Performance of BOADICEA and BRCAPRO genetic models and of empirical criteria based on cancer family history for predicting BRCA mutation carrier probabilities: a retrospective study in a sample of Italian cancer genetics clinics.

PURPOSE: To evaluate in current practice the performance of BOADICEA and BRCAPRO risk models and empirical criteria based on cancer family history for the selection of individuals for BRCA genetic testing. PATIENTS AND METHODS: The probability of BRCA mutation according to the three tools was retrospectively estimated in 918 index cases consecutively undergone BRCA testing at 15 Italian cancer genetics clinics between 2006 and 2008. RESULTS: 179 of 918 cases (19.5%) carried BRCA mutations. With the strict use of the criteria based on cancer family history 173 BRCA (21.9%) mutations would have been detected in 789 individuals. At the commonly used 10% threshold of BRCA mutation carrier probability, the genetic models showed a similar performance [PPV (38% and 37%), sensitivity (76% and 77%) and specificity (70% and 69%)]. Their strict use would have avoided around 60% of the tests but would have missed approximately 1 every 4 carriers. CONCLUSION: Our data highlight the complexity of BRCA testing referral in routine practice and question the strict use of genetic models for BRCA risk assessment.

[Possibility to screen COPD in emergency department]. / Faisabilité d'un dépistage de la BPCO aux urgences.

INTRODUCTION: The COPD is a stake of public health because of its prevalence in the world, its morbi-mortality and its considerable cost (2,2 billion euros/year in France). An early screening allows for a fast and effective intervention. MATERIAL AND METHOD: The prospective study with in the emergency department of Roanne included smokers and ex-smokers, more than 10PY for the 40 years old and older, more than 20PY for the others, and/or symptomatic of COPD. Screening rested on a questionnaire filled out by the patient. Are excluded patients already diagnosed with COPD. This screening is carried out with the FEV1/FEV6. The criterion of principal judgment rests on the time taken for screening and acceptability by the patients. RESULTS: One hundred and twenty-two patients were included, 6.5% refused screening. The average time of screening was 4.8 minutes. There were 27 positive patients with the FEV1/FEV6, 14 came to make the classic spirometry. Only 10.53% have a FEV1/FEV6<0.73. On the whole, 15.86% do not have a COPD, 75,25% are at the risk of COPD, 5,94% have a COPD stage 1, 1,98% are stage 2, 0.99% stage 3 and none stage 4. DISCUSSION: The study thus showed that a screening of the COPD in the emergency rooms is possible because of the simple and reproductible process. Its shows, however its limits since the number of inclusion decrease during days of strong attendance in emergency rooms. CONCLUSION: The screening of the COPD as foreseen in the study is possible.

Microarray application in prenatal diagnosis: a position statement from the cytogenetics working group of the Italian Society of Human Genetics (SIGU), November 2011.

A precise guideline establishing chromosomal microarray analysis (CMA) applications and platforms in the prenatal setting does not exist. The controversial question is whether CMA technologies can or should soon replace standard karyotyping in prenatal diagnostic practice. A review of the recent literature and survey of the knowledge and experience of all members of the Italian Society of Human Genetics (SIGU) Committee were carried out in order to propose recommendations for the use of CMA in prenatal testing. The analysis of datasets reported in the medical literature showed a considerable 6.4% incidence of pathogenic copy number variations (CNVs) in the group of pregnancies with sonographically detected fetal abnormalities and normal karyotype. The reported CNVs are likely to have a relevant role in terms of nosology for the fetus and in the assessment of reproductive risk for the couple. Estimation of the frequency of copy number variations of uncertain significance (VOUS) varied depending on the different CMA platforms used, ranging from 0-4%, obtained using targeted arrays, to 9-12%, obtained using high-resolution whole genome single nucleotide polymorphism (SNP) arrays. CMA analysis can be considered a second-tier diagnostic test to be used after standard karyotyping in selected groups of pregnancies, namely those with single (apparently isolated) or multiple ultrasound fetal abnormalities, those with chromosomal rearrangements, even if apparently balanced, and those with supernumerary marker chromosomes.

Tuberous sclerosis in a term newborn with opisthotonus - The value of ultrasound.

PURPOSE: We describe the clinical findings and the results of cerebral imaging studies [ultrasound (US), magnetic resonance imaging (MRI)] in a full-term newborn with tuberous sclerosis (TS) complex. This condition is inherited as an autosomal dominant trait and characterized by hamartomas involving multiple organs. Diagnosis is based on physical examination together with imaging support. METHODS: Since the TS complex can result in numerous CNS abnormalities, cerebral US should be used to further characterize this malformation. CONCLUSION: Sonography is a useful modality for evaluation of the full-term neonatal brain.

Comparison of four chromogenic media and Hektoen agar for detection and presumptive identification of Salmonella strains in human stools.

Several chromogenic media have been developed to enhance the specificity of Salmonella detection. We compared the performance of four commercial chromogenic media-namely, ABC medium (Lab M. Ltd., Bury, United Kingdom), COMPASS Salmonella agar (Biokar Diagnostics, Beauvais, France), CHROMagar Salmonella agar (CHROMagar Company, Paris, France), and SM ID agar (bioMerieux, Marcy l'Etoile, France)-with conventional Hektoen medium. Nine hundred sixteen stool samples from inpatients at three hospitals were cultured, in parallel, on the five media, both by direct inoculation and after selective enrichment in selenite broth. Sixty-four Salmonella strains with 12 serotypes were isolated on at least one medium. After 48 h of incubation, sensitivity before and after enrichment was 62.5 and 89.1% with ABC medium, 77.1 and 93.8% with COMPASS agar, 66.7 and 89.1% with CHROMagar, 68.8 and 85.9% with SM ID agar, and 85.4 and 98.4% with Hektoen agar, respectively. Broth enrichment and prolonged incubation (48 versus 24 h) increased the sensitivity of all five media. Only one strain was not isolated on Hektoen agar. The number of false-positive isolates was higher with all five media after enrichment in selenite broth and after incubation for 48 h compared to 24 h. The specificity of the four chromogenic media was better than 91% after incubation for 24 h (77.7% with Hektoen agar) and better than 84% after incubation for 48 h (74.8% with Hektoen agar). This higher specificity reduces the need for confirmatory tests, thereby cutting technical time and reagent requirements. Both COMPASS agar and CHROMagar Salmonella, which after simple additional tests showed close efficiencies (96 and 97%, respectively), can be recommended as single-plate media of choice for the detection and presumptive identification of salmonellae in stools.

FISH characterization of a supernumerary r(1)(::cen-->q22::q22-->sq21::) chromosome associated with multiple anomalies and bilateral cataracts.

We describe the case of a 15-year-old girl with multiple congenital anomalies, dysmorphic features, severe kyphoscoliosis, growth and mental retardation, and the absence of speech, in whom 35% of the cells carried a supernumerary ring chromosome 1. Fluorescence in situ hybridization (FISH) analysis using YAC/BAC clones spanning the region from 1p13 to 1q21 made it possible to determine the genomic content and structure of the ring(1), which was found to consist of the cytogenetic bands 1q21-22. A complex structure was delineated in the ring chromosome with a partial inverted duplication delimited by markers WI-7732 and WI-607, with WI-7396 and WI-8386 being the boundaries of the single copy segment. Comparison of the clinical signs of other patients with mosaic r(1) reported in the literature allowed the identification of a patient sharing a number of clinical signs including cataracts. Given that mutations of the GJA8 gene encoding connexin 50 (Cx50) and mapping to 1q21 have been associated with the presence of cataracts, it is possible that a gain in copy number or a rearrangement of GJA8 may contribute to cataractogenesis.

Ultrafiltration with icodextrins in continuous ambulatory peritoneal dialysis and automated peritoneal dialysis.

Icodextrins (Icos) produce constant linear ultrafiltration (UF). This effect allows Icos to replace glucose during long dwells in continuous ambulatory peritoneal dialysis [CAPD (nighttime)] and automated peritoneal dialysis [APD (daytime)]. However, the effectiveness of Icos in producing UF (IcoUF) is limited by lymphatic reabsorption, whose extent depends partly on posture and physical activity. This paper aims to assess whether the difference in posture and physical activity between daytime dwells in APD and nighttime dwells in CAPD affects IcoUF. Patients undergoing first treatment were retrospectively examined. Ten patients were on CAPD [4 males, 6 females; average age, 73.0 +/- 13.4 years; body surface area (BSA), 1.63 +/- 0.21 m2; total volume per day, 5.6 +/- 1.9 L], and ten were on APD (7 males, 3 females; average age, 67.7 +/- 9.8; BSA, 1.75 +/- 0.22 m2; total volume per night, 10.5 +/- 0.9 L). Ultrafiltration was assessed for seven consecutive days preceding a peritoneal equilibration test (PET) and collection of diuresis. In both groups, 3 patients had no diuresis, and the difference between CAPD and APD was not significant (625 +/- 762 mL vs 780 +/- 878 mL). Moreover, no significant difference was seen in 4-hour dialysate-to-plasma creatinine (D/P) between CAPD (0.65 +/- 0.12) and APD (0.64 +/- 0.05). Dwell times with Icos were shorter in CAPD than in APD (11.5 +/- 1.8 hours vs 14.8 +/- 0.5 hours, p < 0.0005), but the fill volume was not significantly different (1760 +/- 286 mL vs 1790 +/- 249 mL). Water excretion owing to diuresis and dialysis [total water excretion (TWE): 1619 +/- 497 mL CAPD vs 1762 +/- 736 mL APD] and dialytic UF (363 +/- 443 mL CAPD vs 748 +/- 479 mL APD), which is not linked to Icos, were not significantly different between the two groups. The IcoUF and the percentage of IcoUF to TWE were significantly higher in CAPD compared to APD [631 +/- 253 mL (44% +/- 27%) vs 234 +/- 215 mL (19% +/- 19%), p < 0.001 (p < 0.05)]. In conclusion, an upright posture and physical activity seem to produce less IcoUF in APD despite the longer dwell. These factors could, indeed, produce greater intraperitoneal pressure, resulting in increased lymphatic reabsorption during a daytime dwell.

Production of platelet-activating factor in patients with sepsis-associated acute renal failure.

BACKGROUND: Studies in experimental animals have suggested that platelet-activating factor (PAF) is a mediator of sepsis-associated acute renal failure (ARF). In the present study we have evaluated whether an increased concentration of PAF within circulation or urine of septic patients correlated with the worsening of renal function. METHODS: The concentration of PAF and selected cytokines (TNF, IL-1, IL-6, IL-8) was evaluated in blood and urine of 12 patients with septic shock and ARF for 4 consecutive days. RESULTS: The data obtained indicate that blood and urinary concentrations of PAF and of IL-1, IL-6 and IL-8 were significantly higher in septic patients than in controls subjects and in patients with chronic renal failure. The concentration of TNF was significantly increased only in urine. A significantly positive correlation was found among blood concentration of PAF and heart rate (r = 0.4193, P < 0.017), serum creatinine (r = 0.3671, P < 0.038), serum IL-6 (r = 0.5475, P < 0.005) and urine excretion of IL-8 (r = 0.3984, P < 0.044), whereas a negative correlation was present with the number of circulating platelets (r = -0.4285, P < 0.018). Moreover, a positive correlation among the concentration of PAF in urine and the serum concentration of IL-6 (r = 0.5654, P < 0.006) and urine excretion of IL-6 (r = 0.6589, P < 0.0008) and IL-8 (r = 0.6371, P < 0.0004) were found. CONCLUSIONS: These results demonstrate in humans during ARF associated with septic shock the production of PAF, a mediator that has been previously implicated in the pathogenesis of experimental endotoxin-induced shock and renal injury. The observation that blood and urinary concentrations of PAF correlated with some of the clinical and laboratory parameters related to the severity of ARF and sepsis suggests that PAF may contribute to the development of renal injury in septic patients.

[Blood lead levels in a non-professionally-exposed population from six Tuscan provinces]. / Livelli ematici di piombo in popolazioni non professionalmente esposte residenti in sei provincie toscane.

We report the results obtained in 1992 concerning the determination of blood lead levels (PbB) in 1321 subjects of the general population living in ten villages/towns of the Florence district characterised by the presence of artistic ceramic factories. We reported also the PbB values found in 2330 adults, 280 children, 39 pregnant women and their correspondent umbilical cords, who were examined during the second biological monitoring campaign against the risk of lead intoxication according to the DPR 496/82. Median PbB values were 92.5 micrograms/l (range 15-520 micrograms/l) for males and 62.5 micrograms/l (range 11-343 micrograms/l) for females. The lower PbB median values were found in the district of Livorno (76.25 micrograms/l and 48.25 micrograms/l in males and females, respectively) and Arezzo (80.5 micrograms/l and 52 micrograms/l in males and females, respectively). In comparison with the results obtained for the general Italian population during the previous biological monitoring campaign carried out in 1985-86 we observed PbB median values about 40% lower for both males and females and PbB median values about 55% lower for children. A significant statistic correlation (r = 0.53) was found between PbB of pregnant women and their umbilical cords.

Calculation of Kt/V and creatinine [correction of creatine] clearance in APD.

The calculation of Kt/V and creatinine clearance per 1.73 m2 of body surface area (CrCl/1.73 m2 of BSA) varies according to whether the post- or pre-nightly dialysis treatment (NDT) values of the serum urea (sUrea), serum creatinine (sCreat), and body weight (BW) parameters are used. The purpose of this paper is to determine the difference between Kt/V and CrCl/1.73 m2 of BSA, calculated using the pre- and post-NDT values, and any correlation of such differences with different automated peritoneal dialysis (APD) methods. We took into consideration patients on APD treated using the tidal method with four different techniques: NTPD (9 patients; no daytime dwell), NTPD-1 (12 patients; one daytime dwell of 4-7 hours), CTPD (10 patients; one daytime dwell), and CTPD-2 (8 patients; two daytime dwells). Body water (V) and body surface area (BSA) were calculated using the Watson and Du Bois formulas. The percentage difference between pre- and post-NDT using the various methods is not statistically significant, while all the post-NDT parameters are significantly lower than the pre-NDT parameters. Since this difference is greater for sUrea (8.8%) and V (1.1%) than for sCreat (4.1%) and BSA (0.8%), the nightly Kt/V variation (11.2%) is greater than the nightly CrCl/1.73 m2 of BSA variation (5.2%). These variations do not differ significantly among the various methods. For APD, therefore, increase is to be expected in the CAPD targets of 10% and 5% respectively for Kt/V and CrCl/1.73 m2 of BSA calculated using the post-NDT values of sUrea and sCreat and the pre-NDT value of BW.

[Insufficient correction of blood bicarbonate levels in biguanide lactic acidosis treated with CVVH and bicarbonate replacement fluids]. / Insufficiente correzione della bicarbonatemia nella acidosi lattica da biguanidi trattata con CVVH e liquido di reinfusione con bicarbonato.

BACKGROUND: In the course of Continuous Veno-Venous Hemofiltration (CVVH), bicarbonate buffer instead of lactate is suitable for the treatment of combined renal and hepatic failure and for patients suffering from lactic acidosis, type A or B, joined with acute renal failure (ARF). METHODS: We applied the CVVH buffered with bicarbonate for the treatment of two patients affected by ARF and severe lactic acidosis type B (due to biguanide intoxication) and we evaluated its ability to correct the acid-base balance. RESULTS: Clinical and laboratory data show that this technique, performed in standard conditions (plasma flow: 70 ml/min, ultrafiltration: 25 ml/min, bicarbonate concentration in the infusion fluid: 30 mEq/L), was inadequate to compensate for the high requirement of bicarbonate (approximately 280 mEq/hr during the first 6 hours of observation) and the severe metabolic acidosis, thus additional bicarbonate infusion was needed. CONCLUSIONS: In particular, from ascertained data and theoretical considerations, in the course of lactic acidosis caused by biguanide, in order to correct acidosis a positive balance of bicarbonate could be obtained only by means of a bicarbonate-based replacement fluid and of a continuous high flow hemofiltration, such as to assure an ultrafiltrate volume exceeding 150 ml/min.

Constitutional trisomy 8 as first mutation in multistep carcinogenesis: clinical, cytogenetic, and molecular data on three cases.

Three patients, with constitutional trisomy 8 mosaicism (CT8M), who developed a malignancy are reported. The diagnoses were refractory anaemia, acute lymphoblastic leukaemia, and idiopathic myelofibrosis. In the child with acute leukaemia, the CT8M was diagnosed at birth due to severe dysmorphisms and malformations; the other two patients showed a milder phenotype, and the CT8M was diagnosed only after the finding of trisomy 8 in neoplastic cells. The review of eight similar, previously reported cases and the clinical, cytogenetic, and molecular studies performed in our patients led us to make the following observations: (I) CT8M predisposes to neoplasms, preferentially to myelo- or lymphoproliferative diseases; (2) a gene dosage effect for glutathione reductase in red blood cells was seen in two of our patients; (3) the wide phenotypic variation of CT8M was confirmed: trisomy 8 in neoplastic cells of phenotypically near-normal cases may be misinterpreted as acquired; and (4) molecular studies suggested a postzygotic origin of the trisomy in our three cases, with the supernumerary chromosome being of paternal origin in one case and of maternal origin in the other two. We postulate that the trisomy 8 in neoplasms may often occur by mitotic nondisjunction in an early embryonic multipotent cell and that what is usually interpreted as an acquired trisomy 8 may in fact be CT8M. The constitutional trisomy 8 would act as a pathogenetically important first mutation in multistep carcinogenesis. Whenever trisomy 8 is found in malignancies, the patient should be reevaluated clinically to exclude CT8M, and CT8M patients should be monitored for the possible development of malignancies.