Physicians and death: Comments and behaviour of 605 doctors in the north-east of Italy

The aim of this study was to determine the influence of socio-demographic and professional factors on physicians' attitudes to the terminally ill. Between May 1992 and May 1993, a survey was conducted in the province of Pordenone (north-east, Italy) in order to analyse a number of specific issues, such as emotional involvement, the need for aggressive treatments and the communication of diagnosis and prognosis. After obtaining a list of board-certified physicians from the Medical Association office in Pordenone, a modification of the cancer questionnaire of Haley and Blanchard (QSPT) was mailed to 916 doctors. Of these, 605 (60%; 487 male, 118 female; mean age 41 ± 11 SD) returned the completed questionnaire. Within the group of responders, we identified three main subgroups, according to their type of activity: general practitioners (175, 29%), hospital doctors (235, 39%) and other doctors (195, 32%). In age, sex and activity, the only significant difference between responders and non-responders was age (mean age 41 and 43 years respeetively). Most of the responders (77%) stated that they were able to deal with the terminally ill patient and his/her needs; 44%, however, admitted that patients' anxiety is sometimes unbearable. For the vast majority of the doctors polled (91%), providing a comfortable environment for an incurable patient was more important than pursuing aggressive treatment, but only 44% were convinced of the uselessness of aggressive care. To the question on whether to disclose information about imminent death to allow patients to prepare spiritually, 37% answered No, 38% Yes, and 25% were uncertain. Almost all responders (95%), however, believed in the beneficial effect of hope on the terminally ill. Ourresults suggest that doctors' professional and, most of all, sociodemographic and cultural factors determine the relationship with the patient on both the emotional and the clinical decision-making levels.     

Mediterranean Diet and Cardiovascular Disease: A Critical Evaluation of A Priori Dietary Indexes

The aim of this paper is to analyze the a priori dietary indexes used in the studies that have evaluated the role of the Mediterranean Diet in influencing the risk of developing cardiovascular disease. All the studies show that this dietary pattern protects against cardiovascular disease, but studies show quite different effects on specific conditions such as coronary heart disease or cerebrovascular disease. A priori dietary indexes used to measure dietary exposure imply quantitative and/or qualitative divergences from the traditional Mediterranean Diet of the early 1960s, and, therefore, it is very difficult to compare the results of different studies. Based on real cultural heritage and traditions, we believe that the a priori indexes used to evaluate adherence to the Mediterranean Diet should consider classifying whole grains and refined grains, olive oil and monounsaturated fats, and wine and alcohol differently.     

Loss of compensatory pro-survival and anti-apoptotic modulator,IKKε, sensitizes ovarian cancer cells to CHEK1 loss through an increased level of p21

Ovarian cancer (OC) is extremely heterogeneous, implying that therapeutic strategies should be specifically designed based on molecular characteristics of an individual''s tumor. Previously, we showed that IKKε promotes invasion and metastasis in a subset of OCs. Here, we identified CHEK1 as an IKKε-dependent lethal gene from shRNA kinome library screen. In subsequent pharmacological intervention studies, the co-inhibition of IKKε and CHEK1 was more effective in killing OC cells than single treatment. At the molecular level, co-inhibition dramatically decreased pro-survival proteins, but increased proteins involved in DNA damage and apoptosis. IKKε-knockdown increased p21 levels, while overexpression of wild-type IKKε, but not a kinase dead IKKε mutant decreased p21 levels. We further demonstrated that the depletion of p21 rendered OC cells more resistant to cell death induced by co-inhibition of IKKε and CHEK1. In conclusion, we revealed a novel interplay between IKKε, CHEK1 and p21 signaling in survival of OC. Our study provides a rationale for the clinical development of specific IKKε inhibitor and for usage of IKKε as an exploratory marker for resistance to CHEK1 inhibitors in the clinic. The interplay provides one potential explanation as to why very few clinical responses were achieved in patients treated with single-agent CHEK1 inhibitors.     

Unbalanced X-chromosome inactivation in haemopoietic cells from normal women

We studied X-chromosome inactivation patterns in blood cells from normal females in three age groups: neonates (umbilical cord blood), 25–32 years old (young women group) and >75 years old (elderly women). Using PCR, the differential allele methylation status was evaluated on active and inactive X chromosomes at the human androgen receptor (HUMARA) and phosphoglycerate kinase (PGK) loci. A cleavage ratio (CR)  3.0 was adopted as a cut-off to discriminate between balanced and unbalanced X-chromosome inactivation. In adult women this analysis was also performed on hair bulbs. The frequency of skewed X-inactivation in polymorphonuclear (PMN) cells increased with age: CR  3.0 was found in 3/36 cord blood samples, 5/30 young women and 14/31 elderly women. Mathematical analysis of patterns found in neonates indicated that X-chromosome inactivation probably occurs when the total number of haemopoietic stem cell precursors is 14–16. The inactivation patterns found in T lymphocytes were significantly related to those observed in PMNs in both young ( P  < 0.001) and elderly women ( P  < 0.01). However, the use of T lymphocytes as a control tissue for distinguishing between skewed inactivation and clonal proliferation proved to be reliable in young females, but not in elderly women, where overestimation of the frequency of clonal myelopoiesis may appear.     

Complete remission of refractory anemia following a single high dose of cyclophosphamide

 We describe a case of stable complete remission in a patient with refractory anemia complicated by severe autoimmune hemolytic anemia, achieved with a single high dose (4 g/m²) of cyclophosphamide (cyclo). Concomitantly, an effective mobilization of CD34-positive cells was induced. Other immunosuppressive approaches including high-dose methylprednisolone, high-dose immunoglobulin, and cyclosporine had been ineffective. This finding suggests that, in selected cases, an immunologic mechanism may mediate cytopenia in myelodysplastic syndromes (MDS). In addition, it demonstrates that successful mobilization of peripheral blood stem cells can be induced with high-dose cyclo in MDS. Received: September 14, 1998 / Accepted: October 9, 1998     

Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: clinical, serological, and HLA class II gene associations. European Concerted Action on the Immunogenetics of SLE

OBJECTIVE: To assay anti-ganglioside antibodies (aGM1) in sera of a large cohort of European patients with systemic lupus erythematosus (SLE) to define the prevalence of these autoantibodies in SLE; to evaluate the association of aGM1 with clinical manifestations and other autoantibodies found in SLE; and to search for aGM1 association with HLA class II alleles. METHODS: Four hundred forty-eight patients with SLE were consecutively enrolled in 8 centers from 6 European countries. All sera were tested for antinuclear antibodies by immunofluorescence on HEp-2 cells as substrate, anti-dsDNA, aGM1, aCL, abeta2-glycoprotein I (abeta2-GPI) antibodies by ELISA, and antineutrophil cytoplasmic antibodies (ANCA) by immunofluorescence and by ELISA. Genomic typing for HLA class II loci was performed by polymerase chain reaction-sequence specific oligonucleotide probe method. Clinical assessment was done at the time of enrolment. RESULTS: We found 41.9% of patients with clinical signs of neuropsychiatric involvement; 15.5% of patients were positive for aGM1, 8% of the IgG isotype and 8.6% of the IgM isotype; aGM1-IgG were associated with neuropsychiatric manifestations (NPM) (RR = 3.7), with migraine (RR = 2.4), with OBS (RR = 7.3), and with peripheral neuropathy (RR = 8.5). aGM1-IgM were associated with NPM (RR = 4) and with depression (RR = 3.4). Furthermore, the genetic study showed that aGM1-IgG were associated with HLA-DQB1*0404 (RR = 7.2) while aGM1-IgM were associated with HLA-DQB1*0605 (RR = 33.3). No associations were found between aGM1 and anti-dsDNA, aCL, abeta2GP1, or ANCA. CONCLUSION: Our results show aGM1 can be found in patients with SLE. aGM1 may play a pathogenetic role for some NPM in this condition.     

Rehabilitation of Fecal Incontinence After Sphincter-Saving Surgery for Rectal Cancer: Encouraging Results

Purpose  Some patients, having undergone sphincter-saving operations for rectal cancer, may suffer from fecal incontinence. This study was designed to evaluate the results of rehabilitative treatment in patients with fecal incontinence after sphincter-saving operations and to identify the negative factors that influence therapeutic success. Methods  Between January 2000 and June 2007, 88 incontinent patients (54 women; age range, 47–73 years; 69 had received a low anterior rectal resection; 19 a straight coloanal anastomosis) were included in the study. After a preliminary clinical evaluation, including the Wexner Incontinence Scale score, anorectal manometry was performed. All 88 patients underwent rehabilitative treatment according to the “multimodal rehabilitative program” for fecal incontinence. At the end of program, all 88 patients were reassessed by means of a clinical evaluation and anorectal manometry; their results were compared with the clinical and manometric data from ten healthy control subjects. Postrehabilitative Wexner Incontinence Scale scores were used for an arbitrary schedule of patients divided into three classes: Class I, good (score ≤3); Class II, fair (score >3 to ≤6); Class III, poor (score >6). Results  After rehabilitation, there was a significant improvement in the overall mean Wexner Incontinence Scale score (P < 0.03) for both surgical operation types (low anterior rectal resection: P < 0.05; coloanal anastomosis: P < 0.02). Only 21 patients (23.8 percent) were symptom-free, and 37 (42 percent) were considered Class III. A significant postrehabilitative direct correlation was found between: 1) Wexner Incontinence Scale score and degree of genital relaxation (rρ _s 0.78; P < 0.001); 2) Wexner Incontinence Scale score and irradiation (rρ _s 0.72; P < 0.01); and 3) Wexner Incontinence Scale score and pelvic (rρ _s 0.65; P < 0.01) or anal surgery (rρ _s 0.68; P < 0.01). No significant differences were found between prerehabilitative and postrehabilitative anal pressures in low anterior rectal resection and coloanal anastomosis patients. Conclusions  After rehabilitation, some patients become symptom-free, many patients show an improvement in the Wexner Incontinence Scale score, and others exhibit the highest grades of fecal incontinence. Genital relaxation, radiotherapy, and previous pelvic, and/or anal surgery are impeding factors to rehabilitative success.