Role of baseline human immunodeficiency virus genotype as a predictor of viral response to tenofovir in heavily pretreated patients

Human immunodeficiency virus (HIV)-infected patients (n = 153) failing antiretroviral therapy after exposure to compounds from all three drug families were monitored for 6 months after beginning a rescue intervention program including tenofovir (TDF). At 3 months, levels of HIV RNA in plasma dropped by a mean of 0.9 log(10) and the mean CD4 count increased by 52 cells/ micro l. At 6 months, HIV RNA levels had dropped by a mean of 1.06 log(10) and the mean CD4 count had increased by 49 cells/ micro l. Only five (3.7%) patients discontinued TDF use due to adverse events. In the multivariate analysis, the presence of M41L and/or L210W at baseline was the only viral determinant of a lower response to TDF.     

Autoreactive CD8 T cells in organ-specific autoimmunity: emerging targets for therapeutic intervention

The importance of CD8 T cells in the pathogenesis of organ-specific autoimmune diseases has not previously been well recognized. Recent evidence, however, indicates that autoreactive CD8 T cells can contribute substantially to tissue damage in both murine and human autoimmune disorders. As such, these T cells now become an attractive target for therapeutic intervention.     

External validation of a prognostic model for predicting survival of cirrhotic patients with refractory ascites

OBJECTIVE: Cirrhotic patients with refractory ascites (RA) have a poor prognosis, although individual survival varies greatly. A model that could predict survival for patients with RA would be helpful in planning treatment. Moreover, in cases of potential liver transplantation, a model of these characteristics would provide the bases for establishing priorities of organ allocation and the selection of patients for a living donor graft. Recently, we developed a model to predict survival of patients with RA. The aim of this study was to establish its generalizability for predicting the survival of patients with RA. METHODS: The model was validated by assessing its performance in an external cohort of patients with RA included in a multicenter, randomized, controlled trial that compared large-volume paracentesis and peritoneovenous shunt. The values for actual and model-predicted survival of three risk groups of patients, established according to the model, were compared graphically and by means of the one-sample log-rank test. RESULTS: The model provided a very good fit to the survival data of the three risk groups in the validation cohort. We also found good agreement between the survival predicted from the model and the observed survival when patients treated with peritoneovenous shunt and with paracentesis were considered separately. CONCLUSION: Our survival model can be used to predict the survival of patients with RA and may be a useful tool in clinical decision making, especially in deciding priority for liver transplantation.     

Early closure of temporary stoma of the small bowel

AIM: Transient small bowel stoma is usually closed 9-12 weeks after initial operation (late closure). Since these stoma have a poor physiological and psychological impact with frequent social consequences, we wanted to estimate feasibility and results of early closure of small bowel stoma. PATIENTS AND METHOD: From January 1998 to December 2001, 39 patients (21 women and 18 men, mean age: 64 years) with a transient small bowel stoma were elected for early closure. Early closure was performed only if the patient was in good condition, and without developing wound or general sepsis. In the other patients, the stoma was closed in the usually recommended delay (> 8 weeks). Fifteen patients had an early closure of their stoma in a mean delay of 10.0 +/- 0.8 days after the initial procedure. Twenty-four patients had a late closure of their stoma in a mean delay of 11.4 +/- 3.7 weeks. RESULTS: There were no postoperative deaths and no intestinal fistula. Four (10%) wound abscesses occurred and were managed without any surgical procedure, 3 in the early closure group (20%) and 1 in the late closure group (4%) (P=0.85, NS). Time to recovered bowel activity and to resumed oral feeding were equivalent in the two groups. The mean length of hospital stay was longer in the delayed group (34.5 +/- 18.6 days) than in the early group (23.1 +/- 4.6 days) (P<0.01). CONCLUSION: Early closure of bowel stoma can be performed without major complications in elective patients. This procedure shortens hospital stay.     

Neuropsychologic differences between bilateral dyskinetic and spastic cerebral palsy

This study compared the neuropsychologic performance of 30 adolescents and adults with bilateral dyskinetic, mixed, and spastic cerebral palsy aged between 16 and 38 years. The sample was relatively homogeneous in terms of motor severity; no patients were able to walk unaided. In all subjects, we evaluated the general function of nonverbal reasoning and the following specific neuropsychologic areas: language, visual perception, memory, praxis, and frontal functions. Individuals with dyskinetic cerebral palsy had better auditory comprehension, visuospatial abilities, immediate visual memory, and working verbal memory than those with spastic cerebral palsy. Frontal function was the only cognitive function on which subjects with dyskinetic cerebral palsy had lower scores. We conclude that the neuropsychologic profiles of dyskinetic and spastic cerebral palsy are different.     

Comparison of enalapril and valsartan in cyclosporine A-induced hypertension and nephrotoxicity in spontaneously hypertensive rats on high-sodium diet

1. We compared the effects of the angiotensin converting enzyme (ACE) inhibitor enalapril and the angiotensin AT(1) receptor antagonist valsartan in cyclosporine A (CsA)-induced hypertension and nephrotoxicity in spontaneously hypertensive rats (SHR). 2. SHR (8 - 9 weeks old) on high-sodium diet were given CsA (5 mg kg(-1)d (-1) s.c. ) for 6 weeks. The rats were treated concomitantly either with enalapril (30 mg kg(-1)d (-1) p.o.) or valsartan (3 or 30 mg kg(-1) d (-1) p.o.). To evaluate the role of bradykinin in the action of enalapril, some rats received a bradykinin B(2) receptor antagonist icatibant (HOE 140, 500 microg kg(-1) d (-1) s.c.) during the last 2 weeks of enalapril treatment. 3. Blood pressure was recorded every second week by tail cuff method. Renal function was measured by serum creatinine, creatinine clearance and urinary excretion of proteins at the end of the experiment. The activity of the renal kallikrein-kinin system was estimated by urinary kallikrein excretion. 4. CsA caused hypertension, impaired renal function and induced morphological nephrotoxicity with glomerular damage and interstitial fibrosis. Enalapril and the lower dose of valsartan attenuated the CsA-induced hypertension to the same extent, while the higher dose of valsartan totally abolished it. Icatibant did not reduce the antihypertensive effect of enalapril. Urinary kallikrein excretion was similar in all groups. 5. Enalapril and valsartan equally prevented the CsA-induced deterioration of kidney function and morphology. 6. The renin-angiotensin but not the kallikrein-kinin system plays a crucial role in CsA-toxicity during high intake of sodium in SHR.     

X-ray computed tomography and synovial chondrometaplasia

Scanography allows diagnosis of radiotransparent intra-articular foreign bodies and establishment of their synovial origin, sometimes even in the absence of joint opacification. It provides an overall assessment of the joint that can be improved by arthrography. Clinical and standard radiologic pictures of primary synovial chondrometaplasia (synovial osteochondromatosis) and intra-articular foreign bodies can cause confusion if the latter are modified by secondary chondrometaplasia. Scanographic analysis of islets of chondrometaplasia suggests their primary nature in the presence of plaques of calcification of a small size, of low density and diffused throughout the image while peripheral, lamellar, dense calcifications are suggestive of secondary lesions.