18F-FDG PET/CT as predictive and prognostic factor in esophageal cancer treated with combined modality treatment

Annals of Nuclear Medicine - [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) is used for diagnosis, staging, response assessment and prognosis...     

Coronary microcirculation in essential hypertension: a quantitative myocardial contrast echocardiographic approach.

AIMS: The aims of the present study were: (a) to demonstrate whether quantitative myocardial contrast echocardiography can detect the increase in coronary flow induced by dipyridamole infusion vasodilation through the myocardial opacification due to the transit of microbubbles, both at rest and after dipyridamole induced vasodilation; (b) to explore the coronary microcirculatory function before and after dipyridamole in two different models: asymptomatic and relatively young hypertensive patients with a mild degree of left ventricular hypertrophy, and healthy controls. METHODS AND RESULTS: Two groups of strictly age-matched males were studied (case-control study): 10, relatively young and asymptomatic essential hypertensive patients with a mild degree of left ventricular hypertrophy with a normal left ventricular function, and 10 healthy controls. The main findings were: the microbubbles' appearance area was significantly lower in hypertensive patients than in controls (P<0.05) because of a significantly lower time to peak. The peak intensity at rest was higher in hypertensives than in controls (P<0.05); but the per cent increase after vasodilatory stimulus was significantly higher in controls (+71% in controls vs +31% in hypertensives; P<0.05). The microbubbles' disappearance area was comparable in both groups at rest; the per cent increase of this parameter after dipyridamole was significantly higher in controls (+124%) than in hypertensives (+90%) (P<0.05). The results achieved in this study documented that the coronary microcirculation in hypertensive patients presenting a mild degree of left ventricular hypertrophy, explored with quantitative myocardial contrast echocardiography, showed a different behaviour in comparison with controls, in the vasodilatory response to dipyridamole. CONCLUSION: The coronary microcirculation in hypertensives showed a reduced vasodilation capacity of the resistance arterioles under dipyridamole induced vasodilatation, and a possible impairment of the endothelium dependent vasodilation. This happened despite an increase in the left ventricular mass, where the relation between capillary bed distribution and hypertrophied myocardium (rarefaction phenomenon) is not completely respected.     

Bone marrow-resident memory T cells survive pretransplant chemotherapy and contribute to early immune reconstitution of patients with acute myeloid leukemia given mafosfamide-purged autologous bone marrow transplantation

OBJECTIVE: Studies of memory T cells transferred with the graft are relevant to better understand the early immune reconstitution of patients given autologous bone marrow transplantation (A-BMT). A critical question is whether memory T cells resident in bone marrow (BM) of patients with hematological malignancies are resistant to either pretransplant chemotherapy or ex vivo pharmacological purging. PATIENTS AND METHODS: To address these issues, we evaluated the frequency of tetanus-toxoid (TT)-specific proliferating T-cell precursors (TT-PTCp) in BM and peripheral blood (PB) of eight patients with acute myeloid leukemia (AML) given A-BMT after in vitro purging of BM with mafosfamide. Patients were studied at the time of BM harvesting and five of them also after A-BMT. RESULTS: The range of TT-PTCp frequencies found after A-BMT were comparable with those observed in PB and in BM at the time of harvesting and did not differ significantly from those of eight age-matched healthy subjects who donated BM for a human leukocyte antigen-identical sibling. TT-PTCp frequencies in BM, studied before and after ex vivo purging, appeared not to be affected by incubation with mafosfamide. We also compared the T-cell receptor (TCR)-Vbeta-repertoire usage of TT-specific T-cell lines (TT-TCL) in BM of patients at the time of harvesting and in their PB 2 months after transplantation. The same TCR-clonotypes were detected in TT-TCL at time of harvesting and after A-BMT. CONCLUSION: These data indicate that BM-resident memory T cells of patients with AML are resistant to both pretransplant chemotherapy and ex vivo pharmacological purging and may contribute to immune reconstitution after A-BMT.     

Primary angioplasty for acute myocardial infarction in a patient with a solitary coronary ostium and a "superdominant" right coronary artery

Coronary artery anomalies (CAAs) are a rare angiographic finding, sometimes associated with acute coronary events. We report on a case of primary angioplasty for inferior acute myocardial infarction (AMI) in a 66-year-old woman with a solitary coronary ostium in the right sinus of Valsalva and a "superdominant" right coronary artery. We also discuss two potential pitfalls of primary angioplasty: correct interpretation of coronary anatomy and approach to challenging lesions.     

Molecular defects in CRM+ factor VII deficiencies: modelling of missense mutations in the catalytic domain of FVII

Summary. The molecular defects causing CRM+ factor VII deficiency were investigated in seven unrelated subjects and several members of their families.
Four missense mutations located in the catalytic domain of factor VII were found. The previously reported ³⁰⁴ArgGln substitution was present in the homozygous and heterozygous forms, with different polymorphic haplotypes, thus demonstrating that it is recurrent and frequent in the Italian population. The ³¹⁰Cys Phe substitution was found in the homozygous form and in the compound heterozygous condition with the nonsense mutation ³⁵⁶Trpstop. Two missense mutations, ²⁹⁸MetIle and ³⁴²GlyArg, were found in the homozygous and in the heterozygous condition respectively.
Molecular heterogeneity was further increased by finding of the ³⁵³ArgGln polymorphism in the doubly heterozygous condition with the 304 and 342 mutations.
Plausible explanations for loss of FVII function were found by inspecting a model of the serine protease domain of factor VIIa. Inefficient activation of the catalytic site is predicted for ²⁹⁸MetIle. ³⁴²GlyArg would directly distort the geometry of the 'oxyanion hole'preventing formation of a substrate enzyme intermediate. ³¹⁰Cyshe is predicted to have an adverse effect on tissue factor interaction. These mutations point to important regions of the factor VII molecule.     

Effect of endogenous thyroid stimulating hormone levels on the secretion of thyroid hormones in man.

The effect of endogenous thyroid stimulating hormone (TSH) on the thyroid secretion of triiodothyronine (T3) and thyroxine (T4) was evaluated by serial determinations of serum T3. T4 and TSH concentrations in the following groups of patients: a) three patients submitted to surgical removal of a solitary, autonomous thyroid nodule which had completely inhibited the extranodular tissue; b) five subjects, with the same disease, in whom functional recovery of the extranodular tissue was induced by increased circulating TSH levels, produced by treatment with methimazole; c) one patient submitted to hemithyroidectomy for multinodular goitre; d) two hyperthyroid patients who had been treated with methimazole. In all these patients serum T3 and T4 levels progressively decreased, with a consequent progressive increase in serum TSH concentrations, leading to stimulation of the thyroid gland. During this TSH-induced stimulation of thyroid tissue, a significant positive correlation was found between the serum TSH concentrations and the corresponding ratio between the serum levels of T3 and T4 (T3/T4), both within each patient group (P less than 0.001) and among all patients (P less than 0.001). The same correlation also governs the relationship between the TSH and the T3/T4 values of 34 euthyroid control subjects and one patient with incipient hypothyroidism. These data strongly suggest that endogenous TSH can induce a preferential secretion of T3 over T4 by the human thyroid.     

Prevalence of C282Y and E168X HFE mutations in an Italian population of Northern European ancestry

BACKGROUND AND OBJECTIVES: In Italy, the prevalence of C282Y is lower than in Northern European countries. We hypothesized a higher prevalence of C282Y in Northern than in Southern Italian populations. We previously identified a nonsense mutation (E168X) in hemochromatosis probands originating from a region in the north-west of Italy. We aimed to define the prevalence of C282Y and E168X in that region and the origin of the E168X mutation by haplotype analysis. DESIGN AND METHODS: Six-hundred and six blood donors were investigated for C282Y, H63D, S65C and E168X mutations by polymerase chain reaction (PCR)-restriction assays. Three hundred were also tested for rare HFE and TFR2 mutations by reverse-hybridization test strips. D6S265, D6S105 and D6S1281 microsatellites were analyzed to define E168X 6p-associated haplotypes. RESULTS: One C282Y homozygote, thirteen C282Y/ H63D compound heterozygotes, four E168X heterozygotes and three E168X/H63D compound heterozygotes were found. The allele frequencies of C282Y, H63D, S65C, and E168X were 4.7%, 14.9%, 0.74% and 0.58%, respectively. INTERPRETATION AND CONCLUSIONS: The prevalence of C282Y in the region investigated was much higher than that previously reported in Italy. This finding is probably due to the heavy Celtic component of this north-western population and suggests that in populations of Northern Italian descent screening studies for hemochromatosis could be cost-effective. The prevalence of E168X in this region, although low, suggests that the mutation probably originated here many years ago and its frequency increased as a result of a local founder effect. Given its severity, we suggest that the E168X mutation should be searched for in all hemochromatosis patients of Northern ancestry with an incomplete HFE genotype.