Precursors of atherosclerosis in children: The Cittadella study. Follow-up and tracking of total serum cholesterol,triglycerides, and blood glucose

As part of a WHO project, precursors of atherosclerosis in children, a survey was made in Cittadella, a town in Northern Italy. Four hundred and eight children (49.7% males) aged 6, 9, 12, and 15 were examined and a blood sample for total cholesterol (TC), triglycerides (TG), and blood glucose (BG) was drawn one hour after an oral glucose load of 50 g. The same procedure was performed in the same subjects 3 years later. The mean values of TC in the age groups 6, 9, 12, and 15 were 155.2, 176.1, 191.5, 170.5 mg/dl, respectively. TG values were 54.4, 53.1, 55.8, 62.2 mg/dl and BG, 108.3, 85.2, 92.1, 97.4 mg/dl, respectively. A marked fall of TC at reexamination was found in initial age groups of 12 and 15. BG levels fell significantly only in those subjects initially examined at age 6, while TG showed a longitudinal increase in all age groups, though more markedly in the younger ones. Different body composition, and possibly a secular trend, might explain these findings. The tracking analysis showed that serum TC tends to maintain its percentile with increasing age in contrast to serum TG and BG tracking which was less consistent, suggesting the influence of factors other than those affecting changes in TC.     

SOD1 mutations in amyotrophic lateral sclerosis

Amyotrophic Lateral Sclerosis (ALS), the most common form among motoneuron diseases, is characterized by a progressive neurodegenerative process involving motor neurons in the motor cortex, brain stem and spinal cord. Sporadic (SALS) accounts for the majority of patients but in about 10% of ALS cases the disease is inherited (FALS), usually as an autosomal dominant trait.In the present study we show the results of a referred based multicenter study on the distribution of SOD1 gene mutations in the largest cohort of Italian ALS patients described so far. Two hundred and sixty-four patients (39 FALS and 225 SALS) of Italian origin were studied. In 7 out of 39 FALS patients we found the following SOD1 gene mutations: i) a new G12R missense mutation in exon 1, found in a patient with a slowly progressive disease course; ii) the G41S mutation, in four unrelated patients with rapidly progressive course complicated with cognitive decline in two of them; iii) the L114F mutation, in a patient with a slowly progressive phenotype; iv) the D90A mutation, in a heterozygous patient with atypical phenotype. In addition, in one SALS patient a previously reported synonymous variant S59S was identified. In 17 (3 FALS and 14 SALS) out of 264 patients (6.4 %) the polymorphism A-->C at position 34 of intron 3 (IVS3: + 34 A-->C) was found, and in one FALS patient a novel variant IVS3 + 62 T-->C was identified.The frequency of SOD1 gene mutations (17.9 %) in FALS cases was comparable with that found in other surveys with a similar sample size of ALS cases. No SOD1 gene mutations have been identified in SALS cases. Within FALS cases, The most frequent mutation was the G41S identified in four FALS.     

Testicular microlithiasis: an unreported feature of McCune-Albright syndrome in males

OBJECTIVE: To ascertain the incidence of testicular microlithiasis (TM) in boys with McCune-Albright syndrome (MAS). STUDY DESIGN: Study population consisted of 8 boys with MAS whose medical records were reviewed with emphasis on their past genitourinary histories. All of the boys underwent a clinical and ultrasonographic (US) scanning of the scrotal and inguinal regions. US results in boys with MAS were compared with those obtained in two control populations consisting of 20 healthy subjects and 12 boys with idiopathic and untreated central precocious puberty (CPP). RESULTS: Clinical examination revealed urological abnormalities in no patients, whereas US showed a typical picture of TM in 5 of 8 boys. TM was observed in none of the subjects belonging to control populations (v=15.2 and 11.3, respectively; P <.001). CONCLUSIONS: In a series of 8 boys with MAS we demonstrated a high prevalence (62%) of TM that was associated with neither malignant nor nonmalignant conditions. This finding is unlikely to be only occasional, considering the very low prevalence of TM reported until now in healthy children and young adults and in our results in control populations. TM may be another marker for MAS.     

Outcome of low-dose ganciclovir for cytomegalovirus disease prophylaxis in renal-transplant recipients

To assess the outcome of low-dose-ganciclovir prophylaxis (500 mg twice a day for 3 months) in renal-transplant recipients, a retrospective analysis of 185 patients transplanted between 1998 and 2001 was performed. There were 29 (15.6%) patients who belonged to the highest risk group, donor cytomegalovirus (CMV) positive, recipient negative (D + R-), and 37 (20%) patients in the lowest risk group, D-R-. Induction immunosuppression consisted of polyclonal antibody or OKT3 (n = 62, 33.5%), interleukin-2 receptor antibody (n = 61, 33%), and no induction (n = 62, 33.5%). CMV disease occurred in 13 (7%) patients. Highest incidence was in D + R- group (17.2%), with no cases in D-R- group (P = 0.03). Tissue-invasive CMV occurred in 4 of these 13 patients. In patients developing CMV disease, there was no evidence of ganciclovir resistance and no mortality over a mean follow-up of 42 months. Low-dose ganciclovir was found to be as effective in decreasing the incidence of clinical CMV disease as high-dose ganciclovir (1 gm three times a day for 3-6 months) in previous studies.     

Cucurbitane triterpenoids from Leucopaxillus gentianeus

In addition to the known bioactive triterpene cucurbitacin B (1), two new cucurbitane triterpenoids, namely, leucopaxillones A (3) and B (4), exhibiting a new oxygenation pattern among cucurbitacins, have been isolated from the mushroom Leucopaxillus gentianeus (syn. L. amarus). Cucurbitacin B (1) imparts a bitter taste to the flesh of the fungus; however, it occurs in the fruiting bodies mainly esterified as tasteless fatty acid esters 2a-c. In vitro growth inhibitory effects of compounds 1-4 on proliferation of four different human tumor cell lines (A549, CAKI-1, HepG2, MCF-7) were evaluated by using a 1-day MTT assay. Only cucurbitacin B was highly active on all lines. Free cucurbitacin B is presumed to be formed in vivo by an enzyme-mediated scission of esters 2a-c, thus constituting a chemical weapon that protects the mushrooms against parasites and predators. Compounds 1-4 are structurally different from the other few cucurbitacins isolated from Basidiomycetes, being, instead, more similar to those occurring in plants. In particular, cucurbitacin B (1) seems to represent an interesting example of secondary metabolite convergence between distant taxa such as fungi and vascular plants, where they likely exert a similar role of protection. The structures of the compounds were established by means of spectroscopic methods and X-ray diffraction on a single crystal. The absolute configuration of leucopaxillone A has been assigned on the basis of CD chirality rules.     

Enhanced efficacy of tumor cell vaccines transfected with secretable hsp70

Tumor immunotherapy has exploited the ability of heat shock proteins to chaperone precursors of antigenic peptides to antigen-presenting cells and to activate efficiently an immune response against tumor-associated antigens. The most common strategy is based on the purification of heat shock protein-peptide complexes from tumor cell lines or from tumor surgical samples for in vivo administration. In this article, we have modified the murine-inducible hsp70 into a secreted protein and engineered tumor cells to secrete constitutively their antigenic repertoire associated with the hsp70 protein. In vitro studies showed that the relocalization of hsp70 from the cytoplasm to the secretory pathway did not modify the ability of hsp70 to interact with peptides derived either from natural tumor-associated antigens or model antigens, and that antigen-presenting cells specifically took up the secreted hsp70 and presented the chaperoned epitopes to T cells. In vivo studies showed that tumors secreting hsp70 displayed increased immunogenicity, with induction of a strong and specific CTL response. Mice injected with hsp70-secreting tumors showed increased survival and impaired tumor take compared with mice bearing parental tumors. More than 70% of mice rejected tumor cells secreting hsp70 through mechanisms that involve T lymphocytes and natural killer cells, with the induction of a memory response in the case of T lymphocytes. Moreover, hsp70 secretion increased the immunogenic potential of tumor cell vaccines.     

Advantages and limits of percutaneous breast core biopsy with Mammotome and stereotactic equipment in upright seated patient

PURPOSE: To confirm the diagnostic accuracy of percutaneous core breast biopsy with Mammotome and stereotactic equipment in upright seated patients, and to compare results from this method with those obtained using the dedicated unit with prone table. MATERIALS AND METHODS: We analysed 72 microbioptic samples from 69 upright seated patients. These samples were obtained in the course of mammographies assisted by digital stereotactic equipment (Diamond Delta32 General Electric Medical System/Instrumen-tarium), and further equipped with a lateral arm to support the Mammotone probe. We studied the following lesions: 57 cases of isolated microcalcification clusters, 12 masses with microcalcification and three cases of plain masses. We describe in detail the various phases of our 30-minute long microbiopsy procedure. All 72 samples were extracted without problems. Only in one case a large haematoma emerged, but quickly disappeared. RESULTS: We were able to characterise the histology of the lesions in all our samples: in 39/72 cases they were identified as benign, 28 were classified as malignant, and the remaining 5 as atypia. In the 39 lesions identified as benign, the microbiopsy procedure could be carried out without surgical biopsy - consequently, these patients were available for routine follow-up exams, which confirmed the benign nature of their lesions. Our identification of the 28 malignant lesions was confirmed by surgical biopsy. The microbiopsy finding and the histological result did not agree in only two cases. The 5 cases with atypical ductal hyperplasia showed no neoplastic alteration following surgical biopsy. In our personal experience, core biopsy with Mammotome achieved a high diagnostic accuracy. CONCLUSIONS: After careful analysis of the results obtained using Mammotome in upright seated patients with stereotactic equipment, we can confirm the diagnostic accuracy of this procedure in mammography alterations not visible in sonography. In agreement with previous studies, we also confirm that the diagnostic accuracy of this approach, as well as possible complications deriving from it, do not depend on the position of the patient.