Mir-21 and Mir-125b as theranostic biomarkers for epithelial ovarian cancer in Tunisian women.

Background: Ovarian cancer (OC) is the third most common cancer in women and the leading cause of death associated with gynecologic tumors. Because this disease is asymptomatic in the early stages, most patients are not diagnosed until the late stages. This highlights the need for the development of diagnostic biomarkers. MicroRNAs (miRNAs), small non-coding RNAs, are currently being explored as potential biomarkers for the early detection of various malignancies in humans. However, their expression and diagnostic value in OC have not been well studied. Materials and Methods: the plasma levels of miR-21, miR-200a, miR-200b, miR-200c, miR-205 and miR-125b were determined in epithelial ovarian cancer (EOC) patients and healthy controls by Reverse Transcription Quantitative Realtime Polymerase Chain Reaction (RT-qPCR). The expression levels of the deregulated microRNAs were analysed according to clinical characteristics. Results: It was found that miR-21 and miR-125b were upregulated in EOC compared with healthy controls. Moreover, decreased miR-125b was associated with resistance to platinum-based chemotherapy. Conclusions: Our data suggest that miR-21 and miR-125b in plasma may serve as potential circulating biomarkers for the early detection of EOC. MiR-125b may also be useful for predicting chemosensitivity in EOC patients.

Low virulence but potentially fatal outcome-Listeria ivanovii.

Of the six known species of Listeria, Listeria monocytogenes is classified as the only human pathogen causing listeriosis, a highly fatal, opportunistic infection contracted via food. Listeria ivanovii is the only other pathogenic species of the genus and is considered to be specific to ruminants, except for extremely rare cases of infection in humans. We report here on a 64-year-old male patient with L. ivanovii who responded favorably to treatment with intravenous ampicillin.

Carcinoma of Papilla Vateri presenting as recurrent acute pancreatitis.

Tumors of the Papilla of Vater can cause several clinical symptoms, the most prominent being jaundice, weight loss, anorexia, fever, abdominal pain and itching (1). Acute pancreatitis as a presenting symptom of ampullary carcinoma is rare. Few previous cases have been described in the literature (2,3). The prognosis of patients with jaundice is unfavorable in comparison with non icteric patients at the time of diagnosis (4) due to different staging, hence more complications, but not due to different histology. We report here a case of recurrent pancreatitis that was the only presentation of Vater ampullary carcinoma diagnosed by endoscopic ultrasound followed by duodenoscopy with guided biopsy. Recurrent pancreatitis without identifiable cause, particularly in elderly patients, could suggest tumor of the head of pancreas or the periampullary region among other causes such as intraductal papillary mucinous tumor, microlithiasis etc. An endoscopic ultrasound can allow earlier diagnosis and mandates biopsy in these cases.

West Nile fever outbreak, Israel, 2000: epidemiologic aspects.

From August 1 to October 31, 2000, 417 cases of West Nile (WN) fever were serologically confirmed throughout Israel; 326 (78%) were hospitalized patients. Cases were distributed throughout the country; the highest incidence was in central Israel, the most populated part. Men and women were equally affected, and their mean age was 54+/-23.8 years (range 6 months to 95 years). Incidence per 1,000 population increased from 0.01 in the 1st decade of life to 0.87 in the 9th decade. There were 35 deaths (case-fatality rate 8.4%), all in patients >50 years of age. Age-specific case-fatality rate increased with age. Central nervous system involvement occurred in 170 (73%) of 233 hospitalized patients. The countrywide spread, number of hospitalizations, severity of the disease, and high death rate contrast with previously reported outbreaks in Israel.

Clinical characteristics of the West Nile fever outbreak, Israel, 2000.

West Nile (WN) virus is endemic in Israel. The last reported outbreak had occurred in 1981. From August to October 2000, a large-scale epidemic of WN fever occurred in Israel; 417 cases were confirmed, with 326 hospitalizations. The main clinical presentations were encephalitis (57.9%), febrile disease (24.4%), and meningitis (15.9%). Within the study group, 33 (14.1%) hospitalized patients died. Mortality was higher among patients >70 years (29.3%). On multivariate regressional analysis, independent predictors of death were age >70 years (odds ratio [OR] 7.7), change in level of consciousness (OR 9.0), and anemia (OR 2.7). In contrast to prior reports, WN fever appears to be a severe illness with high rate of central nervous system involvement and a particularly grim outcome in the elderly.

Characterization of two promoters of the Xenopus laevis elrD gene.

The Xenopus laevis elrD gene belongs to the multigenic elav/Hu family. elrD is exclusively expressed in neural cells, where it could be involved in the posttranscriptional control of mRNAs. Here we report the isolation and characterization of the genomic elrD 5'-flanking region. We localized the transcription initiation sites and thus identified two distinct transcripts, elrD1 and elrD2 by 5' RACE PCR. The two transcripts derive from the use of alternative promoters located 915 bp apart. We show that sequences upstream of the elrD1 and elrD2 transcription units can direct expression of the reporter luciferase gene in Xenopus embryos. We also observed length variation of the ELRD first RNA recognition motif (RRM1).

Comparison of oral fluconazole and itraconazole for progressive, nonmeningeal coccidioidomycosis. A randomized, double-blind trial. Mycoses Study Group.

BACKGROUND: In previous open-label noncomparative clinical trials, both fluconazole and itraconazole were effective therapy for progressive forms of coccidioidomycosis. OBJECTIVE: To determine whether fluconazole or itraconazole is superior for treatment of nonmeningeal progressive coccidioidal infections. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 7 treatment centers in California, Arizona, and Texas. PATIENTS: 198 patients with chronic pulmonary, soft tissue, or skeletal coccidioidal infections. INTERVENTION: Oral fluconazole, 400 mg/d, or itraconazole, 200 mg twice daily. MEASUREMENTS: After 4, 8, and 12 months, a predefined scoring system was used to assess severity of infection. Findings were compared with those at baseline. RESULTS: Overall, 50% of patients (47 of 94) and 63% of patients (61 of 97) responded to 8 months of treatment with fluconazole and itraconazole, respectively (difference, 13 percentage points [95% CI, -2 to 28 percentage points]; P = 0.08). Patients with skeletal infections responded twice as frequently to itraconazole as to fluconazole. By 12 months, 57% of patients had responded to fluconazole and 72% had responded to itraconazole (difference, 15 percentage points [CI, 0.003 to 30 percentage points]; P = 0.05). Soft tissue disease was associated with increased likelihood of response, as in previous studies. Azole drug was detected in serum specimens from all but 3 patients; however, drug concentrations were not helpful in predicting outcome. Relapse rates after discontinuation of therapy did not differ significantly between groups (28% after fluconazole treatment and 18% after itraconazole treatment). Both drugs were well tolerated. CONCLUSIONS: Neither fluconazole nor itraconazole showed statistically superior efficacy in nonmeningeal coccidioidomycosis, although there is a trend toward slightly greater efficacy with itraconazole at the doses studied.

[Contribution of self-surveillance of the personnel by electronic radiation dosemeters in invasive cardiology]. / Apport de l'autosurveillance des opérateurs par dosimètres électroniques sur la radioprotection en cardiologie invasive.

The methods of surveillance of coronary angiography or angioplasty operators vary from team to team. The choice of method implies evaluation of the level of exposition of unprotected areas. The usual methods of surveillance by dosimetry may be complemented by an electronic device used for industrial radiological protection against X and Gamma rays. This instrument emits a sound each time a micro sievert is detected: the operator perceives the photons of diffused rays. The value of protective screens is then directly audible. This instrument does not detect X rays with an energy of less than 50 KeV but there is a good correlation with results measured by thermoluminescent dosimetry. The measurement of irradiation were noted at three points on the body before and after the use of complementary protection which certain operators hesitated to use before this study. The results confirmed the value of these protections: the suspended lead screen reduced cervical irradiations by a factor of 15 and that of the left wrist by 8. Lower down, a flexible lead skirt reduced irradiation of the ankle by a factor of 19. These results underestimate the efficacy of the screen as low energy X rays were not measured and are even more easily absorbed by the screens.

Different components in human serum inhibit multiplication of Cryptococcus neoformans and enhance fluconazole activity.

The inhibitory effect of human serum on the multiplication of Cryptococcus neoformans and the interaction with fluconazole were studied. Compared with cryptococcal multiplication in RPMI 1640 medium alone, 5% human serum in medium inhibited multiplication by 76% +/- 6% (n = 8). The inhibitory effect of human serum was donor independent, [corrected] heat stable (56 degrees C, 30 min), and not due to albumin or globulin. Bovine and murine sera were not inhibitory at that concentration. A fungistatic concentration of fluconazole (5.0 micrograms/ml) in medium plus 5% human serum resulted in 40% +/- 5% (n = 8) killing (reduction of inoculum CFU) in a 24-h assay. Bovine or murine sera did not have the enhancing effect, and this human serum activity was heat stable and donor independent. At 2.5 micrograms of fluconazole per ml, fungistasis by fluconazole plus human serum was significantly greater than with either alone. Higher serum concentrations [corrected] potentiated fluconazole more. At higher fluconazole concentrations (e.g., 20 micrograms/ml) fluconazole alone could kill, but serum potentiated this. A fluconazole-resistant isolate (MIC, 100 micrograms/ml) was not killed by fluconazole (5.0 micrograms/ml) in 5% human serum, but human serum potentiated the partial fluconazole inhibition. When human serum was dialyzed (molecular weight cutoff, 6,000 to 8,000) against phosphate-buffered saline, it lost the ability to synergize with fluconazole for killing Cryptococcus organisms but not the capacity to inhibit multiplication. Filtration of serum suggested the filtrate with a molecular weight of < 10,000 could interact synergistically with fluconazole for killing but could not inhibit cryptococcal multiplication. These findings indicate that human serum has two components, one (macromolecular) with a unique ability to inhibit C. neoformans and a low-molecular-weight component that enhances fluconazole anticryptococcal activity.

Killing of Histoplasma capsulatum by macrophage colony stimulating factor-treated human monocyte-derived macrophages: role for reactive oxygen intermediates.

The interaction of human macrophages with the yeast-form of Histoplasma capsulatum was studied. The use of culture and a short-term assay period instead of microscopy gave direct evidence of the fungicidal activity of human macrophages. The present study reports the novel finding of fungicidal activity of macrophages derived from monocytes in the presence of macrophage colony-stimulating-factor (MCSF). The induction of fungicidal activity by this cytokine was dose dependent. MCSF at 10,000 U/ml was optimal with 73(SD3)% killing. Inhibition of macrophage killing by superoxide dismutase (SOD), but not catalase (CAT) or N-monomethyl-L-arginine (NMMA), established the role of the superoxide anion in the killing mechanism. The fungistatic activity of MCSF-derived human macrophages in a 24-h assay was also dose dependent and was not inhibited by SOD, CAT or NMMA. MCSF at 10,000 U/ml produced optimal macrophage fungistatic activity, 34.6(SD4)%.

Macrophage colony-stimulating factor (M-CSF) induction of enhanced anticryptococcal activity in human monocyte-derived macrophages: synergy with fluconazole for killing.

Induction of enhanced anticryptococcal activity in human monocyte-derived macrophages (HMM) by macrophage colony-stimulating factor (M-CSF) and possible synergy with fluconazole (FCZ) for killing of Cryptococcus neoformans (CN) was studied. Fungistasis by HMM cultured in medium for 3, 5, or 7 days was minimal, 0-17%. The fungistasis of HMM cocultured with M-CSF at 1000, 5000, or 20,000 U/ml for 3, 5, or 7 days was increased significantly (P < 0.02) at all study times and by all concentrations. The optimal M-CSF concentration for HMM treatment for enhanced fungistasis was 5000 U/ml for Day 3 (84%), whereas 1000 U/ml was sufficient with more prolonged HMM culture and M-CSF treatment (Days 5-7). The enhancement by M-CSF was seen with four different donors and three patient isolates of CN. FCZ at 5 micrograms/ml was fungicidal, 28 +/- 17% (n = 8). Killing by FCZ was enhanced by HMM treated with M-CSF 5000 or 20,000 U/ml for 5 days compared to control HMM, 58% (P = 0.001) and 60% (P = 0.002) vs 48%, respectively. This was also seen with HMM cultured with 1000 U/ml M-CSF for 7 days (P < 0.05). M-CSF also induced in HMM enhancement of fungistasis by lower, fungistatic, concentrations of FCZ. These results demonstrate enhancement of anticryptococcal activity by HMM treated with M-CSF and synergy with FCZ for inhibition and killing. These findings may provide a rationale for combined treatment of FCZ and M-CSF against cryptococcosis.

Effect of macrophage colony-stimulating factor on anticryptococcal activity of bronchoalveolar macrophages: synergy with fluconazole for killing.

The anticryptococcal activity of murine bronchoalveolar macrophages (BAM) and their synergy with fluconazole (FCZ) was studied. BAM cultured with tissue culture medium for 48 to 72 h were fungicidal (24 to 39%) in a 3-h killing assay. However, net killing of Cryptococcus neoformans did not continue when culture time was extended to 24 h, although BAM were fungistatic (88 to 98%). Treatment with macrophage colony-stimulating factor (M-CSF; 5,000 U/ml, 48 h) did not significantly increase BAM killing of a low challenge dose in 3-h assays compared with control BAM. However, M-CSF-treated BAM were significantly more fungistatic against higher challenge doses in the 3-h assays. FCZ was not fungicidal at 5 micrograms/ml but was highly fungistatic (98 and 99% at 24 and 48 h, respectively). M-CSF-treated BAM acted synergistically with FCZ (2.5 micrograms/ml) for significantly greater killing than control BAM, 55% versus 20% and 96% versus 45% at 24 h and 48 h, respectively. Killing by M-CSF BAM and FCZ (5.0 micrograms/ml) was significantly (P < 0.01) greater than that by control BAM and FCZ at 48 h. These findings indicate an important collaborative role for BAM and FCZ in killing C. neoformans, and this is enhanced by M-CSF.

Effect of in vivo macrophage colony-stimulating factor on fungistasis of bronchoalveolar and peritoneal macrophages against Cryptococcus neoformans.

Macrophage colony-stimulating factor (M-CSF) given subcutaneously at a dose of 2.5 mg/kg of body weight (4.75 x 10(6) U/kg) to CD-1 male mice 8 to 12 weeks old was found to enhance significantly the fungistasis of bronchoalveolar macrophages (BAM) against Cryptococcus neoformans. When M-CSF was given 1, 3, 7, 9, or 13 days before an ex vivo challenge with C. neoformans, fungistasis was increased (P ranged from < 0.05 to < 0.001) compared with that induced by control BAM. A maximum effect was seen by days 1 and 3 after administration of M-CSF. Twenty-one days after M-CSF, BAM did not produce significantly enhanced fungistasis. M-CSF also significantly enhances the fungistatic effect of peritoneal macrophages (PM) if given 1, 3, and 7 days prior to testing against C. neoformans in comparison with control PM (P ranged from < 0.05 to < 0.001). PM did not produce enhanced fungistasis 9 or 13 days after administration of M-CSF. These studies demonstrating in vivo enhancement of anticryptococcal activity of macrophages with M-CSF provide a rationale for in vivo use of M-CSF to enhance resistance to infection with C. neoformans.

Assessment of the hypothalamic-pituitary-testicular function in male patients with Wilson's disease.

Sixteen male patients with Wilson's disease were studied to detect potential endocrine dysfunctions. There was no clinical evidence of feminization in any of the patients, and the patient group spanned most pubertal stages. Gonadotropin, testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate, androstenedione, estradiol, prolactin, cortisol, thyrotropin, and free thyroxine levels were determined. Low or borderline luteinizing hormone (LH) levels were present in most of the patients. In six of the adult patients, a standard gonadotropin-releasing hormone (GnRH) test was performed. Five of the six patients had blunted LH and follicle-stimulating hormone (FSH) responses to GnRH. Increased androgen levels were found in eight of the patients. Sex hormone-binding globulin was normal in eight of nine tested patients. Three single-dose human chorionic gonadotropin (hCG) stimulation tests of six adult patients showed normal responses. Three other patients who had elevated baseline levels responded with modest increases. Since liver disease is usually associated with decreased androgen levels, it is difficult to account for the elevated androgen levels. Both increased androgen levels and copper accumulation in the hypophysis could be responsible for the blunted GnRH response.

[Bronchial carcinoid. Description of 2 cases]. / Il carcinoide bronchiale. Descrizione di due casi.

Bronchial carcinoid is a rare tumor appearing mostly in young patients, affecting males and females in equal proportion. It has a low grade malignancy. Carcinoid syndrome is infrequent in this condition and the clinical manifestations are those of bronchial obstruction. Two cases of bronchial carcinoid, diagnosed by bronchoscopy are described.