Intestinal T cell lymphoma in coeliac disease. A case report

Primary intestinal T-cell lymphomas account for about 5% of all primary gastrointestinal lymphomas and are mostly associated with coeliac disease. Intestinal lymphomas are usually discovered during the 4th to 5th decade and constitute an exceptional complication of coeliac disease. This lymphoma is generally a high grade pleomorphic cell lymphoma with large cells. Our case concerned a 30 year old woman with a history of coeliac disease who developed a gastro-enteromesenteric lymphoma. Anatomopathological and immunohistochemical analysis showed an enteropathy associated T-cell lymphoma. We suggest that patients with coeliac disease unresponsive to a gluten free diet or with deteriorating clinical condition be investigated for complications such as enteropathy associated T-cell lymphoma. It is also important to avoid this complication by detecting asymptomatic form of coeliac disease that needs a gluten-free diet.     

Sedative practice in intensive care units results of a Maghrebian survey

OBJECTIVES: sedation is central to the management of intensive care patients. The aim of this study was to establish the current sedation practice in Maghrebian intensive care units (ICUs). The use of sedation policies with or without a written protocol, the use of scoring systems, the influence of costs on drug choice, the most common drugs for sedation and the use of neuromuscular blocking agents. METHODS: a self-administered questionnaire composed of 20 items was sent to 138 intensivists in the Maghreb working in 25 teaching hospitals and 16 private clinics. RESULTS: 50 of 138 questionnaires were returned (response rate = 36.2%). Midazolam and Fentanyl were the main sedative agents used (respectively 98% and 87%) less than 14% of the ICUs used the Propofol mainly in the first 48 hours. A sedation policy was adopted in 63.6% with a written protocol in 20% of cases. Sedation scoring systems were noted in 14.3% of cases (RAMSAY scale in 100%). Economic aspect was important for 64.6% of ICUs. DISCUSSION: sedation may seem secondary in the initial management of intensive care patients, only 63% of our respondents had a sedation policy and 20% a written protocol though its use is thought to improve outcome and reduce costs. Economic aspect was important for the choice of the drug to use (64%), this may explain the preferential use of Midazolam 98% in association with an analgesic (Fentanyl: 85%) while Propofol is used only in 14% though pharmacoeconomic studies may be in fact in favor of the latter. Neuromuscular blocking agents are less frequently used (16%) mainly because of the risk of complications.     

Long-term follow-up of Epstein-Barr virus viremia in pediatric recipients of renal transplants

The common observation of Epstein-Barr virus (EBV) viremia in pediatric recipients of renal transplants and the occurrence of an EBV-related pulmonary leiomyoma prompted us to intensify the follow-up of EBV infections from 1995 to October 2000. Follow-up included serology and detection of viral DNA in blood using a semi-quantitative nested polymerase chain reaction (PCR) and later a real-time PCR with higher sensitivity. The aim of this study was the early detection of primary infections or reactivations. We obtained 250 samples from 32 patients. EBV DNA detection was consistently negative in 14 patients. There were 5 patients that were considered at risk for post-transplant lymphoproliferative disease, as they were EBV seronegative and were given a kidney from a positive donor. Of these, 4 had at least one episode of high-level EBV viremia. During these episodes, an absence of noticeable symptoms that could be related to EBV was noted for all but 1 patient. This child presented with severe neutropenia 1 month after grafting and, 28 months later, several nodules of pulmonary leiomyoma, which were found to be EBV related. Four episodes of high-level viremia were observed before the discovery of the leiomyoma. Viral DNA detection is important for the follow-up of such patients that are especially at risk of serious complications of EBV infections.     

Tracheotomy or prolonged tracheal intubation for long-term ventilation

130 critically ill patients undergoing long term mechanical ventilation were divided into two groups, tracheotomy versus translaryngeal intubation. There were no difference in demographic characteristics between the two groups. The incidence of chronic obstructive pulmonary disease (COPD) was also higher in T. The tracheotomy was achieved at mean within 14 days after the beginning of mechanical ventilation. The incidence of pneumonia is the same in the two groups (41% for T versus 39% for I). The length of mechanical ventilation is longer in T (25 +/- 12 d versus 12 +/- 4 d). The COPD represent a risk factor for prolonged mechanical ventilation in T (18 days in COPD patients with tracheotomy versus 9 days in non COPD patients). The length of stay in intensive care unit is higher in T (29 +/- 13 d versus 15 +/- 4 d). The 28th day mortality is similar between the two groups. The tracheotomy didn't allow a shorter duration of mechanical ventilation. That's can be explain by the fact that we performed the tracheotomy in a high risk population for pulmonary complications (COPD) and often after a first failure of weaning form mechanical ventilation.     

Alteration of the PATCHED locus in superficial bladder cancer

Chromosome 9 alterations are the most frequently encountered cytologic anomalies in urothelial carcinoma (UC). We previously screened 139 low-stage UCs for loss of heterozygosity on chromosome 9, and identified five distinct regions likely to harbour tumour-suppressor genes. The present study focused on deletion mapping in the 9q22 region with 11 additional microsatellite markers. New deletions in the 9q22 region were found in five tumours. Deletion mapping allowed us to identify a 0.5 CM common minimal region of deletion between markers D9S280 and D9S1809, encompassing PATCHED (PTC), a gene identified as a tumour suppressor in basal cell carcinoma and in medulloblastoma. A marker located in the first intron of this gene showed the highest percentage of deletion (45%). cDNA sequencing in 15 tumours with deletion of PTC showed no mutation in the remaining allele. However, average expression of PTC mRNA measured by semiquantitative RT-PCR was significantly decreased in tumours with LOH in the 9q22 region, compared to normal urothelium (P=0.04), while it showed marked fluctuations in tumours without deletion. Our results suggest that the PTC gene is a putative suppressor at the 9q22 locus and that haploinsufficiency of this gene may be an early event in the development of papillary bladder tumours.     

Antidyskinetic effect of JL-18, a clozapine analog, in parkinsonian monkeys

Clozapine reduces L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesias in parkinsonian patients. To test if the antidyskinetic effect of clozapine is related to antagonism at the dopamine D(4) receptor, we investigated the effect of 8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b][1, 4]benzodiazepine (JL-18), a structural analog of clozapine which is more selective for this receptor. Four 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys with a stable parkinsonian syndrome and reproducible dyskinesias to L-Dopa were used in this study. They were injected subcutaneously (s.c.) with L-Dopa methyl ester (125 mg per animal) plus benserazide (50 mg per animal; L-Dopa/benserazide) alone or in combination with JL-18 (at the doses of 0.1, 0.3, or 0.9 mg/kg, s.c.). Subcutaneous injection of sterile saline was used as control. L-Dopa/benserazide increased locomotion and improved parkinsonism but also induced dyskinesias. Co-administration of JL-18, at low doses (0.1, 0.3 mg/kg) with L-Dopa/benserazide, produced a dose-dependent reduction in L-Dopa-induced dyskinesias without a parallel return to parkinsonism. The present results suggest that novel selective dopamine D(4) receptor antagonists may represent a useful tool to reduce L-Dopa-induced dyskinesias.     

Significance of systolic anterior motion of the mitral valve during dobutamine stress echocardiography.

Left ventricular outflow tract obstruction related to systolic anterior motion of the mitral valve (SAM) induced during dobutamine stress echocardiography (DSE) is not unusual but its significance is not established. A total of 100 consecutive patients (mean age 62 +/- 12 years; 67% male) without previous transmural myocardial infarction, valvular disease, or hypertrophic cardiomyopathy, undergoing DSE to assess the presence of myocardial ischemia, were prospectively evaluated. A SAM with DSE was searched and correlated with clinical and baseline echocardiographic findings. Patients who demonstrated SAM with DSE were selected for exercise echocardiographic Doppler study with bicycle, within 6 months of the DSE. The development of an intraventricular gradient with DSE or exercise was defined as a new gradient of > or =36 mm Hg. In all, 23 patients developed SAM during DSE with a mean gradient of 79 +/- 33 mm Hg (range: 39-144 mm Hg) and mitral regurgitation related to SAM. Compared with patients without SAM, patients who developed SAM with DSE were characterized at rest by a smaller mitroaortic angle and septoaortic angle, a higher posterior mitral leaflet length, and a smaller left ventricular cavity. Neither ischemic nor hypotensive response during DSE were correlated to SAM. In the group of patients with SAM, of the 9 patients who were referred for unexplained chest pain or dyspnea, 5 reproduced symptoms with DSE, compared with 2 of 17 patients in the group without SAM (P = .005). Despite these findings, only 3 of the 16 patients who underwent exercise echocardiography Doppler study developed SAM (two with symptoms), with a wide range of achieved heart rate, compared with DSE. Although patients with SAM with DSE exhibit predisposing echocardiographic findings, the clinical impact of this phenomenon is real in only a minority of patients, particularly those who experienced unexplained dyspnea or chest pain.     

Defective fatty acid uptake modulates insulin responsiveness and metabolic responses to diet in CD36-null mice

Deficiency of the membrane protein FAT/CD36 causes a marked defect in fatty acid uptake by various tissues and is genetically linked to insulin resistance in rats and humans. Here, we examined insulin responsiveness of CD36-/- mice. When fed a diet high in complex carbohydrates and low (5%) in fat, these animals cleared glucose faster than the wild-type. In vivo, uptake of 2-fluorodeoxyglucose by muscle was increased severalfold, and in vitro, insulin responsiveness of glycogenesis by the soleus was enhanced. Null mice had lower glycogen levels in muscle and liver, lower muscle triglyceride levels, and increased liver triglyceride content--all findings consistent with increased insulin-sensitivity. However, when the chow diet was switched to one high in fructose, CD36-/- mice but not wild-type mice developed marked glucose intolerance, hyperinsulinemia, and decreased muscle glucose uptake. High-fat diets impaired glucose tolerance equally in both groups, although CD36 deficiency helped moderate insulin-responsive muscle glucose oxidation. In conclusion, CD36 deficiency enhances insulin responsiveness on a high-starch, low-fat diet. It predisposes to insulin resistance induced by high fructose and partially protects from that induced by high-fat diets. In humans, CD36 deficiency may be an important factor in the metabolic adaptation to diet and in susceptibility to some forms of diet-induced pathology.     

Antiplatelet effect of once- or twice-daily aspirin dosage in stable coronary artery disease patients with diabetes

The aim of this pilot study was to compare the effect of two different regimens of aspirin dosage on platelet of coronary artery disease (CAD) diabetic patients. Twenty-five CAD diabetic patients were included. Initially, all patients received aspirin 100 mg/day for 10 days. At day 10, aspirin antiplatelet effect was determined by measuring the collagen/epinephrine closure time (CT) 2 h after the last aspirin dosage and the next morning at 8 a.m.. The aspirin regimen was modified to 100 mg twice daily for patients showing a non-optimal platelet-inhibitory effect (CT < 298 s at 8 a.m.). Persistent high platelet reactivity (HPR) was defined by a CT < 160 s. During the 100 mg/day aspirin regimen, the prevalence of HPR at 8 a.m. was 48%, and only 7 patients (28%) had showed an optimal platelet-inhibitory effect. Bridging to the twice-daily regimen, the HPR was significantly reduced (p = 0.025), and the optimal platelet-inhibitory effect was reached for 3 other patients. Our results showed that 100 mg aspirin twice-daily dosing rather than a once-daily dose significantly improves the aspirin effect on platelet of CAD diabetic patients. However, large prospective studies were needed to confirm whether this strategy will be clinically relevant and safe.