Rats genetically selected for low and high aerobic capacity exhibit altered soleus muscle myofilament functions.

Aerobic exercise capacity is critical to bodily health. As a model to investigate the mechanisms that determine health and disease, we employed low (LCR) and high (HCR) capacity running rat models selectively bred to concentrate the genes responsible for divergent aerobic running capacity. To investigate the skeletal muscle contribution to this innate difference in running capacity we employed an approach combining examination of the myofilament protein composition and contractile properties of the fast fiber extensor digitorum longus (EDL) and slow fiber soleus (SOL) muscles from LCR and HCR rats. Intact muscle force experiments demonstrate that SOL, but not EDL, muscles from LCR rats exhibit a three times greater decrease in fatigued force. To investigate the mechanism of this increased fatigability in the LCR SOL muscle, we determined the myofilament protein composition and functional properties. Force-Ca2+ measurements demonstrate decreased Ca2+ sensitivity of single skinned SOL muscle fibers from LCR compared with that of HCR rats. Segregating SOL fibers into fast and slow types demonstrates that the decreased Ca2+ sensitivity in LCR SOL results from a specific decrease in slow-type SOL fiber Ca2+ sensitivity such that it was similar to that of fast-type fibers. These results identify that the altered myofilament contractile properties of LCR SOL slow-type fibers result in a fast muscle type Ca2+ sensitivity and the LCR muscle phenotype. Overall our findings demonstrate alterations of the myofilament proteins could contribute to fatigability of the SOL muscle and the decreased innate aerobic running performance of LCR compared with HCR rats.

Muscle secreted factors enhance activation of the PI3K/Akt and ß-catenin pathways in murine osteocytes.

Skeletal muscle and bone interact at the level of mechanical loading through the application of force by muscles to the skeleton and more recently focus has been placed on molecular/biochemical coupling of these two tissues. We sought to determine if muscle and muscle-derived factors were essential to the osteocyte response to loading. Botox® induced muscle paralysis was used to investigate the role of muscle contraction during in vivo tibia compression loading. 5-6 month-old female TOPGAL mice had their right hindlimb muscles surrounding the tibia injected with either BOTOX® or saline. At four days post injections when muscle paralysis peaked, the right tibia was subjected to a single session of in vivo compression loading at ∼2600 µÎµ. At 24 h post-load we observed a 2.5-fold increase in ß-catenin signaling in osteocytes in the tibias of the saline injected mice, whereas loading of tibias from Botox® injected mice failed to active ß-catenin signaling in osteocytes. This suggests that active muscle contraction produces a factor(s) that is necessary for or conditions the osteocyte's ability to respond to load. To further investigate the role of muscle derived factors, MLO-Y4 osteocyte-like cells and a luciferase based ß-catenin reporter (TOPflash-MLO-Y4) cell line we developed were treated with conditioned media (CM) from C2C12 myoblasts (MB) and myotubes (MT) and ex vivo contracted Extensor Digitorum Longus (EDL) and Soleus (Sol) muscles under static or loading conditions using fluid flow shear stress (FFSS). 10 % C2C12 myotube CM, but not myoblast or NIH3T3 fibroblast cells CM, induced a rapid activation of the Akt signaling pathway, peaking at 15 min and returning to baseline by 1-2 h under static conditions. FFSS applied to MLO-Y4 cells for 2 h in the presence of 10 % MT-CM resulted in a 6-8 fold increase in pAkt compared to a 3-4 fold increase under control or when exposed to 10 % MB-CM. A similar response was observed in the presence of 10 % EDL-CM, but not in the presence of 10 % Sol-CM. TOPflash-MLO-Y4 cells were treated with 10 ng/ml Wnt3a in the presence or absence of MT-CM. While MT-CM resulted in a 2-fold activation and Wnt3a produced a 10-fold activation, the combination of MT-CM + Wnt3a resulted in a 25-fold activation of ß-catenin signaling, implying a synergistic effect of factors in MT-CM with Wnt3a. These data provide clear evidence that specific muscles and myotubes produce factors that alter important signaling pathways involved in the response of osteocytes to mechanical load. These data strongly suggest that beyond mechanical loading there is a molecular coupling of muscle and bone.

Skeletal muscle secreted factors prevent glucocorticoid-induced osteocyte apoptosis through activation of ß-catenin.

It is a widely held belief that the sole effect of muscle on bone is through mechanical loading. However, as the two tissues are intimately associated, we hypothesized that muscle myokines may have positive effects on bone. We found that factors produced by muscle will protect osteocytes from undergoing cell death induced by dexamethasone (dex), a glucocorticoid known to induce osteocyte apoptosis thereby compromising their capacity to regulate bone remodeling. Both the trypan blue exclusion assay for cell death and nuclear fragmentation assay for apoptosis were used. MLO-Y4 osteocytes, primary osteocytes, and MC3T3 osteoblastic cells were protected against dex-induced apoptosis by C2C12 myotube conditioned media (MT-CM) or by CM from ex vivo electrically stimulated, intact extensor digitorum longus (EDL) or soleus muscle derived from 4 month-old mice. C2C12 MT-CM, but not undifferentiated myoblast CM prevented dex-induced cell apoptosis and was potent down to 0.1 % CM. The CM from EDL muscle electrically stimulated tetanically at 80 Hz was more potent (10 fold) in prevention of dex-induced osteocyte death than CM from soleus muscle stimulated at the same frequency or CM from EDL stimulated at 1 Hz. This suggests that electrical stimulation increases production of factors that preserve osteocyte viability and that type II fibers are greater producers than type I fibers. The muscle factor(s) appears to protect osteocytes from cell death through activation of the Wnt/ß-catenin pathway, as MT-CM induces ß-catenin nuclear translocation and ß-catenin siRNA abrogated the positive effects of MT-CM on dex-induced apoptosis. We conclude that muscle cells naturally secrete factor(s) that preserve osteocyte viability.

Peripheral neuropathy in patients with primary antiphospholipid (Hughes') syndrome.

The involvement of the peripheral nervous system in diverse autoimmune diseases is well established. However, no appropriately designed studies have been performed in primary antiphospholipid syndrome (PAPS)-related peripheral neuropathy. We aimed to investigate the occurrence of peripheral neuropathy in patients diagnosed with PAPS. Twenty-six consecutive patients with PAPS (Sapporo criteria) and 20 age- and gender-matched healthy controls were enrolled at two referral centers. Exclusion criteria were secondary causes of peripheral neuropathy. A complete clinical neurologic exam followed by nerve conduction studies (NCS) was performed. Paresthesias were reported in eight patients (31%). Objective mild distal weakness and abnormal symmetric deep tendon reflexes were observed in three patients (11.5%). With regard to the electrophysiologic evidence of peripheral neuropathy, nine patients (35.0%) had alterations: four (15.5%) had pure sensory or sensorimotor distal axonal neuropathy (in two of them a carpal tunnel syndrome was also present) and one (4%) had sensorimotor demyelinating and axonal neuropathy involving upper and lower extremities, while four patients (15.5%) showed isolated carpal tunnel syndrome. Clinical and serologic results were similar in all the patients with PAPS, regardless of the presence of electrophysiologic alterations. In conclusion, peripheral neuropathy is a common asymptomatic abnormality in patients with PAPS. The routine performance of NCS may be considered when evaluating such patients.

Inhibition of thromboxane A2-induced arrhythmias and intracellular calcium changes in cardiac myocytes by blockade of the inositol trisphosphate pathway.

We have recently reported that left atrial injections of the thromboxane A(2) (TXA(2)) mimetic, (5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2 -oxabicyclo[2.2.1]hept-5-yl]-5-heptenoic acid (U46619), induced ventricular arrhythmias in the anesthetized rabbit. Data from this study led us to hypothesize that TXA(2) may be inducing direct actions on the myocardium to induce these arrhythmias. The aim of this study was to further elucidate the mechanism responsible for these arrhythmias. We report that TXA(2)R is expressed at both the gene and protein levels in atrial and ventricular samples of adult rabbits. In addition, TXA(2)R mRNA was identified in single, isolated ventricular cardiac myocytes. Furthermore, treatment of isolated cardiac myocytes with U46619 increased intracellular calcium in a dose-dependent manner and these increases were blocked by the specific TXA(2)R antagonist, 7-(3-((2-((phenylamino)carbonyl)hydrazino)methyl)-7-oxabicyclo(2.2.1)hept-2-yl)-5-heptenoic acid (SQ29548). Pretreatment of myocytes with an inhibitor of inositol trisphosphate (IP(3)) formation, gentamicin, or with an inhibitor of IP(3) receptors, 2-aminoethoxydiphenylborate (2-APB), blocked the increase in intracellular calcium. In vivo pretreatment of anesthetized rabbits with either gentamicin or 2-APB subsequently inhibited the formation of ventricular arrhythmias elicited by U46619. These data support the hypothesis that TXA(2) can induce arrhythmias via a direct action on cardiac myocytes. Furthermore, these arrhythmogenic actions were blocked by inhibitors of the IP(3) pathway. In summary, this study provides novel evidence for direct TXA(2)-induced cardiac arrhythmias and provides a rationale for IP(3) as a potential target for the treatment of TXA(2)-mediated arrhythmias.

Physiological role of Kvß2 (AKR6) in murine skeletal muscle growth and regulation.

AIM: Potassium channel accessory subunits (Kvß) play a key role in cardiac electrical activity through ion channel modulation. In this study, we hypothesize that Kvß2 regulates skeletal muscle growth and fibre phenotype via protein-protein interactions. METHODS: Kvß2 knockout mouse model was used for morphometric, immunohistochemical and biochemical analysis to evaluate the role of Kvß2 in skeletal muscle physiology. RESULTS: Deletion of Kvß2 gene in mice (Kvß2 knockout, KO) leads to significant decrease in body weight along with skeletal muscle size. Key hindlimb muscles such as biceps, soleus and gastrocnemius were significantly smaller in size in KO mice compared to that of wild type. Morphometric measurements and histological analysis clearly point that the fibre size is decreased in each of the muscle type in KO compared with wild-type mice. In addition, Kvß2 deletion contributes to fibre-type switching from fast to slow fibre as indicated by more abundant MHCI-expressing fibres in gastrocnemius and soleus muscles, which may underscore the smaller muscle size alongside increase in U3 ubiquitin ligase; NEDD4 expression. Using targeted siRNA knockdown approach, we identified that Kvß2 knockdown does not affect the myoblasts proliferation. However, Pax7 expression was significantly decreased in 4-week-old gastrocnemius muscle, suggesting that cellular reserve for growth may be deficient in KO mice. This is further supported by decreased migratory capacity of C2C12 cells upon siRNA-targeted Kvß2 knockdown. CONCLUSION: Overall, this is the first report identifying that genetic deletion of Kvß2 leads to decreased skeletal muscle size along with isotype switching.

Functional properties of skeletal muscle from transgenic animals with upregulated heat shock protein 70.

The influence of inducible heat stress proteins on protecting contracting skeletal muscle against fatigue-induced injury was investigated. A line of transgenic mice overexpressing the inducible form of the 72-kDa heat shock protein (HSP72) in skeletal muscles was used. We examined the relationship between muscle contractility and levels of the constitutive (HSC73) and inducible (HSP72) forms of the 72-kDa heat shock protein in intact, mouse extensor digitorum longus (EDL), soleus (SOL), and the diaphragm (DPH). In all transgenic muscles, HSP72 was expressed at higher levels compared with transgene-negative controls, where HSP72 was below the level of detection. At the same time, HSC73 levels were downregulated in all transgenic muscle types. Shipment-related stress caused an elevation in the levels of HSP72 in all muscles for 1 wk after arrival of the animals. We also found that, although no statistical differences in response to intermittent fatiguing stimulation in the contractile properties of intact transgene-positive muscles compared with their transgene-negative counterparts were observed, the response of intact transgene-positive EDL muscles to caffeine was enhanced. These findings demonstrate that elevated HSP72 does not protect EDL, SOL, or DPH muscles from the effects of intermittent fatiguing stimulation. However, HSP72 may influence the excitation-contraction coupling (ECC) process, either directly or indirectly, in EDL muscle. If the effects on ECC were indirect, then these results would suggest that manipulation of a specific gene might cause functional effects that seem independent of the manipulated gene/protein.

Increased susceptibility to fatigue of slow- and fast-twitch muscles from mice lacking the MG29 gene.

Mitsugumin 29 (MG29), a major protein component of the triad junction in skeletal muscle, has been identified to play roles in the formation of precise junctional membrane structures important for efficient signal conversion in excitation-contraction (E-C) coupling. We carried out several experiments to not only study the role of MG29 in normal muscle contraction but also to determine its role in muscle fatigue. We compared the in vitro contractile properties of three muscles types, extensor digitorum longus (EDL) (fast-twitch muscle), soleus (SOL) (slow-twitch muscle), and diaphragm (DPH) (mixed-fiber muscle), isolated from mice lacking the MG29 gene and wild-type mice prior to and after fatigue. Our results indicate that the mutant EDL and SOL muscles, but not DPH, are more susceptible to fatigue than the wild-type muscles. The mutant muscles not only fatigued to a greater extent but also recovered significantly less than the wild-type muscles. Following fatigue, the mutant EDL and SOL muscles produced lower twitch forces than the wild-type muscles; in addition, fatiguing produced a downward shift in the force-frequency relationship in the mutant mice compared with the wild-type controls. Our results indicate that fatiguing affects the E-C components of the mutant EDL and SOL muscles, and the effect of fatigue in these mutant muscles could be primarily due to an alteration in the intracellular Ca homeostasis.

Bradykinin receptor localization and cell signaling pathways used by bradykinin in the regulation of gonadotropin-releasing hormone secretion.

In a previous publication we provided evidence of a novel neuronal pathway for the control of GnRH secretion by bradykinin. The action of bradykinin appeared to be exerted through the bradykinin B2 receptor. In this study we demonstrated that the bradykinin B2 receptor is densely localized in the arcuate nucleus, median eminence, organum vasculosum of the lamina terminalis, and preoptic area, regions known to be critical for the control of GnRH secretion. To determine the mechanism of action of bradykinin in stimulating GnRH release, we used immortalized GnRH (GT1-7) cells in vitro. Bradykinin stimulation of GnRH secretion from GT1-7 cells appears to involve activation of the phospholipase C signaling pathway and mobilization of extracellular and intracellular calcium stores. Evidence to support this contention was derived from the observations that incubation of the phospholipase C inhibitor, U-73122 with bradykinin, blocked the ability of bradykinin to stimulate release from GT1-7 cells. This effect was specific, as a nitric oxide synthase inhibitor and a cyclooxygenase inhibitor were found to have no effect on bradykinin-induced GnRH secretion, suggesting that nitric oxide and PGs do not mediate bradykinin effects. Pertussis toxin also had no effect on bradykinin action. This suggests that the bradykinin B2 receptor may be coupled to a pertussis toxin-insensitive G protein in GT1-7 cells. With respect to calcium involvement in bradykinin action, fura-2 calcium indicator studies revealed that bradykinin can rapidly increase intracellular Ca2+ levels in GT1-7 cells. A role for intracellular Ca2+ in bradykinin action was further suggested by the finding that an intracellular calcium chelator, 1,2-bis(O-aminophenoxy)]ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester, significantly attenuated the effects of bradykinin on GnRH release. The elevation of intracellular calcium by bradykinin appears to be due to mobilization of calcium from the endoplasmic reticulum, as incubation of the Ca2+-adenosine triphosphatase inhibitor thapsigarin, which depletes endoplasmic reticulum Ca2+ stores, significantly attenuated bradykinin action on GnRH release. Extracellular calcium may also be involved in bradykinin action, as the L-type Ca2+ channel blockers verapamil and nifedipine had no effect on bradykinin-induced GnRH release, whereas the nonselective Ca2+ channel blocker, nickel chloride, attenuated bradykinin-induced GnRH release. Taken as a whole, these studies demonstrate that the bradykinin B2 receptor is densely localized in key hypothalamic nuclei responsible for regulation of GnRH release, and that the mechanism of bradykinin stimulation of GnRH secretion involves activation of the phospholipase C signaling pathway, with a critical role implicated for calcium in bradykinin action in GT1-7 cells.

A novel stop codon mutation in the PMP22 gene associated with a variable phenotype.

The most frequent inherited peripheral neuropathy is the peripheral myelin protein 22 (PMP22) gene related disease. Duplication, deletion, and point mutations in that gene are associated with phenotypic variability. Here we report a family carrying a novel mutation in the PMP22 gene (c. 327C>A), which results in a premature stop codon (Cys109stop). The family members who carry this mutation have a Charcot-Marie-Tooth type 1 variable phenotype, ranging from asymptomatic to severely affected. These findings suggest that the fourth transmembrane domain of the PMP22 gene may play an important role, although the intrafamilial clinical variability reinforces the observation that pathogenic mutations are not always phenotype determinant and that other factors (genetic or epigenetic) modulate the severity of the clinical course.

Hydrogen peroxide disrupts Ca2+ release from the sarcoplasmic reticulum of rat skeletal muscle fibers.

Reactive oxygen species such as superoxide (O2-) and H2O2 are produced at low levels in resting muscles and at substantially higher levels in exercising muscles. Increased respiratory activity with exercise leads to O2- production by the NADPH oxidase reaction and the subsequent generation of H2O2 from O2- by spontaneous dismutation or by the superoxide dismutase reaction. The long-lasting (24-h) depression of contractile function after exercise has been linked to damage of one or more proteins important in the excitation-contraction coupling process. We studied mechanically and chemically skinned fibers from the extensor digitorum longus muscle of the rat to evaluate the effects of a 5-min exposure to 1.0 mM H2O2 on muscle function. We found that H2O2 had no effect on the isometric force-producing properties of the contractile apparatus or on Ca2+ uptake by the sarcoplasmic reticulum. It did, however, significantly affect Ca2+ release from the sarcoplasmic reticulum. Maximum depolarization-induced Ca2+ release was inhibited, and the sensitivity to depolarization was decreased. Ca(2+)-induced release was completely blocked. We conclude that elevated levels of H2O2 with exercise are capable of damaging one or more proteins of the excitation-contraction coupling process to produce a disruption in function that can account, at least in part, for the long-lasting effects of fatiguing stimulation.

Hyperekplexia, a cause of neonatal apnea: a case report.

We report a case of non-familial hyperekplexia which characteristically developed apnea and feeding difficulties in the neonatal period. The abnormal startle response was evident from the second week of life onwards. The infant showed a marked improvement of the startle response and muscle hypertonia with clonazepam. Clobazam was also tried with no apparent response. A prominent long latency C response was observed on EMG examination, suggesting a possible cortical neuronal hyperexcitability origin for the abnormal startle response observed in hyperekplexia.

Elevation of intracellular Ca2+ concentration in rabbit nonpigmented ciliary epithelial cells by allicin.

A previous study has shown that allicin produces changes in aqueous humor dynamics, and this study was conducted to examine possible cellular mechanisms. In rabbit nonpigmented ciliary epithelial cells, basal levels of [Ca2+]i were determined to be 164 +/- 34 nM. Allicin, a sulfhydryl-reactive agent, induced Ca2+ transients at 0.01 mM and at 0.2 mM, the Ca2+ transient peaked at 732 +/- 35 nM. Allicin-induced Ca2+ transients were prevented by pretreatment with dithiothreitol which did not affect the basal Ca2+ levels. Allicin had only a slight, insignificant, effect on L-type Ca2+ currents, and allicin-induced Ca2+ transients were also present under extracellular Ca(2+)-free conditions. These data suggest that intracellular Ca2+ stores are the most probable source of allicin's effect. Pretreatment of cells with ryanodine, an inhibitor of Ca(2+)-induced-Ca(2+)-release, inhibited allicin-induced Ca2+ transients, but the basal Ca2+ levels were unaffected by ryanodine. Thus, allicin-induced Ca2+ transients are most likely mediated through ryanodine-sensitive intracellular Ca2+ stores.

Aggressive angiomyxoma of the vulva: expression of estroprogestinic receptors and follow-up.

PURPOSE OF INVESTIGATION: To analyze aggressive angiomyxoma hormone-dependency. METHOD: Estroprogestinic receptor expression was studied by immunohistochemistry in 5 patients with aggressive angiomyxoma of the vulva. RESULTS: The immunohistochemical results confirm the positivity of angiomyxoma for estrogen and progesterone receptors. CONCLUSIONS: We hypothesized that the concomitant factor favoring neoplastic growth is a different genetic substrate specific in the female sex. Analysis of the data regarding the distribution of angiomyxomas in different age groups has strengthened this hypothesis suggesting that this tumor is correlated with complete maturity, in all probability hormonal. However it cannot be excluded that the tumor begins to develop at an early age, but since it has a slow growth rate, the phenomenon is delayed and is related to hormonal stimulation.

Rectosigmoid endometriosis: diagnosis and surgical management.

The recurrence of endometriosis varies from 6% to 10% and, among the non-gynaecological sites, the bowel is involved in 12%-37%. Various symptoms, such as dysmenorrhea, dyspareunia, chronic pelvic pain, diarrhoea, constipation, cyclic rectal bleeding, colic-abdominal pain up to intestinal occlusion characterize this pathology. Surgery seems to be the best treatment especially for gastrointestinal symptoms; conservative surgery should be performed, particularly in young patients. Four cases of intestinal endometriosis were reevaluated.

[Congenital progressive muscular dystrophy of Fukuyama type: report of a case]. / Distrofia muscular progressiva congênita tipo Fukuyama: descrição de um caso.

The authors report the first Fukuyama type congenital progressive muscular dystrophy case described in Brazil, and confirmed through clinical findings and complementary tests. Emphasis is given to the presence of early fibrotendinous retractions and impairment of the central nervous system, which constitute the fundamental characteristics of this affection. This disease is very common in Japan but very seldom described in other countries. Its etiopathogeny has not yet been defined.

[Adrenoleukodystrophy (melanodermic leukodystrophy). Report of an anatomo-clinical case]. / Adrenoleucodistrofia (leucodistrofia melanodérmica). Registro de um caso anátomo-clínico.

The case of a 14-year-old boy with "diffuse cerebral sclerosis", preceded by signs of primary adrenal cortical insufficiency for 7 years with familiar antecedents is reported. This disorder, named adrenoleukodystrophy, has a sex-lin(ed recessive inheritance. The clinical picture is characterized by mental deterioration, gait disturbances, visual impairment, associated with primary adrenal cortical insufficiency. Confirming the data from literature, in our case the pathological study showed myelin degeneration and diffuse gliosis in the cerebral white matter, with no involvement of subcortical fibers. Inflammatory cells are common, and have a perivascular distribution. In the fasciculata and reticular zones of the adrenal gland, "baloon-shaped" cells are evident, most of them presenting a vacuolized and striated cytoplasm. Similar lipidic inclusions have been found in the Schwann cells of the periheral nerves and testis. The findings are compared with twenty cases from the literature.

[Increased muscular irritability syndrome: treatment with nifedipine. Report of a case]. / Síndrome de irritabilidade muscular aumentada: tratamento com nifedipina. Registro de um caso.

In 1980 Alberca et al. described a patient with a syndrome of increased muscle irritability, who presented ondulating muscle rolling movements and electrically silent cramps, myoedema and muscle reactions to mechanical stimulation similar to myotonic response, suggesting a disfunction at myofibrillar level. We saw a similar case, of a male patient, 21 years of age, who complained of cramps of severe intensity for the past four years. These cramps were painful in the upper and lower limbs and impaired his locomotion; they were electrically silent. At percussion the patient showed severe idiomuscular contraction, with a period of increased relaxation, similar to a myotonic reaction and also, prolonged myoedema and rolling muscle contractions. Electromyography was normal, as were histochemical and electron microscopy studies. We carried out a therapeutic trial with niphedipine (a calcium antagonist), on the assumption that the patient showed a disturbance of the myofibrillar function--even though physiopathogenesis of the hyperirritability muscle syndrome was not yet clearly defined--and with a basis on the importance of the intracytoplasmatic level of Ca++ free in the muscle contraction mechanism, not only as the initiating factor of the contractile process, but also as a quantitative controller of the mechanic tension development through regulation of the amount of ATP metabolized during muscle activity. Administration of the drug in a dose of 40 mg daily, per os, brought a remission of the symptoms after two weeks, and the patient could walk normally again. On the introduction of a placebo, on two different opportunities, there occurred a recrudescence of the symptoms after about one week's time.(ABSTRACT TRUNCATED AT 250 WORDS)

Autosomal recessive nondystrophic myotonia. Report of a case with unusual clinical course.

We describe the case of a girl with a probable autosomal recessive form of nondystrophic hereditary myotonia whose clinical findings are more compatible with the dominant ones mainly myotonia congenita of Thomsen or myotonia fluctuans. Besides the clinical aspects of the atypical form presented by our patient, the efficacy of the more available drugs employed for the treatment of myotonia congenita is briefly discussed.

Monophasic synovial sarcoma of hypopharynx: case report and review of the literature.

Synovial sarcoma (SS) is a malignant mesenchymal neoplasm usually involving the lower limbs of young adults. Localization in head-neck district is rare. Histologically, these are characterised by a biphasic or monophasic variant, the latter being more rare and difficult to identify. Immunohistochemistry plays a crucial role in the diagnosis. Cytogenetics also play an important role since both the monophasic and the biphasic forms are characterised by a reciprocal translocation (x;18) (p 11.2;q 11.2). Treatment options include an aggressive surgical approach and radiotherapy, whereas the role of chemotherapy remains to be defined. The case is described of monophasic synovial sarcoma located in the hypopharynx and a review is made of the literature concerning this rare neoplasm.