Characterization of the frequency stability of an optical frequency standard at 1.39 µm based upon noise-immune cavity-enhanced optical heterodyne molecular spectroscopy.

Frequency fluctuations of an optical frequency standard at 1.39 µm have been measured by means of a highly-sensitive optical frequency discriminator based on the fringe-side transmission of a high finesse optical resonator. Built on a Zerodur spacer, the optical resonator exhibits a finesse of 5500 and a cavity-mode width of about 120 kHz. The optical frequency standard consists of an extended-cavity diode laser that is tightly stabilized against the center of a sub-Doppler H(2) (18)O line, this latter being detected by means of noise-immune cavity-enhanced optical heterodyne molecular spectroscopy. The emission linewidth has been carefully determined from the frequency-noise power spectral density by using a rather simple approximation, known as ß-line approach, as well as the exact method based on the autocorrelation function of the laser light field. It turns out that the linewidth of the optical frequency standard amounts to about 7 kHz (full width at half maximum) for an observation time of 1 ms. Compared to the free-running laser, the measured width corresponds to a line narrowing by a factor of ~220.

Plerixafor for PBSC mobilisation in myeloma patients with advanced renal failure: safety and efficacy data in a series of 21 patients from Europe and the USA.

We describe 20 patients with myeloma and 1 with primary amyloidosis from 15 centres, all with advanced renal failure, most of whom had PBSC mobilised using plerixafor following previous failed mobilisation by conventional means (plerixafor used up-front for 4 patients). For 15 patients, the plerixafor dose was reduced to 0.16 mg/kg/day, with a subsequent dose increase in one case to 0.24 mg/kg/day. The remaining six patients received a standard plerixafor dosage at 0.24 mg/kg/day. Scheduling of plerixafor and apheresis around dialysis was generally straightforward. Following plerixafor administration, all patients underwent apheresis. A median CD34+ cell dose of 4.6 × 10(6) per kg was achieved after 1 (n=7), 2 (n=10), 3 (n=3) or 4 (n=1) aphereses. Only one patient failed to achieve a sufficient cell dose for transplant: she subsequently underwent delayed re-mobilisation using G-CSF with plerixafor 0.24 mg/kg/day, resulting in a CD34+ cell dose of 2.12 × 10(6)/kg. Sixteen patients experienced no plerixafor toxicities; five had mild-to-moderate gastrointestinal symptoms that did not prevent apheresis. Fifteen patients have progressed to autologous transplant, of whom 12 remain alive without disease progression. Two patients recovered endogenous renal function post autograft, and a third underwent successful renal transplantation. Plerixafor is highly effective in mobilising PBSC in this difficult patient group.

The addition of plerixafor is safe and allows adequate PBSC collection in multiple myeloma and lymphoma patients poor mobilizers after chemotherapy and G-CSF.

We report 13 multiple myeloma (MM) or lymphoma patients who were failing PBSC mobilization after disease-specific chemotherapy and granulocyte-CSF (G-CSF), and received plerixafor to successfully collect PBSCs. Patients were considered poor mobilizers when the concentration of PB CD34(+) cells was always lower than 10 cells/µL, during the recovery phase after chemotherapy and/or were predicted to have inadequate PBSC collection to proceed to autologous transplantation. Plerixafor (0.24 mg/kg) was administered subcutaneously for up to three consecutive days, while continuing G-CSF, 10-11 h before the planned leukapheresis. Plerixafor administration was safe and no significant adverse events were recorded. We observed a 4.7 median fold-increase in the number of circulating CD34(+) cells after plerixafor as compared with baseline CD34(+) cell concentration (from a median of 6.2 (range 1-12) to 21.5 (range 9-88) cells/µL). All patients collected >2 × 10(6) CD34(+) cells/kg in 1-3 leukaphereses. In all, 5/13 patients have already undergone autograft with plerixafor-mobilized PBSCs, showing a rapid and durable hematological recovery. Our results suggest that the pre-emptive addition of plerixafor to G-CSF after chemotherapy is safe and may allow the rescue of lymphoma and MM patients, who need autologous transplantation but are failing PBSC mobilization.

BU/melphalan and auto-SCT in AML patients in first CR: a 'Gruppo Italiano Trapianto di Midollo Osseo (GITMO)' retrospective study.

AML patients (total 129; median age =50 years; range 16-72) in first CR received BU and melphalan (BU/Mel) as conditioning regimen before auto-SCT. In all, 82 patients (63.6%) received PBSCs and 47 patients (36.4%) received BM cells. The distribution of cytogenetic categories was conventionally defined as favorable (15.5%), intermediate (60.1%) and unfavorable (24.3%). With a median follow-up of 31 months, the 8-year projected OS and disease-free survival (DFS) was 62 and 56% for the whole population, respectively. The relapse rate was 46% and the non-relapse mortality was 4.65%. Although PBSC transplantation led to a faster hematological recovery than BM transplantation, in univariate analysis the stem cell source, cytogenetics and different BU formulations did not significantly affect OS and DFS, whereas age and the number of post-remission chemotherapy cycles did have a significant effect on the clinical outcome. Multivariate analysis identified age <55 years as the only important independent predictor for OS and DFS. Our data suggest that BU/Mel, being associated with a low toxicity profile (mainly mucositis) and mortality, is an effective conditioning regimen even for high-risk AML patients in first CR undergoing auto-SCT.

The Prospective Oral Mucositis Audit: relationship of severe oral mucositis with clinical and medical resource use outcomes in patients receiving high-dose melphalan or BEAM-conditioning chemotherapy and autologous SCT.

The Prospective Oral Mucositis Audit was an observational study in 197 patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) undergoing, respectively, high-dose melphalan or BEAM chemotherapy and autologous SCT at 25 European centres. We evaluated the relationship between severe oral mucositis (SOM; WHO Oral Toxicity Scale grade 3-4) and local and systemic clinical sequelae and medical resource use. SOM occurred in 44% of patients. The duration of SOM (mean 5.3 days) correlated with time to neutrophil engraftment. The following parameters increased gradiently with maximum grade of oral mucositis: duration of pain score >or=4, opioid use, dysphagia score >or=4, total parenteral nutrition (TPN) use, incidence and/or duration of fever and infection, and duration of antibiotic use. SOM increased the duration of TPN use by 2.7 days (P<0.001), opioids by 4.6 days (P<0.001), and antibiotics by 2.4 days (P=0.045). SOM prolonged hospital stay by 2.3 days (P=0.013) in MM patients, but not in NHL patients (who tended to have a longer hospital stay). In conclusion, this analysis of prospectively collected observational data provides important insight into the scope and impact of SOM in the European transplant setting.

[2 cases of Beckwith-Wiedemann syndrome. Morphogenetic characteristics, cardiac involvement and current diagnostic possibilities]. / A proposito di due casi di sindrome di Beckwith-Widemann. Caratteristiche morfogenetiche, interessamento cardiaco ed attuali possibilità diagnostiche.

This report describes two new cases of BWS. This diagnosis of BWS may be missed because of variable or incomplete clinical expression. Recognition of such patients is important, however, because they have the potential for development of neoplasias. There also appears to be an increased risk of malignancies associated with hemihypertrophy and BWS.

[The instrumental and clinical laboratory follow-up of congenital hypothyroidism]. / Il follow-up laboratoristico strumentale e clinico dell'ipotiroidismo congenito.

Early diagnosis, L-tiroxine therapy and adequate follow-up are determinant to remove the damages resulting from hormone deficiency in congenital hypothyroidism (CH). In order to achieve a better intellectual development, the authors suggest some guidelines for a correct follow-up on the basis of their personal experience on a population of 160 children with CH. These guidelines include monitored therapy, biochemical controls, instrumental investigations, clinical and auxological serial examinations. To better predict the mental outcome of these patients as adults, the authors propose a longer follow-up till adolescents, especially in the children with more severe hypothyroidism at diagnosis.

[A case of the cardiofacial syndrome (Cayler's syndrome)]. / Su di un caso di sindrome cardio-facciale (sindrome di Cayler).

We report a case of cardiofacial syndrome that seems to be genetically transmitted as an autosomal dominant trait. It is characterized by hypoplasia of depressor anguli oris muscle and perimembranous ventricular septal defect. We emphasize the importance of performing diagnostic tests in these patients (cardiac assessment, spinal x-ray, renal echo) in order to rule out associated malformations.

Echocardiographic evaluation of left ventricular outflow tract obstruction in complete transposition of the great arteries.

Subpulmonic stenosis in complete d-transposition of the great arteries (d-TGA) is a frequently associated malformation, the precise diagnosis of which is essential for optimal medical and surgical treatment. Sixteen patients with d-TGA and subpulmonic stenosis have been studied by M-mode and two-dimensional (2DE) echocardiography and cardiac catheterization. Dynamic obstruction was found in six patients and fixed stenosis in 10. Systolic anterior motion of the mitral valve without fixed obstruction of the left ventricular outflow tract (LVOT) was present in patients with dynamic stenosis. Measurements of left ventricular end-diastolic posterior wall thickness to minor semiaxis ratio correlated well (p less than 0.001) with the pressure gradient across the LVOT. Various types of anatomic fixed obstruction are described. M-mode echocardiography provides assessment of dynamic obstruction but does not allow quantitative evaluation of the length of the narrowed segment. The latter can be achieved by 2DE, which offers improved definition of different anatomic types.

[Echocardiography for the evaluation of tricuspid atresia. I. Morphological analysis (author's transl)]. / Valutazione dell'atresia della tricuspide mediante ecocardiografia. I) Analisi morfologica.

Twenty-five patients with tricuspid atresia, ranging in age between 3 months and 23 years, were studied by M-mode and two-dimensional (2D) echocardiography. In all of them diagnosis was confirmed by cardiac catheterization and angiocardiography and in most of them at surgery or autopsy. Some anatomical specimens of tricuspid atresia were analyzed in order to be correlated with corresponding two-dimensional pictures. Contrast 2D echocardiography was performed in 12 of 25 patients. M-mode scanning right atrium-left ventricle showed a rudimentary echo coming from the atretic valve but didn't show its relations with the membranous portion of ventricular septum. 2D echocardiography in (two chambers) or (four chambers) view was particularly useful to distinguish tricuspid atresia from other hypoplastic right heart syndromes with functioning tricuspid valve. Peripheral contrast injection enhances diagnostic capability of 2D echocardiography, especially for the assessment of right ventricular dimensions, differentiation between atretic and imperforate valve and evaluation of ventricular septal defect.

[Echocardiography for the evaluation of tricuspid atresia. II. Analysis of the left ventricular function (author's transl)]. / Valutazione dell'atresia della tricuspide mediante ecocardiografia. II) Analisi della funzionalità ventricolare sinistra.

Twenty-five patients with tricuspid atresia, ranging in age between 2 months and 23 years, previously morphologically studied, were assessed by M-mode echocardiography with regard to left ventricular function. Fifteen of them underwent palliative cardiac surgery (systemic-pulmonary anastomosis). Thirty normal subjects, same age and sex, were selected as controls. Patients with tricuspid atresia had a significant increase of left ventricular dimensions and mass and significant decrease of shortening fraction and ejection fraction. The left ventricular pre-ejection/ejection ratio (LPEP/LVET) was significantly higher in patients with tricuspid atresia compared to normals. In patients without surgical shunt there was no significant correlation between Qp/Qs determined by oximetry and the end-diastolic dimension and left ventricular function parameters. In patients with surgical shunt a significant correlation was found between ejection fraction, shortening fraction, systolic time intervals and Qp/Qs. Qp/Qs significantly correlated with end-diastolic dimension. Shortening fraction and ejection fraction were higher in patients with satisfactory systemic saturation, while left ventricular mass was increased in patients with longstanding surgical shunt. These data suggest that patients with tricuspid atresia, with or without surgical shunt, may present with a decreased left ventricular function, early detectable by echocardiography.

[Absent pulmonary valve. Report of 4 cases, echocardiographic assessment and review of the literature (author's transl)]. / L'assenza delle valvole polmonari. Descrizione di quattro casi, valutazione ecocardiografica e rivisione della letteratura.

Four cases of "absent pulmonary valve" (APV) are described. This congenital heart disease consists of aplasia or extreme hypoplasia of pulmonary semilunar cusps and is always combined with aneurysmatic dilatation of pulmonary artery. In two of them the diagnosis was confirmed at autopsy. The remaining two are clinical reports surgically confirmed. One of them was studied by single cristal and two-dimensional echocardiography. In three cases APV was associated with tetralogy of Fallot, while in one case there was an intact ventricular septum. Review of literature allowed us to select 149 cases of APV anatomically confirmed, besides our ownes. It is stressed on that APV is usually associated with dextroposition of the aorta and ventricular septal defect by conoventricular malallignment. It is suggested that pathogenesis of this malformation is a consequence of an anomalous development of mesenchimal tissue of pulmonary cusps rather than an asymmetrical truncal sepimentation. We favour the hypothesis that aneurysmatic dilatation of pulmonary artery is caused by altered hemodynamics acting both in foetal and extrauterine life, even if differently expressed. Pathophysiologic and diagnostic value of cyanosis, dyspnea, and systo-diastolic murmur are discussed. Some outlines of the most important diagnostic procedures are reviewed and particularly echocardiography, which shows aortic overriding and dilatation of right ventricular outflow tract and pulmonary artery separated by a restricted pulmonary annulus. Prognosis and therapy are also mentioned.