Molecular cytogenetic characterization of a complex rearrangement involving chromosomes 9 and 22 in a case of Ph-negative chronic myeloid leukemia

The "golden path", produced by the Human Genome Project effort, is composed of a collection of overlapping and fully sequenced BAC/PAC clones covering almost completely the human genome. These clones can be advantageously exploited as fluorescence in situ hybridization (FISH) probes for the characterization of rearrangements frequently found in tumors. Breakpoint characterization can be further refined by generating additional smaller FISH probes through LONG-PCR amplification of specific DNA segments, 5-10 kb in size, using appropriate BAC/PAC probes as template. We report here an example of this approach that has been used to characterize a complex Ph-negative chronic myeloid leukemia (CML Ph-) case in which the BCR/ABL fusion gene was found located on chromosome 9.     

Serum complement pattern in essential mixed cryoglobulinaemia

In twenty-six patients affected by essential cryoglobulinaemia, 188 determinations of serum complement components (SCC) were made. A peculiar pattern was observed which was characterized by: (a) low levels of early components (Clq, Cls and C4), (b) normal levels of C3 and high concentrations of late components (C5, C9) and (c) CH50 values significantly lower than normal. No relationship could be observed between early SCC and C3 levels. Thirty-three crossed immunoelectrophoreses were performed in thirteen patient's blood samples. The C3c peaks were not different from normal. Follow-up data (156 serum samples from twenty-four patients) during a 6-40 month period showed a non-homogeneous SCC behaviour. However, no relationship was found between the complement concentrations and clinical score. These findings suggest that SCC abnormalities are related to a complement hyposynthesis, which could be caused by a reduced C2 production or by a negative feedback effect of active components or their fragments.     

The regulation of blood sugar in the aging blowfly, Phormia regina

The adult blowfly, Phormia regina, reveals a substantial homeostatic capability when examined for its ability to regulate externally administered additions to its blood sugar. As well, results of experiments done at intervals throughout the entire adult life of the fly show that there is no decrease over time in the efficiency of operation of the complex system involved in the control of the blood sugar level. Taken together with other independent investigations of Phormia metabolism, the research indicates that this animal, in contrast to the rat, possesses a number of physiological systems which embody regulatory processes that may be only marginally subject to the normal "aging" process.     

Effect ofd-fenfluramine on the indole contents of the rat brain after treatment with different inducers of cytochrome P450 isoenzymes

The effects of pretreatment with inducers of hepatic cytochrome P450 isoenzymes (phenobarbital, dexamethasone and-naphthoflavone) on the metabolism ofd-fenfluramine (d-F) and its acute and long-lasting indole-depleting effects were studied in rats, in an effort to obtain further information on the importance of hepatic drug metabolism in relation to its neurochemical actions. Twenty-four hours after the last dose of each inducer, rats were injected withd-F hydrochloride (5 mg/kg, IP) and killed at various times thereafter for parallel determination of indoles and drug concentrations in plasma and brain. Additional rats were treated as above and killed 1 week afterd-F hydrochloride (5 and 10 mg/kg) to study the recovery of indole in the cortex, a particularly sensitive brain area. Phenobarbital and-naphthoflavone and, to a lesser degree, dexamethasone, stimulated the metabolism ofd-F, as evidenced by a decrease in plasma and brain areas under the curve (AUC) compared to vehicle-treated rats. This indicated that multiple isoenzymes are capable of mediating the drug's metabolism, primarily byN-dealkylation tod-norfenfluramine (d-NF). None of the inducers raised plasma and brain AUC of the nor-derivative, and in fact phenobarbital and particularly-naphthoflavone reduced it. These different effects were even apparent in rats givend-NF (2.5 mg/kg), indicating that both phenobarbital and-naphthoflavone also stimulate the sequential metabolism of the nor-metabolite (byN-deamintaion) which, however, is apparently enhanced most actively by-naphthoflavone-inducible forms of P-450. Total active brain concentrations (d-F+d-NF) after the different pretreatments were in the order of-naphthoflavone < phenobarbital < dexamethasone vehicle. Interestingly,-naphthoflavone rapidly reversed the depletion of brain indoles caused byd-F (andd-NF); phenobarbital provided partial protection and dexamethasone did not appreciably modify either the acute or long-term neurochemical effects of the drug. The fact that phenobarbital affectedd-NF kinetics less than-naphthoflavone, and provided only partial protection against the acute and long-lasting neurochemical effects of high doses ofd-F, further stresses the critical role ofd-NF in the neurochemical outcome of its parent drug. These findings support the view that the degree and duration of the indole-depleting effects are related to critical brain concentrations of the parent compound and its nor-derivative, and provide indirect evidence that hepatic metabolites other thand-NF are unlikely to play any role in the neurochemical effects of high doses ofd-F in rats.     

In-vitro activity of cefpodoxime proxetil (RU 51807): a comparative disk diffusion study on isolates from geriatric patients

997 strains isolated from clinical specimens arrived at the "Pio Albergo Trivulzio" microbiology laboratory were tested using disks of cefpodoxime, amoxicillin + clavulanic acid, cefaclor, cefuroxime, ofloxacin, cotrimoxazole, ceftriaxone and cefalexin. Gram-positive strains were tested also with erythromycin, while gram-negative bacteria were tested against aztreonam. Cefpodoxime overall activity was well above the effectiveness of the other oral cephalosporins and on the same order as ceftriaxone and ofloxacin. Cefpodoxime proved to be also more active than the combination amoxicillin-clavulanic acid.     

Relationship between diffusion parameters derived from intravoxel incoherent motion MRI and perfusion measured by dynamic contrast‐enhanced MRI of soft tissue tumors

Our aim was to evaluate the link between diffusion parameters measured by intravoxel incoherent motion (IVIM) diffusion‐weighted imaging (DWI) and the perfusion metrics obtained with dynamic contrast‐enhanced (DCE) MRI in soft tissue tumors (STTs). Twenty‐eight patients affected by histopathologically confirmed STT were included in a prospective study. All patients underwent both DCE MRI and IVIM DWI. The perfusion fraction f, diffusion coefficient D and perfusion‐related diffusion coefficient D* were estimated using a bi‐exponential function to fit the DWI data. DCE MRI was acquired with a temporal resolution of 3–5 s. Maps of the initial area under the gadolinium concentration curve (IAUGC), time to peak (TTP) and maximum slope of increase (MSI) were derived using commercial software. The relationships between the DCE MRI and IVIM DWI measurements were assessed by Spearman's test. To exclude false positive results under multiple testing, the false discovery rate (FDR) procedure was applied. The Mann–Whitney test was used to evaluate the differences between all variables in patients with non‐myxoid and myxoid STT. No significant relationship was found between IVIM parameters and any DCE MRI parameters. Higher f and D*f values were found in non‐myxoid tumors compared with myxoid tumors (p = 0.004 and p = 0.003, respectively). MSI was significantly higher in non‐myxoid tumors than in myxoid tumors (p = 0.029). From the visual assessments of single clinical cases, both f and D*f maps were in satisfactory agreement with DCE maps in the extreme cases of an avascular mass and a highly vascularized mass, whereas, for tumors with slight vascularity or with a highly heterogeneous perfusion pattern, this association was not straightforward. Although IVIM DWI was demonstrated to be feasible in STT, our data did not support evident relationships between perfusion‐related IVIM parameters and perfusion measured by DCE MRI. Copyright © 2015 John Wiley & Sons, Ltd.     

A prospective randomized evaluation of three schedules of mesna administration in patients receiving an ifosfamide-containing chemotherapy regimen: sustained efficiency and simplified administration

Chemotherapy with oxazaphosphorines, such as ifosfamide, is often limited by unacceptable urotoxicity. Without uroprotection hemorrhagic cystitis becomes doselimiting. Mesna, a thiol compound, is a drug able to bind the toxic metabolites, forming nontoxic compounds in the urine. A total of 122 patients were enrolled in this study and 228 chemotherapy cycles with an ifosfamide-containing regimen were performed (225 evaluable). Mesna was given at the same total dose as the ifosfamide in all arms. On arm A, mesna was given i. v. in equal doses 15 min before and 4 h and 8 h following the ifosfamide dose. On arm B, mesna was given in three equivalent doses 15 min before (i.v.) and 4 h (i.v.) and 8 h (p.o., double dose) following ifosfamide. On arm C, mesna was given i.v. intwo equal doses given 15 min before and 4 h following. The incidence of urotoxicity was very low (lower than 15%) in the three arms, 0% in A, 1.36% in B and 2.70% in C. All three arms were equally efficient. Schedule C was considered superior to the others, since it was equally effective, simpler and more convenient.     

"Home-brew" FISH assay shows higher efficiency than BCR-ABL dual color, dual fusion probe in detecting microdeletions and complex rearrangements associated with t(9;22) in chronic myeloid leukemia

We carried out fluorescence in situ hybridization (FISH) studies on 18 Ph+ chronic myeloid leukemia (CML) cases with chromosome 22 genomic deletions with the Vysis BCR-ABL dual-color/dual-fusion probe (BCR-ABL DC/DF) to compare the hybridization patterns obtained with this approach to those obtained with the "home brew" BAC/PAC system. Our results are the following: chromosome 22 microdeletions less than 400 kilobases (Kb) were not detected by the BCR DC/DF probe; FISH analysis with the BCR DC/DF probe in cases bearing chromosome 22 microdeletions ranging from 400 to 700 Kb produced a faint signal on the der(9); and the BCR-ABL DC/DF FISH pattern was comparable to the one obtained by the home brew probe in the presence of a 900-Kb chromosome 22 microdeletion. Our home-brew FISH system represents an accurate method for revealing a subset of CML patients with der(9) microdeletions.     

Contraceptive methods,induced abortion,first sexual intercourse age,in a group of 1635 students of the University of Rome

The authors report some data about contraceptive choice among young women examined in the Preventive Medicine Center of the University of Rome. Menarche age, menstrual cycle, age at 1st sexual intercourse, contraceptive method used, number of abortions, and pregnancies were examined. Moreover, the relationships between age at 1st sexual intercourse and contraceptive method and abortion were considered. Mean age at 1st intercourse was about 17.5 years. Pill and IUD were used by 11% and 5% respectively of the female students. Coitus interruptus was used among 83.3% of the cases. The prevalence of previous abortion was about 12.6%. The menstrual cycle characteristics did not influence the contraceptive choice of these students. Finally, previous abortion or pregnancy influenced contraceptive choice; in fact about 15% and 16.5% of the women with previous abortion performed or pregnancy experienced adopted the pill and IUD as contraceptive methods. (author's modified)