[Acute gastrointestinal bleeding]. / Hémorragie digestive aiguë.

Gastrointestinal bleeding is among the major clinical challenges for the gastroenterologists and the initial approach is very complex. For a big part of bleeding lesions, it is important to perform an endoscopic hemostatis after the introduction of an intravenous treatment (that has to be started as soon as there is a clinical suspicion of an upper gastrointestinal bleeding). The significant progresses made during the last years have allowed firstly to see the entire small bowel mucosa (video capsule) and secondly new treatments have successfully replaced surgical interventions.

[Progress in 2008 for acid related diseases]. / Maladies peptiques.

The treatment of reflux disease did not change in the review period. PPI therapy remains the first line treatment and surgery the second line approach. Endoscopic anti-reflux procedures should be only performed in controlled studies. Beside the classic triple therapy, sequential treatment of Helicobacter pylori infection can today be considered as a first line therapy. PPI are effective in the prevention of gastroduodenal lesions and in the treatment of dyspeptic symptoms induced by NSAIDs treatment. Only patients younger then 65 years and without any risk factors do not need a preventive PPI prescription during classic NSAIDS treatment.

[Stomach diseases]. / Maladies peptiques.

A new generation of PPI are presently in clinical trials. They are characterized by a quicker and longer effectiveness, very useful for reflux disease treatment. We have to note that the enthusiasm towards the endoscopy treatment for reflux disease is clearly deceasing and two types of procedures have even been recalled from the market. In Helicobacter pylori eradication treatments the tendency tends towards high doses of antibiotics for the second option treatments. The indication for a COX-2 treatment is largely reduced due to the cardiac side effects of certain COX-2. For the patients with high risk of gastro-duodenal toxicity through AINS, the alternative remains the classical non-specific AINS treatment associated with a PPI.

Systemic acupuncture in patients with faecal incontinence.

CONTEXT: Faecal incontinence is defined as the involuntary loss of intestinal contents (whether faeces or gas). Although it is not frequently reported, it does cause physical and psychological distress. Traditional Chinese medicine believes that the healthy human body is originally in a state of balanced energy (Qi) between Yin and Yang, and all disorders that occur in the body are explained by disruptions in this energy balance. Acupuncture is a valuable therapy and is used as a therapeutic approach for the treatment of pelvic floor dysfunction. Data regarding faecal incontinence and acupuncture is scarce. This research describes the efficacy of using acupuncture in patients with faecal incontinence. PATIENTS AND METHODS: Eighteen adults (2 men and 16 women) underwent acupuncture therapy with traditional acupuncture needles for 10 weeks. Before and after treatment, all patients completed a Fecal Incontinence Quality of Life (FIQL) survey and the incontinence intensity was assessed using a visual analogue scale. RESULTS: After 10 sessions of acupuncture, all patients reported an improvement, and the vast majority of patients showed statistically significant improvements in both tests. CONCLUSION: Therefore, evidence now shows that acupuncture can improve the quality of life of patients undergoing faecal incontinence treatment.

[Peptic diseases]. / Maladies peptiques.

The therapeutical acquisitions of the year 2004 are: 1. The sequential treatment of the Helicobacter pylori infection reaches an eradication rate of 95%. 2. The use of COX-2 inhibitors reduced significantly the gastrointestinal side effects of anti-inflammatory treatments. Since cardiac averse effects of certain COX-2 inhibitors had been reported, the treatments with COX-2 inhibitors came widely into question. In the case of patients with risk of NSAID induced gastrointestinal toxicity, the alternative is to return to a treatment with non specific NSAID associated to an prophylactic PPI treatment.

Treatment of first tonic-clonic seizure does not improve the prognosis of epilepsy. First Seizure Trial Group (FIRST Group).

It is widely agreed that after two or more seizures patients should be given antiepileptic treatment, but there is still controversy about the treatment of patients after a first unprovoked seizure. In a multicenter, randomized, open trial, patients with a first tonic-clonic seizure were randomized to immediate treatment (carbamazepine, phenytoin, phenobarbital, or sodium valproate) or to treatment only after another seizure. Fifty-two (24%) of the 215 patients randomized to immediate treatment and 85 (42%) of the 204 randomized to delayed treatment experienced seizure recurrence during follow-up. Age, acute treatment of the seizure with benzodiazepines, remote etiologic factors, and EEG abnormalities were significant predictors of relapse. Of the immediately treated patients, 87% had no seizures for a year and 68% had no seizures for 2 years, whereas only slightly fewer initially untreated patients (83% and 60%) achieved these endpoints. Patients treated after the first seizure and those treated after seizure relapse had the same time-dependent probability of achieving 1 and 2 seizure-free years. None of the variables that were prognostic predictors of relapse was significantly associated with the probability of having 1 or 2 years of seizure control. Anticonvulsants in patients presenting a first tonic-clonic seizure reduce the risk of relapse; however, 50% of patients who are not treated will never experience a second seizure. Moreover, the probability of long-term remission is not influenced by treatment of the first seizure.

Synthesis and pharmacological evaluation of enantiomerically pure 4-deoxy-4-fluoromuscarines.

Four isomers of [(4-fluoro-5-methyl-tetrahydrofuran-2-yl)methyl]trimethylammonium iodide (4-deoxy-4-fluoro-muscarines) were prepared in enantiomerically and diastereomerically pure form from (S)-(-)-methyl 4-methylphenyl sulfoxide, ethyl fluoroacetate, and allyl bromide. Their absolute configurations were assigned by 1H NMR analyses. The four optically pure compounds were tested in vitro on guinea pig and their muscarinic potency was evaluated at M3 (ileum and bladder) and M2 (heart) muscarinic receptor subtypes. Compound 1a, the most potent isomer of the series, was also tested in vivo on pithed rat and its muscarinic activity at the M1 receptor subtype was compared with that of muscarine. Moreover, affinity and relative efficacy were calculated in vitro for this compound at M2 (heart force and rate) and M3 (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The 4-deoxy-4-fluoromuscarines display a similar trend of potency as the corresponding muscarines and compound 1a shows differences in the affinity constants among the studied tissues. Replacement of a hydroxyl group for a fluorine atom in the 4 position of muscarine produces 1 order of magnitude increase in affinity for cardiac M2 muscarinic receptors controlling rate, while the affinity at cardiac M2 muscarinic receptors controlling force is unchanged, opening the possibility of a further classification of cardiac muscarinic receptors.

The effect of intra-gastric acidity and flora on the concentration of N-nitroso compounds in the stomach.

BACKGROUND: Correa's hypothesis proposes that gastric carcinogenesis is due to atrophic gastritis and hypochlorhydria which permit gastric bacterial colonization, the reduction of dietary nitrates to nitrites and the formation of potentially carcinogenic N-nitroso compounds (NOCs). OBJECTIVE: To test the hypothesis that omeprazole-induced hypochlorhydria is associated with increased intra-gastric concentrations of nitrate-reducing bacteria (NRB), nitrites and NOCs. DESIGN: Single-blind study in healthy volunteers. PARTICIPANTS: Fourteen healthy subjects (seven female, mean age 24 years), free of Helicobacter pylori infection, received a one-week course of placebo followed by a two-week course of omeprazole, 20 mg daily. METHODS: Fasted gastric samples, aspirated using a sterile double-lumen nasogastric tube at the end of the 1 st week (placebo) and the 2nd and 3rd weeks (omeprazole), were cultured aerobically and anaerobically; gastric pH and intra-gastric concentrations of nitrates, nitrites and NOCs were also determined. RESULTS: After weeks 1, 2 and 3, the intra-gastric concentrations of nitrate-reducing bacteria exceeded 10(5) colony-forming units (c.f.u.)/ml in 3, 7 and 9 subjects, respectively (P > 0.05). A gastric pH greater than 4.0 was associated with increased NRB (P < 0.05); however, neither increased gastric pH nor increased NRB, alone or in combination, was associated with increased intra-gastric concentrations of nitrites or NOCs (P > 0.05). CONCLUSIONS: A two-week increase in gastric pH in healthy, H. pylori-negative subjects was associated with increased intra-gastric concentrations of nitrate-reducing bacteria but not of nitrites or N-nitroso compounds. These data suggest that reduced gastric acid secretion is not a necessary precursor to the formation of carcinogenic N-nitroso compounds and that other mechanisms should be invoked to explain gastric carcinogenesis.

Seizure and EEG patterns in Angelman's syndrome.

We studied the seizure and polygraphic patterns of 18 patients with Angelman's syndrome. All patients showed movement problems. Eleven patients were also reported to have long-lasting periods of jerky movements. The polygraphic recording showed a myoclonic status epilepticus in nine of them. Seven patients had partial seizures with eye deviation and vomiting, similar to those of childhood occipital epilepsies. These seizures and electroencephalographic patterns suggest that Angelman's syndrome occurs in most of the patients as a nonprogressive, age-dependent myoclonic encephalopathy with a prominent occipital involvement. These findings indicate that, whereas ataxia is a constant symptom in Angelman's syndrome, the occurrence of a transient myoclonic status epilepticus may account for the recurrence of different abnormal movements, namely the jerky ones.

Synthesis and evaluation of the antiviral activity of acyclic nucleosides carrying fluorine and sulfur substituents.

-2',3'-Seco nucleosides 5 carrying fluorine and sulfur substituents at C-3' and C-5', respectively, of acyclic sugar moiety were synthesized in enantiomerically and diastereoisomerically pure form. These products and some structurally similar 1',2'-seco-2'-nor-and 1',2'-seco-nucleosides 3 and 4 were tested in vitro for cytotoxicity and antiviral activity. At non-cytotoxic concentrations the compounds were inactive against human immunodeficiency virus and herpes simplex virus type-1.

[Long-term results of conservative management of reflux esophagitis]. / Langzeitergebnisse der konservativen Behandlung der Refluxösophagitis.

Reflux esophagitis is a frequent and chronic disease. Impairment of the quality of life by the reflux symptoms and the risk of complications are the most important indications for a long-term treatment. The base of the treatment of reflux esophagitis is the inhibition of the gastric acid secretion with proton pump inhibitors (PPI) or by H2-receptor antagonist. In general, PPI's are more efficient in the treatment of refluxesophagitis as compared to H2-receptor antagonists blockers regarding the relieve of symptoms and the healing of erosive esophageal lesions. The use of an antacids and procinetics in the long-term treatment is not indicated. The treatment strategy depends on the severity of the symptoms and the esophageal lesions. Patient with mild esophagitis can be treated either with H2-receptor antagonists or with PPI's on demand or continuous. In the case of severe esophagitis, a long-term treatment with PPI's is indicated to avoid complications. Recurrence of esophagitis during a long-term therapy should be treated by PPI's. After healing the long-term treatment should be adapted either by increasing the given dose of the medicament or by a switch to more effective medicaments in acid suppression.

Sonographic assessment of vessel invasion by cervical masses in dogs / Avaliação ultrassonográfica da invasão vascular por massas cervicais em cães

Tumor invasion of the vessels displays both therapeutic and prognostic implications and represents a challenge for head and neck surgeons. Although previous research has shown that ultrasound can detect such invasions, accurate sonographic parameters to do so have not yet been established. We sought to determine sonographic criteria which are able to characterize these invasions. A high-resolution transducer was used to perform ultrasound examinations of 15 patients selected from a group with inconclusive radiography and computed tomography diagnosis. We found that encasement of the vessel, tumor immobility or fixation in the vessel wall, and narrowing and/or deformity of the lumen were the best criteria. Indeed, when loss of hyperechoic interface of the vessel wall was used as a single criterion it generated false positive results. This study shows that a combination of parameters can be used to provide the best sensitivity and specificity values to produce conclusive diagnosis of vessel invasion by tumors in the cervical region.

Determinaram-se critérios ultrassonográficos capazes de caracterizar a invasão vascular por tumores em cães. Utilizaram-se transdutores de alta resolução para os exames ultrassonográficos realizados em 15 pacientes, selecionados de um grupo submetido previamente à radiografia e tomografia computadorizada, com resultados inconclusivos. Os melhores critérios encontrados foram: encarceramento do vaso, imobilidade do tumor ou aderência na parede vascular e estreitamento ou deformidade luminal. A perda de definição da interface hiperecoica da parede vascular quando foi usada como critério isolado produziu resultados falso positivos. O estudo demonstrou que uma combinação de parâmetros pode ser usada para aumentar a sensibilidade e especificidade diagnóstica, produzindo diagnósticos mais conclusivos e precisos pra definir a invasão vascular por tumores na região cervical ventral.

Unimolecular decomposition of M+. and [M+H]+ species of some fluorosubstituted acyclic nucleoside analogs.

Electron ionization and fast-atom bombardment mass spectrometry are shown to provide a valid analytical tool for the structural characterization of the title compounds. In fact, diagnostic fragmentation pathways were observed depending on the presence of different substituents (benzyloxy, (benzyloxy, p-tolylthio, p-tolylsulphinyl) as well as of different bases. Regioisomeric compounds could be differentiated by kinetic energy release measurements.

Infantile febrile status epilepticus: risk factors and outcome.

The medical records of 68 children who had had infantile febrile status epilepticus (FSE) were examined. Follow-up periods ranged from three to 28 years (mean 8 years 10 months). Details were abstracted of relevant medical events prior to FSE, diagnosis of the febrile illness, age at onset and main characteristics of FSE, and outcome (subsequent febrile convulsions and/or epilepsy, neurological and psychiatric disorders). Neither medical events prior to FSE nor aetiology of fever were associated with subsequent febrile convulsions, epilepsy, or neurological or psychiatric abnormalities. There was a significant association between age at onset of FSE and both subsequent epilepsy and CNS disorders. 12 of the 13 children who had had transient or persistent post-ictal hemiparesis subsequently developed epilepsy. Of the 46 children who later developed epilepsy, 34 had partial seizures and 12 had generalized seizures. The latter were more common among children who had had FSE before the age of one year. Likewise, all those who developed severe myoclonic epilepsy in infancy had their first FSE before age one. These findings suggest that age at onset of FSE is the most important feature determining long-term outcome.

Infantile spasms combined with partial seizures: electroclinical study of eleven cases.

We studied 11 infants (7 males) with combined infantile spasms (IS) and partial seizures. The age of onset of the spasms ranged from 6 days to 9 months. All of the children had neurological or CT/MRI abnormalities, and five also had a family history of epilepsy. The clinical and polygraphic patterns of the clusters of spasms combined with partial seizures were analysed. Ten infants were followed-up for a mean period of 3 years, 4 months (range 1 year 10 months to 4 years 11 months). At the last check-up, the seizures were controlled in 2 patients; the others continued to have spasms and/or partial seizures. All of the patients developed mild to severe psychomotor retardation. This condition defines a subgroup of infants presenting with IS, which is distinct from West syndrome.

Classifications of epileptic syndromes: advantages and limitations for evaluation of childhood epileptic syndromes in clinical practice.

The advantages and limitations of the two most recent International League Against Epilepsy classifications of the epilepsies and epileptic syndromes have been assessed after examining the clinical records of 645 consecutive outpatients aged 1 month to 15 years followed at the Children's Epilepsy Center of the University of Milan, Italy, from 1977 through 1985. The percentage of cases that could be classified according to the 1970 and 1985 proposals for classification were 94.1 and 98.1%, respectively. According to the 1985 proposal, partial epilepsies (PE) and generalized epilepsies (GE) were almost equally represented (45.0 vs. 47.2%). Among PE, symptomatic epilepsies were the commonest variety. In the group of GE, idiopathic and/or symptomatic epilepsies were most common. Childhood absence epilepsy was the largest subgroup among idiopathic GE. Newly diagnosed patients, a less biased sample of the epileptic population represented 38.9% of the entire sample, and a proper classification was possible in 96% of cases. Idiopathic epilepsies were about twice as frequent and idiopathic and/or symptomatic GE less frequent in newly diagnosed patients when compared with the remainder. Marked differences in the frequency of the epilepsies were found in comparison with other reports in the literature which used the 1970 classification. This finding probably depends on different diagnostic assessment, selection bias, and different geographic and ethnic components, but it can also reflect the variable interpretation of the clinical and EEG features of a patient with epilepsy in the light of the artifactual categories of the classification.

A randomized trial on the treatment of the first epileptic seizure. Scientific background, rationale, study design and protocol. First Seizure Trial Group (FIR.S.T. Group).

Observational studies suggest that the sooner treatment is started after the onset of seizures the better is the outcome of the disease. However, when to start antiepileptic treatment is still debated and this may explain the different behaviour of practising physicians. For these reasons, a multicenter randomized controlled trial comparing the treatment of the first seizure and the treatment of the recurrences (the two most common strategies in clinical practice) has been started in Italy. The scientific background, the study rationale and design, and the general characteristics of the study population (498 patients) are presented here.

Angelman's syndrome in the first year of life.

Angelman syndrome usually has been considered to be rare and sporadic. However, recent reports suggest a sibling recurrence risk of just under 25 per cent, so early diagnosis is very important. The authors report Angelman syndrome in a child of seven months. The early features of this syndrome (jerky movements, EEG characteristics, chromosomal abnormalities in half the cases) should make it possible to diagnose or suspect the syndrome in the first year of life.

Comparative pharmacokinetic study of chewable and conventional carbamazepine in children.

Fifteen children (7 boys and 8 girls) with generalized tonic-clonic seizures (GTCS) and partial seizures with elementary or complex symptomatology, treated with carbamazepine (CBZ) alone (n = 7) or in combination with either phenobarbital (PB, n = 6) or clobazam (CLB, n = 2) given for at least 3 months at stable individualized doses and regimens, entered an open, within-patient, change-over study of consecutive periods, each lasting 2 weeks. During period 1, conventional CBZ was given; during period 2, a chewable CBZ formulation was substituted for conventional CBZ and given at the same total daily dosage with the same schedule as in period 1. Blood samples for measuring plasma concentration of both total CBZ and CBZ-10,11 epoxide (CBZ-E) were taken on the last day of each period. No significant difference between the two periods was noted in the mean +/- SD of Cmax, Css mean, and area under the curve (AUC) of total CBZ and CBZ-E. The two different CBZ formulations, administered at the same total daily dosage, can be considered bioequivalent.