Constitutional FLCN mutations in patients with suspected Birt-Hogg-Dubé syndrome ascertained for non-cutaneous manifestations.

Birt-Hogg-Dubé syndrome (BHDS) is characterized by a clinical triad including cutaneous hamartomas originating from hair follicles, lung cysts/pneumothorax, and kidney tumors. Inactivating mutations of the tumor suppressor gene FLCN are identified in most families with BHDS. Usually, patients are referred for genetic examination by dermatologists because of the presence of typical multiple skin tumors with or without additional symptoms. However, because of phenotypic variability and incomplete penetrance, the clinical presentation of BHDS is not yet fully defined. Criteria for genetic testing and diagnosis that take into account variable manifestations have recently been proposed by the European BHD Consortium. We sequenced the FLCN gene coding region in a series of 19 patients selected for kidney and/or lung manifestations. Overall, FLCN mutations were found in 9 of 19 (47%) families and were detected only in probands who had either >2 components of the clinical triad or a single component (renal or pulmonary) along with a family history of another main BHDS manifestation. Typical cutaneous lesions were present only in 8 of 21 FLCN mutation carriers aged >20 years identified in the mutation-positive families. In addition, we provide clinical and molecular evidence that parotid oncocytoma, so far reported in six BHDS cases, is associated with this condition, based on the observation of a patient with bilateral parotid involvement and marked reduction of the wild-type FLCN allele signal in tumor DNA. Overall, the results obtained in this study contribute to the definition of the phenotypic characteristics that should be considered for BHDS diagnosis and FLCN mutation testing.

[Neonatal group B Streptococcus infection: an integrated approach (of clinical pathologists, gynecologists, midwives, pediatricians-neonatologists) of the functional area of Cuneo (Italy)]. / Infezione neonatale da Streptococco B: un approccio multidisciplinare integrato (di laboratoristi, ginecologi, ostetriche e pediatri-neonatologi) del Quadrante di Cuneo.

The frequency of early-onset neonatal sepsis without prophylaxis is 1-5/1.000 live births. Since year '70 the most frequent causative microorganism is the group B Streptococcus (S. agalactiae, GBS), followed by Escherichia coli. The mortality rate is now reduced to 4% due to the improvement of neonatal intensive care. In the USA, the incidence of GBS early-onset neonatal sepsis has been markedly reduced by the application of the guidelines released by the Centers for Disease Control (CDC). This strategy, however, is not effective on occurrence of late-onset neonatal group B streptococcal disease. In Italy, the application of CDC guidelines is not customary, and different, often complex, protocols of obstetrical-neonatological integrated approach are applied. The frequency of infectious risk has made the GBS a paramount problem for the neonatologist, even for the legal responsibility issues resulting from the multiplicity of possible options. To reach the best level of protection of the newborn against early-onset GBS infection, the working group of providers of prenatal, obstetric, and neonatal care of the functional area of Cuneo issued an integrated protocol, in order to perform the GBS screening with the optimal culture method suggested by CDC guidelines in the highest possible number of pregnant women, and to standardize the obstetrical and neonatal management.

Use of IgG Avidity test in case definitions of toxoplasmosis in pregnancy.

A survey network for congenital toxoplasmosis (TOXO-NET) was set up in December 1996 in Piedmont (Italy). Participants were asked to classify the infections in pregnant mothers and newborns by the criteria of the European Network on Congenital Toxoplasmosis published by Lebech in 1996. Because the IgG Avidity test is largely employed as a 2nd level test in toxoplasmosis diagnosis and it could be helpful to date infection, the co-ordinators of TOXO-NET suggested including it in the "case definition" of "probable" infection and "unlikely" infection. 117 cases of toxoplasmosis in pregnancy divided into the risk categories under Lebech's criteria were re-examined using the "new" case definitions. 77 out of 117 (65.8%) Toxoplasma gondii infections during pregnancy could be defined with only one serum sample using the IgG Avidity test. The IgG Avidity test proved a useful method to classify the Toxoplasma gondii infections in pregnancy, especially when we had only one serum sample.

Haemostatic abnormalities in lung cancer: prognostic implications.

Both experimental and clinical data have shown that coagulation disorders are common in patients with cancer although clinical symptoms occur rarely. A prethrombotic state is probably involved in the mechanism of metastatic spread. Anticoagulant treatment, with either warfarin or heparin, has been shown to have a positive influence in small cell lung cancer. The purpose of this study was to evaluate the prethrombotic state as a possible marker of the outcome of lung cancer. Pretreatment prothrombin time (PT), partial thromboplastin time (PTT), antithrombin III (AT-III), platelet blood count (P), fibrinogen (F) and D-dimer (DD) were prospectively recorded in a series of 286 consecutive patients with a new primary lung cancer. Other recorded variables (32 in all) consisted of a set of anthropometric, clinical, physical, laboratory, radiological and pathological data. All patients were carefully followed up, and their subsequent clinical course recorded. Spearman rank correlation tests between coagulation factors were weakly significant, or more often non-significant. The best correlation index was that between PT and PTT (ra = -0.25). Univariate analyses of survival showed that a prolonged value of PT (P = 0.00167) and higher values of F (P = 0.00143) and DD (P = 0.0005) were associated with a poor prognosis. A few, weak relationships between well-known prognostic variables and coagulation abnormalities were also found. Because of the weakness of this correlation pattern, coagulation factors emerged in all the Cox's regression analyses as important predictors of survival, regardless of the number and type of cofactors used. A prethrombotic state (depicted by a prolongation of PT and increase of DD) is confirmed in this study as an aggravating condition in lung cancer. Studies attempting to reverse possible haemostatic abnormalities with the use of anticoagulants are justified by the present data.