Stem cell research and cell transplantation for myocardial regeneration.

Several human organs are not capable of functional regeneration following a tissue defect and react with scar formation. In stem cell transplantation, undifferentiated or partly differentiated precursor cells are applied to defective tissue for therapeutic regeneration. After promising preclinical investigations, the transplantation of autologous stem cells for myocardial infarction treatment is being transferred to clinical use. Mesenchymal stem cells and endothelial precursor cells derived from the bone marrow or circulating blood as well as skeletal myoblasts are employed in clinical trials. Furthermore, indications for cell transplantation and delivery routes vary considerably throughout current investigations. Initial results suggest a potential for restoration of cardiac function in stem cell-treated patients; however, the mechanisms are not fully understood. This overview will focus on objectives, recent achievements, and future perspectives of diverse stem cell transplantation approaches.     

False-negative diffusion-weighted MR findings in acute ischemic stroke

BACKGROUND AND PURPOSE: Lesions associated with acute stroke are often missed by diffusion-weighted imaging (DWI), suggesting that the sensitivity of this technique for detecting acute ischemic stroke may not be as high as initially thought. Our aim was to estimate the rate of false-negative DWI studies in patients with persistent neurologic deficit due to an ischemic stroke and to identify which stroke lesions are most likely to be missed by DWI. METHODS: We reviewed MR images obtained within 48 hours after stroke onset in 139 patients admitted for symptoms consistent with ischemic stroke in whom the deficit lasted more than 24 hours. Cases of negative initial DWI findings with an ischemic lesion visible on follow-up MR studies and a final diagnosis of arterial ischemic stroke were analyzed in terms of delay between onset of symptoms and initial DWI (MR latency), size and vascular distribution of the lesions, and relationship to findings in patients with positive initial DWI results. RESULTS: We found eight cases (5.8%) of false-negative initial DWI studies, of which four were positive on initial fluid-attenuated inversion recovery (FLAIR) imaging. Follow-up FLAIR/DWI showed a hyperintensity matching clinical presentation in all eight patients. The mean size of the lesion was 0.19 +/- 0.16 cm3. False-negative studies occurred more often in cases of stroke in the posterior (19%) than in the anterior (2%) circulation or when DWI was obtained within 24 hours after symptom onset. Of the six false-negative vertebrobasilar stroke lesions, five were located in the brain stem. In all, 31% of patients with vertebrobasilar ischemic stroke had a false-negative initial DWI study during the first 24 hours. CONCLUSION: A false-negative DWI study is not uncommon during the first 24 hours of ischemic stroke. Vertebrobasilar stroke should therefore not be ruled out on the basis of early negative DWI, especially when symptoms persist and are suggestive of this diagnosis.     

Ventral hernia repair: a study of current practice

Ventral wall hernias are common; despite this, there are no guidelines on the best surgical management. The aim of this study was to examine the types of repair in use for abdominal wall hernias in the West of Scotland over a 3-month period. Data were gathered on 120 patients. There were 60 incisional, 32 umbilical, and 28 epigastric hernias. The main indication for repair was pain (78%), while 12 patients (10%), presented acutely with incarceration or strangulation. The most common method of repair was sutured (55%), followed by mesh (29%) and Mayo repair (16%). There was no correlation between use of mesh and hernia size or whether repair was for a recurrent hernia. Surgical practice varies widely in the repair of ventral wall hernias. Clinical trials are required to establish the best method of repair for this common condition. Electronic Publication     

Cochlear implant benefits in deafness rehabilitation: PET study of temporal voice activations.

Cochlear implants may improve the medical and social prognosis of profound deafness. Nevertheless, some patients have experienced poor results without any clear explanations. One correlate may be an alteration in cortical voice processing. To test this hypothesis, we studied the activation of human temporal voice areas (TVA) using a well-standardized PET paradigm adapted from previous functional MRI (fMRI) studies. METHODS: A PET H(2)(15)O activation study was performed on 3 groups of adult volunteers: normal-hearing control subjects (n = 6) and cochlear-implanted postlingually deaf patients with >2 y of cochlear implant experience, with intelligibility scores in the "Lafon monosyllabic task" >80% (GOOD group; n = 6) or <20% (POOR group; n = 6). Relative cerebral blood flow was measured in 3 conditions: rest, passive listening to human voice, and nonvoice stimuli. RESULTS: Compared with silence, the activations induced by nonvoice stimuli were bilaterally located in the superior temporal regions in all groups. However these activations were significantly and similarly reduced in both cochlear implant groups, whereas control subjects showed supplementary activations. Compared with nonvoice, the voice stimuli induced bilateral activation of the TVA along the superior temporal sulcus (STS) in both the control and the GOOD groups. In contrast, these activations were not detected in the POOR group, which showed only left unilateral middle STS activation. CONCLUSION: These results suggest that PET is an adequate method to explore cochlear implant benefits and that this benefit could be linked to the activation of the TVA.     

Automatic prediction of infarct growth in acute ischemic stroke from MR apparent diffusion coefficient maps

RATIONALE AND OBJECTIVES: We introduce a new approach to the prediction of final infarct growth in human acute ischemic stroke based on image analysis of the apparent diffusion coefficient (ADC) maps obtained from magnetic resonance imaging. Evidence from multiple previous studies indicate that ADC maps are likely to reveal brain regions belonging to the ischemic penumbra, that is, areas that may be at risk of infarction in the few hours following stroke onset. MATERIALS AND METHODS: In a context where "time is brain," and contrarily to the alternative-and still-debated-perfusion-diffusion weighted image (PWI/DWI) mismatch approach, the DWI magnetic resonance sequences are standardized, fast to acquire, and do not necessitate injection of a contrast agent. The image analysis approach presented here consists of the segmentation of the ischemic penumbra using a fast three-dimensional region-growing technique that mimics the growth of the infarct lesion during acute stroke. RESULTS: The method was evaluated with both numerical simulations and on two groups of 20 ischemic stroke patients (40 patients total). The first group of patient data was used to adjust the parameters of the model ruling the region-growing procedure. The second group of patient data was dedicated to evaluation purposes only, with no subsequent adjustment of the free parameters of the image-analysis procedure. Results indicate that the predicted final infarct volumes are significantly correlated with the true final lesion volumes as revealed by follow-up measurements from DWI sequences. CONCLUSION: The DWI-ADC mismatch method is an encouraging fast alternative to the PWI-DWI mismatch approach to evaluate the likeliness of infarct growth during the acute stage of ischemic stroke.     

Cyclosporine withdrawal from a mycophenolate mofetil-containing immunosuppressive regimen in stable kidney transplant recipients: a randomized,controlled study

BACKGROUND: Long-term maintenance immunosuppression with cyclosporine (CsA) is associated with chronic transplant nephropathy and adverse effects on blood pressure and lipid profile. Several nonrandomized studies suggest that CsA might safely be withdrawn from immunosuppressive regimens containing mycophenolate mofetil (MMF; CellCept). METHODS: A randomized, controlled study with 187 patients enrolled from 21 centers was conducted to compare CsA withdrawal with ongoing CsA therapy in stable renal transplant recipients receiving a triple-drug immunosuppressive regimen of MMF (2 g/day), CsA (Neoral), and corticosteroids. The primary endpoint was creatinine clearance at 6 months after complete withdrawal. RESULTS: In the intent-to-treat population, CsA withdrawal was associated with lower total cholesterol and low-density lipoprotein cholesterol (-0.3 mmol/L, P=0.02; -0.4 mmol/L, P=0.015). There was a trend toward improved creatinine clearance (4.5 mL/min, P=0.16) and serum creatinine (-1 vs. +4 micromol/L, P=0.34). In the per-protocol population, which excluded patients with acute rejections, the improvements in creatinine clearance and serum creatinine were statistically significant (7.5 mL/min, P=0.02; -11 vs. +4 micromol/L, P=0.0003). Reversible acute rejections, the majority of which were mild, occurred in nine CsA withdrawal versus two CsA continuation patients (10.6% vs. 2.4% of each group, P=0.03), with no graft loss. CONCLUSION: Withdrawal of CsA from an MMF-containing triple-drug immunosuppressive regimen improves renal function and lipid profile at the cost of a modest increase in acute rejections, without graft loss.     

Implantation of endoprostheses in aortocoronary bypass. Preliminary experience at the Thoraxcenter of Rotterdam

An intraluminal stent was implanted in 5 patients after dilatation of an aorto-coronary venous graft. In the first 4 patients the procedure was motivated by restenosis after angioplasty. In the 5th patient the stent was implanted as a first-line measure in a case of dilated venous bypass stenosis. Stent implantation carries a risk of thrombosis and requires effective anticoagulation. Thus, one of our patients had to be reoperated upon for prosthetic thrombosis facilitated by the withdrawal of anticoagulants owing to a gastrointestinal haemorrhage. After a 3-month follow-up, the results seem to be encouraging in spite of a case of restenosis located at the proximal end of the tutor. However, more time will be needed to determine precisely the effectiveness of stents in the prevention of restenosis after venous graft dilatation.     

Response to Diazepam in Sons of Alcoholics

Alcohol exerts several of its actions via the chloride channel associated with the central GABA-benzodiazepine receptor complex. To explore a possible role for this receptor complex in risk for alcoholism, and to determine whether risk for alcoholism is associated with risk for benzodiazepine abuse, the authors administered intravenous diazepam to 18 sons of male alcoholics (SOAs) and 18 control subjects. Four logarithmically increasing doses of diazepam and matched volumes of placebo were given in randomized order on separate days about 1 week apart. SOAs were significantly more likely than controls to report euphoric responses to diazepam. At some diazepam doses, SOAs were more likely to report feeling "high" and "intoxicated." SOAs and controls did not differ in feeling "drugged." SOAs and controls may differ in expectations regarding the subjective effects of drugs and/or in the function of the central GABA-benzodiazepine receptor complex. These findings also add further evidence for increased pleasurable effects, and thus possibly increased risk for benzodiazepine abuse, in a subgroup of SOAs.