Long-term safety of orbital radiotherapy for Graves' ophthalmopathy

We investigated the long-term side-effects of orbital radiotherapy (OR) in 204 patients with Graves' ophthalmopathy (GO), irradiated from 1972-1996 [44 by cobalt unit (CU) and 160 by linear accelerator (LA), mostly combined with glucocorticoids], with a 5- to 25-yr follow-up (median, 11 yr). Cataract was observed in 21 patients (10%) 3-21 yr after OR, with a higher (not significant) prevalence in CU-treated patients (18% vs. 8% in LA-treated patients). The prevalence of cataract was higher, although not significantly, in CU-treated patients aged less than 60 yr, but not in LA-treated patients, compared with the general population. Mild, asymptomatic retinopathy was observed in 1 of 7 patients (14%) with diabetes and hypertension, in 1 of 31 patients (3%) with hypertension alone, and in 0 of 11 patients with diabetes alone. No tumors were observed in 157 patients submitted to computed tomography scan of orbital and adjacent regions. In conclusion, OR is a safe treatment, not associated with an increased frequency of cataract, provided a high voltage apparatus is used. Hypertension, especially if associated with diabetes, may represent a relative contraindication, as it may cause retinopathy. Although no secondary tumors were detected, due to the long latency of radiation-induced tumors, OR should be restricted to patients older than 35 yr.     

Long-term adiposity changes are related to a glucocorticoid receptor polymorphism in young females

Male and female preadolescents and adolescents who participated in phase 1 of the Québec Family Study, and who were retested about 12 yr later, were recruited and subdivided on the basis of a genetic variant within the intron 2 of the glucocorticoid receptor (GRL IVS2-BclI). The increase in sc adiposity over the 12-yr follow-up period in the 4.5/2.3 genotype female subgroup was more than twice that observed in the 4.5/4.5 and the 2.3/2.3 genotype subgroups (P < 0.01). The statistical significance of this difference was essentially unchanged after adjusting for changes, over time, in percent dietary energy as fat, alcohol consumption, and participation in vigorous physical activity. In male subjects, the same trend was found, but it did not reach statistical significance. In conclusion, this study suggests that a significant interaction effect exists between variation in the glucocorticoid receptor gene and body fat gain in female subjects experiencing the transition between adolescence and adulthood. Further research will, however, be necessary to characterize the lifestyle factors promoting fat accumulation, over time, among genetically susceptible individuals.     

Transforming growth factor-beta released by PPD-presenting malignant mesothelioma cells inhibits interferon-gamma synthesis by an anti-PPD CD4+ T-cell clone

Besides acting complexly on both normal and tumor cells, transforming growth factor-beta (TGF-beta) can determine the nature of the response to the antigen, strongly inhibiting the differentiation of naive CD4+ T-cells toward a T helper-1 (Th-1) phenotype; in a number of experimental models, TGF-beta also appeared to be a potent immunosuppressant factor. TGF-beta was shown to be released by some human malignant mesothelioma (MMe) cells, which affects the immune response to this tumor. Thus, for a better understanding of the role of TGF-beta in the immune response to MMe cells, we evaluated the production of a Th-1 cytokine (IFN-gamma) and of a Th-2 cytokine (IL-4), following Purified Protein Derivative (PPD) recall antigen presentation by human MMe cells to a class-II major histocompatibility complex (MHC-II)-matched PPD clone (PPD clone). Our data confirm that human MMe cells possess the unusual capability of presenting a common recall antigen to CD4+ lymphocytes but also show that these tumor cells can abrogate Th-1 immune response, as evidenced by a shift in favor of the production of IL-4 over that of IFN-gamma, through a TGF-beta-mediated pathway; only the simultaneous block of TGF-beta1 and beta2 effects can significantly restore a typical Th-1 pattern of cytokine production by PPD clone in response to PPD presentation by MMe. Even though the role of TGF-beta in the promotion of MMe growth should be further and better defined, this effect should be considered when designing new therapeutical approaches aimed at improving the immune response to MMe.     

Iron as the malignant spirit in successful ageing

Iron enhances the production of the highly reactive and toxic hydroxyl radical, thus stimulating oxidative damage. Iron has been associated with a number of oxidative injury-dependent, age-related conditions and diseases. Indeed, oxidative injury is a major factor of (accelerated) ageing. This commentary reviews part of the existing literature on iron's deleterious effects, particularly in the context of ischemia-reperfusion injury and cardiovascular, brain and muscle diseases as well as skin ageing. Furthermore, the advantages of iron chelation are presented. Indeed, iron chelation or deprivation has been shown to act as a potent anti-oxidant in a variety of animal models of human diseases, preventing oxidative stress to tissues and organs. Iron chelators favor successful ageing in general, and when applied topically, successful skin ageing. It has also been proposed that gender-related differences in iron status are responsible for the increased longevity of women as compared to men. Despite this evidence, the role of iron in ageing and the possibilities of pharmacologically targeting iron have remained essentially unexplored. Iron thus appears as the "malignant spirit" in successful ageing.     

The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study

OBJECTIVES: We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD). BACKGROUND: Endothelial dysfunction foretells cardiovascular events and can be genetically determined. METHODS: We genotyped for the promoter (T(-786)C) and exon 7 (Glu298Asp, G(894)T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5'- and 3'-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T(-786)C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD. RESULTS: The overall genotype distribution of T(-786)C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T(-786)C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T(-786)C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041). CONCLUSIONS: The C allele at the T(-786)C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians.     

Quantitative ultrasound for the assessment of osteopenia in preterm infants

OBJECTIVE: To evaluate the potential role of quantitative ultrasound (QUS) investigation in assessing the osteopenia of prematurity. DESIGN: QUS parameters measured at the time of discharge were related to the anthropometric characteristics and age (postnatal and gestational) of 51 (34 female and 17 male) preterm infants fed fortified human milk. METHODS: QUS evaluation was performed at the humerus (h) by measuring two parameters: ultrasound velocity (hSOS, in m/s) and bone transmission time (hBTT, in micros). A group of 43 term infants (29 female and 14 male) was also evaluated. RESULTS: In preterm infants, significant correlations were found for hSOS and hBTT vs gestational age (r=0.504, 0.477, P<0.0001), length (r=0.641, 0.594, P<0.0001) and weight (r=0.580, 0.562, P<0.0001) at birth, and length (r=0.341, 0.332, P<0.05) and weight (r=0.331, r=0.362, P<0.05) at QUS measurement. In preterm infants, both QUS parameters were negatively correlated with age (r=-0.536, P<0.0001, r=-0.443, P<0.001) and were significantly lower than in the term infants (hSOS: 1664+/-42 m/s vs 1734+/-28 m/s, P<0.0001; hBTT: 0.58+/-0.24 micros vs 1.06+/-0.15 micros, P<0.0001) even when adjusted for body length (P<0.05). In preterm infants, hSOS was also negatively correlated with postconceptional age (r=-0.322, P<0.05). CONCLUSIONS: This study suggests that bone mineral accrual is mainly determined by the development in utero, and that prematurity induces a halt in the bone development process in the early postnatal period. QUS parameters are correlated with the severity of prematurity and might therefore have clinical applications when bone maturation in early life needs to be determined.     

Systematic coronary stenting after failed thrombolysis in high-risk patients with acute myocardial infarction: procedural results and long-term follow-up

BACKGROUND: Stenting in acute myocardial infarction (AMI) represents a feasible and effective revascularization strategy. However, very little information is available for patients who receive a stent after failed thrombolysis (so-called 'rescue' stenting). METHODS: We analysed the procedural results and the 2-year follow-up of all consecutive patients with moderate-to-large AMI treated with rescue stenting in the period 1996-2001. RESULTS: The study cohort includes 123 patients (mean age 60+/-12 years, 78% men). Coronary angiography showed multivessel disease in 47% of patients; the infarct-related vessel was the left anterior descending coronary artery in 47%, the right coronary artery in 41%, the left circumflex coronary artery in 9.5% and a saphenous vein graft in 2.5%. Baseline Thrombolysis in Myocardial Infarction (TIMI) flow was grade 0-1 in 65% and grade 2 in 25%. Coronary stenting was attempted in all 123 patients and was successful in 119 out of 123 (96.7%); abciximab was used in 57 out of 123 (46%) and intra-aortic balloon pumping in 35 out of 123 (28%). At the end of the procedure, TIMI 3 flow was obtained in 104 out of 123 (85%) and TIMI 2 flow in 14 out of 123 (11%). There were 10 in-hospital deaths and four late deaths, with a long-term survival of 88.6%. This figure increases to 95.2% if patients presenting with cardiogenic shock are excluded. A new revascularization procedure was performed in 21% of discharged patients (in the target vessel for 12% and in non-target vessels for 9%). Overall, event-free survival at 2 years was 69%. At multivariate analysis, independent predictors of survival were age (P=0.014) and ejection fraction (P=0.006). CONCLUSIONS: This report represents one of the first series concerning long-term follow-up after rescue stenting. The main results include a high procedural feasibility, a low late mortality and a target vessel revascularization rate in the range expected with stenting. These data must be viewed as part of the constant effort to optimize revascularization strategies in AMI.     

Significant factors associated with fatal outcome in emergency open surgery for perforated peptic ulcer

AIM: To evaluate the main factors associated with mortality in patients undergoing surgery for perforated peptic ulcer referred to an academic department of general surgery in a large southern Italian city. METHODS: One hundred and forty-nine consecutive patients (M:F ratio=110:39, mean age 52 yrs, range 16-95) with peptic ulcer disease were investigated for clinical history (including age, sex, previous history of peptic ulcer, associated diseases, delayed abdominal surgery, ulcer site, operation type, shock on admission, postoperative general complications, and intra-abdominal and/or wound infections), serum analyses and radiological findings. RESULTS: The overall mortality rate was 4.0%. Among all factors, an age above 65 years, one or more associated diseases, delayed abdominal surgery, shock on admission, postoperative abdominal complications and/or wound infections, were significantly associated (chi2) with increased mortality in patients undergoing surgery (0.0001相似文献   

Mutations of the X-linked lymphoproliferative disease gene SH2D1A mimicking common variable immunodeficiency

Common variable immunodeficiency (CVID) and X-linked lymphoproliferative (XLP) disease are two immunodeficiencies that may share a similar immunological phenotype making differential diagnosis difficult. We report two patients initially diagnosed as affected with CVID who, using molecular analysis, have been subsequently found to be affected with XLP disease. Distinguishing between these two diseases is essential since they have different prognosis, treatment and genetic counselling. CONCLUSION: current techniques, such as genetic analysis of the SH2D1A gene and expression of signalling lymphocyte activation molecule-associated protein, allow a definite diagnosis of X-linked lymphoproliferative disease.