Left ventricular mass regression after aortic valve replacement with 17-mm St Jude Medical mechanical prostheses in isolated aortic stenosis

OBJECTIVE: The present study investigated the outcomes of aortic valve replacement with 17-mm mechanical prostheses in patients with isolated aortic stenosis. METHODS: Between January 1997 and January 2003, 35 patients (mean age, 63.4 +/- 17 years; median age, 70 years; age range, 16-84 years) underwent isolated aortic valve replacement with a 17-mm St Jude Medical Hemodynamic Plus (16 [45.7%] patients) or a St Jude Medical Regent prosthesis (19 [54.3%] patients). The paired Student t test or the paired Wilcoxon rank sum test were used to compare preoperative with follow-up echocardiographic measurements. RESULTS: Thirty-two (91.4%) patients were female, mean height was 154.4 +/- 8.3 cm, mean weight was 62.2 +/- 9.2 kg, and mean body surface area was 1.59 +/- 0.13 m 2 . The preoperative average New York Heart Association class was 2.8 +/- 0.8. The mean preoperative left ventricular mass index was 135.2 +/- 31 g/m 2 . Preoperative echocardiography showed an average gradient of 65.7 +/- 19.2 mm Hg (mean) and 103.6 +/- 30.7 mm Hg (peak) and a mean indexed effective orifice area of 0.40 +/- 0.1 cm 2 /m 2 . Echocardiographic follow-up time averaged 28.2 +/- 22.7 months (range, 13-72 months). Follow-up was 100% complete (1131.7 patient-months). Hospital mortality was 8.6% (3 patients). Actuarial 5-year survival was 94.7%. The mean postoperative New York Heart Association class was 1.13 +/- 0.34 ( P < .001), with 27 (87.1%) patients in class I and 4 patients in class II. A significant regression of the indexed left ventricular mass was found (postoperative mean value, 107.8 +/- 22.8 g/m 2 ; P < .0001), despite a mean indexed effective orifice area of 0.67 +/- 0.14 cm 2 /m 2 (median, 0.66 cm 2 /m 2 ). CONCLUSIONS: Selected patients with aortic stenosis can experience satisfactory clinical improvement and significant indexed left ventricular mass regression after aortic valve replacement with modern small-diameter bileaflet prostheses.     

Ninety-five percent insulin independence rate 3 years after pancreas transplantation alone with portal-enteric drainage

AIMS: Portal-enteric drainage (PED) might be particularly suitable for pancreas transplantation alone (PTA), since it has been associated with an immunologic advantage and achieves excellent metabolic results. We describe our experience with a consecutive series of 40 PTAs with PED. METHODS: Between April 2001 and March 2004, 40 consecutive PTAs were performed with PED. Recipients were selected according to the American Diabetic Association recommendations. Donors were selected according to standard criteria irrespective of HLA match, although matching for A and B loci was considered at the time of graft allocation. Immunosuppression consisted of induction treatment with basiliximab (n = 34) or thymoglobulin (n = 6), and maintenance therapy with steroids, mycophenolate mofetil, and tacrolimus. RESULTS: After a mean cold ischemia time of 690 minutes (range, 517-965 min) all pancreases functioned immediately. Three grafts were lost due to hyperacute or accelerated rejection. No graft was lost to vascular thrombosis, although 5 (12.5%) nonocclusive thromboses were identified and the grafts were rescued with intravenous heparin infusion. A repeat laparotomy was required in 7 recipients (17.5%) No patient required multiple repeat laparotomies, and none died. After a mean follow-up of 16.4 months (range, 1-36 mo), 2 recipients were diagnosed with rejection episodes, which were reversed with steroid boluses. Actuarial 3-year patient, and graft survival rates were 100% and 94.9%, respectively. The following parameters showed significant improvement compared with pretransplantation evaluation: hemoglobin A1C concentration, total and high-density lipoprotein cholesterol levels, arterial blood pressure, cardiac performance, retinopathy, proteinuria, and neuropathy. CONCLUSIONS: Pancreas transplantation alone with PED provides high rates of long-term insulin-independence.     

Different patterns of extracellular matrix protein expression in the convexity and the concavity of the dilated aorta with bicuspid aortic valve: preliminary results

OBJECTIVE: This study aimed to assess extracellular matrix protein expression patterns at the convexity (right anterolateral wall) and the concavity of the dilated ascending aorta in patients with bicuspid aortic valve disease. METHODS: Aortic wall specimens were retrieved from the convexity and the concavity in 27 bicuspid aortic valve patients (12 with stenosis and 15 with regurgitation) and 6 heart donors (controls). Morphometry, immunohistochemistry, Western blot, and polymerase chain reaction were performed, focusing on matrix proteins involved in vascular remodeling. RESULTS: Type I and III collagens were significantly decreased in bicuspid-associated dilated aortas versus controls (P < .001), particularly at the convexity (P < .05 vs concavity). Expression of messenger RNA for collagens was lower than normal only in the regurgitant subgroup. At immunohistochemistry, proteins whose overproduction has been demonstrated in response to abnormal wall stress, such as tenascin and fibronectin, were more expressed in the convexity than in the concavity, especially in the stenosis subgroup. Tenascin, which is produced by smooth muscle cells in the synthetic phenotype, was nearly undetectable in controls. Fewer smooth muscle cells (stenosis, P = .017; regurgitation, P = .008) and more severe elastic fiber fragmentation (P = .029 and P < .001) were observed in the convexity versus the concavity. CONCLUSIONS: In bicuspid-associated aortic dilations, an asymmetric pattern of matrix protein expression was found that was consistent with the asymmetry in wall-stress distribution reported previously. Differences exist between patients with stenosis and those with regurgitation in terms of protein expression and content in the aortic wall. Further studies could clarify the relations between these findings and the pathogenesis of aortic dilatation in bicuspid aortic valve patients.     

Enhanced trigemino-cervical-spinal reflex recovery cycle in pain-free migraineurs

OBJECTIVE: To evaluate trigemino-cervical-spinal reflexes (TCSRs) in a group of migraine patients during the pain-free period. BACKGROUND: TCRSs are part of a complex nocifensive response involving the cervical and the upper limb muscles, and are modulated by supraspinal inhibitory pathways; it may, thus, be possible to use TCRSs to explore the trigeminal system in migraineurs. METHODS: A total of 43 migraine patients without aura (MWoA, 32 patients) or with typical aura (MWA, 11 patients) and 30 age- and sex-matched healthy subjects took part in the study. TCRSs were obtained by stimulating the supraorbital nerve and recorded from the semispinalis capitis muscle and the biceps brachii. The latency (L, msec), area (A, mVms) and recovery cycle of the reflexes were recorded. The effects of heterotopic painful stimulation on the neurophysiological parameters were studied by a validated cold pressor test (CPT). RESULTS: No significant changes were found between either migraine patients and controls or MWoA and MWA patients in the mean values in the L and A of TCRSs (t-test, P > .05). The recovery curve of the trigemino-cervical reflexes (TCRs) was significantly faster in migraine patients than in controls, while no differences were found in the trigemino-spinal reflexes (TSRs) (t-test, P < .01). Activation of the diffuse inhibitory controls through the CPT induced a significant reduction in the TCRs and TSRs area in both migraine patients and controls (paired t-test, P < .01), though the extent of this reduction did not differ significantly between migraineurs and controls (t-test, P > .05). COMMENTS: Our data suggest that the pain-free period in migraine patients is characterized by a hyperexcitability of the trigeminal pathways and of their anatomical and functional connections with the upper cervical cord neurons, and that this abnormal hyperexcitability does not appear to be due to a lack of a supraspinal inhibitory modulation.     

Neurology residency training in Europe: an Italian perspective

Education is the most important part of medical-science training. Assessment of training programmes and examination of trainees' skills are necessary to guarantee that trainees develop competence. Training programmes vary between and within countries. The impending integration of the medical-job market among European countries highlights the need for people training to be specialists to achieve a certain standard. Here, we review the neurological training programmes in Europe, principally those in Italy, and discuss the standardisation of the training of residents in Italy and the quality control of current residency training, or its absence, in Europe.     

Hereditary ferritinopathy: a novel mutation, its cellular pathology, and pathogenetic insights

We report a family of French Canadian and Dutch ancestry with hereditary ferritinopathy (neuroferritinopathy) and a novel mutation (C insertion at nt646-647 in exon 4) in the ferritin light chain gene, resulting in a longer than normal protein. Our failure to immunostain most of the abnormal ferritin deposits in the proband with a conformation-dependent monoclonal antibody to ferritin light chain supported a previously postulated conformational change of ferritin light chain in this disease. The posterior putamen and cerebellum were the primary pathologic loci in our proband, but asymptomatic hepatocytic intranuclear accumulations of iron and ferritin also were present. Both neurons and glia displayed highly distinctive, if not pathognomonic, swollen to vacuolated nuclei containing ferritin and iron. Hyaline deposits, again staining for both ferritin and iron, were additional morphologic features that may be unique to the ferritinopathies. The iron, at least in putamen where there was a nearly 40-fold increase, appeared to be both in the ferrous (Fe2+) and ferric (Fe3+) form; it was the most likely cause of the observed neuronal and glial apoptosis. We found morphologic evidence of both lipid peroxidation and abnormal nitration of proteins in putaminal neurons and glia, confirming the expected oxidative stress due to this excessive iron. Biochemical and immunohistochemical abnormalities in mitochondria also were demonstrated, probably due to an imbalance in iron homeostasis that had a deleterious effect on the respiratory chain.     

Testicular extramedullary myeloid cell tumor: report of a case with unique clinicopathologic features and a brief review of the literature

We report a case of testicular extramedullary myeloid cell tumor in a 37-year-old man who presented with an acute testicular hemorrhage. A pathologic examination revealed no gross tumor mass. A well-differentiated extramedullary myeloid cell tumor infiltrate was seen histologically, localized largely to the seminiferous tubules. The patient had no evidence of any past or concurrent myeloid disorders. The lack of the usual clinical features of a testicular mass and the presence of an intratubular pattern of infiltration can further compound the challenges in diagnosing this entity.     

Mechanisms of HIV receptor and co-receptor down-regulation by prostratin: role of conventional and novel PKC isoforms

Prostratin is an unusual non-tumour promoting phorbol ester with potential as an inductive adjuvant therapy for highly active antiretroviral therapy (HAART) due to its ability to up-regulate viral expression from latent provirus. In addition, prostratin is also able to inhibit de novo HIV infection most probably because it induces down-regulation of HIV receptors from the surface of target cells. In this study, we investigate the mechanisms by which prostratin down-regulates HIV receptor and co-receptor surface expression in lymphocytic and monocytic cell lines. Our results indicate that prostratin induces down-regulation of surface expression of CD4 and CXCR4, but not CCR5, in various cell lines. Down-regulation of CD4 and CXCR4 by prostratin is achieved by internalization through receptor-mediated endocytosis and/or macropinocytosis, which is then followed by degradation of these molecules. Because prostratin is a protein kinase C (PKC) activator, we next examined the potential contribution of distinct PKC isoforms to down-regulate CD4 and CXCR4 in response to prostratin stimulation. Although exposure of cells to prostratin or phorbol-myristate-acetate (PMA) induces the translocation of several PKC isoforms to the plasma membrane, the use of specific PKC inhibitors revealed that novel PKCs are the main mediators of the prostratin-induced CD4 down-regulation, whereas both conventional and novel PKCs contribute to CXCR4 down-regulation. Altogether these results showed that prostratin, through the activation of conventional and/or novel PKC isoforms, rapidly reduces cell surface expression of CD4 and CXCR4, but not CCR5, by inducing their internalization and degradation.