Onychotillomania: 2 case reports

Onychotillomania is an uncommon condition characterized by self-destruction of the fingernails and/or toenails by compulsive manipulation. We report 2 cases of onychotillomania with differing presentations in a young man and in an older man. Onychotillomania may be a form of obsessive-compulsive disorder (OCD), and we discuss the psychologic factors and current treatments for this condition.     

A multicenter,randomized, double blind placebo-controlled trial of amoxicillin/clavulanate for the prophylaxis of fever and infection in neutropenic children with cancer

AIM OF THE STUDY: To evaluate the effectiveness of oral amoxicillin/clavulanate (25 mg/kg every 12 h) for prevention of fever and/or infection in neutropenic children with cancer. METHODS: Multicenter, prospective, randomized, double blind placebo-controlled trial. RESULTS: In the intention-to-treat analysis, amoxicillin/clavulanate had a 12% benefit increase in terms of reduction in the incidence of febrile or infectious episodes, compared with placebo [44 of 83 (53%) vs.55 of 84 (65%); 95% confidence interval, -28% to +3%; P = 0.101]. This benefit was also associated with a 30% increase in the probability of failure-free survival at Day 15 (P = 0.138). A logistic regression analysis showed the effect of prophylaxis to be relevant, especially in patients with leukemia or lymphoma and in those not receiving hematopoietic growth factors, with 17 and 15% absolute benefit increases (logistic P = 0.014 and 0.034, respectively). Compliance with oral drugs was good, with very few and nonsevere drug-related adverse events. CONCLUSIONS: In this study amoxicillin/clavulanate was associated with a detectable clinical effect in the reduction of fever and infection in neutropenic children with cancer, especially those with acute leukemia and not receiving growth factors; the study was not powered to demonstrate a statistically significant effect in the overall patient population.     

Organotypic slices in vitro: repeated,same-cell,high-resolution tracking of nuclear and cytoplasmic fluorescent signals in live,transfected cerebellar neurons by confocal microscopy

The culture of organotypic slices for the purposes of tracking dynamic cellular events within the same live cell at high resolution, as a function of development in vitro has not been previously reported. The present study was undertaken to define the conditions most suitable for both the in vitro organotypic development of Purkinje neurons in cerebellar slices of neonatal mice, and the repeated visualization of nuclear signals within such cells. Slices of cerebella were maintained on 25 mm diameter, collagen-coated Anodisc membranes, placed in six-well plates and raised to the air-medium interface by use of glass fibre filter supports. This system permits cultures to be repeatedly observed both by phase contrast microscopy and, upon biolistic transfection, by laser confocal microscopy using 40x, 60x, and 100x water-immersion objectives, at high resolution. Upon co-transfection with two plasmids, differentiation of the same transfected Purkinje neurons was followed across in vitro development for periods of up to 10 days. Despite the relative thickness of the slice culture, even small, punctate, nuclear signals, were detectable. The results show that Purkinje neurons in cerebellar slices explanted from postnatal day 2 mice, developed cytotypically, although some were ectopically located. In contrast, Purkinje neurons in slices from postnatal day 6 cerebella developed in an organotypic manner. It is concluded that this culture system serves as an ideal tool for applications in experimental biology where high resolution tracking of cellular signals, over extended time periods, is of interest.     

Current role of bed-rest in threarened abortion

BACKGROUND: The aim of this study was to evaluate the efficacy of bed-rest in the treatment of threatened abortion. This is based on the extensive use made today of this practice, although there are no studies that suggest or prove its therapeutic success, and on the contrary many of them demonstrate its possible risks. METHODS: The efficacy of bed-rest is evaluated by comparing the abortion rate in patients treated with bed-rest those who received no treatment. A retrospective study was made on data obtained from interviews with 226 patients with previous threatened abortion hospitalised for pregnancy-related reasons at the Obstetrics and Gynecology Clinic of Policlinico Umberto I in Rome between October 1998 and June 1999. RESULTS: The following results were obtained: 84% of the 146 patients treated with bedrest continued pregnancy beyond week 20, whereas 16% aborted before week 20. Of the 80 patients who were not treated, 80% continued pregnancy beyond week 20 and 20% aborted before week 20. These results do not show statistically significant differences between the two groups (c2=0.4 p=NS). CONCLUSIONS: These results suggest that bed-rest does not improve the prognosis of threatened abortion.     

Three new active cisplatin-containing combinations in the neoadjuvant treatment of locally advanced and locally recurrent breast carcinoma: a randomized phase II trial

We designed three new four-drug cisplatin-containing combinations and evaluated their activity in a randomized phase II study including patients with locally advanced (stage III) and locally recurrent breast carcinoma. All combinations included methotrexate (M) on day 1 and cisplatin (P) on day 2 (MVAC-like combinations) and differed from one another by the addition of Epirubicin (Epi), Vincristine (V), Etoposide (E), Mitomycin (Mi). Based on the administered agents, they were named MPEMi, MPEpiE, MPEpiV. The combinations were randomly assigned to 101 patients, 57 with locally advanced and 44 with locally recurrent breast carcinoma. Response was evaluated after 4 cycles. The complete response (CR) rates were 7% and 43% and the CR plus partial response (PR) rates were 84% and 89% in locally advanced and in locally recurrent disease, respectively. In locally advanced disease, a pathologic CR (pCR) was assessed in seven of 57 patients (12%). There were no significant differences among the three combinations. The toxicities were at times severe, but generally tolerable, as demonstrated by the high cumulative doses of the drugs received by the patients. In conclusion, these three innovative chemotherapy regimens induced high CR plus PR rates in the neoadjuvant treatment of stage III and of locally recurrent breast carcinoma, and a high rate of pCR in stage III disease. These regimens warrant testing in phase III trials.     

Phase I study of temsirolimus in combination with EKB-569 in patients with advanced solid tumors

Purpose Activation of EGFR can stimulate proliferative and survival signaling through mTOR. Preclinical data demonstrates synergistic activity of combined EGFR and mTOR inhibition. We undertook a phase I trial of temsirolimus (T, an mTOR inhibitor) and EKB-569 (E, an EGFR inhibitor) to determine the safety and tolerability. Methods The primary aim was to determine the maximally tolerated dose (MTD) of this combination in adults with solid tumors. Following the dose-escalation phase, (Cohort A), two subsequent cohorts were used to assess any pharmacokinetic (PK) interaction between the agents. Results Forty eight patients were enrolled. The MTD of this combination was E, 35 mg daily and T, 30 mg on days 1-3 and 15-17 using a 28-day cycle. The most common toxicities were nausea, diarrhea, fatigue, anorexia, stomatitis, rash, anemia, neutropenia, thrombocytopenia, and hypertriglyceridemia. Sixteen patients (36%) had at least one grade 3 toxicity. The most frequent grade 3/4 toxicities were diarrhea, dehydration, and nausea and vomiting (19% each). No grade 5 events were seen. Four patients had a partial response and 15 had stable disease. Clinical benefit was seen across a range of tumor types and in all cohorts. PK analysis revealed no significant interaction between E and T. Conclusions This combination of agents is associated with tolerable toxicities at doses that induced responses. PK studies revealed no interaction between the drugs. Further investigations of this targeting strategy may be attractive in renal cell carcinoma, non-small cell lung cancer, alveolar sarcoma, and carcinoid tumor.     

Olaparib , PARP1 inhibitor in ovarian cancer

Introduction: Ovarian cancer is the most important cause of gynecological cancer-related mortality. Conventional treatments for advanced or recurrent disease offer limited results in terms of long-term responses and survival. Researches have recently focused on target therapies, which represent a new, promising, therapeutic approach, able to maximizing tumor kill and minimizing toxicity. The family of polyadenosine diphosphate-ribose polymerase (PARP) inhibitors is currently one of the most hopeful and investigated alternatives. Areas covered: Preclinical and clinical studies of Olaparib , the most investigated PARP inhibitor in ovarian cancer, are analyzed and discussed. Data were obtained by searching for all English peer-reviewed articles on Medline, on Cochrane Database and all on-going Phase I and II studies registered on National Cancer Institute Clinical Trials; also any related abstracts recently presented on Olaparib at major international congresses will be included. Expert opinion: Bad prognosis and drug resistance usually affect ovarian cancer. Recent trends toward the knowledge of molecular-specific pathways have produced new target drugs. PARP inhibition mediated by Olaparib in BRCA1 (breast cancer 1) and BRCA2 (breast cancer 2)-mutated and in sporadic ovarian cancer represents a promising field of investigation. Further studies are needed to confirm initial exciting results.