Motor impairment on awakening in a patient with an EEG pattern of "unilateral, continuous spikes and waves during slow sleep".

Movement disorders are rarely described in association with the "continuous spikes and waves during slow sleep (CSWS)" EEG pattern. We report the case of a young girl affected by an epileptic encephalopathy who, from the age of seven years and four months, has twice presented a movement disorder affecting the right arm, manifesting on awakening and disappearing by early afternoon. Sleep EEG during these periods showed continuous, high-amplitude, diphasic spikes and slow waves over the left hemisphere. Association of clobazam, valproic acid and, on the second occasion, ethosuccimide led to disappearance of the above-described EEG picture and associated motor symptoms. Neurophysiological investigations excluded other possible aetiologies. In view of this, and of the close relationship between the EEG picture and clinical course, we interpret the patient's impairment as "motor neglect" secondary to the continuous electrical activity recorded during sleep over the left hemisphere and involving the associative areas. This electrical activity in sleep, may be regarded as a "functional lesion" whose clinical consequences can be correlated with the site of the abnormalities.[Published with video sequences].     

Efficacy of bortezomib therapy for extramedullary relapse of myeloma after autologous and non-myeloablative allogeneic transplantation

We report the successful use of bortezomib to treat a patient with multiple myeloma (MM) who had extramedullary relapse (paraspinal and thoracic masses and multiple cranial nerve palsy) after autologous and non-myeloablative allogeneic hematopoietic stem cell transplantation (HSCT).     

A pilot study of nurse-led, home-based telecardiology for patients with chronic heart failure

We assessed the feasibility of home-based telecardiology for patients with chronic heart failure (CHF). Seventy-four CHF patients were enrolled into a programme of telephone follow-up and single-lead electrocardiography (ECG) monitoring. The patients transmitted their ECG data by fixed telephone line to a receiving station, where a nurse was available for an interactive teleconsultation. Patients were followed up for a mean (SD) of 307 (108) days; 1467 calls were analysed (213 ad hoc consultations and 1254 scheduled consultations). A total of 124 cardiovascular events were recorded. Modifications to therapy were suggested in response to 119 calls; hospital admissions were suggested for 13 patients, further investigations for 7 and a consultation with the patient's general practitioner for 13. No action was taken after 1330 calls. Twenty-two ECG abnormalities were recorded. In 63 patients receiving the beta-blocker carvedilol, the mean dosage increased from 36 to 42 mg. In the previous year there were 1.8 hospitalizations per patient, while in the follow-up period there were 0.2 hospitalizations per patient. Following up CHF patients using a nurse-led telecardiology programme seems to be feasible and useful.     

Benign breast diseases in breast cancer screening programs in Italy (2000-2001)

AIMS AND BACKGROUND: Screening mammography has been shown to be effective in reducing breast cancer mortality in several randomized clinical trials. One major side effect of screening is the diagnosis of benign breast disease (BBD), which is considered as a nonprogressive lesion, except for a small percentage of lesions considered at high risk. We present data referring to service screening programs active in Italy in 2000 and 2001 and participating in the national survey carried out by the Italian Group for Mammography Screening (GISMa). METHODS: To all centers participating in the GISMa National Survey, we submitted a questionnaire regarding the service screening protocol and main indicators of performance of the local program in the years 2000 and 2001. RESULTS: A total of 657 detected BBD cases, registered by 23 Italian breast cancer screening centers in women 50 to 69 years of age, are included in this study. The BBD detection rate was 2.5 per 1000 at the first screening test and 1.05 per 1000 at repeated tests. The benign/malignant ratio was 0.34 at the first and 0.22 at the repeated test. CONCLUSIONS: Detection of BBD occurred frequently in breast screening programs, and prognostic implications should be further investigated. Women should be individually informed at screening, and with greater detail at the moment of the recall for assessment, of the implications of BBD detection and receive the necessary, also psychological, counseling to avoid the possible harm related to breast cancer screening.     

Free to total PSA ratio is not a reliable predictor of prostate biopsy outcome

AIMS AND BACKGROUND: The aim of this study was to assess the validity of predictors of prostate biopsy outcome in order to improve their positive predictive value. MATERIAL AND METHODS: The study material consisted of a consecutive series of 410 prostate biopsies performed during 2003. The variables tested as possible predictors were age, findings at palpation (DRE) and ultrasonography (TRUS), total prostate-specific antigen (PSA), and free-to-total prostate-specific antigen (F/T) ratio. The association with biopsy outcome (cancer vs non-cancer) was investigated by univariate and multivariate analysis. RESULTS: All tested variables showed a statistically significant and independent association with biopsy outcome both in univariate and multivariate analysis. Nevertheless, no variable had good performance as a biopsy indicator: depending on the considered variable, three to nine cancer biopsies would be delayed in order to avoid ten benign biopsies. Using 0.12, 0.15 and 0.20 as the cutoff for F/T would avoid 77.3%, 64.4% and 43.1% of benign biopsies but would delay 54.0%, 35.6% and 21.0% of cancer biopsies, respectively. CONCLUSION: Although it may contribute to diagnostic suspicion, F/T should never exclude a biopsy indicated because of suspicion arising from other diagnostic tests.     

Tankyrase, a positive regulator of telomere elongation, is over expressed in human breast cancer

Tankyrase promotes telomere elongation by interaction with the telomeric protein binding factor TRF1, a negative regulator of telomere extension. We measured tankyrase mRNA by real-time RT-PCR in 66 breast cancers and in paired normal tissues. Results were compared with hTERT mRNA expression. The levels of tankyrase in breast cancers were significantly higher in comparison to normal tissues (P<0.0001) and significantly related to the status of progesterone receptors. No relationship was found between tankyrase and hTERT mRNA expression in breast cancers. According to our results, tankyrase expression appeared up regulated in breast cancers.     

Spleen-preserving total pancreatectomy with conservation of the spleen vessels:: operative technique and possible indications

Conventional distal pancreatectomy (cDP) and total pancreatectomy (cTP) also involve removal of the spleen. The spleen, however, is an important organ in the immunologic defense of the host and is worthy of preservation if this can be safely achieved. We performed a spleen-preserving total pancreatectomy (SPTP), with good results, in a Caucasian woman, 66-year-old, affected by pancreatic metastases of renal clear cell carcinoma. This is the first report of a SPTP for pancreatic metastases to our knowledge, and we therefore wish to describe the surgical technique and to suggest the possible indications for this new technique.     

Influence of polymorphisms in the factor VII gene promoter on activated factor VII levels and on the risk of myocardial infarction in advanced coronary atherosclerosis

In this study, we investigate the influence of three factor VII (FVII) gene polymorphisms on activated FVII levels (FVIIa), and also on the risk of myocardial infarction (MI) in patients with advanced coronary atherosclerotic disease (CAD). The -323A2 allele in the promoter is known to be associated with low FVII levels, and has been suggested to protect against MI in some studies. The -402GA promoter polymorphism, that in vitro has been associated with having opposite effect, is less well studied clinically. For this study, plasma FVIIa levels and three FVII gene polymorphisms were assessed in 934 subjects of both sexes, all with an angiographic documentation of coronary vessels. Our results show that two promoter polymorphisms, plasma cholesterol, and gender, were significant predictors of FVIIa levels. The -402A allele was associated to a significant increase of FVIIa levels in males (by 19.2%). In a selected clinical model including the patients with severe CAD, with or without a thrombotic complication (MI), male carriers of the -402A had an increased risk of MI (OR=1.79; 95% CI 1.15-2.80). The -323A2 allele was associated to a significant decrease in FVIIa (by 36.02% in males, and 39.7% in females). Male carriers of the -323A2 were protected from MI (OR=0.6; 95% CI 0.39-0.94), but only after correction for the confounding effect of combined heterozygosity for the promoter polymorphisms. We can conclude that FVII gene polymorphisms with an opposite effect on FVIIa levels may modulate the risk of MI in males with advanced CAD. This study highlights a "within-gene" interaction, and the need to explore polymorphisms in candidate gene(s) in detail.     

Leucinostatin-A loaded nanospheres: characterization and in vivo toxicity and efficacy evaluation

Leucinostatin A (Leu-A) is a nonapeptide exerting a remarkable activity especially against Candida albicans and Cryptococcus neoformans; nevertheless, its employment is limited due its toxicity. Therefore, we recently developed liposomal formulations, as suitable delivery systems, in order to increase its therapeutic index. However, liposomes present disadvantages related to their long-term instability. For this reason poly(lactic-co-glycolic) nanospheres (NS) were chosen as alternative colloidal carriers for Leu-A delivery. NS were formulated by spontaneous emulsification solvent diffusion method. This study investigates the effects of different parameters on drug encapsulation efficiency and particle size as well. The best preparation obtained was also characterized for its in vitro release, in vivo acute toxicity (LD50), and effectiveness against C. albicans in mice. In vitro release was performed over 100 h and resulted sufficiently sustained with more than 93% of the peptide released. Acute toxicity showed that the LD50 was increased more than 18-fold and the study on systemic candidiasis models revealed high effectiveness of the NS in reducing either the growth of fungal colonies in infected mice liver or in the mortality index. In conclusion, we can propose that Leu-A loaded NS could represent a new promising therapeutic system against Candida infection.