Prevalence of thyroid dysfunctions in systemic lupus erythematosus

The association of systemic lupus erythematosus (SLE) and thyroid autoimmunity has been reported by several studies in a wide range of variability. However, from a review of the literature, discrepant results have been reported. The aim of the study was to evaluate the prevalence of clinical and subclinical thyroid disorders in patients with SLE vs sex- and age-matched controls. Thyroid hormones and the presence of antithyroid antibodies were tested and thyroid ultrasonography was performed in 213 patients with SLE vs 426 sex- and age-matched controls, from the same geographic area, with a well-defined status of iodine intake. The odds ratio for subclinical hypothyroidism for female patients with SLE with respect to controls was 4.5 (95% confidence interval [CI], 2.5-8.4); for antithyroid peroxidase antibody (AbTPO) positivity, it was 2.6 (95% CI, 1.7-4.1); and for thyroid autoimmunity, it was 2.9 (95% CI, 2.0-4.4). The mean values of thyroid-stimulating hormone and AbTPO were higher in female SLE patients than in controls (P < .01). A significantly (P < .01) higher prevalence of clinical hypothyroidism and Graves disease was observed in female SLE patients than in controls. No significant difference between SLE patients and controls was detected with regard to free triiodothyronine and thyroxine. In our series, 3% of SLE patients had “nonthyroidal illness syndrome” vs 0 control. Thyroid function and AbTPOs should be tested and ultrasonography should be performed as part of the clinical profile in SLE patients. Subjects at high risk (women, positive AbTPOs, hypoechoic, and small thyroid) should have thyroid function follow-up and appropriate treatment in due course.     

White matter lesions and the risk of incident hip fracture in older persons: results from the progetto veneto anziani study

BACKGROUND: White matter lesions (WMLs) are associated with hypertension, an increased risk of falling, and impaired physical and cognitive performance that may affect the mechanical effect of falls. METHODS: We hypothesized that WMLs are a risk factor for hip fracture (HF). We studied a sample of 820 community-dwelling Italian persons 65 years and older from the cohort of the Progetto Veneto Anziani Study who underwent brain magnetic resonance imaging at baseline. Subjects were classified as having no lesions, focal lesions, or diffuse WMLs. RESULTS: Compared with those with no lesions, participants with diffuse WMLs were older, reported more falls, and had worse physical and cognitive performance, all factors implicated in the causal pathway to HF. During 9 years of follow-up, 51 HFs occurred. Hip fracture risk associated with diffuse WMLs markedly differed between participants younger than 80 years vs those 80 years and older. After adjustment among participants younger than 80 years, diffuse WMLs compared with no lesions were associated with a 2.7-fold (95% confidence interval, 1.1-7.1) increase in the risk of HF. Focal lesions were not statistically significantly associated with an increased risk of HF in the same age group (hazard ratio, 2.0; 95% confidence interval, 0.6-7.6). No associations between diffuse WMLs, focal lesions, and HF were evident among participants 80 years and older, possibly because of the limited sample size. CONCLUSIONS: White matter lesions represent an independent risk factor for HF in persons younger than 80 years. Older persons with diffuse WMLs should be considered candidates for multifactorial interventions aimed at reducing the risk of falling and fractures.     

Colocalization of ribonuclear inclusions with muscle blind like-proteins in a family with myotonic dystrophy type 2 associated with a short CCTG expansion

Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystemic disorder caused by a CCTG repeat expansion in intron 1 of the zinc finger protein 9 (ZNF9) gene. We present a three first-degree relative Italian family (proband, his mother and his sister) with a mild DM2 phenotype associated with a short (CCTG)(100) expansion as far as regards the proband and his mother, while his sister shows larger expansion correlated to a more severe phenotype. FISH analysis with (CAGG)(5) probe demonstrated that nuclear foci of mutant RNA were present in the proband muscle and co-localized with muscleblind-like proteins, determining their sequestration in the nucleus. This is one of the smallest expansion reported and the shortest with the evidence of nuclear foci. These data contribute to the clinical and molecular correlation of ZNF9 gene short expansion.     

Vasculature-targeted tumor necrosis factor-alpha increases the therapeutic index of doxorubicin against prostate cancer

BACKGROUND: Poor penetration and uneven distribution of doxorubicin in tumors limits the efficacy of this drug in patients with prostate cancer (PC). Aim of the study was to investigate whether pre-treatment with NGR-TNF, a tumor necrosis factor-alpha derivative able to target tumor vessels and alter vessel permeability, increases the penetration and the efficacy of doxorubicin in pre-clinical models of PC. METHODS: Wild type C57BL/6 mice bearing androgen-independent TRAMP-C1 PC and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, which spontaneously develop PC and metastasis, were treated with repeated cycles of doxorubicin, administered either alone or following NGR-TNF. Tumor growth and drug uptake by cancer cells was evaluated. RESULTS: Doxorubicin as a single agent blocked the growth of TRAMP-C1 cells in vitro but not in vivo. Pre-treatment of mice bearing subcutaneous TRAMP-C1 tumors with NGR-TNF favored doxorubicin penetration into the tumor mass, and in both TRAMP-C1 and TRAMP models significantly delayed tumor growth without increasing drug-related toxicity. CONCLUSIONS: Pre-treatment with NGR-TNF significantly expanded the therapeutic index of doxorubicin in mouse models of hormone-dependent and -independent PC.     

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer

This study was performed to assess the efficacy and safety of docetaxel, cisplatin and fluorouracil combination in patients with unresectable locally advanced oesophageal squamous cell carcinoma. Treatment consisted of docetaxel 60 mg m(-2), cisplatin 75 mg m(-2) on day 1 and fluorouracil 750 mg m(-2) day(-1) on days 2-5, repeated every 3 weeks for three cycles, followed by carboplatin 100 mg m(-2) week(-1) for 5 weeks and concurrent radiotherapy (45 Gy in 25 fractions, 5 days week(-1)). After radiotherapy, eligible patients either underwent an oesophagectomy or received high dose rate endoluminal brachytherapy (HDR-EBT). Thirty-one out of 37 enrolled patients completed the planned chemotherapy and 30 completed chemoradiation. After completion of chemotherapy, 49% (95% CI: 32.2-66.2) had a clinical response. Twelve patients (32%) underwent a resection, which was radical in 60% (postoperative mortality: 0%). A pathological complete response was documented in four patients (11% of enrolled, 30% of resected). The median survival was 10.8 months (95% CI: 8.1-12.4), and the 1- and 2-year survival rates were 35.1 and 18.9%, respectively. Grade 3-4 toxicities were neutropoenia 32%, anaemia 11%, non-neutropoenic infections 18%, diarrhoea 6% and oesophagitis 5%. Nine patients (24%) developed a tracheo-oesophageal fistula during treatment. Even if the addition of docetaxel to cisplatin and 5-fluorouracil (5-FU) seems to be more active than the cisplatin and 5-FU combination, an incremental improvement in survival is not seen, and the toxicity observed in this study population is of concern. In order to improve the prognosis of these patients, new drugs, combinations and strategies with a better therapeutic index need to be identified.     

Organized cervical cancer screening for underpriviledged women

Individual cervical screening with pap-smears is the major cause of the decrease in incidence and mortality of cervical cancer in France since more than 30 years. But, for the last ten years, the decrease in mortality is limited due to the persistence of poor prognostic cases and the insufficiency of treatment efficacy in such patients. These cases are mostly observed in women who did not participate to regular screening. They are generally from low socioeconomic levels or migrant populations, or both. Such an observation leads us to organize 3 successive pilot campaigns (2001, 2003, 2005) in the Northern part of Marseille city where the rate of such poor population is high (37 to 45%). The women without a pap-smear indexed in the National Insurance Register for the last 3-2 years were invited by individual mailing to perform, free of charge, a pap-smear. The evaluation of each campaign helps us to improve the next one. The major changes from the 1st one to the 3rd one were to increase the number of free screening services, to send a second invitation to the non responders, and to organize local meetings with social workers and nurses to explain to the women the importance of performing regular screening tests. The final results after the 3 campaigns showed : out of the eligible women the participation rates are dramatically low evolving from 1,56 % to 2,48% and 6,87% of pap-smears done along the 3 campaigns ; the selection of women "without pap-smear" from the national Insurance register was not good, a great number of missing data was identified, explaining partly the extremely low rate of participation ; the factors increasing a little the participation are the second mailing of invitation (39 % of pap-smears realised) ; the total gratuitous of the screening (both sampling and reading) ; the oral information delivered locally by social workers and the proximity of the places to perform the test ; the quality of the pap-smears collected by gynecologists was good but insufficient for other health professionals, requiring a specific training for cervical cell collection. The organization of such pilot projects need to be followed to find better solutions to increase the participation to cervical screening of such populations who are at high risk of poor prognosis cervical cancers.     

The spatial encoding of body parts in patients with neglect and neurologically unimpaired participants

Body parts are represented in the brain in a very specific fashion, as compared to other three-dimensional objects, with reference to their prototypic shape and multisensory coding. However, evidence is lacking about the spatial representation of body parts. To address this issue, in Experiment 1 we first compared the metric representation of body parts and of non-bodily objects in 14 right-brain-damaged patients with left unilateral spatial neglect (USN), and in 14 neurologically unimpaired control participants. Participants bisected, by manual pointing, a three-dimensional object, or their own left forearm. Patients showed the well-known ipsilesional rightward displacement of the subjective midpoint, in both forearm and solid bisection. Both USN patients and control participants were overall more accurate in the bisection of their own forearm, relative to the extracorporeal object. In four patients this advantage of the forearm was significant in a single-case analysis, while two patients showed the opposite dissociation, being more accurate with the solid object. In Experiment 2 neurologically unimpaired participants were more accurate in the bisection of a fake forearm, as well as of their own forearm, as compared to the extrapersonal object. Overall, the results indicate that the representation of the metric of the body is more reliable than that of extrapersonal objects, and also more resistant to the disruption of spatial representations brought about by USN, possibly due to the prototypical shape of body parts. Furthermore, the double dissociation found in USN patients suggests that the metrics of body parts and of extrapersonal objects are supported by independent spatial processes.