabolic differentiation of the human longus colli muscle]. / Différenciation métabolique du muscle longus colli chez l'Homme.

The cervical muscles have a dual postural and dynamic function, in order to ensure both the stability and the motility of the cervical spine. The functional duality together with the complexity of the cervico-cephalic system render the study of the cervical muscles difficult, and their physiology is not fully understood in humans. This study has been carried out on ten samples from the m. longus colli, taken during a surgical procedure in patients aged between 36 to 62 years. The histological study combined enzyme histochemical (ATPases) and immunohistochemical techniques (using antibodies specific for the slow and the fast isoforms of the myosin heavy chains). Our results indicate that, in all cases, the m. longus colli is composed of muscle fibers with peripheral nuclei and with a relative dispersion in size. Histochemically, the type 1 and type 2 fibers express exclusively either the slow or the fast myosin heavy chain. From a quantitative point of view, the proportion of the slow fibers varies between extreme values of 30 and 73%; in addition, the dispersion in fiber size predominates on the fast type 2 fibers which are smaller than the slow type 1 fibers. Thus, most of the muscles that we have studied have histologically a slow predominance. This predominant expression of a slow phenotype in the m. longus colli corresponds to its important postural function, in addition to its phasic role during the flexion of the cervical spine.

[Appearance of the branchial system in cervicofacial embryology]. / A propos de la notion d'appareil branchial en embryologie cervico-faciale.

The aortic arch, vascular component of the branchial segment, is considered as its determining element. This is only justified in the conception of a branchial primordium, although this has now been discarded. The direct objections against this theory of a vascular preeminence are presented. Therefore, a revision of cervicofacial morphogenesis (formations cranial to the mandibular arch) is mandatory, based on somitomeres, neural systematization, evidence obtained from heterograft experiments and genetics, allowing to recognize in the "branchial" organization its proper somatic participation. The repartition of elements deriving from the para-axial in the "branchial" segmentation suggests that both types of segmentation represent two coordinate expressions of a single process.

Anatomical and sonographical studies on the development of fecal continence and sphincter development in human fetuses.

The aim of this study was to specify the sonographic, anatomical and morphological aspects of the fetal anal sphincter and to compare them with pathological and physiological findings. The sphincter was examined by serial sectioning and staining of embryo and fetal tissue and by real-time ultrasound. Its function was analysed using amniotic fluid digestive enzyme assays in cases of anorectal atresia and cystic fibrosis. Morphological findings indicate that the functional components of the anal sphincter do not differentiate before 30 weeks and therefore do not account for the observed anal continence at 22 weeks. Ultrasound measurements of the sphincter indicate three developmental phases: 1) slow growth from 14 to 19 weeks; 2) rapid growth from 19 to 30 weeks; 3) subsequently, no further increase, but contractions indicative of peristaltism. Amniotic fluid digestive enzyme assays indicate that anal sphincter maturation begins with perforation of the anal membrane at 12 weeks. Comparison of pathological cases (anorectal atresia and cystic fibrosis) suggests two possible explanations of fetal anal obstruction: increasing viscosity of digestive secretion or the presence of the three anal sphincter muscles, even if still immature. Our results clarify the evacuation and retention of meconium during fetal life and the role of the terminal part of the digestive tract, notably the anal sphincter. Prenatal diagnosis of anorectal atresia is therefore possible before 20 weeks of gestation by measurement of amniotic fluid digestive enzymes and ultrasonography, thus enabling better neonatal management.

[The first appearance of Meckel's cartilage in the fetus]. / Le cartilage de Meckel au début de la période foetale.

Meckel's cartilage plays an important role in the topographical organisation and in the differentiation of the facial structure during the embryonal and even much later during the foetal period. Our observations on serial sections carried out in two human foetuses aged 12 and 16 weeks indicate that the two dorsal (tympanic) and ventral (mandibular) branches of Meckel's cartilage are perfectly defined at 16 weeks. In the dorsal branch, the primordia of the incus and of head of the malleus are still composed on non-ossified cartilage. In the ventral branch, it is also possible to describe at 16 weeks three posterior, medial and anterior parts which are composed of cartilage. The initiating role played by the ventral part of Meckel's cartilage on the ossification of the mandible leads during the embryonal period to the formation of the mandibular primary growth center, which is therefore clearly defined in our first stage at 12 weeks. The partial fibrous evolution and the regression of the major part of the ventral branch of Meckel's cartilage only start after 16 weeks of intrauterine life.

Shorter telomeres in dystrophic muscle consistent with extensive regeneration in young children.

Muscular dystrophies are characterised by continuous cycles of degeneration and regeneration resulting in an eventual diminution of the muscle mass and extensive fibrosis. In somatic cells chromosomal telomeres shorten with each round of cell division and telomere length is considered to be a biomarker of the replicative history of the cell. We have previously shown that human myoblasts have a limited proliferative capacity, and that normal skeletal muscle has a very low level of nuclear turnover. However, in patients suffering from muscular dystrophy the satellite cells will be forced to make repeated rounds of cell division, driving the cells towards senescence. In this study we have used the telomere length to quantify the intensity of the muscle cell turnover in biopsies from dystrophic patients of different ages. Our results show that as soon as the first clinical symptoms become apparent the muscle has already undergone extensive regeneration and the rate of telomere loss is 14 times greater than that observed in controls. This confirms that the decline in regenerative capacity is due to the premature senescence of the satellite cells induced by their excessive proliferation during muscle repair.

[Dorso-ventral gradient of maturation for puborectalis muscle]. / Gradient dorso-ventral de maturation du muscle puborectalis.

Foetal maturation of the skeletal fibers in the anorectal sphincter and in the vesico-urethral sphincter follows a dorso-ventral gradient, in parallel with the development of their motor innervation. The anatomical situation of the m. puborectalis, which early development plays an important role in the establishment of the foetal anal continence, suggests that this muscle should also be submitted to this gradient. We have studied in parallel the development of both the ventral and the dorsal parts of the m. puborectalis in human foetuses aged between 19 and 40 weeks of pregnancy. The results indicate that the transversal thickness of the muscle increases progressively during pregnancy, with a dorsal part being always thicker than the ventral one. More interestingly, the increase in the diameter of the muscle fibers becomes significantly more important at the level of the dorsal part between 25 and 40 weeks of pregnancy. This last result confirms the existence of a dorso-ventral gradient of growth and maturation of the m. puborectalis, as part of the global mechanisms involved in the development of the striated musculature of the pelvic organs.

[Growth of spinal muscles in the human fetus]. / Croissance des muscles spinaux chez le foetus humain.

The spinal muscles, located in the paravertebral region, derive embryologically from the medial part of the somites. It has been shown in different animals that their differentiation occurs within the somite itself following the action of diffusible factors of chordal, neural and epiblastic origin. In these animal species, it thus appears that several factors determine the potential of migration as well as the muscular specification of the somitic cells. In 13 human foetuses, aged from 12 to 40 weeks of pregnancy, without any neuro-muscular disorder, transversal sections of both the vertebral and the paravertebral regions have been made at the level of the thorax and of the abdomen. Following rapid fixation, decalcification and paraffin embedding, semi-serial histological sections of 10 microns have been stained with H&E or Masson's trichrome and examined under light microscopy. Our results confirm that the primordia of the spinal muscles are present before the end of the embryonic period proper. The main modifications observed during foetal life concern the overall growth of the muscular mass, with a neat preeminence of the lombar region after 18 weeks. The differentiation of the individual muscle fibers is similar to that observed in other territories in the developing organism, with a craniocaudal gradient of maturation. Thus, if myogenic specificities really exist in the medial part of the somites in humans, it is likely that they concern the initial mechanisms involved in the activation of the myogenic program and not the mechanisms leading to the subsequent differentiation and growth of the fibres.

[Intrication of smooth and striated muscle during the development of the ano-rectal sphincter]. / Intrication de muscle lisse et de muscle strié au cours du développement du sphincter ano-rectal.

The development of the foetal anorectal continence is related to the appearance of the anatomical components of the sphincter. The present study has been carried out in order to analyse the development of the smooth and striated components of the anorectal sphincter, in a series of 7 embryo and foetuses aged from 10 to 40 weeks of pregnancy. Our results indicate that the external sphincter, the puborectalis muscle and the internal sphincter are present before 24 weeks, although they obviously play variable roles in the establishment of the foetal continence. The internal sphincter becomes quantitatively important after 14 weeks, and is likely to be responsible for the establishment of the initial continence. The growth of the striated components during the foetal period corresponds to the maturation of the innervation and of the voluntary mechanisms controlling continence. Intrication of smooth and striated muscle components in the external sphincter starts after the end of the embryonic period. All the anatomical components of the anorectal sphincter are present at birth.

45,X/46,XY mosaicism: report of 27 cases.

OBJECTIVES: There exist substantial differences between prenatally and postnatally diagnosed cases of 45,X/46,XY mosaicism. Ninety percent of prenatally diagnosed cases show a normal male phenotype, whereas the postnatally diagnosed cases show a wide spectrum of phenotypes. This 10% risk of an abnormal outcome in prenatally diagnosed cases requires further attention. The purpose of the present study is to provide more information on the postnatally diagnosed 45,X/46,XY mosaicism cases. To date, only a few series have been reported. An accurate diagnosis in these patients is essential not only to their follow-up, but also to providing appropriate genetic counselling and subsequent prenatal diagnosis to their parents. METHODS: The clinical, cytogenetic, endocrinologic, histologic and molecular biological findings of 27 patients with 45, X/46,XY mosaicism are analyzed. RESULTS: The reported cases showed a wide spectrum of phenotypes as Turner syndrome, mixed gonadal dysgenesis (MGD), male pseudohermaphroditism (MPH) and apparently normal male. However, Ulrich-Turner stigmata were the most common features found in this series. Patients with MGD or MPH presented with various degrees of sex reversal such as hypospadias and/or abnormal internal genitalia. No correlation between the proportion of the 45,X/46,XY cell lines in the blood or the fibroblasts and the phenotype was found. Mild mental retardation was present in 4 of the patients and 2 patients showed signs of autism. CONCLUSIONS: Two major points are emphasized in this series: 1) the presence in 7 histologically analyzed streak gonads of a homogeneous 45,X chromosomal complement suggests that the invasion of the primitive genital ridge by a such a cell line may induce abnormal gonadal development; 2) 3 males, apparently normal at birth, developed late onset abnormalities such as dysgenetic testes leading to infertility, Ulrich-Turner stigmata, dysmorphic features, and mild mental retardation. These data indicate the importance of an accurate clinical and histologic evaluation of any patient presenting with 45, X/46,XY mosaicism.

Temporomandibular region in the Franceschetti's Syndrome. Anatomical study.

Franceschetti's syndrome is a rare, non-fatal, hereditary malformation, usually bilateral, which symmetrically affects orbits, mandible and ear. The authors propose an anatomical description of the temporomandibular region after the dissection of a newborn baby suffering from Franceschetti's Syndrome, dead soon after the birth. A discussion on the different etiopathogenical theories is made. The authors conclude that an alteration of the development of nerve trigeminal branches is the cause of the malformations.

The four populations of myoblasts involved in human limb muscle formation are present from the onset of primary myotube formation.

To understand how and when myogenic precursor cells become committed to their particular developmental programs, we have analysed the different populations of myoblasts which grow out from explants of muscle tissue isolated from human limb buds from the beginning of primary fibre formation throughout subsequent development and post-natal growth. Four phenotypically distinct types of myoblasts were identified on the basis of their expression of desmin, myogenin and myosin heavy chain isoforms (MyHC), and after 5 and 20 divisions, cells were cloned. All four types of myoblasts were present at the beginning of primary myogenesis. Each respective phenotype was stably heritable through cloning and subsequent proliferation. The type 1 clones correspond to a novel class of myoblasts never described during human development, that biochemically differentiates, but does not fuse. Type 2 clones are composed of small myotubes expressing only embryonic MyHC. Type 3 clones are composed of thin and long myotubes expressing both embryonic and fetal MyHCs. The type 4 clones are composed of myotubes that have a phenotype very similar to human satellite cells. Contrasting with others species, no other population of myoblasts appear during fetal development and only the relative number of these four types changes.

Effect of metronidazole resistance on bacterial eradication of Helicobacter pylori in infected children.

A prospective study was performed with 23 Helicobacter pylori-infected children (mean age, 9.5 +/- 4.4 years) with clinical symptoms of gastritis and positive results of culture and histologic examination of gastric biopsy specimens to evaluate the influence of antibiotic resistance on eradication. Positive children were treated for 4 weeks with lansoprazole and for 2 weeks with either amoxicillin-metronidazole or spiramycin (a macrolide)-metronidazole. At endoscopy 1 month after the discontinuation of therapy, the eradication rate and improvement of histologically related gastritis were significantly dependent on the susceptibility or the resistance of the infecting organism to metronidazole (83 versus 17% and 88 versus 16.6%, respectively). Pretreatment determination of the susceptibility is appropriate in any anti-H, pylori regimen, including one with metronidazole.