Sensory neuronopathy is a specific and disabling neurological manifestation of autoimmune hepatitis.

BACKGROUND AND PURPOSE: Neurological manifestations have been identified in the context of autoimmune hepatitis (AIH). Previous case reports highlighted the association between AIH and sensory neuronopathy (SN). Despite that, little is known about the frequency of AIH-related SN and its clinical/neurophysiological profile. Moreover, it is not clear whether SN is an AIH-specific manifestation or related to chronic liver damage. METHODS: Seventy consecutive AIH patients were enrolled and their characteristics were compared with 52 consecutive patients with chronic active hepatitis B. All subjects underwent clinical and neurophysiological evaluation. Further comparisons were performed between AIH SN and AIH non-SN patients. RESULTS: Mean ages and male:female proportions in the AIH and chronic active hepatitis B groups were 42.2 ± 16.3/51.7 ± 13.6 years and 14:56/29:23, respectively. The frequencies of carpal tunnel syndrome, radiculopathy and polyneuropathy were similar between groups. In contrast, SN was identified only in AIH patients (5/70 vs. 0/52, P = 0.04); the overall prevalence of AIH-related SN was 7% with an average profile of a woman in her 40s with asymmetric onset of sensory deficits that chronically evolved to disabling proprioceptive ataxia associated with marked dysautonomia. Neurological disability and hepatocellular damage did not follow in parallel. Anti-fibroblast growth factor receptor type 3 antibodies were found in 3/5 (60%) of the patients with AIH-related SN. Clinical or demographic predictors of SN in the context of AIH could not be identified. CONCLUSION: Sensory neuronopathy, but not other peripheral nervous system diseases, is a specific AIH neurological manifestation. It is often disabling and, in contrast to hepatocellular injury, does not respond to immunosuppression.

Percutaneous headless screws and wide-awake anesthesia to fix metacarpal and phalangeal fractures: outcomes of the first 56 cases.

Phalangeal (P) and metacarpal (MC) fractures are very common injuries, with potentially disabling, residual impairment, deformities or stiffness. Conservative treatment represents the strategy of choice in most cases, but in unstable fractures and/or high-demanding patients, surgical fixation could be required. Ideally, the best treatment choice will be the intramedullary fixation systems, if possible without the implant protruding from the skin. Intramedullary headless screw fixation could be the reliable option to achieve a primary fixation, allowing an early active movement, with regard to the fractures site. The Authors analyzed the results achieved after 56 extra-articular unstable fractures (31 phalangeal fracture and 25 metacarpal fracture) treated with intramedullary headless compression screws. After surgery, patients underwent early mobilization without splinting. The results of the study suggest that this technique could be a reliable therapeutic option in order to obtain early mobilization and quick return to work after a phalangeal or metacarpal fracture, especially for high-demanding patients.

Genetic profile of Brazilian patients with dystrophinopathies.

Different types of mutations in the DMD gene underlie Duchenne muscular dystrophies (DMD) and Becker muscular dystrophies (BMD). Large deletions and duplications are the most frequent causative genetic alterations worldwide, but little is known about DMD/BMD genetic profile in Brazil. Hence, we recruited patients with DMD and BMD from 8 neuromuscular reference centers along the country, and performed a comprehensive molecular investigation that included Multiplex Ligation-dependent Probe Amplification and Next generation sequencing (NGS) analyses. We evaluated 199 patients from 177 unrelated families: 166 with DMD, 32 with BMD and 1 1.5 years old asymptomatic patient with persistent hiperCKemia. Overall, large deletions (58.2%) followed by nonsense mutations (12.4%) and large duplications (11.3%) were the most frequent variants in Brazilian families. Large deletions were less frequent in BMD than in DMD (44.8% vs 60.8%). We identified 19 new DMD variants. Nonsense mutations were significantly more frequent in patients from northeastern region than from southern/southeastern regions of Brazil (27.7% vs 8.5%, P < .05). Genetic profile of Brazilian patients with DMD/BMD is similar to previously reported cohorts, but it is not uniform across the country. This information is important to plan rational clinical care for patients in face of the new coming mutation-specific therapies.

Choosing the proper implant for extra-articular fractures of proximal phalanges: A study on 75 cases.

INTRODUCTION: Phalangeal fractures are the most common fractures of the hand and in particular the proximal phalanx of the long fingers is the most involved. These fractures can ben conservatively managed but, when the fracture pattern is considered unstable, surgical treatment is recommended. However, there is no consensus in literature about the proper surgical option for extra-articular proximal phalanx fractures. MATERIAL AND METHODS: We compared clinical and radiographical results after treatment of 75 cases of extra-articular proximal phalanx fractures using three different surgical techniques: closed reduction and internal fixation (CRIF) with Kirschner wires (G1 group), open reduction internal fixation (ORIF) with plates and screws or lag screws (G2 group), and closed reduction and intramedullary screw fixation (CRIMEF)(G3 group). RESULTS: We found no significant differences in term of union rate and time to fracture healing between the three groups. However, we found a significant reduction in time to return at work and in TAM at the final follow-up examination in G3 group (treated with CRIMEF) when compared with both G1 and G2. No differences in complications rate were found between three groups. DISCUSSION: The surgical variability in the management of extra-articular phalanx fractures create lacks on standard guide for treatment. CONCLUSIONS: In conclusion, our results showed good clinical and radiographical results with all the three surgical options. However, the closed reduction and internal fixation with intramedullary screws (CRIMEF) seems to be better in terms of time to return to work and TAM at the final follow-up, probably due to good primary stability and little risk of soft tissue adherence development.

Clinical correlates of autonomic dysfunction in patients with Machado-Joseph disease.

BACKGROUND: Autonomic dysfunction is a usual feature of several neurological conditions characterized by either extra-pyramidal and/or peripheral damage, such as those seen in Machado-Joseph disease (MJD). AIMS OF THE STUDY: We used clinical evaluation and sympathetic skin responses (SSR) to assess autonomic function in a large series of patients with MJD. METHODS: A total of 50 patients were enrolled in this study and all of them had the molecular confirmation of MJD by DNA genotyping. In addition, a group of 20 control subjects was included. RESULTS: Overall, autonomic complaints were more frequent in patients than in control subjects, especially those related to the genitourinary and sudomotor systems. Eighteen patients (36%) presented abnormal SSR. Age at onset, duration of disease and length of expanded (CAG)(n) were not different between patients with and without dysautonomia. However, severe dysautonomia was significantly associated with polyneuropathic or parkinsonian phenotypes in patients with MJD. CONCLUSION: Autonomic symptoms are common, but possibly under recognized in patients with MJD; therefore, we believe that autonomic complaints should be sought in patients with MJD, especially in those with parkinsonian or polyneuropathic phenotypes.

Sleep symptoms and their clinical correlates in Machado-Joseph disease.

OBJECTIVE: To evaluate the presence of sleep symptoms in Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3). SUBJECTS/METHODS: We used a sleep questionnaire and the Epworth Sleepiness Scale to compare 53 patients with MJD/SCA3 and 106 controls. RESULTS: Patients with MJD/SCA3 reported more symptoms of insomnia, restless leg syndrome and REM sleep behavior disorder as well as nocturnal cramps, snoring and nocturnal apnea. Insomnia was the most frequently reported sleep-related complaint in the MJD/SCA3 group. CONCLUSIONS: Our results indicate that sleep disorders are common in patients with MJD/SCA3 and probably have a multifactorial etiology, with components of a primary sleep disorder in addition to sleep-disrupting symptoms such as nocturia and cramps.

Chronic acquired sensory neuron diseases.

BACKGROUND AND PURPOSE: Sensory neuron diseases (SND) represent a specific subgroup of peripheral nervous system disorders that are becoming increasingly recognized. We aimed to analyze clinical, neurophysiological, and MRI features in patients with SND. METHODS: We reviewed clinical and electrophysiological data of 20 individuals fulfilling SND criteria. Patients underwent an additional neurological evaluation and cervical spine MRI. RESULTS: Sensory neuron diseases was associated with dysimmune conditions in six, hepatitis C in one, B12 deficiency in another, and in one patient SND was related to organophosphate intoxication. In the remaining eleven, it was considered as idiopathic. Nineteen patients experienced sensory symptoms. Worse ataxia was related with longer disease duration (P = 0.02). Early CSF assessment was related to higher protein level (P = 0.008). All patients showed widespread impairment in sensory nerve action potential amplitudes. High signal intensity in the posterior columns was observed in most patients when MRI was performed more than 3 years after disease onset. DISCUSSION: Sensory neuron diseases usually presents with sensory symptoms and ataxia. A high index of suspicion is important because inflammatory changes might be more prominent initially, a period when immunotherapy could be more valuable. Early diagnosis should be based mainly on electrophysiological and clinical grounds, as MRI may be normal initially.

Compressive Femoral Neuropathy Associated with Iliopsoas Hematoma Complicating Hip Hemiarthroplasty: A Case Report.

INTRODUCTION: Femoral nerve compression caused by iliopsoas hematoma is a rare complication after hip surgery. To the best of our knowledge, this is the first case after hemiarthroplasty. In this case, iliacus hematoma resulted from spontaneous bleeding favored by anticoagulant therapy. CASE REPORT: A 78-year-old female developed left groin pain associated with typical symptoms of femoral nerve palsy about 2weeks after left hip hemiarthroplasty[1, 2, 3]. Computed tomography revealed the presence of a left iliopsoas hematoma that was surgically drained. Inguinal pain was immediately relieved, while nerve palsy recovered only partially, but the quality of life drastically improved and she was able to walk using a walker without pain. CONCLUSION: Even if it is a rare condition, the formation of a hematoma of iliopsoas muscle should be considered in patients that present symptoms of femoral nerve palsy, especially if treated with heparin or other anticoagulant drugs. Surgical drainage of the hematoma is indicated when symptoms are severe and disabling, and in this way, surgery could improve quality of life.

Diagnostic accuracy of anti-gliadin antibodies in Non Celiac Gluten Sensitivity (NCGS) patients: A dual statistical approach.

BACKGROUND: Gluten is the target of several diseases such as wheat allergy (WA), celiac disease (CD) and non-celiac gluten sensitivity (NCGS). NCGS is a new clinical entity characterized by gastrointestinal and extraintestinal symptoms comparable to those of CD patients but to date still lacking of specific biomarkers so that NCGS diagnosis can be reached only by excluding CD and WA, and based on the direct association between gluten ingestion and symptoms onset. Previous studies showed that antigliadin antibodies (AGA) IgG are the most prevalent positive antibodies in NCGS population. AIM: The first aim of the study was to estimate AGA distribution and prevalence in a NCGS population. The second aim was to identify a serological pattern to help the diagnosis and/or to mark the NCGS disease. METHODS: Sera from 59 patients with suspected NCGS, 90 CD patients and 70 healthy individuals were assessed for AGA IgG/IgA, IgG/IgA deamidated gliadin peptide antibodies (DGP-AGA), tissue transglutaminase antibodies IgA (tTGA), endomysial antibodies IgA (EmA) and HLA typing (Eurospital, Trieste, Italy). RESULTS: We evaluated data by a dual statistical approach: logistic regression and receiver operating characteristic (ROC) analysis; therefore, we showed a poor diagnostic accuracy of AGA IgG in NCGS condition. CONCLUSION: Our preliminary data showed that AGA IgG didn't seem to be a strongly sensitive marker, even if it has been recently proposed as promising marker for NCGS condition, together with negativity for other celiac disease related antibodies. It can partially help the NCGS diagnosis, if it is integrated in the overall management of the patient. More in-depth clinical and laboratory researches are mandatory.

Massive spinal cord necrosis in schistosomiasis.

Spinal cord lesions are rare in schistosomiasis. Schistosomal ova usually elicit a granulomatous myelitis in which necrotic foci are sometimes observed, but necrotic foci are sometimes observed, but extensive cord necrosis is exceptional. A 19-year-old Brazilian woman had transverse myelitis that ended fatally one month and a half thereafter. Autopsy disclosed a total myelonecrosis below T-4, and ova at Schistosoma mansoni were demonstrated in the necrotic cord tissue and leptomeniges. This is, to our knowledge, the most extensive necrosis of the spinal cord reported to date in schistosomiasis.

Review article: cardiac adverse effects of gastrointestinal prokinetics.

Gastrointestinal prokinetics, such as metoclopramide, cisapride and levosulpiride, are widely used for the management of functional gut disorders. Recently, several studies have shown that cisapride (a partial 5-HT4 receptor agonist) can induce dose-dependent cardiac adverse effects, including lengthening of the electrocardiographic QT interval, syncopal episodes and ventricular dysrhythmias. Until recently, it was not clear whether these effects were dependent on 5-HT4 receptor activation or related to peculiar characteristics in the molecular structure of single agents within the benzamide class. Experimental evidence now favours the second hypothesis: cisapride possesses Class III antiarrhythmic properties and prolongs the action potential duration through blockade of distinct voltage-dependent K+ channels, thus delaying cardiac repolarization and prolonging the QT interval. Patients at risk of cardiac adverse effects are children, subjects with idiopathic, congenital or acquired long QT syndrome and, in particular, those receiving concomitant medication with Class III antiarrhythmic agents, some H1-receptor antagonists (e.g. terfenadine), or drugs such as azole antifungals (e.g. ketoconazole, itraconazole, miconazole and fluconazole) and macrolide antibacterials (e.g. erythromycin, clarithrod-mycin and troleandomycin), which can inhibit cisapride metabolism by interfering with the CYP3A4 isoenzyme.

Histology of the metal-bone interface: interpretation of plastic embedded slides.

The interference of processing and preparation of histological slides for the study of morphology and morphometry of bone-implant interfaces was investigated in an experimental model, in which a titanium plate was inserted through the cortical bone into the medullary cavity of rat tibiae. The thickness of the sections, burr and notching of the cut border, and staining properties of the embedding resin were found to significantly influence the appearance of the bone-implant interface and, when morphometry was applied, the extent of direct bone-metal contact. The model of the interface resulting from this study is that of some bony processes abutting on the metal surface, while most of the contact is between metal and connective tissue or vascular spaces.

Experimental model in vivo for quantitative assessment of bone resorption inhibition.

Quantitative assessment of bone resorption inhibition in vivo is not easily accomplished; methods relying on a count of osteoclasts are questionable, and histomorphometric evaluation of the bone mass presents several technical problems as well. The authors developed a simple method to measure the inhibition of bone resorption by study of the proximal tibial metaphysis of growing rats: the height of the perichondrial bone ring was taken as an index of the balance between osteoblastic and osteoclastic activity because any agent that inhibits osteoclasts (without interference with osteoblasts) produces an increase in the height of this anatomical structure. Since the ring is well demarcated by surrounding tissues, its height can be measured with accuracy and used for quantitative assessment of bone resorption inhibition. This model was tested with salmon calcitonin, and it provides evidence in vivo that this hormone inhibits osteoclastic bone resorption.

Motor neurone disease with neurofibrillary tangles in a Brazilian woman.

The occurrence of neurofibrillary tangles in both the cerebral cortex and brain stem is typically seen in the Guam type of amyotrophic lateral sclerosis, but is exceedingly rare in the classical form of the disease. Only 3 cases of sporadic amyotrophic lateral sclerosis with such histopathologic features have so far been reported, all in the United States. A 49-year-old Brazilian woman had an 18-month history of amyotrophic lateral sclerosis involving predominantly the left-sided extremities with prominent bulbar signs. Autopysi disclosed moderate to severe loss of motor neurones in the hypoglossal nuclei and anterior spinal horns, absence of pyramidal tract demyelination, depigmentation of the substantia nigra and numerous neurofibrillary tangles in the hypothalamic region, parahippocampal gyrus, reticular substance of the mesencephalon and pons and in some brain stem nuclei. The topographical distribution of these changes was closely similar to that of Guamanian amyotrophic lateral sclerosis.

Endomorphin-1 and endomorphin-2 activate mu-opioid receptors in myenteric neurons of the guinea-pig small intestine.

The novel opioid tetrapeptides, endomorphin-1 and endomorphin-2, recently isolated from bovine and human brain bind with high affinity and selectivity to central mu-opioid receptors. In the digestive tract, a comprehensive pharmacological analysis of the receptors involved in endomorphin action has not been reported. In this study, we analyzed the effects of endomorphin-1 and endomorphin-2 on longitudinal muscle-myenteric plexus preparations (LMMPs) from the guinea-pig ileum. Both peptides (30 pM - 1 microM) inhibited (-log EC50 values: 8.61 and 8.59, respectively) the amplitude of electrically-induced twitch contractions in a concentration-dependent fashion, up to its abolition. Conversely, in unstimulated LMMPs, they failed to affect contractions to applied acetylcholine (100 nM). In stimulated LMMPs, the highly selective mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), caused a concentration-dependent (30 nM-1 microM), parallel rightward shift of endomorphin-1 and endomorphin-2 inhibitory curves, without depression of their maximum. Following Schild analysis, calculated pA2 values were 7.81 and 7.85, respectively, with slopes not different from unity. Concentration-response curves to both peptides were not affected by 30 nM naltrindole (a selective delta-receptor antagonist) or 30 nM nor-binaltorphimine (a selective kappa-receptor antagonist). These results demonstrate that endomorphins selectively activate mu-opioid receptors located on excitatory myenteric plexus neurons, and that they act as full agonists.

A re-appraisal of the nature of the atropine-resistant contraction to electrical field stimulation in the human isolated detrusor muscle.

We investigated whether in human isolated detrusor strips the atropine-resistant contractile response to electrical field stimulation was mediated by ATP (or a related purine), as previously shown in the urinary bladder of other mammalian species. Electrical stimulation (1-50 Hz for 5 s at 1 min intervals, 0.1 ms pulse width, 60 V) elicited reproducible, frequency-dependent twitch contractions, which were markedly reduced by atropine (10 microM). Tetrodotoxin (TTX: 1 microM) inhibited contractile responses to a similar degree. When applied together, atropine and TTX caused an inhibition which was superimposable to that caused by either drug alone. The TTX-resistant contractions were totally unaffected by omega-conotoxin GVIA (omega-CTX: 0.1 microM). The atropine-resistant contractions were unaffected by the P2-purinoceptor antagonists suramin (300 microM) and PPADS (30 microM), at concentrations which virtually suppressed the contractile response induced by applied ATP (10 microM(-1) mM). As previously described, antagonism of the ATP-induced contractions by suramin (30, 100, 300 microM) and PPADS (3, 10, 30 microM) was insurmountable, with apparent 'pA2' values (calculated at the lowest antagonist concentrations) of 4.9 and 5.2, respectively. It is concluded that, under our experimental conditions, the non-cholinergic (atropine-resistant) component of the excitatory transmission in the human detrusor is not mediated by neural release of ATP, in spite of the presence of excitatory P2-purinoceptors on the effector cells. The TTX- and omega-CTX-resistant, non-cholinergic component might be related to the release of unknown transmitter(s) through a mechanism independent of both Na+- and N-type Ca2+-channels. More likely, the atropine-resistant component may reflect direct smooth muscle excitation since the human detrusor has a very short chronaxie (Sibley 1984).

Effects of ethanol administration on cerebral non-protein sulfhydryl content in rats exposed to styrene vapour.

Glutathione (GSH) and other non-protein sulfhydryls (NPS) are known to protect cells from oxidative stress and from potentially toxic electrophiles formed by biotransformation of xenobiotics. This study examined the effect of a simultaneous administration of styrene and ethanol on NPS content and lipid peroxidation in rat liver and brain. Hepatic cytochrome P450 and cytochrome b5 content, aniline hydroxylase and aminopyrine N-demethylase activities as well as the two major urinary metabolites of styrene, mandelic and phenylglyoxylic acids were also measured. Groups of rats given ethanol for 3 weeks in a liquid diet were exposed, starting from the second week, to 326 ppm of styrene (6 h daily, 5 days a week, for 2 weeks). In control pair-fed animals, styrene produced about 30% depletion of brain NPS and 50% depletion of hepatic NPS. Subchronic ethanol treatment did not affect hepatic NPS levels, but caused 23% depletion of brain NPS. Concomitant administration of ethanol and styrene caused a NPS depletion in brain tissue in the order of 60%. These results suggest that in the rat, simultaneous exposure to ethanol and styrene may lead to considerable depletion of brain NPS. This effect is seen when both compounds are given on a subchronic basis, a situation which better resembles possible human exposure.

Review of the implications of dietary tryptophan intake in patients with irritable bowel syndrome and psychiatric disorders.

In this review, we address the possible role of the essential amino acid L-tryptophan or its metabolic derivative 5-hydroxytryptophan in the modulation of serotonin (5-hydroxytryptamine) synthesis and thereby in affecting the pathophysiology of central and peripheral nervous system disorders, including depression and irritable bowel syndrome. L-Tryptophan may represent a link between apparently disparate functional disorders and is of interest for general gastroenterologists, neurogastroenterologists, and neurologists. On the basis of estimates showing that approximately 20% of patients with functional bowel disorders seeking care in referral centres have psychiatric comorbidity, we attempt to provide a conceptual framework for defining the possible role of L-tryptophan in this population.

5-HT4 receptors contribute to the motor stimulating effect of levosulpiride in the guinea-pig gastrointestinal tract.

BACKGROUND: The dopamine D2 receptor antagonist levosulpiride is a substituted benzamide derivative, whose gastrokinetic properties are exploited clinically for the management of functional dyspepsia. However, for other benzamide derivatives, such as cisapride and mosapride, agonism towards serotonin 5-HT4 receptors is considered the main mechanism leading to gastrointestinal prokinesia. AIMS: To assess whether levosulpiride is able to activate 5-HT4 receptors in the guinea-pig isolated gastrointestinal tract. MATERIALS AND METHODS: Circular muscle strips from gastric antrum, and colonic longitudinal muscle strips were used to detect electrically stimulated neurogenic contractions. The effect of levosulpiride was assessed in the absence and presence of GR125487, a selective 5-HT4 receptor antagonist. Furthermore, potential interaction of levosulpiride with 5-HT3 receptors and tissue cholinesterases was assessed in unstimulated ileal longitudinal muscle-myenteric plexus preparations. RESULTS: Antral and colonic strip contractions were cholinergic/tachykinergic in nature. Micromolar concentrations of levosulpiride potentiated submaximal responses, through a mechanism competitively antagonized by GR125487 (pKB=9.4). In LMMPs, levosulpiride slightly affected contractions caused by the 5-HT, receptor agonist 2-methyl-5-HT, and had no effect on contractions to exogenous acetylcholine. CONCLUSIONS: Our results indicate that levosulpiride acts as a moderate agonist at the 5-HT4 receptor. This property, together with antagonism at D2 receptors, may contribute to its gastrointestinal prokinetic effect.

Effects of silver in isolated rat hepatocytes.

Addition of silver nitrate or silver lactate to freshly isolated hepatocytes caused dose-dependent loss of cell viability, measured by trypan blue exclusion, at concentrations within 30-70 microM. Silver cytotoxicity was accompanied by a decrease in hepatic thiol concentration and an increase in lipid peroxidation. Treatment of hepatocytes with the reduced glutathione (GSH)-depleting agent diethylmaleate markedly increased their vulnerability to silver toxicity whereas protective effects were produced by the thiol-reducing agent, dithiothreitol. Both alpha-tocopherol, which protected from the onset of silver-associated lipid peroxidation, and the iron chelator agent, deferoxamine failed to prevent loss of cell viability. These data suggest that perturbation of intracellular thiol homeostasis may play a critical role in the mechanism underlying silver-induced lethal damage to isolated rat hepatocytes.