Autologous Unpurged Bone Marrow Transplantation for Acute Non Lymphoblastic Leukemia in First Remission

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT.

The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.     

Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer

Carcinogenesis, 25, 229–235, 2004 We reported the association of     

Immunological and echocardiographic evaluation of decellularized versus cryopreserved allografts during the Ross operation.

OBJECTIVE: Compare the immunological and echocardiographic data of decellularized versus cryopreserved allografts used for RVOT reconstruction during Ross operation. METHODS: From 16/01/03 thru 07/10/03, 20 Ross operations were performed using decellularized (n=11) or cryopreserved (n=9) allografts. Echocardiography was done at discharge, 1, 3, 6 and 12 months and annually thereafter. Samples for determination of antibodies against HLA class I and II were obtained preoperatively and at days 5, 10, 30, 90 and 180 postoperatively. These samples were tested by the ELISA method in LAT-M dishes (unspecific) for identification of circulating antibodies and the results expressed as mean sample values (Is=DO/cutoff). If positive, LAT-E (specific) was performed and PRA levels determined. RESULTS: There was no mortality. Cryopreserved allografts showed marked Is values elevations for class I and II antibodies which started at the first month and remained elevated up to 6 months. In contrast, of the patients receiving decellularized allografts, seven remained negative, two patients had only marginal elevation of class I antibodies and two patients showed abnormal elevations of PRA levels. This response happened earlier than in the cryopreserved group, starting on the 5th postoperative day and has returned to baseline levels in one case. Echocardiography showed mild, but significant, elevation of gradients in cryopreserved valves but none in the decellularized. CONCLUSIONS: Decellularized allografts had normal function up to 18 months and showed important reduction of the immunogenic response when compared to cryopreserved valves.     

Homocysteine-Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS-Based Study

Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine-lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5-methyl-tetrahydrofolate (n=22), or standard therapy (control group, n=22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra-vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate-treated patients (p<0.001), coronary intimal area increased similarly in the two groups (p>0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p<0.04), independently from folate intake. Sub-group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n=19; p=0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p=0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia. Despite effective in prevent hyperhomocysteinemia after heart transplantation, folate therapy does not seem to affect early CAV onset. However, sub-group analysis suggests that folate therapy may delay CAV development only in patients with baseline hyperhomocysteinemia, while may favor CAV progression in recipients with normal baseline homocysteinemia.     

Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha.

The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.     

Diffusion-weighted imaging study of patients with essential tremor.

The pathophysiology of essential tremor (ET) is unknown. PET and fMRI studies have revealed bilateral activation and (1)H-MRS studies metabolic abnormalities in the cerebellum and other functionally related brain structures in ET. Diffusion-weighted imaging (DWI) was used to search for evidence of tissue integrity abnormalities in these areas in ET patients and 10 matched controls by calculating water apparent diffusion coefficients (ADCs). Regions of interest included the left and right cerebellum, red nucleus, thalamus, caudate, putamen, pallidum, and frontal white matter. Histograms of ADCs were generated for all pixels in the infratentorial compartment and manually segmented areas corresponding to brainstem, vermis, and cerebellar hemispheres. ADC values were similar in all brain areas in patients and controls. Our study did not detect changes affecting the investigated brain regions in ET patients. These findings argue against major structural damage in the ET brain, although more subtle neurodegenerative changes cannot be ruled out.     

Isolated right atrial appendage (RAA) rupture in blunt trauma – a case report and an anatomic study comparing RAA and right atrium (RA) wall thickness

Background  

Heart chambers rupture in blunt trauma is uncommon and is associated with a high mortality. The determinant factors, and the incidence of isolated heart chambers rupture remains undetermined. Isolated rupture of the right atrium appendage (RAA) is very rare, with 8 cases reported in the reviewed literature. The thin wall of the RAA has been presumed to render this chamber more prone to rupture in blunt trauma.     

Right upper lobe 'window' in right main bronchus stenting.

Stent insertion for bronchial stenosis has become common practice in lung transplantation and advanced lung malignancy, and for external compression of the airways for other reasons. Right main bronchus stenting may require blocking the right upper lobe by the stent, placing the patient at risk of recurrent pneumonia and atelectasis. In this study, three patients after insertion of a metal stent to the right main bronchus are described. In all cases, the right upper lobe was covered by the stent, and a laser (Nd:YAG) procedure was used to open a 'window' in the stent toward the right upper lobe with a follow-up of 1 year. We conclude that stent insertion to the right main bronchus may be followed by a laser therapy to open a 'window' toward the right upper lobe.     

Effects of phorbol ester on carbachol-induced contraction in bovine ciliary muscle: possible involvement of protein kinase C

The aim of the research was to characterize muscarinic receptors of bovine ciliary muscle and to investigate the desensitization process. The role of protein kinase C was analyzed. The results show that muscarinic receptors of bovine ciliary muscle have the pharmacological characteristics of the M₃ subtype. Acute exposure to phorbol esters (1 μM phorbol 12,13-dibutyrate, PDB, or 0.1 μM phorbol 12-myristate 13-acetate, PMA, for 15 and 5 min, respectively) resulted in antagonism of muscarinic receptor-mediated contraction. Long-term pretreatment (18 h) with PMA to down-regulate protein kinase C resulted in potentiation of carbachol-induced contraction, reduction of agonist-induced desensitization and loss of phorbol ester-induced desensitization. Staurosporine (3 μM) and H₇ [1-(5-isoquinolinesulfonyl)-2-methyl-piperazine] (1 μM), protein kinase C inhibitors, produced a significant potentiation of the contractile effect of carbachol, reduced the desensitization produced by repeated addition of carbachol and suppressed that induced by phorbol esters. In vitro incubation with carbachol, PDB or PMA did not cause any modification of the binding of labeled [³H]quinuclidinyl benzilate. In vitro incubation with PDB and PMA produced, as expected, a significant translocation of protein kinase C from the cytosol to the membrane. The incubation of the ciliary muscle with carbachol, using the protocol of exposure that induced maximal desensitization of contractile responses, produced a significant redistribution of the enzyme from the cytosol to the membrane. These findings suggest that agonist-induced modulation of functional cholinergic sensitivity in ciliary muscle is correlated, at least partially, to the translocation of protein kinase C from the cytosol to the membrane. The desensitization by phorbol esters is completely due to protein kinase C activation; during the desensitization process, direct modification of the density and affinity of muscarinic receptors is not involved.