Survival and toxicity of radical radiotherapy (with or without brachytherapy) for FIGO stage I and II cervical cancer: a mono-institutional analysis.

PURPOSE OF INVESTIGATION: To add to the existing outcome data regarding radical radiotherapy (RT) for FIGO Stage I and II cervical cancer in a mono-institutional series and to evaluate the cost-benefit ratio of the addition of brachytherapy (BRA) to external-beam radiotherapy (EBRT). MATERIALS AND METHODS: The authors report on 240 patients (pts) with FIGO Stage I and II cervical cancer, consecutively treated with radical RT from 1990 through 2009 at the Istituto del Radio "O. Alberti" (EBRT alone, 32, EBRT and BRA, 189, BRA alone, 19). BRA was delivered with low dose rate (LDR, 133.64%) until 2003 and then with high dose rate (HDR, 75.36%). RT was associated with concomitant chemotherapy (CHT), mainly weekly cisplatin 40 mg/m2, in 87 pts, mostly after 2000. The Chi-square test was used to compare the different variables, the Log-Rank test to compare the actuarial survival values, and the Cox-model for the multivariate analysis. RESULTS: Five-year actuarial overall survival (OS) equalled 65%, disease specific survival (DSS) 77%. Regardless of disease stage, better DSS was evident in pts treated with EBRT and BRA compared with those treated with EBRT alone (82% and 58% respectively, p = 0.005); pts treated with concomitant CHT (dose intensity > or = 50%) and higher RT doses (RT cumulative EQD2 > or = 75 Gy) obtained better DSS. Complete response (CR) rate approached 88.4% (206/233 evaluable pts) and more than half of the subsequent failures (21/36) were in distant sites. Older patients and those given BRA had better OS and DSS, while BRA dose rate did not result related with these outcomes. Chronic G3/G4 toxicity involved more frequently the intestinal/rectal tract than other organs at risk. Rectal and vaginal serious chronic sequelae developed mainly in pts treated with EBRT and BRA and suggest the need for more advanced treatment techniques. CONCLUSIONS: the present mono-institutional analysis confirms the efficacy of radical RT for the treatment of cervical cancer and provides support to the role of BRA to obtain better outcomes. An effort to reduce long-term toxicity of the treatment is needed.

Standardization of the Maristán Scale of Informal Care in people with schizophrenia and other psychoses.

OBJECTIVE: No instrument has been developed and validated across cultures to measure the degree of support provided by informal carers to people with schizophrenia. We aimed to develop such a measure. METHOD: The Maristán Scale of Informal Care was developed directly from the views of patients with schizophrenia in six countries. Face-to-face interviews were carried out with participants and 103 were repeated after 30 days. Principal Axis Factoring followed by Promax rotation evaluated the structure of the scale. Horn's parallel combined with bootstrapping determined the number of factors. Cronbach's alpha estimated the scale's internal consistency and intra-class correlation its test-retest reliability. RESULTS: A total of 164 interviews were undertaken, 103 with re-test. The Horn's Parallel Analysis and the analysis of the Promax rotation revealed one factor. Cronbach's alpha was 0.89. Intra-class correlation coefficient was 0.56 (95% CI 0.42-0.68) and this increased to 0.64 (95% CI 0.51-0.75) after removing two outlying values. Patients from Argentina recorded the lowest scores (poor informal support/care). CONCLUSION: The Maristán Scale of Informal Care is a reliable instrument to assess the degree of support provided by informal carers to people with schizophrenia across cultures. A confirmatory factor analysis is needed to evaluate the stability of its factor structure.

Risk factors for Sjögren's syndrome: a case-control study.

OBJECTIVE: The aim of this study was to investigate potential risk factors for Sjögren's syndrome (SS) by means of a multi-centre case-control study, focusing in particular on familial and environmental risk factors. 140 female SS patients and 109 female controls with orthopaedic problems were consecutively enrolled in seven university hospitals in Italy. METHODS: Information regarding the patient's lifestyle, her medical, menstrual and pregnancy history, and any family history of autoimmune diseases (AD) was obtained through a detailed structured questionnaire. The odds ratio (OR) and 95% confidence interval (95%CI) were calculated using unconditional logistic regression, adjusting for age and family size. The probability of first-degree relatives developing an autoimmune disease was also investigated. RESULTS: A positive family history of AD was significantly associated with SS. Subjects with a first-degree relative (FDR) with AD showed a seven-fold increase in the risk for SS compared to controls (OR=7.4, 95%CI 2.8-20.1); the strength of this association increased with the number of relatives affected. Similarly, the FDR of SS patients had a higher risk of AD in comparison to subjects without FDR affected by SS. Women with one or more pregnancies had an increased risk of SS (OR=2.1, 95%CI 1.0-4.3). CONCLUSION: This study suggests that a family history of AD is associated with SS.

Response to tetanus vaccination in infants exposed in utero to immunosuppressants for maternal autoimmune disorders.

Immunosuppressive drugs given during pregnancy to mothers suffering from a systemic autoimmune disease (AID) can cross the placenta, thus being potentially able to affect the offspring immune system. Aim of our study was to evaluate the in vivo immune function of a series of these newborns. Twenty-two babies born from mothers suffering from autoimmune diseases (AID) who had been taking immunosuppressive drugs during pregnancy were evaluated for their response to vaccination with C. Tetani toxoid. Six babies born from mothers receiving low-dose aspirin only were used as controls. The immune response to C. Tetani vaccination was evaluated with an ELISA to detect circulating antibodies. Five children out of 28 (17%) did not achieve a protective titer of anti C. Tetani toxoid IgG. No clear relationship was found between specific drug exposure and antibody response. Our findings suggest that maternal immunosuppressive treatment given for a systemic AID can affect the response to an active immunization, without specificities for drug types used.

Intravenous cyclophosphamide therapy for systemic sclerosis. A single-center experience and review of the literature with pooled analysis of lung function test results.

OBJECTIVE: Oral cyclophosphamide (CYC) is a promising therapy for Systemic Sclerosis (SSc)-related interstitial lung disease (ILD). The use of intravenous (i.v.) pulses has been considered as an alternative route of drug administration, possibly associated with reduced toxicity. Our objectives were to re-evaluate our experience with i.v. CYC, to review the literature, and to pool our results with those available from other groups, improving the statistical power of the analysis. METHODS: 1) Retrospective analysis of our center experience on 16 patients with SSc and active alveolitis, treated with i.v. CYC 750 mg + 6-methylprednisolone 125 mg every 3 weeks. 2) Pooled analysis of papers published in peer-reviewed journals reporting detailed data on each patient treated with i.v. CYC. The end-point was modification in the results of lung function tests (LFT) after 6 months. Piecewise regression analysis was performed using a linear mixed-effects model adjusted for baseline values to evaluate the changes in LFT. RESULTS: Retrospective analysis. In the period before therapy there was a significant deterioration in FVC (in 6 months: -4.3%; p=0.0009) and DLCO (-2.1%; p=0.018). After 6 months of treatment there was a modest improvement in the FVC (+2.7% p=0.08) and DLCO (+2.2%; p=0.08). Pooled analysis. In 53 evaluable patients, the improvement in LFT reached conventional statistical significance (FVC: +2.85%; 95% confidence intervals: +0.04, +5.66%; p=0.04. DLCO: +4.4%; 95% confidence intervals: +1.2%, +7.5%; p<0.001). CONCLUSION: i.v. CYC for 6 months can achieve a small, but significant improvement of LFT in patients with SSc and active alveolitis.

The immune development in a child born to a cyclosporin A-treated woman with systemic lupus erythematosus/polymyositis.

The case of a woman affected by an overlap syndrome systemic lupus erythematosus/polymyositis (PM), who presented with active myositis at the start of the pregnancy, is reported. Therapy with cyclosporin, corticosteroids, hydroxychloroquine and high-dose intravenous immunoglobulin induced a progressive remission of clinical and laboratory signs of myositis. At 33 weeks of gestation, after a premature pre-term rupture of membrane, a male child was delivered. Although premature, and small for gestational age, he had a normal growth, and did not show any clinical sign suggestive of immune deficiency. Lymphocyte phenotypical and functional studies, as well as response to vaccination, were also normal.

Systemic sclerosis therapy with iloprost: a prospective observational study of 30 patients treated for a median of 3 years.

Iloprost is useful in the short-term treatment of severe Raynaud's phenomenon and ischaemic ulcers in patients with systemic sclerosis (SSc), but its long-term effects are largely unknown. The aim of this study was to report long-term outcome (median follow-up 36 months) in a prospective observational study of a cohort of 30 consecutive patients with SSc who received iloprost therapy with maintenance infusions every 3 weeks after an initial cycle of 5 consecutive days. At the end of the observation, compared to the pretreatment point, we observed complete healing of digital ulcers in 19/21 patients (90%), a decrease of the Raynaud's phenomenon visual analogue score from 10/10 (25th-75th percentile 7-10) to 5/10 (4-6.75) ( P <0.001) and, in patients with diffuse cutaneous involvement, of the modified Rodnan skin thickness score from 25.5 (16.5-31.5) to 16 (13.5-20) ( P = 0.02), minimal improvement of the Health Assessment Questionnaire from 0.87 (0.68-1.37) to 0.75 (0.62-1.25), which was neither statistically nor clinically significant. The forced vital capacity was not significantly changed, but the diffusion capacity corrected for the alveolar volume decreased from 71% (54-76.7) of the expected value to 62% (51.5-71) ( P = 0.02). In one patient with limited SSc a positive effect on pulmonary hypertension was observed. Six patients, after a median of 25 months of treatment and healing of digital ulcers, discontinued the therapy; after a median of 10 months ulcers did not recur in five of these six. Other reasons for discontinuation were: tolerability (1), disease progression (normotensive renal crisis: 1), and death due to intracranial haemorrhage (1). This same patient had previously suffered a central retinal vein thrombosis. In conclusion, long-term therapy with iloprost in patients with SSc has a durable effectiveness on ischaemic ulcers and Raynaud's phenomenon, but it is not possible to conclude that the natural history of the disease was modified.

[Neonatal lupus: clinical features and risk of congenital cardiac heart block in newborns from mothers with anti Ro/SSA antibodies] / Lupus neonatale: manifestazioni cliniche e rischio di blocco cardiaco congenito in neonati da madri con anticorpi antiRo/SS-A.

OBJECTIVE: To assess the prevalence of Congenital Heart Block (CHB) in newborns from anti Ro/SS-A antibodies positive mothers affected by connective tissue diseases (CTD) and to evaluate the prevalence of other manifestations of Neonatal Lupus (NL) and the electrocardiographic abnormalities. METHODS: A prospective study was conducted on 100 anti Ro/SS-A positive mothers that were followed before and during their 118 pregnancies (4 twin pregnancies and 18 second pregnancies). Counterimmunoelectroforesis (CIE) and immunoblot (IB) were used to test antibodies to extractable nuclear antigens (ENA). RESULTS: Only 2 cases of CHB (1.8%) were found among the 112 living newborns. In one case the mother with primary Sjögren's Syndrome (pSS) was anti Ro 60 and 52kD positive while in the other case the mother affected by undifferentiated connective tissue disease (UCTD) was anti Ro 60kD and anti La positive. No fetal death was due to CHB. There were no cutaneous rashes at birth while mild hepatic enzyme alterations were observed in 21 (68%) of the 31 tested newborns. In 22 healthy newborns an ECG have been registered and in 4 cases (18.2%) sinus bradycardia was found. During the follow up 7 suckling showed Cutaneous Neonatal Lupus. Moreover a six month girl developed Kawasaki Syndrome. CONCLUSIONS: The risk of delivering a child with CHB is 1.8% in anti Ro/SS-A positive mothers with CTD. This finding is extremely important in the preconceptional counseling of anti-Ro/SS-A positive women. Furthermore mild electrocardiographic abnormalities may be found in their healthy newborns.

Characterization of gammadelta T cells expressing CD158b, a killer cell inhibitory receptor, in a patient with chronic CD4(+) lymphocytopenia and disseminated Mycobacterium intracellulare infection.

A population of Vdelta1(+)Vgamma9(-) gammadelta T cells that represented almost the totality (84%) of circulating lymphocytes in a patient with chronic, non-HIV-related, CD4 lymphocytopenia complicated by a disseminated Mycobacterium intracellulare infection was characterized. These gammadelta(+) T cells expressed a single killer inhibitory receptor (CD158b) and their phenotype (CD8(+)CD57(+)CD27(-)CD28(-)) indicated that, although CD45RA(+), they were not naive. However, the absence of large granular lymphocyte morphology, the impaired proliferative activity, the high susceptibility to apoptosis, and the total lack of cytotoxic ability suggested that these gammadelta cells were in a resting state. A high percentage of the cells did not harbor the CD11b integrin alpha chain and exhibited a decreased capability to bind endothelial cells. This defect might represent the mechanism whereby they remained trapped in the circulation.

Reversed-phase high-performance liquid chromatographic determination of cocaine in plasma and human hair with direct fluorimetric detection.

A simple, but sensitive and specific, high-performance liquid chromatographic assay for cocaine with direct fluorimetric detection, particularly intended for the routine analysis of hair and blood samples, is described. Benzoylecgonine, eluting before cocaine in a completely resolved peak, is also detectable. Detection is based on the weak native fluorescence of cocaine and benzoylecgonine, depending on the benzene ring present in both molecules. Hair samples (20-200 mg) were incubated overnight in 2 ml of 0.25 M HCl at 45 degrees C and extracted with a commercial liquid-liquid method; the dried residue reconstituted with 500 microliters of 0.05 M NaH2 PO4 (PH 5.2) was injected. Blood plasma samples (200 microliters) were mixed with 150 microliters of 0.1 M Na2 HPO4 (pH 8.9) and extracted with 5 ml of chloroform-2-propanol (9:1); the organic phase was evaporated and the residue dissolved and injected as above. Isocratic reversed-phase liquid chromatography was carried out on a column (150 x 4.6 mm I.D.) packed with spherical 5-microns poly(styrene-divinylbenzene) particles; the mobile phase was 0.1 M potassium phosphate (pH 3)-methanol-tetrahydrofuran (70:25:5). The excitation and emission wavelengths were set at 230 and 315 nm, respectively. Under the described conditions, cocaine eluted in a symmetrical peak with a capacity factor of about 5. The limit of detection was about 1 ng/ml (0.2 ng injected), with a signal-to-noise ratio of 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Capillary zone electrophoresis determination of phenylalanine in serum: a rapid, inexpensive and simple method for the diagnosis of phenylketonuria.

A simple, rapid, and quantitative capillary zone electrophoresis method for phenylalanine analysis in serum has been developed, with the aim of providing an analytical tool, as an alternative to liquid and gas chromatography, for the routine laboratory diagnosis of phenylketonuria. Electrophoresis was carried out in a 65 cm long, 50 microns wide bare silica capillary, using 0.025 M borate (adjusted to pH 10 with 1 M NaOH) at a potential of 20 kV, with in-column UV detection at 214 nm. Under these conditions, the three aromatic amino acids (tryptophan, phenylalanine and tyrosine) migrated according to the pKs of the respective amine (and hydroxyl) groups. The efficiency of separation was about 150,000 plates/column for phenylalanine. Diprophylline was adopted as internal standard. The injection of ethanol-deproteinized normal control serum gave rise to only a few major peaks not interfering with phenylalanine; phenylalanine in serum at normal concentrations appeared in a clean region of the electropherogram as a symmetrical peak with a migration time of about 11 min. The sensitivity was > or = 3 micrograms/mL, with s/n ratio = 3. The linearity, in the range of 5-175 micrograms/mL, was described by the equation y = 1.407-0.583 x, r2 = 0.9998. Accuracy and precision were satisfactory, with intra-day and inter-day coefficients of variation lower than 4% and 7%, respectively. The injection of sera from five phenylketonuria patients gave electropherograms clearly showing huge peaks of phenylalanine, thus allowing an easy laboratory diagnosis of phenylketonuria.

High-sensitivity low-cost methods for determination of cocaine in hair: high-performance liquid chromatography and capillary electrophoresis.

Free solution capillary electrophoresis and high performance liquid chromatography were applied to the analysis of cocaine in hair. Capillary electrophoresis conditions were as follows. Background electrolyte: 0.050 M borate, pH 9.2; capillary: bare silica, 40 cm long, 50 micrograms i.d.; potential: 15 kV; detection: UV at 238 nm wavelength. In addition, the separation was accomplished in a 50 cm x 75 microns capillary with an instrument with a photodiode array detector, recording on-line UV spectra of peaks from 200 to 400 nm. The isocratic high performance liquid chromatographic method with fluorimetric detection used 230 nm (ex.) and 315 nm (em.) wavelengths. Cocaine separation was carried out under conditions summarized as follows: column packed with spherical polystyrene-divinylbenzene 5 microns particles, mobile phase 0.1 M potassium phosphate (pH 3.0)/methanol/THF (70:25:5) at a flow rate of 0.5 ml/min and at room temperature. Liquid-liquid and solid-liquid sample preparation methods were used. Typically, levels of cocaine in hair as low as 0.15-0.30 ng/mg were detected by capillary electrophoresis, while HPLC allowed the determination of concentrations lower by one order of magnitude (0.015 ng/mg). Intra- and inter-assay precision data of the two techniques were comparable and characterized by relative standard deviations in the range from 3 to 7%. On the other hand, the sample throughput of capillary electrophoresis (7-10 injections/h) was higher than high performance liquid chromatography (2 injections/h). A good correlation of the results (r2 = 0.92) between the two techniques was observed in the assay of real cases.

Karyotypic variability in plants of Solanum melongena regenerated from callus grown in presence of culture filtrate of Verticillium dahliae.

Plantlets were regenerated from calli derived from leaf expiants of three genotypes of Solanum melongena (two parental genotypes and their hybrid). The cytological analysis showed that a) plants regenerated were all mixoploid, b) toxic medium (basal medium added with filtrate culture of Verticillium dahliae) was able to evidence karyotypic differences between genotypes not displayed by plants regenerated from callus grown on control medium, c) chromosomal mosaicism persists up to plant maturity and also in the selfed progeny. The results are discussed in terms of a selective process involving genes controlling chromosome number and/or a direct effect of toxic medium on the activity of the same genes.