Incidence and spatial distribution of adult-onset primary malignant and other central nervous system tumors in Southern Sardinia,Italy

Neurological Sciences - To study for the first time the incidence of adult-onset CNS tumors in Southern Sardinia, Italy. Clinical records of patients > 18 years old who...     

Baseline staging tests after a new diagnosis of breast cancer: further evidence of their limited indications.

BACKGROUND: Bone scanning (BS), liver ultrasonography (LUS) and chest radiography (CXR) are commonly used in patients with newly diagnosed breast cancer as part of baseline staging. However, in the absence of symptomatic disease, the usefulness of this routine diagnostic work-up is not evidence-based. METHODS: We selected the study sample from 516 consecutive patients with newly diagnosed invasive breast cancer. For each diagnostic test (BS, LUS, CXR), we analyzed the prevalence defined as the number of patients with diagnosis of metastatic disease after an imaging technique divided by the total number of patients tested. In addition, sensitivity and specificity were calculated. Initial suspicion was confirmed by other independent tests (bone X-ray, computerized tomography scan, magnetic resonance imaging) in order to identify "true" positive diagnoses. RESULTS: At baseline, BS was carried out in 412 patients, LUS in 412 patients and CXR in 428 patients. Thirty-three patients were correctly diagnosed by the initial staging investigations as having metastatic disease (true positive cases). BS detected skeletal metastases in 6.31% of patients, LUS detected liver metastases in 0.72% of patients and CXR detected lung metastases in 0.93% of patients. Before imaging tests, all patients with either LUS or CXR evidence of metastases were previously classified as having stage III disease. On the other hand, only 26.9% of bone metastases were detected in patients with stage III. Accordingly, the detection rate in stage III patients was 14%, 5.6% and 7.2%, respectively for BS, LUS and CXR. CONCLUSIONS: These findings indicate that a complete diagnostic work-up to detect metastases is unnecessary in the majority of patients with newly diagnosed breast cancer, whereas it may be indicated for specific patient categories such as those with stage III disease.     

LAMA2 gene analysis in congenital muscular dystrophy: new mutations, prenatal diagnosis, and founder effect

OBJECTIVE: To determine if laminin-alpha2 deficiency is due to mutations in the LAMA2 gene or secondary to mutations in other congenital muscular dystrophy genes. METHODS: We performed molecular analysis of LAMA2, by single-strand conformation polymorphism and sequencing, in 15 patients with undetectable or greatly reduced laminin-alpha2 expression. We also performed 4 prenatal diagnoses and investigated a founder effect. RESULTS: We found 1 known and 9 previously undescribed LAMA2 mutations spanning all protein domains. These were nonsense or frameshifts causing laminin-alpha2 absence or, in 1 case, a homozygous missense mutation producing partial protein expression and milder phenotype. LAMA2 mutations were undetected in 5 patients, in 2 of whom FKRP mutations explained the phenotype. In 3 prenatal cases, the fetus was heterozygous for the mutation of interest and pregnancy continued; in 1 case, the fetus was affected and aborted. In 2 patients, the Cys967Stop mutation and identical haplotypes flanking the LAMA2 gene indicated a founder effect. CONCLUSIONS: The clinical phenotype was severe in most patients with LAMA2 mutations and associated with undetectable protein expression. One case with no protein and another with partial expression had milder phenotypes. Typical white matter alterations on magnetic resonance imaging were found in all patients with LAMA2 mutations, supporting the utility of magnetic resonance imaging in differential diagnosis. The founder mutation (Cys967Stop) probably originated in Albania. Genetic characterization of affected families is mainly of use for prenatal diagnosis.     

Validation of serum ferritin values by magnetic susceptometry in predicting iron overload in dialysis patients

BACKGROUND: Guidelines for treating anemia in dialysis patients accept, as high-end range of serum ferritin useful to optimize erythropoietin therapy, values high as 500 to 900 microg/L, on the hypothesis that ferritin might be not representative of iron overload. METHODS: A superconducting quantum interference device (SQUID) was used to make direct noninvasive magnetic measurements of nonheme hepatic iron content in 40 dialysis patients treated with intravenous iron, and liver iron content was compared with biochemical markers of iron status. RESULTS: Only 12/40 (30%) patients showed normal hepatic iron content (SQUID <400 microg/g), while 32.5% had mild (400 to 1000 microg/g) and 37.5% severe (>1000 microg/g) iron overload, although 28/40 patients (70%) had serum ferritin below 500 microg/L. Among many parameters, hepatic iron content was only correlated with ferritin (r= 0.324, P= 0.04). The receiver operating characteristic (ROC) analysis showed the best specificity/sensitivity ratio to identify iron overload for ferritin >340 microg/L (W = 0.716). Multivariate logistic regression analysis demonstrated that an increase in serum ferritin of 100 microg/L and female gender were independent variables associated with moderate to severe hepatic iron overload: OR 1.71 (95% CI 1.10 to 2.67) and OR 10.68 (95% CI 1.81 to 63.15), respectively. CONCLUSION: Hepatic iron overload is frequent in dialysis patients with ferritin below currently proposed high-end ranges, and the diagnostic power of ferritin in indicating true iron stores is better than presumed. Safety concerns should prompt a reevaluation of acceptable iron parameters, focusing on potential gender-specific differences, to avoid potentially harmful iron overload in a majority of dialysis patients, mainly females.     

BRCA2 germline mutations in primary cancer of the fallopian tube

Germline mutations of BRCA1 and BRCA2 genes confer susceptibility to breast and ovarian cancer. It has been recently reported that BRCA1/2 mutations may also predispose to fallopian tube cancer. We report the presence of germline BRCA2 gene mutations in three out of four subjects with fallopian tube cancer diagnosed in a two-year time span at our clinic. The mothers of two of these women suffered from breast or ovarian carcinoma. These results suggest on one hand that in patients with a history suggestive for a heredofamilial breast/ovarian cancer syndrome fallopian tube carcinoma is associated with high risk of BRCA2 mutation, and on the other hand that in patients/individuals with germline BRCA2 gene mutations in whom a prophylactic oophorectomy is performed, removal of fallopian tubes may be considered.     

Preliminary report on a new and noninvasive method for the assessment of fetal lung maturity

OBJECT: Several patterns of fetal breathing movements (FBMs), i.e. abdominal wall movements (AWm), thoracic wall movements (TWm) and nasal fluid flow velocity waveforms (NFFVW), were investigated by ultrasound (US) technology and related to fetal pulmonary maturity and immaturity, i.e. fetal lung maturity (FLM) tests, in order to validate the hypothesis that they may indicate whether the fetal lung is mature or immature, regardless of gender, weight and gestational age. MATERIAL AND METHODS: We prospectively enrolled 143 high-risk pregnancies in which a complete US study of FBMs and FLM tests was performed. Among them 43 women satisfied the inclusion criteria. US-FLM was defined as the presence of regular NFFVW detected by pulsed Doppler and spectral analysis, or irregular NF-FVW synchronous with TWm detected by M-mode. An US guided amniocentesis was performed in order to collect amniotic fluid (AF) and FLM was evaluated by L/S (lecithin/sphingomyelin) determination, presence of phosphatidylglycerol (PG) and lamellar bodies (LBs) count. At the end of the study the diagnostic accuracy of US-FLM was compared to that of FLM tests. RESULTS: Diagnostic accuracy for US evaluation of FLM was as follows: sensitivity: 89.6%; specificity: 85.7%; PPV: 92.8%; NPV: 80%. Diagnostic accuracy of FLM tests was as follows: sensitivity: 100%; specificity: 51.7%; PPV: 100%; NPV: 50%. L/S determination predicted lung maturity with a sensitivity of 100%; specificity of 93.1%; PPV of 100%; NPV of 87.5%. CONCLUSION: Presence of regular NFFVW or irregular NFFVW and TWm correlate accurately with conventional FLM tests. We suggest that this noninvasive procedure may be helpful for assessing FLM, particularly under certain circumstances, e.g., oligo-anhydramnios, laboratory logistic equipment difficulties or heavily stained AF samples, amniocentesis refusal, religious concerns.     

The safety and effectiveness of deferiprone in a large-scale, 3-year study in Italian patients

In 1997, the Italian Ministry of Health created a special programme for the controlled distribution of deferiprone to collect data and to evaluate its safety and effectiveness in long-term use. Five hundred and thirty-two thalassaemia patients from 86 treatment centres were enrolled in this programme. One hundred and eighty-seven patients (32%) experienced a total of 269 events that led to a temporary interruption or, in some cases, to a discontinuation of treatment. The incidence of agranulocytosis and milder neutropenias were 0.4/100 and 2.1/100 patient-years respectively. Neutropenia occurred predominantly in younger and non-splenectomized patients. Transient alanine transaminase increase, gastrointestinal discomfort and arthralgia were the other most commonly reported events. Ferritin levels showed a significant decrease in time after 3 years of therapy. This is the largest number of deferiprone-treated patients to have been reported to date. These data show that the drug was effective in reducing serum ferritin levels and the incidence of adverse events was not greater than the frequency reported in clinical trials.