Morphometry and 1H-MR spectroscopy of the brain stem and cerebellum in three patients with fragile X-associated tremor/ataxia syndrome.

SUMMARY: Morphometry and spectroscopy were performed in 3 patients with fragile X-associated tremor/ataxia syndrome (FXTAS). The brain stem and cerebellum were atrophic and satisfied criteria for olivopontocerebellar atrophy in 2 patients. However, the vermis was relatively spared and the basis pontis maintained its oval shape. The only spectroscopic abnormality was a decrease of the pontine N-acetylaspartate/creatine ratio in 1 patient. Atrophy and metabolic changes in FXTAS differ to some extent from those of olivopontocerebellar atrophy.

[Neuromuscular occlusion in the orthodontic treatment of craniomandibular disorders. A clinical case]. / L'occlusione neuromuscolare nella terapia ortodontica del paziente con disordini craniomandibolari. Caso clinico.

In the last few years, it has been observed a considerable increase of cranio-mandibular disorders which presently represent one of the most common commitments for dentists and, in particular, for orthodontists. The aim of this paper is to evaluate the efficacy of Jankelson's therapeutic protocol, followed by an orthodontic treatment, in a patient with cranio-mandibular disorders associated with occlusal pathologies. The cranio-mandibular electromyography and kinesiography promoted by Jankelson provide objective diagnostic measurements, while tens, relaxing masticatory muscles, allows a correct recording of myocentric occlusion. In this case, the authors utilise these devices, according to a well established diagnostic and therapeutic protocol. The first step is purely gnatologic, and consists of the application of an orthotic to temporarily treat pain and dysfunction. The following phase is a simple orthodontic treatment representing the final therapy. Orthodontic and/or prosthodontic rehabilitation of dentition, in fact, is the ultimate step of the therapeutic scheme which allows long-lasting RESULTS.

Intact colonic motor response to sudden awakening from sleep in patients with chronic idiopathic (slow-transit) constipation.

PURPOSE: There are few data about the relationships between colonic motor behavior and higher brain functions, such as sleep. Previous studies were done in healthy subjects, and it is unknown whether patients with functional motor disorders of the colon behave differently. This study was designed to characterize colonic motor activity in patients with constipation, both during sleep and after sudden awakening, and to compare it with that of healthy subjects. Our working hypothesis was that patients with constipation would have an impaired response to sudden awakening. PATIENTS AND METHODS: Twelve chronically constipated women, 22 to 49 years old, were recruited for the study, and their data were compared with those obtained from 12 healthy female volunteers, 21 to 38 years old. Manometric studies were performed in the descending and sigmoid colon for 30 minutes during sleep (immediately before awakening) and 30 minutes after being awakened suddenly. A motility index was calculated before and after the stimulus. RESULTS: In both groups motility in the descending and the sigmoid colon was almost absent during sleep and significantly increased after sudden awakening. No difference in postawakening values was found between patients with constipation and controls. CONCLUSIONS: In patients with chronic constipation, the brain-gut control of some fundamental mechanisms governing colonic motility is preserved. These data suggest that the alterations of colonic motility described in chronic constipation may be caused by an intrinsic dysfunction of the viscus.

NSAIDs upregulate beta 2-integrin expression on human neutrophils through a calcium-dependent pathway.

BACKGROUND: Margination of circulating neutrophils (PMN) into the gastric microcirculation is an early and critical event in the pathogenesis of non-steroidal antinflammatory drug (NSAID)-induced gastropathy. This effect is mediated through the upregulation of beta 2 integrins on the PMN surface. AIMS: To investigate whether indomethacin modulates: (1) Mac-1 expression; (2) Ca2+ mobilization ([Ca2+]i), protein kinase C and nitric oxide accumulation; and (3) mitogen-associated protein kinase phosphorylation in human PMN. METHODS: Human PMN were isolated by centrifugation through a double Ficoll gradient. [Ca2+]i was measured in PMN loaded with fura-2 and Mac-1 expression by flow cytometry. RESULTS: Indomethacin caused a concentration- and time-dependent upregulation of CD11b and CD18 expression and PMN adhesion to endothelial cells. Maximal upregulation of Mac-1 expression (40-50%) occurred after a 30-min incubation with 0.1mM indomethacin. The effect was prevented by removing the Ca2+. Ionomycin and thapsigargin caused a 7-10-fold increase in [Ca2+]i and a 2-4-fold increase in Mac-1 expression. Indomethacin induced a concentration-dependent phosphorylation of a 41-kDa mitogen-associated protein kinase. Tyrosine kinase inhibitors prevented the effect of indomethacin on Mac-1 expression and Ca2+ mobilization. Indomethacin and ionomycin increased superoxide generation, myeloperoxidase secretion and PMN adherence to endothelial cells and stimulated nitric oxide production. Indomethacin-induced Mac-1 upregulation was prevented by a nitric oxide synthase inhibitor. CONCLUSIONS: Indomethacin-induced upregulation of Mac-1 is mediated by changes in [Ca2+]i and nitric oxide. Phosphorylation of the 41-kDa mitogen-associated protein isoform is a previously unreported target of NSAID action. These effects might help to explain the ability of indomethacin to cause gastric neutrophil margination.

Interleukin 10 reduces lethality and hepatic injury induced by lipopolysaccharide in galactosamine-sensitized mice.

BACKGROUND & AIMS: Tumor necrosis factor alpha (TNF-alpha) release plays a pivotal role in the pathogenesis of liver injury induced by lipopolysaccharide (LPS) administration in D-galactosamine (GalN)-sensitized mice. Interleukin (IL) 10 is an anti-inflammatory cytokine that inhibits TNF-alpha synthesis and release both in vitro and in vivo and prevents lethality from experimental endotoxemia. The present study was designed to ascertain whether in vivo treatment with IL-10 protects mice against LPS/GalN-induced liver injury. METHODS: Mice were treated with an intraperitoneal dose of LPS/GalN with or without IL-10 pretreatment. Liver injury was assessed biochemically and histologically, and plasma TNF-alpha levels, liver myeloperoxidase activity, and adhesion molecule expression were determined. RESULTS: Administration of LPS in GalN-sensitized mice caused lethal shock and massive hepatic necrosis in almost 100% of the mice. The effect was associated with a significant increase in plasma TNF-alpha concentrations, liver myeloperoxidase activity, and up-regulation of adhesion molecules on liver specimens and circulating neutrophils. Pretreatment with IL-10 reduced plasma TNF-alpha concentrations and LPS/GalN-induced liver injury and lethality. Moreover, IL-10 reduced the LPS/GalN-induced liver neutrophil margination and up-regulation of adhesion molecules both on liver specimens and circulating neutrophils. CONCLUSIONS: The present results suggest that IL-10 therapy could be useful in the treatment of TNF-alpha-mediated liver diseases.

[Oto-vestibular symptoms in patients with temporomandibular joint dysfunction. Electromyographic study]. / I sintomi otovestibolari nei pazienti con disfunzioni dell'articolazione temporomandibolare. Studio elettromiografico.

The authors analyse the otovestibular symptoms (acoupheny, muffled hearing, vertigo, hypoacusia, otalgia) present among other symptoms of craniomandibular dysfunctions. A number of hypotheses have been advanced regarding the etiopathogenesis of these symptoms, but all stem from three theories. The first theory is based on the possibility of a mechanical transmission of force from the temporomandibular joint to the middle ear by the discomalleolar ligament. Another theory hypothesises the possible direct irritation by the condyl on the auriculotemporal nerve. The most widely credited etiopathogenetic theory, which is examined in this study, is that the hypertone of the tensor muscle of the tympanum and the tensor muscle of the velum palatinum, which are innervated like the masticatory muscles of the mandibular branch of the trigeminal nerve is the effect of these same muscles' hypertone. A group of 53 adult patients was selected to verify this theory. All patients were receiving treatment for dysfunctions of the temporomandibular articulation. Initial data were collected relating to the prevalence of each of the otovestibular symptoms studied; each patient then underwent computerised electromyographic analysis while the right and lefthand masseter and temporal muscles were resting. All tests were performed by the same operator. When analysing the results, patients were divided into two groups: one group contained those patients who had no symptoms relating to the ear, and the other contained patients with at least one symptom relating to the ear. Moreover, the group of symptomatic patients was divided into subgroups of patients with 1, 2, 3, and 4 of the symptoms studied. The mean electromyographical values for each muscle examined were then compared. The following results were obtained: 67.9% of subjects examined presented at least one otovestibular symptom; the symptom that was most frequently found was the feeling of muffled hearing (41.5%), followed by otalgia and vertigo; the prevalence of otalgia was much lower (7.5%). The most interesting finding emerged from a comparison between electromyographical values in patients suffering from otovestibular symptoms and the asymptomatic group. There was no significant difference in this series between this two groups, and the mean electromyographical value was higher in the group of asymptomatic patients.

Idiopathic megarectum in adults. An assessment of manometric and radiologic variables.

Outlet obstruction is thought to be one of the major factors responsible for idiopathic constipation. However, outlet obstruction itself may be due to several mechanisms. Among these, the presence of a megarectum is a leading one. Pathophysiological studies in adult patients with idiopathic megarectum are scarce. We studied by manometric and defecographic means 15 adult subjects with idiopathic megarectum and severe chronic constipation. Twenty-five healthy volunteers of both sexes acted as controls. Manometric variables showed significant differences between patients and controls with respect to internal anal sphincter pressure (P = 0.02), minimum relaxation volume (P < 0.001), defecatory sensory threshold (P < 0.001), mean rectal tolerable volume (P < 0.001), and rectal compliance (P < 0.001). An altered response to straining was observed in 46.6% of patients and in 12% of controls (P < 0.04); the ability to expel a 50-ml balloon per anum was 13.3% in patients and 100% in controls (P < 0.001). Although all patients opened the anorectal angle and had descent of the pelvic floor, thereby confirming an adequate expulsion effort, evacuation of contrast material appeared extremely difficult. In fact, no subject was able to expel more than 30% of the rectal contents during fluoroscopic screening. These results confirm previous hypotheses that idiopathic megarectum displays features of a neuropathic process as an underlying mechanism. Further studies are needed that also take into consideration the muscle tone component of the rectum in these patients.

Severe gastric mucosal damage induced by NSAIDs in healthy subjects is associated with Helicobacter pylori infection and high levels of serum pepsinogens.

Helicobacter pylori infection and NSAIDs are considered the two most important exogenous factors in ulcer disease. The interrelation between the two factors is not, however, clear. Moreover, serum pepsinogen has been suggested as a risk marker for the development of NSAID-induced gastrointestinal lesions. Fifty-one healthy volunteers, enrolled in a prospective, double-blind study carried out to evaluate gastrointestinal side effects of meloxicam and piroxicam, were analyzed to determine whether: (1) the prevalence of H. pylori correlates with the occurrence and severity of NSAID-induced gastrointestinal lesions, and (2) serum pepsinogen A and C levels could be used as markers of NSAID-induced mucosal damage. Upper endoscopy was performed by the same investigator before and after 28 days of treatment with placebo, meloxicam (7.5 mg/day and 15 mg/day), or piroxicam (20 mg/day). NSAID-induced damage was graded separately for hemorrhages and erosion ulcers according to Lanza's scale. There were no statistically significant differences in the prevalence of H. pylori in subjects with and without NSAID-induced mucosal lesions. However, there was a positive association between H. pylori infection and the severity of mucosal damage: total mean endoscopic score was 2.9 +/- 0.3 in H. pylori-positive subjects versus 1.6 +/- 0.5 in H. pylori-negative subjects (P < 0.05). Pepsinogen A and C levels increased from 55.3 +/- 3 to 149.4 +/- 15 and from 6.3 +/- 0.5 to 11.5 +/- 2.2, respectively (P < 0.05) in subjects who developed severe endoscopic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

[Standard electromyographic and kinesiographic parameters in a sample of healthy population]. / Ricerca parametri elettromiografici e kinesiografici standard in un campione di popolazione sana.

The authors have examined through the electromygraphic-kinesiographic system provided, the mandibolar movements and the electric activity of the masseter and temporal muscles of group of 25 subjects, aged 22-25 (15 women and 10 men), with complete natural dentition, whose history and clinical examination of cranio-mandibular disorders were negative. The aim of the study is to analyse the values come out by these instrumental researches and to compare them with the already existing literature, trying to obtain standard data of "normality", to be used as comparative and diagnostic parameters for this age range and, on the other hand, as a further method of evaluation for electromyiografic-kinesiographic and electromyiographic analysis of subjects suffering from algic-dysfunctional pathology of the cranio-mandibular apparatus. The analysed champion of healthy subjects, with symmetrical electromyiographic normal values (temporan muscles 0.5-2.5 microvolts, masseter muscles 0.5-2.0 microvolts), presents physiological mandibular movementes along the three space axes: furthermore the results outlined by the existing literature, according to which the female champion has a lower muscular electric potential and mandibular dinamic paths than the male champion, are confirmed. The authors point out the importance of computerised clinical research, not only to get data, but also to store them and to be able to compare them in long term.

Circadian variations in gastric acid and pepsin secretion and intragastric bile acid in patients with reflux esophagitis and in healthy controls.

OBJECTIVES: Duodenogastric reflux is a physiological phenomenon in both fasting and postprandial state. Because this suggests that bile acids may reflux into the esophagus together with the acid in patients with reflux esophagitis, we investigated the circadian variations of acid and pepsin secretion and intragastric bile acid concentrations in 25 patients with reflux esophagitis and in 15 healthy controls. METHODS: Between-meal, nocturnal gastric and meal-stimulated acid and pepsin secretion and bile acid concentrations were measured by continuous gastric aspiration and intragastric titration. RESULTS: Bile acids were found in 85 and 59% of gastric samples (p < 0.05). Intragastric bile acid concentrations were 6-8-fold higher in esophagitis patients than controls during the day. Approximately 10% of gastric samples from reflux esophagitis patients had a pH greater than 7, and all contained more than 500 mumol/L bile acids. Bile acids and pepsin were simultaneously revealed in 98% of the gastric samples from patients with reflux esophagitis with pH less than 4. Mean daily acid output (meal excluded) averaged 3.5 +/- 0.1 in healthy subjects and 2.7 +/- 0.2 mmol/30 minutes in esophagitis patients (p < 0.05); meal-induced acid secretions were similar. Total (24-h) acid secretion averaged 192.3 +/- 12.4 and 162.4 +/- 10.5 mmol/24 h (p < 0.05). There were no differences in the daily pepsin output. CONCLUSIONS: Our data indicate that almost all "acid" gastroesophageal refluxes should be considered as "mixed" refluxes. Because bile acids are found in the stomach irrespective of whether the environment was acid or alkaline, pH-metry provides no useful information on the pattern of duodenogastric reflux into the esophagus. Variability in the composition of the gastro-esophageal refluxate may explain why the severity of esophageal lesions differs in patients with similar pattern of acid refluxes.

Pentoxifylline prevents indomethacin induced acute gastric mucosal damage in rats: role of tumour necrosis factor alpha.

Neutrophil adherence within the gastric microcirculation is thought to be a major step in the pathogenesis of gastric mucosal damage induced by indomethacin. Pentoxifylline, a methylxanthine derivative, prevents leukocyte adherence to vascular endothelium and protects organs from shock by reducing tumour necrosis factor alpha (TNF alpha) concentrations. Rats were treated with 20 mg/kg oral indomethacin, pretreated with vehicle or with four different doses of pentoxifylline intraperitoneally, and killed after three hours. The gross gastric mucosal injury, neutrophil margination into the gastric microcirculation, mucosal concentrations of 6-keto-prostaglandin F1 alpha (PGF1 alpha), and PGE2 and serum TNF alpha values were measured. Whether the pentoxifylline induced protection involved nitric oxide mediated pathways or gastric acid secretion was evaluated. The data indicate that pentoxifylline reduces indomethacin induced mucosal damage and neutrophil margination in a dose dependent manner without exerting any effect on gastric mucosal prostaglandin concentrations. The maximally effective dose (200 mg/kg) of pentoxifylline reduced gastric damage by 90% and slightly stimulated acid secretion. The effect of pentoxifylline was not affected by pretreatment with the nitric oxide inhibitor. Pentoxifylline prevented the indomethacin induced increase in TNF alpha concentrations in a dose dependent fashion. Serum TNF alpha values were 30.5 (7.0) IU/ml (mean (SEM)) in rats treated with indomethacin alone and 5.0 (2.5) IU/ml (p < 0.01) in rats treated with indomethacin plus 200 mg/kg pentoxifylline. Pentoxifylline, therefore, prevents the acute gastric mucosal damage and neutrophil margination induced by indomethacin and reduces indomethacin induced release of TNF alpha.

[Goniotomy in congenital glaucoma: therapeutic results]. / La goniotomie dans le glaucome congénital: résultats thérapeutiques.

Sixty-eight eyes presenting with congenital glaucoma and operated on by goniotomy, have been followed up for 1 to 10 years. Intra-ocular pressure was normalized in 91.18 p. cent of cases by one or more goniotomies with or without medical treatment. We have also analyzed the functional results of these operations.

[Lipid parameters in a homogeneous population sample in relation to age and sex]. / Studio dei parametri lipidici in un campione omogeneo di popolazione in rapporto all'età ed al sesso.

The authors have examined the total cholesterol, the HDL cholesterol, the LDL cholesterol, triglycerides, and the HDL cholesterol/total cholesterol ratio on 313 men and 305 women divided into groups in relation with age (40 years, 40-60 years, 60 years). Significant differences have emerged comparing these different subgroups as regards the considered parameters. About examined population, we have observed higher value of all principal seric lipids than national media. Implications of these data in the evaluation of cardiovascular disease are discussed.

[Urinary infections in patients in the U.S.L. 25 Val di Cornia. Percentage frequency and sensitivity to antibiotics]. / Infezioni urinarie in pazienti nella U.S.L. 25 Val di Cornia. Frequenza percentuale e sensibilità agli antibiotici.

In order to estimate the present situation concerning bacterial resistance to a group of widely-used antibiotics, the results of several antibiograms, which were carried out from October 1984 to February 1985 on bacterial stocks isolated from urinary cultures sent to the Laboratory of Clinical Chemistry at the Campiglia Marittima Hospital U.S.L. 25 (Livorno) have been collected. The bacterial species most frequently observed are Gram-negative, namely: Escherichia coli (54%), Proteus (19%), Klebsiella (13%) and Pseudomonas (9%). E. coli turned out to be particularly sensitive to cephotaxim, phosphomicin, nalidixic acid but only slightly to gentamycin. Klebsiella was very sensitive to cephotaxim, gentamycin and amikacin, while Proteus reacted positively against cephotaxim, aztreonam and oxolinic acid. Pseudomonas was resistant to nearly every antibiotic examined, except amikacin and aztreonam. Overall analysis reveals that cephotaxim an aztreonam are the most active on E. coli, Proteus and Klebsiella, while gentamycin is only slightly.

Mechanism of smooth muscle relaxation by rociverine.

Experiments were carried out in vitro on a new antispasmodic drug, 2-(diethylamino)-1-methylethyl-cis-1-hydroxy[bicyclohexyl] -2-carboxylate (rociverine), to elucidate further the mechanism of its smooth-muscle relaxation. On the furtrethonium contractions of rat jejunum rociverine exerts both a competitive antagonism, about 3000 times less than that of atropine, and a noncompetitive antagonism equal to that of papaverine. Both on rat vas deferens and on rabbit aorta rociverine at low doses slightly potentiates the response to norepinephrine (unrelated to any inhibition of uptakes), whereas at higher doses it depresses the maximum effect, 10 times more on the vas deferens than on the aorta. Against calcium in the same preparations rociverine behaves as a competitive antagonist with 10 times less potency than verapamil on the vas deferens and 300 times less on the aorta. In negative inotropic and chronotropic action on guinea-pig atria rociverine is 300 and 100 times, respectively, less potent than verapamil and in negative inotropic action on KCl-depolarized guinea-pig ventricular strips, whose contractility is restored by histamine, it is 70 times less potent than verapamil. In sum, the smooth-muscle relaxant action of rociverine depends on a modest antimuscarinic action and a direct myolytic action, the latter probably being due to an inhibitory action on the transmembrane fluxes of Ca2+. The potency ratio relative to verapamil indicates that the anti-Ca2+ action of rociverine is greater on the visceral smooth muscle than on cardiac and vascular muscle.

Effects of spasmolytics on K+-induced contraction of rat intestine in vivo.

Eight spasmolytic drugs commonly used in the treatment of the irritable bowel syndrome were compared to verapamil with respect to their effects (all drugs injected i.v.) on the contraction of duodenum, ileum and colon induced by high K+ topical application in the anaesthetized rat. Verapamil greater than rociverine greater than papaverine greater than mebeverine greater than dicyclomine antagonized dose-dependently the contraction of duodenum and colon, the activity on duodenum being from 2 (rociverine) to 10 (verapamil) fold higher. Verapamil and rociverine, but not the other drugs mentioned above, were also active on ileum. N-Butylscopolammonium bromide, phloroglucinol and trimebutine were inactive against the contraction of the three intestinal tracts and prifinium bromide was inactive on duodenum and ileum, while it had remarkable activity on colon, unrelated to its antimuscarinic activity. The results are discussed briefly with reference to the pharmacological therapy of the irritable bowel syndrome.