Hormones in male breast cancer

Urinary levels of testosterone, 5 alpha-androstanediol, 17-hydroxycorticosteroids, pregnanediol, and circulating levels of testosterone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, prolactin, luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin, were measured in 10 male patients with breast cancer and in a suitable group of healthy controls. No difference, either in blood or in urine, was observed between the two groups in the hormonal levels. The lack of abnormalities in peripherally detectable hormones suggests that the well recognized hormone dependency of male breast cancer may be due to some endocrine imbalance in the central (diencephalic) regulation of the sex steroids pathway. Alternatively, abnormal response of breast tissue to normal hormonal stimuli might be hypothesized in these patients.     

Network bursting by organotypic spinal slice cultures in the presence of bicuculline and/or strychnine is developmentally regulated

Organotypic cocultures of dorsal root ganglia and spinal cord from embryonic rats provides direct access to spinal interneurons in a culture system in which the cytoarchitectural organization of the spinal cord slice is maintained. This preparation was used to investigate the possible induction of rhythmic behaviour at different times of development in vitro. Spontaneous rhythmic bursts induced by coapplication of strychnine (1 μm ) and bicuculline (20 μm ) were observed with patch-clamp recordings from ventral interneurons. Ventral horn interneurons consistently developed a very regular pattern of activity which was superimposed on a background of sustained synaptic activity. The pattern of the spontaneous bursting following application of strychnine and bicuculline showed a developmentally regulated difference in frequency between two distinct stages of in vitro development.     

Quantitation of Human herpes virus 6 genome in children with acute lymphoblastic leukemia

Acute lymphoblastic leukemia is the main type of leukemia in children. An infectious etiology has been suspected and the role of the Human herpesvirus-6 (HHV-6) has been suggested. Several studies have tried to establish a link between HHV-6 infections and hematological malignancies, with discordant results. The potential role of HHV-6 in the pathogenesis of pediatric acute lymphoblastic leukemia was investigated. HHV-6 genome copy number was measured by quantitative real-time PCR (RQ-PCR) in bone marrow or peripheral blood samples obtained from 36 children (median age = 4 years) with B acute lymphoblastic leukemia (n = 31) and T acute lymphoblastic leukemia (n = 5) at diagnosis and during complete remission. Positive samples were further characterized to define viral variant, A or B. A total of 24.7% of samples were positive for HHV-6 genome: 13.9% were leukemia samples and 34.1% were complete remission samples. Viral load was low with values lower at diagnosis (median viral copy number = 22.9) than at complete remission (median copy number = 60.1). Among the 17 patients with positive samples, 15 were typed as B-variant whereas 2 could not be typed. These results argue against a role of HHV6 infection in the development of pediatric acute lymphoblastic leukemia. They also suggest that HHV-6 may infect latently bone marrow progenitors but seems not able to infect leukemic cells, raising again the question of the mechanism of virus fusion and entry. This observation shows that a reactivation may be observed during complete remission supporting the possibility of virus reactivation in immunocompromised hosts.     

A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy

Several studies suggest that the histocompatibility complex (HLA) class I region harbours genes modulating multiple sclerosis (MS) susceptibility independently from the effect of class II alleles. A candidate gene in this region is MOG, encoding the myelin oligodendrocyte glycoprotein. A significant association with the missense variation V142L (rs2857766) was previously reported in a small sample of 50 Italian MS patients. We confirmed this result in two independent Italian sample sets consisting of 878 MS patients and 890 matched controls (P=6.6 x 10(-4)) and 246 trio families (P=1.5 x 10(-3)). The comparison of genotype frequencies suggested a dominant-protective effect of L142. In the combined sample sets L142 conferred an odds ratio (OR)=0.70 (95% confidence interval (CI): 0.60-0.82) that remained similar after accounting for HLA-DRB1(*)15 carrier status. The association with MOG V142L was still significant after conditioning for all DRB1 alleles (P=0.035). Eleven additional single nucleotide polymorphisms in the MOG gene (namely -1077T/C, -910T/C, -875A/G, -93T/C, S5S, Indel L22, V145I, +814C/T, +900A/G, +1024A/T, +1059C/T), two microsatellites in the MOG 5' flanking (MOGCA) and 3' untranslated (MOGTAAA) regions and four microsatellites in the HLA-class I region, from HLA-B to HFE, (namely MIB, D6S265, D6S1683 and D6S2239) were tested by transmission disequilibrium test in 199 trio families. None of these polymorphisms or of their haplotypic combinations showed a significant transmission distortion, in the absence of V142L. In conclusion, MOG V142L, or an untested variant in tight-linkage disequilibrium with it, is an independent MS susceptibility-modulating factor in the HLA class I region.     

Klebsiella oxytoca septicemia following platelet transfusion]

Two fractions of a three-day-old apheresis platelet collection from a known habitual donor were transfused to two children with thrombocytopenia and bleeding. Both patients developed evidence of severe infection during the transfusion. One died despite intensive care and antimicrobial therapy. The other, whose transfusion was cut short, recovered. A Klebsiella oxytoca strain was recovered from the two transfusion bags, from a third unused bag, and from blood samples from the patient who died. Genotyping results established that all these isolates were identical. Tests for K. oxytoca were negative on the batches of blood donation material, the bottle of antiseptic used, and throat and stool specimens from the donor and phlebotomists. The most likely hypothesis is that the donor developed transient asymptomatic bacteremia during the 136-minute-long collection procedure and that the organism subsequently grew in the platelet collections, which were kept at 20-24 degrees C with agitation for three days before being used.     

Cultures of glial cells release purines under field electrical stimulation: the possible ionic mechanisms

Dissociated primary cultures of glial cells released a remarkable amount of purines, at rest and during field electrical stimulation. The HPLC identification of labelled compounds derived from 3H-Adenosine (3H-Ado) (employed to preload the cultures) indicated that nucleotides and nucleosides were represented in the superfusate in equivalent proportions (43.86% and 56.14% respectively). Very much higher amounts of unlabelled purines prevalently constituted by nucleotides compounds (91.10%) were also released and detectable in the superfusate. In all the experimental conditions their evoked release did not result frequency-dependent. Since: a linear increase related to the stimulation frequencies was found for the released labelled compounds; no labelled purines were assayed in 5 x 10-5M Dipyridamole-treated cultures; any significant presence of labelled nucleotides, inosine and hypoxantine was not found in cultures simultaneously treated with 1 x 10-5M 2'-deoxycoformycin and 1 x 10-4M 1-(-5-isoquinolinsulfonyl)-2-methylpiperizine (H7) (3H-Ado amounts resulted more than doubled in these experimental conditions); labelled compounds have been assumed as tracers of a glial purine rate whose release can be connected to electrically-evoked action potentials. Purine outflow from glial cells is not sodium dependent, in fact TTX (5 x 10-7M) did not affect their basal or electrically-evoked release. A remarkable calcium-dependence was also evidentiated by the 1 x 10-4M Verapamil-induced inhibition of basal and evoked release. TEA (1 x 10-2M), a specific inhibitor of potassium efflux throughout calcium-mediated specific channels, strongly reduced the evoked purine outflow and any additive effect of its was not detectable when administered simultaneously to the calcium antagonist. These findings indicate that the frequency-dependent purine release from cultured glial cells is linked to ionic mechanisms, which calcium and potassium are mainly involved in.     

Diagnostic work-up of unselected patients with suspected coronary artery disease: complementary role of multidetector computed tomography, symptoms and electrocardiogram stress test

AIM: We evaluated the accuracy of multidetector computed tomography in detecting coronary artery disease and how it could change the indication to coronary angiography in patients with suspected cardiac chest pain. METHODS AND RESULTS: We enrolled 142 consecutive patients who had already performed an exercise electrocardiogram test referred to our hospital and scheduled for coronary angiography for chest pain. According to the characteristics of chest pain and the results of exercise electrocardiogram, patients were divided into four groups: atypical chest pain and negative exercise electrocardiogram (group 1); typical chest pain and negative exercise electrocardiogram (group 2); atypical chest pain and positive exercise electrocardiogram (group 3); and typical chest pain with positive exercise electrocardiogram (group 4). We evaluated the accuracy of multidetector computed tomography and whether it could reduce the number of unnecessary coronary angiography in the study groups. Of 1801 segments larger than 1.5 mm, 1696 (94%) were assessable. In a segment based-model, sensitivity, specificity, negative predictive value, positive predictive value and accuracy were 81% (95% confidence interval 75-89%), 94% (95% confidence interval 90-98%), 96% (95% confidence interval 93-98%), 75% (95% confidence interval 69-82%) and 91% (95% confidence interval 89-93%), respectively. In a patient-based model, sensitivity, specificity, negative predictive value, positive predictive value and accuracy were 95% (95% confidence interval 91-99%), 78% (95% confidence interval 67-89%), 88% (95% confidence interval 79-97%), 89% (95% confidence interval 83-95%) and 89% (95% confidence interval 84-94%). Unnecessary coronary angiography may be avoided by multidetector computed tomography results particularly in group 2 (16%) and group 3 (24%), whereas in groups 1 and 4 the role of multidetector computed tomography in facilitating the correct indication to coronary angiography was less relevant. CONCLUSIONS: Multidetector computed tomography is a particularly helpful technique in patients with discordance between the clinical features of chest pain and stress-test results. This technique may be introduced in the diagnostic work-up of patients with suspected coronary artery disease and may potentially reduce the number of unnecessary coronary angiography.     

Allogeneic bone marrow transplantation (BMT) for adults with acute lymphoblastic leukemia (ALL): predictive role of minimal residual disease monitoring on relapse

We developed a PCR-based method to monitor clonogenic IgH VDJ rearrangement as a possible predictor of relapse in patients with acute B-ALL after allogeneic bone marrow transplantation (BMT). We studied 23 patients at diagnosis, before and after BMT. At the time of BMT, 13 patients were in first complete remission, eight in second complete remission and two in relapse. Four patients were PCR negative before BMT and remained PCR negative also after BMT (-/- pattern). They are still in remission after a median follow-up of 41 months. Nineteen patients were MRD-positive before BMT: three were PCR negative at first determination after BMT (+/- pattern) and maintain remission. Sixteen patients were PCR-positive at first determination after BMT (+/+ pattern): five became PCR negative (+/+/- pattern) (four with chronic graft-versus-host disease (GVHD) and two after donor lymphocyte infusions (DLI)). Nine patients remained PCR-positive (+/+/+ pattern) (four remain in remission, and six relapsed); two patients died before transplant. In conclusion, PCR negative patients before BMT remained negative post-BMT; many pre-BMT positive patients had initial MRD positivity after BMT: 37% of them achieved a molecular remission with cGVHD or DLI.