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Objectives: To evaluate the importance of leukocyturia in detecting the transition from asymptomatic bacteriuria to symptomatic infection in women with recurrent urinary tract infections., Methods: In this cross-sectional study, we evaluated all women with recurrent urinary tract infection and asymptomatic bacteriuria who had been enrolled in two previous studies. Data from urological visits, urine analyses and microbiological evaluations were collected. Patients were divided into two groups: patients with symptomatic recurrence (group A) and patients without recurrence (group B), with a mean follow-up period of 38.8 months. Data on leukocyturia and clinical data were compared. Logistic regression analyses were carried out and areas under the receiver operating characteristic curves were calculated., Results: A total of 301 women with symptomatic urinary tract infection were included in group A, whereas 249 women without clinical infection were included in group B. Group A showed a higher level of leukocytes in the urinary analysis taken at the moment of recurrence when compared with the baseline value (mean leukocytes per high power field 54 ± 5 vs 19 ± 6 at baseline; P < 0.0001). When an increase of leukocytes/mm 3 of >150% from baseline was used for logistic regression, the area under the receiver operating characteristic of the model was 0.82 (95% CI 0.78-0.94; P = 0.01). An increase of leukocytes/mm 3 of >150% from baseline had a sensitivity of 90.1% and a specificity of 91.2% for symptomatic urinary tract infection., Conclusions: This study shows that an increase of leukocyturia of >150% from baseline has a predictive role for the transition from asymptomatic bacteriuria to symptomatic urinary tract infection in women with recurrent urinary tract infections., (© 2018 The Japanese Urological Association.)

Purpose: Prostate calcifications are a common finding during transrectal prostate ultrasound in both healthy subjects and patients, but their etiopathogenesis and clinical significance are not fully understood. We aimed to establish a new methodology for evaluating the role of microbial biofilms in the genesis of prostate calcifications., Materials and Methods: Ten consecutive patients who had undergone radical prostatectomy were enrolled in this study. All of the patients presented with prostate calcifications during transrectal ultrasound evaluation before surgery and underwent Meares-Stamey tests and clinical evaluation with the National Institutes of Health Chronic Prostatitis Symptom Index and the International Prostate Symptom Score. At the time of radical prostatectomy, the prostate specimen, after removal, was analyzed with ultrasonography under sterile conditions in the operating room. Core biopsy specimens were taken from the site of prostate calcification and subjected to ultrastructural and microbiological analysis., Results: The results of the Meares-Stamey test showed only 1 of 10 patients (10%) with positive cultures for Escherichia coli . Two of five patients (40%) had positive cultures from prostate biopsy specimens. Enterococcus faecalis , Enterococcus raffinosus , and Citrobacter freundii were isolated. Ultrastructural analysis of the prostate biopsy specimens showed prostate calcifications in 6 of 10 patients (60%), and a structured microbial biofilm in 1 patient who had positive cultures for E. faecalis and E. raffinosus ., Conclusions: Although the findings are supported by a low number of patients, this study highlights the validity of the proposed methodology for investigating the role of bacterial biofilms in the genesis of prostate calcification., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

A potyvirus causing necrosis and leaf distortion on lettuce was found in the Lazio region of Italy. Host range analysis showed its ability to infect only Chenopodium quinoa and C. amaranticolor in addition to some lettuce cultivars. The virus could be transmitted by aphids of the species Myzus persicae. The complete 9829-nt genome was characterized. BLAST analysis of sequence of the complete encoded polyprotein showed that the most closely related virus is asparagus virus 1, with 52 % amino acid sequence identity. These results suggest that this virus should be considered a member of a new species in the genus Potyvirus.

Asymptomatic bacteriuria (ABU) is a common clinical condition that often leads to unnecessary antimicrobial use. The reduction of antibiotic overuse for ABU is consequently an important issue for antimicrobial stewardship and to reduce the emergence of multidrug resistant strains. There are two issues in everyday urological practice that require special attention: the role of ABU in pre-operative prophylaxis and in women affected by recurrent urinary tract infections (rUTIs). Nowadays, this is the time to think over our practice and change our way of thinking. Here, we aimed to summarize the current literature knowledge in terms of ABU management in patients undergoing urological surgery and in patients with rUTIs. In the last years, the approach to patient with ABU has changed totally. Prior to all surgical procedures that do not enter the urinary tract, ABU is generally not considered as a risk factor, and screening and treatment are not considered necessary. On the other hand, in the case of all procedures entering the urinary tract, ABU should be treated in line with the results of a urine culture obtained before the procedure. In patients affected by rUTIs, ABU can even have a protective role in preventing symptomatic recurrence, particularly when Enterococcus faecalis (E. faecalis) has been isolated.

We evaluated, in a preliminary study, the efficacy of umbelliferone, arbutin, and N-acetylcysteine to inhibit biofilm formation on urinary catheter. We used 20 urinary catheters: 5 catheters were incubated with Enterococcus faecalis (control group); 5 catheters were incubated with E. faecalis in presence of umbelliferone (150 mg), arbutin (60 mg), and N-acetylcysteine (150 mg) (group 1); 5 catheters were incubated with E. faecalis in presence of umbelliferone (150 mg), arbutin (60 mg), and N-acetylcysteine (400 mg) (group 2); and 5 catheters were incubated with E. faecalis in presence of umbelliferone (300 mg), arbutin (60 mg), and N-acetylcysteine (150 mg) (group 3). After 72 hours, planktonic microbial growth and microorganisms on catheter surface were assessed. In the control group, we found a planktonic load of ≥10(5) CFU/mL in the inoculation medium and retrieved 3.69 × 10(6) CFU/cm from the sessile cells adherent to the catheter surface. A significantly lower amount in planktonic (p < 0.001) and sessile (p = 0.004) bacterial load was found in group 3, showing <100 CFU/mL and 0.12 × 10(6) CFU/cm in the incubation medium and on the catheter surface, respectively. In groups 1 and 2, 1.67 × 10(6) CFU/cm and 1.77 × 10(6) CFU/cm were found on catheter surface. Our results document that umbelliferone, arbutin, and N-acetylcysteine are able to reduce E. faecalis biofilm development on the surface of urinary catheters.

Background: Women suffering from recurrent urinary tract infections (rUTIs) are routinely treated for asymptomatic bacteriuria (AB), but the consequences of this procedure on antibiotic resistance are not fully known. The aim of this study was to evaluate the impact of AB treatment on antibiotic resistance among women with rUTIs., Methods: The study population consisted of 2 groups of women who had previously been enrolled in a randomized clinical trial: group A was not treated, and group B was treated. All women were scheduled for follow-up visits every 6 months, or more frequently if symptoms arose. Microbiological evaluation was performed only in symptomatic women. All women were followed up for a mean of 38.8 months to analyze data from urine cultures and antibiograms., Results: The previous study population consisted of 673 women, but 123 did not attend the entire follow-up period. For the final analysis, 257 of the remaining 550 patients were assigned to group A, and 293 to group B. At the end of follow-up, the difference in recurrence rates was statistically significant (P < .001): 97 (37.7%) in group A versus 204 (69.6%) in group B. Isolated Escherichia coli from group B showed higher resistance to amoxicillin-clavulanic acid (P = .03), trimethoprim-sulfamethoxazole (P = .01), and ciprofloxacin (P = .03) than that from group A., Conclusions: This study shows that AB treatment is associated with a higher occurrence of antibiotic-resistant bacteria, indicating that AB treatment in women with rUTIs is potentially dangerous., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Flavescence dorée phytoplasma (FDp) infections seriously affect production and survival of grapevine. We analysed the changes in the flavonoid pathway occurring in two red cultivars, the highly susceptible Barbera and the less susceptible Nebbiolo, following FDp infection. A combination of metabolic and transcript analyses was used to quantify flavonoid compounds and expression of a set of genes involved in their biosynthesis. Quantification of anthocyanins, flavonols, proanthocyanidins and related biosynthetic enzymes was performed over the vegetative season, at four time points, on healthy, infected and recovered plants. A strong activation of anthocyanin accumulation was observed in infected Barbera leaves, while the response was less marked in Nebbiolo. Proanthocyanidins also accumulated mainly in infected Barbera leaves, even if basal proanthocyanidin concentration was higher in healthy and recovered Nebbiolo. Biochemical data were supported by transcript analysis: genes of the stem flavonoid pathway and of the anthocyanin and proanthocyanidin branches were expressed at a higher level in infected than in healthy plants, with a different magnitude between the two cultivars. Based on our results, we hypothesize that flavonoid accumulation is a physiological consequence of FD infection without affecting phytoplasma multiplication, although proanthocyanidin accumulation could help repel further infection by the insect vector., (© 2014 John Wiley & Sons Ltd.)

Purpose: Plants extracts are used in urology to manage urinary tract infections. We aimed to evaluate the efficacy of a preparation with solidago, orthosiphon, birch and cranberry extracts (CISTIMEV PLUS(®)) in reducing microbial colonization and biofilm development in patients with indwelling urinary catheters., Methods: All consecutive outpatients attending our department between January and June 2010 for the substitution of indwelling catheters were considered for this single-blinded, randomized and controlled pilot study to test superiority of the preventative management (CISTIMEV PLUS(®), 1 tablet daily for 30 days) in respect to no treatment. A sample size of 10-40 participants per group was considered adequate. All patients underwent urine culture the same day of the catheter substitution and were then randomized into test group (n = 48) and control group (n = 35). Ultrastructural analysis was also performed. After 30 days, the catheter was replaced and the analysis repeated. The primary outcome was the rate of positive urinary culture at the end of the entire study period., Results: Ten patients abandoned the study. At 30 days, according to per-protocol analysis, the groups statistically differed regarding the rate of positive urine cultures: test group 10/43 and control group 16/30 (p = 0.013) (-30.1 % [95 % CI -51.94 to -8.21]). The most common isolated bacteria were Escherichia coli and Enterococcus faecalis., Conclusions: The use of solidago, orthosiphon, birch and cranberry extracts resulted in a significant reduction of microbial colonization in patients with indwelling urinary catheters. Larger clinical trials are needed to demonstrate that the effects here reported are sufficient to reduce symptomatic catheter-associated urinary tract infections.

Viral infections are known to have a detrimental effect on grapevine yield and performance, but there is still a lack of knowledge about their effect on the quality and safety of end products. Vines of Vitis vinifera cv. Nebbiolo clone 308, affected simultaneously by Grapevine leafroll-associated virus 1 (GLRaV-1), Grapevine virus A (GVA), and Rupestris stem pitting associated virus (RSPaV), were subjected to integrated analyses of agronomical performance, grape berry characteristics, instrumental texture profile, and proteome profiling. The comparison of performance and grape quality of healthy and infected vines cultivated in a commercial vineyard revealed similar shoot fertility, number of clusters, total yield, with significant differences in titratable acidity, and resveratrol content. Also some texture parameters such as cohesiveness and resilience were altered in berries of infected plants. The proteomic analysis of skin and pulp visualized about 400 spots. The ANOVA analysis on 2D gels revealed significant differences among healthy and virus-infected grape berries for 12 pulp spots and 7 skin spots. Virus infection mainly influenced proteins involved in the response to oxidative stress in the berry skin, and proteins involved in cell structure metabolism in the pulp., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The adoption of Quality Indicators (QIs) has prompted the development of tools to measure and evaluate the quality and effectiveness of laboratory testing, first in the hospital setting and subsequently in ambulatory and other care settings. While Laboratory Medicine has an important role in the delivery of high-quality care, no consensus exists as yet on the use of QIs focussing on all steps of the laboratory total testing process (TTP), and further research in this area is required., Methods: In order to reduce errors in laboratory testing, the IFCC Working Group on "Laboratory Errors and Patient Safety" (WG-LEPS) developed a series of Quality Indicators, specifically designed for clinical laboratories. In the first phase of the project, specific QIs for key processes of the TTP were identified, including all the pre-, intra- and post-analytic steps. The overall aim of the project is to create a common reporting system for clinical laboratories based on standardized data collection, and to define state-of-the-art and Quality Specifications (QSs) for each QI independent of: a) the size of organization and type of activities; b) the complexity of processes undertaken; and c) different degree of knowledge and ability of the staff. The aim of the present paper is to report the results collected from participating laboratories from February 2008 to December 2009 and to identify preliminary QSs., Results and Conclusions: The results demonstrate that a Model of Quality Indicators managed as an External Quality Assurance Program can serve as a tool to monitor and control the pre-, intra- and post-analytical activities. It might also allow clinical laboratories to identify risks that lead to errors resulting in patient harm: identification and design of practices that eliminate medical errors; the sharing of information and education of clinical and laboratory teams on practices that reduce or prevent errors; the monitoring and evaluation of improvement activities.

TaqMan one-step real-time qRT-PCR assays were developed for the quantitation of Grapevine leafroll associated virus-1 and -3 (GLRaV-1 and -3), Grapevine virus A (GVA), Grapevine fanleaf virus (GFLV) and Grapevine fleck virus (GFkV) in Vitis vinifera L. Virus load in the progenies of three 'Nebbiolo' clones planted in two experimental vineyards in Piemonte (northwestern Italy), and carrying the viruses in different combinations, was evaluated. Quantitation primers were designed on the RNA-dependent RNA polymerases (RdRp) of each virus to exclude the amplification of subgenomic mRNAs. Viral quantity was referred to as the concentration of the V. vinifera glyceraldehyde-3P-dehydrogenase (GAPDH) housekeeping gene. A TaqMan protocol for the quantitation of the 'Nebbiolo' GAPDH mRNA was also optimised. The absolute quantitation of viral RNA and GAPDH mRNA was achieved using external standard curves from 10-fold dilutions of viral RdRp in vitro transcripts, ranging between 10(9) and 10(3) RNA copies. The relative quantity of viral genome units per GAPDH mRNA copy was calculated as the difference between the Log virus quantity and the corresponding Log GAPDH transcript quantity. The mean load of each virus was determined for 10 infected vines and ranged between 3 (GLRaV-1 and GFLV) and 5700 (GFkV) viral genomes per 100 V. vinifera GAPDH transcripts, with GLRaV-3 and GVA within this range., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The capsid protein (CP) of the monopartite begomovirus Tomato yellow leaf curl Sardinia virus (TYLCSV), family Geminiviridae, is indispensable for plant infection and vector transmission. A region between amino acids 129 and 152 is critical for virion assembly and insect transmissibility. Two previously described mutants, one with a double Q129P Q134H mutation (PNHD) and another with a further D152E change (PNHE), were found nontransmissible (NT). Another NT mutant with a single N130D change (QDQD) was retrieved from a new mutational analysis. In this study, these three NT mutants and the wild-type (wt) virus were compared in their relationships with the whitefly vector Bemisia tabaci and the nonvector Trialeurodes vaporariorum. Retention kinetics of NT mutants were analyzed by quantitative dot blot hybridization in whiteflies fed on infected plants. The QDQD mutant, whose virions appeared nongeminate following purification, was hardly detectable in either whitefly species at any sampling time. The PNHD mutant was acquired and circulated in both whitefly species for up to 10 days, like the wt virus, while PNHE circulated in B. tabaci only. Using immunogold labeling, both PNHD and PNHE CPs were detected in B. tabaci salivary glands (SGs) like the wt virus, while no labeling was found in any whitefly tissue with the QDQD mutant. Significant inhibition of transmission of the wt virus was observed after prior feeding of the insects on plants infected with the PNHE mutant, but not on plants infected with the other mutants. Virion stability and ability to cross the SG barrier are necessary for TYLCSV transmission, but interactions with molecular components inside the SGs are also critical for transmissibility.

In spite of advancement in biomaterials and biomechanics, in development of new osteo-integrative materials and coatings, and in macro- micro- component design, a non negligible fraction of the implanted prosthesis fails before the expected lifetime. A prospective observational clinical study has been conducted to define and apply a set of experimental techniques to in-deep assess the failure of joint prosthesis. Microbiological, histological and micro-structural techniques were implemented to specifically address phenomena occurring at the tissue-implant interface. Results obtained from 27 cases of prosthetic joint failure are discussed in terms of sensitivity and specificity. A procedural flow-chart is finally proposed for the assessment of joint prosthesis failure.

Tomato yellow leaf curl Sardinia virus (TYLCSV) (Geminiviridae) is an important pathogen severely affecting tomato production in the Mediterranean basin. Although diagnostic protocols are available for its detection in plants and its vector Bemisia tabaci (Gennadius), suitable tools for estimating and comparing viral loads in plant and insect tissues are needed. In this paper, real-time PCR methods are described for quantitation of TYLCSV in both tomato plant and whitefly extracts. The DNA extraction method was optimised on TYLCSV-infected tomato tissue. The amount of virus was determined using specific primers and probe and standardised to the amount of DNA present in each sample, using selected endogenous tomato or Bemisia genes as internal references. The distribution of TYLCSV was relatively quantified within the four uppermost leaves of plants. An absolute estimation of the amount of TYLCSV in the first leaf below the apex was obtained. The kinetics of virus retention within different batches of viruliferous whiteflies was also analysed. The real-time PCR was 2200-fold more sensitive than membrane hybridisation, allowing detection of as few as 10 viral copies in a sample. These methods are potentially suitable for several applications, such as plant breeding for resistance, analysis of virus replication, and virus-vector interaction studies.

Electrophysiology and ablation cardiac catheters, which come in contact with blood during clinical use, are required to be non-pyrogenic (<20 endotoxin units (EU)/device). This study aimed to quantify the residual endotoxin load in reprocessed devices as a mandatory step to guarantee safe reuse. We monitored the pyrogenic status of the device (n=61) in three fundamental steps of the reprocessing protocol: after clinical use, after decontamination-cleaning treatments and after complete reprocessing, including sterilization by hydrogen peroxide gas plasma. Finally, a depyrogenation test was produced for evaluating the depyrogenation efficiency of the sole hydrogen peroxide sterilization treatment. Results showed that standard clinical use did not represent a source for endotoxin contamination, while the use of tap water and manual cleaning processing could increase the pyrogenic load in a significant way. The introduction of the sterilization by hydrogen peroxide gas plasma resulted in effective reduction of the endotoxin contamination and in safe reprocessing of 15 of 15 clinically used catheters. In addition, tests conducted on in vitro spiked catheters showed that initial pyrogenic loads of 40, 80, 200EU/device were reduced to less than 11EU/device. Depyrogenation testing demonstrated efficiency in endotoxin reduction of more than 62 times (1.8log). These results show the determining role of hydrogen peroxide gas-plasma sterilization in the reduction of pyrogenic load on medical devices. Considering actual hygienic requirements at single-use device reprocessing, hydrogen peroxide gas-plasma sterilization can be considered as an efficient treatment at non-lumen cardiac electrophysiology catheter reprocessing.

To evaluate RNA silencing for the control of geminivirus infection, two classes of post-transcriptionally silenced (PTS) plants were tested using Tomato yellow leaf curl Sardinia virus (TYLCSV) Rep-210-transgenic plants, a sensexantisense hybrid and two multicopy sense lines. In both classes, PTS plants accumulated low or undetectable amounts of Rep-210 protein and mRNA but high amounts of Rep-210 small interfering RNAs. PTS plants were susceptible to TYLCSV when challenged by agroinoculation or using high viruliferous whitefly (Bemisia tabaci) pressure, although some plants were resistant at low whitefly pressure. Delayed infections were also observed, indicating that TYLCSV could overcome transgene silencing of rep and of the nested C4 gene. TYLCSV infection boosted transgene silencing but this did not lead to recovery. The data suggest that if the virus reaches a threshold level of expression/replication in the initially infected cells then virus spreading can no longer be prevented.

Detection of antinuclear antibodies (ANA) is a fundamental laboratory test for diagnosing systemic autoimmune diseases. Currently, the method of choice is indirect immunofluorescence (IIF) on a HEp-2 cell substrate. The goal of this study was to evaluate the diagnostic accuracy of five commercially available enzyme immunoassay (EIA) kits for ANA detection and to verify the possibility of using them as an alternative to the IIF method. The study involved 1513 patients, 315 of whom were diagnosed with a systemic autoimmune disease and 1198 in whom an autoimmune disorder was excluded. For all sera, ANA detection was performed via IIF and with five different EIA kits. The results were evaluated in relation to clinical diagnosis and the presence of possible specific autoantibodies (anti-ENA or anti-dsDNA); lastly, they were compared with the results obtained using ANA-IIF as the method of reference. The positive rate of the ANA-IIF test in subjects with systemic autoimmune diseases was 92%, whereas in the five ANA-EIA kits there was broad diversity in terms of response, with positive rates ranging from 74 to 94%. All the EIA kits correctly detected the presence of antibodies (anti-dsDNA, anti-RNP, anti-Ro/SSA) responsible for homogeneous and speckled fluorescence pattern, but at the same time they showed substantial inaccuracy with the nucleolar pattern, with a mean sensitivity of approximately 50% in this case. Instead, there was a large kit-to-kit difference in terms of identification of anti-Scl70 and centromere patterns, for which sensitivities ranged between 45 and 91%, and between 49 and 100%, respectively. The results of the study demonstrate that the commercially available ANA-EIA kits show different levels of sensitivity and specificity. Some of them have a diagnostic accuracy that is comparable and, in some cases, even higher than the IIF method. Consequently, these could be used as an alternative screening test to IIE. However, others do not ensure acceptable results. Therefore, careful evaluation of the various kits on the market is advisable before including any of these methods in the clinical and diagnostic testing.

Unlabelled: Patients with severe aplastic anemia (SAA; n = 46) were studied in long-term bone marrow culture (LTBMC) systems and compared with allogeneic marrow transplant (BMT) recipients (n = 16) (within 30 days following BMT) and normal control patients (n = 12). SAA patients were divided in two groups: transfusion-dependent (Tx-D) SAA patients (group A; n = 15) and transfusion-independent (Tx-I) patients after treatment with antilymphocyte globulin (group B; n = 31). Cultures were analyzed at three levels: stromal layer (SL) formation (score: 0, no SL; 1, half confluent SL; and 2, confluent SL), number of nucleated cells in suspension, and growth of CFU-GM colonies. SL formation was rapid and complete in SAA patients, groups A and B (mean score on day 14: 1.3 and 1.4), similar to controls (mean score on day 14: 1.3), whereas an impairment of SL formation was seen in BMT recipients (mean score on day 14: 1.0). The number of nucleated cells in suspension increased significantly on day 7 of culture in controls (7.6-fold), significantly more than in BMT and SAA patients, and declined thereafter. Colony formation was also significantly increased on day 7 in Tx-I SAA patients, BMT recipients, and normal controls (4-, 5-, and 16-fold, respectively), lasting respectively 2, 3, and 4 weeks. Increments of colony formation were also obtained in Tx-D SAA patients, but in the first week of culture only., In Conclusion: 1) a significant impairment of SL formation was seen in BMT recipients, but not in SAA patients; 2) a significant increment of granulocyte-macrophage colony-forming units (CFU-GM) growth can be obtained in patients with marrow failure early after starting long-term culture; 3) the number of CFU-GM grown in these culture conditions from Tx-I SAA patients parallels the number of progenitors from early post-BMT recipients; and 4) progenitor cells from Tx-D SAA patients are not only reduced in numbers, but also exhibit a poor ability to survive in LTBMC.

The aim of this study was to test whether large amounts of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) are capable of promoting the growth of hemopoietic progenitors from patients with marrow failure. For this purpose 0.1, 100, 1000, 10,000 and 20,000 ng/ml of rhGM-CSF were added to 10(5) light-density (adherent cell-depleted) bone marrow cells from 9 normal controls and from 52 patients with aplastic anemia, 25 cases of which were transfusion-dependent (Tx-D) aplastic anemia (AA) and 27 of which were transfusion-independent (Tx-I) aplastic anemia (AA). A dose-dependent increase of granulocyte-macrophage colony-forming units (CFU-GM) was observed in healthy donors, from 81 to 247 colonies at 0.1 and 1000 ng/ml of rhGM-CSF, with a plateau thereafter. Tx-I AA patients showed the best increase of CFU-GM in response to colony-stimulating factor, from 0.1 to 32.7 mean colonies at 0.1 and 20,000 ng/ml of rhGM-CSF, and the increment was greater when compared to controls. The ratio of CFU-GM grown from these patients and controls was 1:810 at 0.1 ng/ml of rhGM-CSF and 1:7.9 at 20,000 ng/ml. Eleven patients were studied at diagnosis; there was no in vitro response to rhGM-CSF (0 and 1.8 mean colonies/10(5) cells at 0.1 and 10,000 ng/ml). Overall, Tx-D AA patients showed minimal increments of CFU-GM growth at very high doses of rhGM-CSF. Two suggestions come from this study: 1) maturation of CFU-GM from recovering AA patients appears to require larger doses of GM-CSF than normal controls, and 2) very high doses of rhGM-CSF have little or no effect on CFU-GM growth in AA patients. This may be relevant for clinical studies designed to improve hemopoiesis in patients with marrow failure.

In 1975, Flitter et al. proposed a Doppler technique for evaluating CSF shunt patency. Owing to the presence of many false positives, a new method of investigation is proposed in order to achieve more reliable results by using the Doppler technique after air has been injected into the shunt reservoir. Ninety patients with a CSF shunt were examined. Fifty cases were studied both immediately after surgery (7-10 days) and at a later date (more than 2 months from surgery) in order to obtain a control group. In a further 38 cases with signs of intracranial hypertension, it was possible, by means of the air test, to distinguish surgical and non-surgical cases. In 2 cases with clinical signs of hypotension, it was possible, by means of the test, to demonstrate the hyperfunctioning of the shunt. The "Flitter test" proved to be useful in the early post-operative period only.

Many experimental findings suggest that the administration of exogenous Norepinephrine (NE), in cerebral cortical slices surviving in vitro, increases cyclic AMP (cAMP) levels, although the NE receptor turns out to be different for the different animal species. Likewise, in the same experimental model, Adenosine (A) increases the cAMP intracellular levels. Furthermore, A sites seem to be linked with adrenoreceptors related to the cAMP-generating system. In this report we studied the interaction of NE on the cAMP system of human cerebral tissue slices, normal and tumoral. In the normal slices, NE increases cAMP levels in a dose-dependent manner, probably through beta-receptors; in fact, Propranolol counteracts this effect. Also A induces a dose-dependent rise of cAMP levels; Theophylline prevents, while low doses of Dipyridamole potentiate, this effect. The contemporaneous administration of NE and A produces an effect on cAMP levels greater than that displayed by each drug alone. Probably the enhanced cAMP increase is due to the endogenous release, evoked by NE. In fact, Propranolol reduces, but does not completely prevent, the effect of NE. In cortical tumor slices, the effect of NE on the cAMP-generating system is very reduced. This suggests that the membrane damage of neoplastic cells affects the availability of adrenoreceptors. On the other hand, the responsiveness of A sites is deeply altered. The receptor antagonists or the re-uptake inhibitors of this Adenine nucleotided do not exert their effect selectively.