An open prospective pilot study on the use of rapamycin after penetrating high-risk keratoplasty

BACKGROUND: The purpose of this study was to prove efficacy and safety of systemic immunosuppression with rapamycin following penetrating high-risk keratoplasty. Rapamycin has shown its immunosuppressive potential in the rat keratoplasty model and is a component of several immunosuppressive protocols after solid organ transplantation. In this pilot study, we compared the efficacy and safety of rapamycin and mycophenolate mofetil (MMF). METHODS: Ten patients (group 1) undergoing high-risk keratoplasty were included in this study, receiving rapamycin as postoperative immunoprophylaxis. Rapamycin was administered orally once daily (blood trough level 4-10 ng/ml) for 6 months. Thereafter, it was tapered over 2 weeks. The control group (group 2) consisted of 24 patients who received 1000 mg MMF twice daily for 6 months. All of the patients received postoperative medication with fluocortolone 1 mg/kg/day (tapered over 3 weeks) and prednisolone acetate eyedrops 5 times per day (tapered over 5 months). RESULTS: Mean follow-up of all patients (n=34) was 739 days. No immune reaction was observed in groups 1 and 2 during the first 6 months under immunosuppression. Two immune reactions occurred in group 1, and five in group 2 within a 2-year follow-up. All of the immune reactions were reversible. The side effects observed in both groups were mostly reversible. CONCLUSIONS: Rapamycin and mycophenolate mofetil seem to be similarly efficacious in preventing immune reactions after high-risk keratoplasty, as long as they are administered. However, we observed a broad spectrum of side effects from rapamycin.     

The first case of coronary artery by-pass grafting surgery (CABG) in a patient on maintenance dialysis in Iaşi

Coronary artery disease has a significantly higher prevalence in chronic dialysis patients compared to the general population, explained by a cluster of non-specific and specific (uremia-associated) cardiovascular risk factors, typical for these patients. Nephrologists and cardiovascular surgeons worldwide are rather reluctant to offer CABG to dialysis patients, because of concerns about higher risks associated with this procedure in this frail population. However, there is an increasing opinion supporting a more aggressive management of coronary artery disease in uremic individuals. To illustrate this "positive attitude", we report here the first dialysis patient ever treated by CABG in Ia?i; his good outcome was both rewarding and encouraging for us all.     

Tensile strength of clots of recalcified plasma and fibrinogen-thrombin-calcium systems

Experiments were performed on plasma clots to determine their tensile strength. Fibrinogen, thrombin and Ca⁺⁺ concentration and the pH of the system determined the tensile strength. Tensile strength could be increased markedly when concentrations and pH were optimal. The clots formed were soluble in bile and non-adherent to Tygon tubing. These were used successfully in patients for the extraction of calculi from the biliary tree.     

Cholinotoxicity of the ethylcholine aziridinium ion in primary cultures from rat central nervous system

The cytotoxic effects of ethylcholine aziridinium ion (AF64A) were studied in primary cultures prepared from either whole brain, septum, or midbrain of fetal rats. AF64A, at concentrations up to 22.5 microM, significantly reduced the number of acetylcholinesterase-stained cells without affecting the number of dopaminergic neurons or their ability to take up and release [3H]dopamine. Many of the survived acetylcholinesterase-stained cells appeared with intact somata but damaged processes, indicating a retrograde degeneration starting at the nerve terminal. Higher concentrations of AF64A (greater than 22.5 microM), caused general toxicity which was expressed by degeneration of various neuronal and glial cells. Choline (500 microM), significantly protected the cells from AF64A induced cytotoxicity. The results are consistent with a previously described kinetic model, that predicted a dual action of AF64A: selective cholinotoxicity at low concentrations and non-selective cytotoxicity at higher concentrations.     

Inflammatory reaction in chronic periodontopathies in patients with diabetes mellitus. Histological and immunohistochemical study

Chronic periodontopathies and diabetes mellitus are two clinical entities, which reciprocally condition one another. The periodontal disease is considered a major complication, which induces an unfavorable evolution of diabetes mellitus. Diabetes mellitus is an endocrine disease which favors the occurrence of periodontopathy through gum's microvascular disorders, the selection and development of an aggressive bacterial plaque and through an exaggerate inflammatory response to the microflora within the oral cavity. Both diabetes mellitus and periodontal disease have an increasing incidence in the whole world. Development of periodontopathy is related to the aggression of bacterial flora in dental plaque, flora that is influenced on its turn by the evolution of diabetes mellitus. In our study, we have evaluated the inflammatory reaction in periodontium in patients with slowly and progressive periodontitis in patients with diabetes mellitus who had diabetes longer than five years. It has been found that all patients presented a chronic inflammatory infiltrate, abundant, with round mononuclear cells of lymphocyte, plasma cells and macrophage type, with non-homogenous arrangement, more intensely where the covering epithelium presented erosions or necrotic areas. Out of the immunity system cells, the most numerous where of T-lymphocytes type.     

Duplex ultrasound and renin ratio predict treatment failure after revascularization for renal artery stenosis

BACKGROUND: The aim of this study was to find predictors to identify patients with hypertension who will not improve after removal of renal artery stenosis (RAS). METHODS: Prospective study of patients with unilateral stenosis (>60% diameter reduction) and hypertension in 24-h measurements despite antihypertensive drugs, who underwent revascularization (surgery/angioplasty). Examinations were performed before treatment and after 3 and 6 months after exclusion of restenosis. Studies included 24-h blood pressure, creatinine clearance, 99Tc MAG3 scintigraphy, and measurements of renal vein plasma renin activity (PRA). Intrarenal resistance indices (RI) were determined with duplex ultrasound before and 30 min after administration of intravenous enalaprilat. Improvement of hypertension was defined by a score consisting of 24-h mean arterial pressure and the number of antihypertensive drugs. RESULTS: From December 2000 to December 2003, 50 patients completed the study. Improvement of hypertension was observed in 18 patients (36%). Comparison between responders (n = 18) and nonresponders (n = 32) revealed significant differences only for RI and PRA measurements. The largest area under the curve in receiver-operating characteristic (ROC) analysis for prediction of no improvement of hypertension was found for RI (stenosis side), which was nearly identical for measurements before and after administration of angiotensin-converting enzyme (ACE) inhibitor. The highest sensitivities and specificities predicting which patients will not improve were found for RIs > or = 0.55. The highest univariate odds ratio (OR 44, confidence interval [CI] 4.8-404) was found for the parameters of RI > or = 0.55 and a renin ratio of <1:1.5. CONCLUSIONS: Resistance indices of the poststenotic kidney above 0.55 and a negative renin ratio can predict a poor outcome concerning arterial blood pressure response after restoration of renal blood flow for unilateral renal artery stenosis.     

Neural substrate of the cognitive and emotional interference processing in healthy adolescents

Emotion regulation is essential for adaptive functioning and social integration. However, it is not clear to what extent the responsible brain mechanisms are similar to those invoked in cognitive control in a non-emotional context. The aim of this study was to compare the neural circuitry of cognitive and emotional interference resolution in healthy adolescents, employing variants of the counting Stroop task. Cognitive and emotional interference processing engaged predominantly brain regions belonging to the dorsal- and the ventral attentional systems, respectively, and commonly the inferior frontal gyrus, IFG (Broca's area, left BA 45, but also right BA 45). These results suggest that BA 45 is a bridge of interaction between the dorsal- and the ventral attentional systems implicated in top-down orienting of attention and, respectively, in bottom-up processing of salient stimuli. Reaction time data showed that some participants tend to respond faster, while others respond slower to negative emotional compared to neutral trials. The emotional interference maps revealed that fast responders recruit the right temporo-parietal junction and to a larger extent the right BA 45 and the bilateral cuneus, suggesting that they engage more efficient cognitive control mechanisms to override the attentional bias. No anterior cingulate (ACC) activation was observed in either cognitive, or emotional interference; this supports the view that ACC is not involved specifically in mediating Stroop selection.