Discovery of novel and potent benzhydryl-tropane trypanocides highly selective for Trypanosoma cruzi.

A benzhydryl tropinone oxime that is potently toxic to Trypanosoma cruzi has been previously identified. An SAR investigation determined that no part of the original compound was superfluous and all early SAR probes led to significant drops in activity. The only alteration that could be achieved without loss of activity was replacement of the aryl chloride substituent with chloro homologues. This led to the discovery of a trifluoromethyl-containing analogue with an EC(50) against T. cruzi of 30 nM and a cytotoxicity selectivity index of over 1000 relative to rat skeletal myoblast L-6 cells.

FRAXE mutation in a mentally retarded subject and in his phenotypically normal twin brother.

The FRAXE fragile site, 600 kb distal to the more common FRAXA, has been reported to be expressed in subjects with mild non-syndromal mental retardation (MR). Amplification of more than 200 GCC repeats, associated with methylation of the adjacent CpG island at Xq28, leads to the expression of the fragile site. In 1996 a large gene, FMR2, transcribed distally from the CpG island and downregulated by repeat expansion and methylation, was identified. Among 232 mentally retarded patients, tested FRAXA negative, we identified an Italian family segregating a hypermethylated expansion at the FRAXE locus in two dizygotic twin brothers, their sister and their mother. The index case was referred at 23 years of age with severe MR, epilepsy, a dysmorphic face with a high arched palate, marfanoid habitus and hyperreflexia of the lower limbs. His brother was referred to as normal and psychometric tests confirmed he is not mentally retarded. All members of the family underwent FRAXE molecular analysis, after cytogenetic expression of the fraX site and negative FRAXA test. Interestingly, an expansion and a hypermethylation at the FRAXE locus were found in all of them. Fibroblasts from the clinically normal brother were assayed for FMR2 expression and the transcription of the gene was found to be silenced. The presence of a phenotypically normal male with absent FMR2 expression in fibroblasts suggests that the relationship between the FRAXE mutation, FMR2 expression and MR needs to be further investigated.

[Right atrial thrombosis with concomitant thrombus attached to a central venous catheter. Clinical case]. / Trombosi atriale destra con concomitante trombo adeso al catetere venoso centrale. Caso clinico.

A clinical case of a patient in whom a right atrial thrombosis was casually discovered by transthoracic echocardiography is described. The hypothesis that also the central venous catheter (CVC) could be seat of thrombosis was done, and was confirmed by chest X-ray with dye injection in the CVC. A thrombolytic therapy with plasminogen tissular activator and with heparin infusion was started. After 24 hours from the beginning of therapy instrumental control were performed (transesophageal echocardiography ECOTEE, chest X-ray with dye injection in CVC), showing the completely dissolution of the thrombus. It is observed that, when in a patient with CVC high degree of thrombogenic factors (age over 60 years, presence of cardiac arrhythmias with ventricular hypokinesis, polyglobulia due to chronic obstructive pulmonary disease, CVC, low levels of antithrombin III) are present, the usual prophylactic measures (subcutaneous heparin, hydrophylic catheter) couldn't be sufficient to avoid superior caval vein thrombosis. The conclusion is drawn that these patient should be studied with ECOTEE and eco Doppler. Chest tomography and superior caval venography are also useful its early diagnosis of superior caval thrombosis.

Tertiary hepatic syphilis. A treatable cause of multinodular liver.

Although the incidence of syphilis is increasing, liver involvement in tertiary syphilis remains exceptional. We report a case of tertiary syphilis revealed by liver localization. The clinical picture was misleading, mimicking multinodular hepatic metastasis. The final diagnosis was suspected following a fine-needle ultrasound-guided biopsy of a liver nodule showing granulomas as well as acellular necrosis and confirmed by positive serum syphilitic reactions and the presence of spirochetes in the liver. The outcome was uneventful following antibiotic treatment. It is important to be aware of the misleading picture of the disease, which has a favorable prognosis provided that simple treatment is rapidly initiated.

Carcinomas of the colon with multidirectional differentiation. Report of two cases and review of the literature.

Two cases of colonic carcinomas with multidirectional differentiation are presented. Both tumors showed light microscopic and immunohistochemical evidence of areas of adenocarcinomatous, squamous cell carcinomatous, and neuroendocrine differentiation. Only six similar cases have been previously reported. These highly malignant tumors support the recent concept of a multipotential stem cell within the mucosa of the gastrointestinal tract capable of differentiation in several directions.

Epileptic seizures in patients with acute catatonic syndrome.

Acute catatonic syndrome is a condition that can be caused by a variety of metabolic, neurological, psychiatric, and toxic conditions, including neuroleptic malignant syndrome. Although ictal catatonia as a manifestation of non-convulsive status epilepticus has been described, reference to the occurrence of seizures in patients with acute catatonic syndrome is anecdotal. Twenty nine patients with acute catatonic syndrome were reviewed to identify patients with seizures after the onset of acute catatonic syndrome. Patients were divided into four diagnostic groups: affective (15), schizophrenic (eight), toxic (two), and organic (four). Seizures occurred in four patients (13.8%): two patients with dystonic seizures had viral encephalitis and schizophrenic disorder respectively; one patient with complex partial seizures had viral encephalitis and one patient with absence status had neuroleptic malignant syndrome. The results indicate the value of EEG in detection of epileptic activity in patients with acute catatonic syndrome, both at onset and in the course of such disturbance, particularly to provide a differential diagnosis between pseudo-seizures and neuroleptic-induced acute dystonia.

Hypnotic relaxation: a new sedative tool for colonoscopy?

Sedation is often justified in patients requiring colonoscopy. We investigated the potential usefulness of hypnotic relaxation in 13 women and 11 men (median age, 43 years; range, 22-67) for whom other forms of anesthesia were not available. Hypnotic relaxation resulted in moderate or deep sedation in 12 patients (nine women; p < 0.05). In the patients in whom hypnosis was successful, pain was less intense than in patients in whom hypnosis was unsuccessful (p < 0.001). In addition, all colonoscopies were completed in the successful group, versus 50% in the unsuccessful group (p < 0.05). The patients in the successful group all agreed to another examination under the same conditions, whereas only 2% in the unsuccessful group agreed (p < 0.001). Our study suggests that, in a subgroup of hypnotizable patients, hypnotic relaxation may be a safe alternative to drug sedation and merits further study.

[Aneurysmal malformation of the extrahepatic portal vein]. / Malformation anévrismale de la veine porte extrahépatique.

Malformations of extrahepatic portal vein are rare. We report a case of extrahepatic portal vein aneurysm which was incidentally found in a female patient, aged 67, suffering from alcoholic cirrhosis. This malformation was located at the portal bifurcation and presented ultrasonically as an oval, non-echogenic, parahilar mass, 38 mm in diameter, and in continuity with the portal trunk. On CT-scan and angiography, diagnosis of portal vein aneurysm located at its extrahepatic segment was confirmed. The cause of extrahepatic portal vein aneurysm remains controversial. A congenital and/or acquired origin induced by portal hypertension explains their development.

Ischemic stroke and atrial fibrillation. A clinical study.

In view of the higher prevalence of severe ischemic stroke among patients with atrial fibrillation (AF) and of the recently reported higher frequency of stroke with AF in females, 516 consecutive patients with ischemic stroke, of whom 93 had AF, were retrospectively evaluated. The main anamnestic, clinical and laboratory features of the AF and non-AF groups were statistically compared and the features of the AF group were statistically evaluated according to gender and age. Our results confirm the greater severity of stroke in AF patients than in non-AF patients and the higher frequency of stroke with AF in female patients. Moreover, a significantly higher frequency of stroke with AF was found in the male 60-69 and the female 80-89 age groups than in the other age groups. Relevant risk factors in females aged 80-89 were hypertension and left ventricular hypertrophy (LVH), while diabetes, alcohol, smoking and LVH prevailed among 60-69 year old males.

Wernicke-Korsakoff Encephalopathy Following Biliopancreatic Diversion.

Wernicke-Korsakoff disease with sensory-motor neuropathy was diagnosed in three out of a series of 1,663 patients (0.18%), with onset 2, 3 and 5 months after biliopancreatic diversion. Precipitating factors were vomiting, minimal food intake, anorexia, rapid weight loss, and glucose-containing intravenous feeding. Recovery was partial in two and complete in one of the patients. In the early postop, prophylactic thiamine should be given to the patients with excessively limited eating capacity. Larger doses of thiamine should be instituted parenterally either in the case of suspected Wernicke-Korsakoff encephalopathy or before starting feeding for protein malnutrition.

Transient global amnesia: a quantified electroencephalographic study.

In 13 patients who experienced transient global amnesia (TGA), quantified electroencephalographic (qEEG) records were carried out within 1 week of the episodes, and compared with those in 13 cases with cerebral transient ischemic attacks (TIA), and 13 normal controls, matched for age and sex. A statistical comparison of the absolute power showed few differences between TGA and TIA patients, and many statistical differences between TGA patients and controls. The qEEG pattern reveals an involvement of the temporo-parietal structures in TGA patients. These findings suggest the presence of subclinical sequelae, after the TGA attack.

[Septicemias after endoscopic retrograde cholangiopancreatography. Risk factors and antibiotic prophylaxis]. / Scepticémies après cholangiopancréatographie rétrograde endoscopique. Facteurs de risque et antibioprophylaxie.

The infection following endoscopic retrograde cholangiopancreatography (ERCP) is one of the most severe complications. The aim of the present study was to assess the prevalence and the prognosis of this complication, to look for the risk factors and to define bacterial ecology in order to put forward the most appropriate antibiotherapy. Two thousand and ten patients were included in this study. Among these, 51 (2.5%) had a septic complication following ERCP. Endoscopy biliary drainage was complete in 24 cases, incomplete in 19 and lacking in 8. Transhepatic biliary drainage was carried out in 17 cases. Sixteen patients (31%) with tumor obstructions died within 30 days after ERCP. Four risk factors were isolated when comparing infected patients with other patients: the completeness of biliary obstruction (90 vs 48%, P < 0.001); multiple cannulation attempts (1.76 +/- 1.12 vs 1.25 +/- 0.70, P < 0.001); the malignant nature of the obstruction (80 vs 23%, P < 0.002) and the lack of satisfactory drainage following endoscopy (53 vs 23%, P = 0.009). Pseudomonas aeruginosa was the most frequently isolated species, both from blood cultures (30%) and bile samples (23%). The preventive therapy of septic complications following ERCP must include strict rules concerning the disinfection of endoscopic material.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative electroencephalography in Parkinson's disease, dementia, depression and normal aging.

The relationship between depression and dementia in Parkinson's disease (PD) has rarely been explored. Using a quantitative EEG (qEEG) parameter, we studied four groups of subjects: PD, demented Alzheimer's type and major depressed patients and normal controls. The qEEG data were compared with those of the Mini-Mental State and the Hamilton Depression Scale. The qEEG pattern was different in the four groups of subjects. Moreover, there was a significant correlation between the qEEG data and the other variables, and, particularly, with the cognitive performances. Our findings demonstrate that the qEEG method of assessment may give valuable data for a better classification of dementia syndromes and for a distinction between dementia and pseudodementia.