Increase of serum interleukin-2 and regression of myeloma after rhGM-CSF treatment of drug induced bone marrow aplasia

Recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) was administered to a patient with multiple myeloma (IgA, stage IIA) who had a chemotherapy-induced bone marrow aplasia with granulocytopenia complicated by severe pneumonia and septicemia. The rhGM-CSF was given as i.v. infusions, 300-400 micrograms daily, for three weeks. The patient responded both hematologically and clinically with improved granulocyte counts and clearance of massive pulmonary infiltrates. We also observed a partial remission of the myeloma with decreasing s-IgA levels and reduced plasma cell infiltration of the bone marrow during a period of up to four months after the rhGM-CSF treatment. Immunological studies performed during and after cytokine administration showed an increase in serum interleukin-2 (IL-2) levels and HLA-DR positive T-lymphocytes indicating an activation of the immune system. It is suggested that rhGM-CSF induced immunological changes which may have contributed to the partial regression of the myeloma.     

Similar discontinuation symptoms for withdrawal from medium-dose paroxetine and venlafaxine after nine years in the same patient

A woman who had developed a discontinuation syndrome nine years ago with paroxetine tapered from 10 to 5 mg/day represented the same syndrome recently when she occasionally missed her 75 mg q 12 h venlafaxine doses. The symptoms, comprising agitation, numbness, pricking sensations, sweating, difficulty concentrating, weakness, derealisation and perceived xerophthalmia, immediately subside upon drug dose reinstitution. The patient had used cannabis irregularly before the onset of pauci-symptomatic panic attacks, but none of her panic symptoms were present in her withdrawal symptomatology. Some symptoms waxed and waned during the withdrawal period. The syndrome is compatible with both hyper- and hypoactivity of the central serotonergic system.     

Epstein-Barr virus induces aggressive lymphoproliferative disorders of human B cell origin in SCID/hu chimeric mice.

C.B-17 scid mice were reconstituted by intraperitoneal injection of human tonsil cells or PBL from EBV-seronegative donors. Subsequent injection of EBV resulted in the rapid development (within 19-33 d) of aggressive, fatal, lymphoproliferative disorders of human B cell origin. Autopsies revealed solid tumors in the abdomen, and occasionally in the liver, thymus, or spleen. Histopathologic analysis showed that the tumors were high-grade immunoblastic lymphomas and FACS analyses of tumor cells indicated that they were of human B-lymphoid origin. The tumor cells grew in vitro and induced new tumors on injection into severe combined immunodeficient (SCID) mice. Karyotypic analysis and Southern blots for c-myc or bcl-2 rearrangements revealed no chromosomal abnormalities and translocations. Southern blot analysis also showed that the cells possessed EBV DNA sequences. Although these tumors undoubtedly reflect infection of the transferred B cells with EBV in vivo, intraperitoneal transfer of short-term lymphoid cell lines transformed in vitro with EBV resulted in ascites production without evidence of tumor formation.     

Recombinant adenovirus vector activates and protects human monocyte-derived dendritic cells from apoptosis

The aim of this study was to examine the effect of two of the most commonly used viral vectors, that is, retrovirus and adenovirus, on the antigen presentation of dendritic cells (DCs). DCs were generated from CD34(+) hematopoietic precursors and CD14(+) monocytes of the same prostate cancer patients. Adenoviral transduction of monocyte-derived DCs (MO-DCs) resulted in upregulation of CD80, CD86, and CD83 expression. Adenovirus-transduced MO-DCs were also more potent stimulators of allogeneic lymphocytes, produced increased amounts of the cytokines tumor necrosis factor alpha and interleukin 12 p70, and exhibited increased expression of NF-kappaB and antiapoptotic molecules Bcl-X(L) and Bcl-2. Enhanced expression of the antiapoptotic molecules correlated with increased resistance of adenovirus-transduced MO-DCs to spontaneous as well as Fas-mediated cell death. In contrast to the adenoviral construct, no significant transduction of MO-DCs with the retrovirus could be obtained. Transduction of CD34(+) cell-derived DCs with the retrovirus or the adenovirus did not significantly alter expression of the costimulatory molecules or cytokines studied. At lower stimulation ratios, CD34(+) cell-derived DCs transduced with retrovirus were less potent in their ability to stimulate allogeneic lymphocytes in comparison with nontransduced DCs. Our results indicate that adenoviral vectors may be more suitable for gene delivery to DCs for immunotherapy.     

Fungal infection in a patient with multiple sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system, whose causes are still unknown. We have proposed that MS, as well as some ophthalmologic diseases, are associated with fungal infection. In the present study, we closely monitored a patient with MS over a three-year period. Antibodies against different Candida spp. were detected in peripheral blood serum, although the titer of these antibodies fluctuated. The presence of fungal macromolecules, such as proteins, polysaccharides, and DNA, was also tested. In several sera samples, antigens related to C. famata were evidenced by the slot-blot test using a rabbit polyclonal antibody against these species, while high levels of β-1,3 glucan were detected with the commercial Fungitell assay. Despite the variations by sample, we concluded that all fungal macromolecules, that is, proteins, polysaccharides, and DNA, were present in blood from the MS patient which was analyzed. Several fungal species were identified using polymerase chain reaction (PCR) followed by sequencing. Antibodies against Candida spp. as well as C. famata-related antigens were also detected in cerebrospinal fluid (CSF). Our findings provide support for the notion that disseminated mycosis is present in this patient.     

Fully covered self-expandable metallic stents in benign biliary strictures: a multicenter study on efficacy and safety

Background and study aim: Benign biliary diseases include benign biliary stricture (BBS), lithiasis, and leaks. BBSs are usually treated with plastic stent placement; use of uncovered or partially covered metallic stents has been associated with failure related to mucosal hyperplasia. Some recently published series suggest the efficacy of fully covered self-expandable metal stents (FCSEMSs) in BBS treatment. We aimed to assess the efficacy and safety of FCSEMS in a large series of patients with BBS and a long follow-up.?Patients and methods: Prospective multicenter clinical study at three tertiary referral centers: ISMETT/UPMC Italy, Palermo, San Paolo Hospital, Milan, and the ARNAS Civico Hospital, Palermo, Italy. All consecutive patients with BBS were treated with placement of FCSEMS rather than plastic stents, as first approach (11 patients, 17.7?%), or as a second approach after failure of other treatments (51 patients, 82.2?%). Results: From January 2008 to March 2011, 62 patients (40 male) were included. Mean period of FCSEMS indwelling was 96.7 days (standard deviation [SD] 6.5 days). In 15 patients (24.2?%) the SEMS migrated. Resolution of BBS occurred in 56 patients (90.3?%), while in 6 (9.6?%) the treatment failed. Mean (SD) follow-up after SEMS removal was 15.9 (10) months. FCSEMS placement as first- or second-line approach showed no difference in failure. Recurrence was observed in 4?/56 patients (7.1?%); all were transplant recipients: P?=?0.01; odds ratio (OR) 1.2, confidence interval (CI) 1.1?-?1.3.Conclusions: Despite the noteworthy migration rate, FCSEMSs should be considered effective for refractory benign biliary strictures. Further studies are needed to assess their role as a first approach in the management of BBS.     

Open-label trial on efficacy and security of treatment with gemcitabine and oral modulation with tegafur and levofolinic acid (GEMTG) in patients with advanced pancreatic cancer

Aim

Advanced pancreatic cancer has a bad prognosis, with a median overall survival (OS) no longer than 4–6 months. Since the end of last century, monotherapy with gemcitabine has remained the elective therapy, but new schedules are needed in order to improve these results. We aim to evaluate the efficacy of tegafur and levofolinic acid (LV) associated with gemcitabine, as well as its toxicity, progressionfree survival and OS in advanced pancreatic cancer.

Patients and methods

An open-label, multicentric, prospective, non-controlled trial was carried out on patients with advanced or disseminated pancreatic cancer. Gemcitabine 1250 mg/m² was administered on the 1st and 8th days of the cycle, tegafur 750 mg/m²/day for 21 consecutive days and LV 25 mg/day continuously, every 28 days, with a maximum of six cycles. The primary variable was tumour overall response rate (ORR). Secondarily, time to progression (TTP), OS and scheme toxicity were determined.

Results

Forty patients were recruited; the male/female ratio was 30:10, with a mean age of 61 years. Forty percent had a Karnofsky index of 90% or 100%. Only 11 patients (27%) completed the six cycles of treatment, but more than 50% received three or more cycles. Dose intensity was 89.56% for gemcitabine and 87.36% for tegafur. Efficacy ORR was 22.5% (CI 95%, 6–37%). TTP was 3.87 months (CI 95%, 2.1–5.6), time to treatment failure was 2.97 months (CI 95%, 2.43–4.67) and OS 6.3 months (CI 95%, 4–7). The chemotherapeutic combination was well accepted; most haematologic and non-haematologic toxicities were grade 1 or 2. The most prevalent grade 3/4 toxicities were asthenia (30%), liver biochemistry disorders (25%), diarrhoea (15%) and stomatitis (12%).

Conclusions

The administration of gemcitabine, associated with oral tegafur and leucovorin, has activity against advanced pancreatic cancer, with an adequate toxicity profile.     

Association between multiple sclerosis and Candida species: evidence from a case-control study

Candida infection among multiple sclerosis (MS) patients has not been studied in depth. We determined whether there is an association between serological evidence of Candida infection and MS. Blood specimens were obtained from 80 MS patients and 240 matched controls. Immunofluorescence analysis and ELISA were used to detect Candida species antibodies and slot-blot to detect antigens. Using immunofluorescence analysis, moderate to high concentrations of serum antibodies to Candida famata were present in 30 (37.5%) MS patients vs. 30 (12.5%) controls (p < 0.001). Results for Candida albicans were 47.5% (38/80) in MS patients vs. 21.3% (51/240) in controls (p < 0.001), for Candida parapsilosis 37% (28/80) vs. 17.1% (41/240) (p < 0.001) and for Candida glabrata 46.3% (37/80) vs. 17.5% (42/240) (p < 0.001), respectively. After adjusting for age and gender, the odds ratios (95% confidence intervals) for MS, according to the presence of Candida antigens were: 2.8 (0.3–23.1, p = 0.337) for Candida famata; 1.5 (0.7–3.4, p = 0.290) for Candida albicans; 7.3 (3.2–16.6, p < 0.001) for Candida parapsilosis; and 3.0 (1.5–6.1, p = 0.002) for Candida glabrata. The results were similar after excluding ten patients on immunosuppressants. The results of this single study suggest that Candida species infection may be associated with increased odds of MS.     

TEMPS-A (Rome): psychometric validation of affective temperaments in clinically well subjects in mid- and south Italy

BACKGROUND: Our aim was to study the psychometrics and factor structure replicability of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) in its Italian (Rome) Version. The questionnaire is a self-report 110-item measure that postulates five affective temperaments-the depressive, cyclothymic, irritable, hyperthymic, and anxious-which embody both strengths and liabilities along affective reactivity. In Italian, the TEMPS has previously been validated in its original 32-item version, the TEMPS-I (Pisa), one which did not yet include an anxious subscale. METHODS: The present sample consisted of 948 nonclinical subjects (27.39 years+/-8.22 S.D.). There were 476 men (50.2%: 28.56 years+/-8.63 S.D.) and 472 women (49.8%: 26.21 years+/-7.61 S.D.). Reliability and validity were assessed by standard psychometric tests. RESULTS: Principal Components Analysis with Varimax rotation resulted in a 3-factor solution: the first with highest explained variance (8.84%) represents Dysthymic, Cyclothymic and Anxious (Dys-Cyc-Anx) temperaments combined; the second identifies Irritable temperament (5.65% of variance); and the third Hyperthymic temperament (5.16% of variance). Cronbach Alpha coefficients for the three subscales were respectively .89, .77 and .74. The rates for the Dys-Cyc-Anx were 2.7%, and for the Irritable 3.1%. Despite the low rate of the Hyperthymic temperament (.2%), nonetheless 16% were between 1st and 2nd SD. Exploratory factor analysis revealed a positive loading combining Dys-Cyc-Anx with the Irritable; the Hyperthymic loaded negatively on this factor. In terms of dominant temperaments, based on z-scores, 2.7% were dysthymic, 1.7% cyclothymic, .7% hyperthymic, 3.5% irritable and 3% anxious. LIMITATION: Although developed for self-rated use, the Italian authors nonetheless administered the TEMPS-A in an interview format. It is uncertain in what ways this procedure could have influenced our results, if any. Another limitation is that we did not assess test-retest reliability. CONCLUSIONS: These data identify at least 3-factors, Dys-Cyc-Anx and Irritable (which are correlated), and Hyperthymic, which is uncorrelated with the others. Though our data are reminiscent of the neuroticism-extraversion distinction, importantly traits are operationalized in affective terms. Beyond the well-known relationship between the Dysthymic and Cyclothymic subscales and that between the Dysthymic and Anxious, the present data reveal a strong relationship between the Cyclothymic and Anxious as well, which is of great relevance for bipolar II. It is also provocative that much of hyperthymia (16%) in the +SD is between the 1st and 2nd SD, thereby "normalizing" this temperament in Italy, as previously reported by TEMPS-I (Pisa) from Northern Italy (and TEMPS-A from Lebanon and Argentina).