Oral health conditions in Wilson's disease patients: A clinical diagnostic study.

AIM: The aims of this study were: To evaluate oral health conditions, oral health behaviours and eating habits in Wilson's disease (WD) patients; to assess the possible relationship between oral health status and long-term pharmacological therapies undertaken. METHODS: Sixty WD patients were selected and their data were compared to those of an age-matched control group of 62 subjects. Clinical examinations were carried out and a questionnaire on oral health behaviours and eating habits was submitted to both groups. WD patients were interviewed on long-term pharmacological therapies undertaken. Statistical analysis was performed. RESULTS: The mean DMFT value was 3.75±4.65 in the WD group and 2.81±4.65 in the control group. The difference in the mean DMFT value between the two groups was not statistically significant. Modified Dental Enamel Defects (DDE) Index showed significantly higher values in WD group than in control group. No statistical differences in Visible Plaque Index (VPI), Gingival Bleeding Index (GBI) and malocclusions were observed between groups. In relation to the questionnaire, the differences between groups were statistically significant for: dental visits in a year; brushing teeth after a snack; drinking soft beverages; using mouthwash. For WD patients no statistical correlation between oral health status and long-term pharmacological therapies undertaken was observed. CONCLUSION: WD patients did not show worse oral health conditions than the control group, despite worse oral health behaviours and eating habits. Nerveless, WD patients showed higher presence of dental enamel defects. Finally, for WD group oral health status was not correlated to the long-term pharmacological therapies.

Rice diversity panel provides accurate genomic predictions for complex traits in the progenies of biparental crosses involving members of the panel.

KEY MESSAGE: Rice breeding programs based on pedigree schemes can use a genomic model trained with data from their working collection to predict performances of progenies produced through rapid generation advancement. So far, most potential applications of genomic prediction in plant improvement have been explored using cross validation approaches. This is the first empirical study to evaluate the accuracy of genomic prediction of the performances of progenies in a typical rice breeding program. Using a cross validation approach, we first analyzed the effects of marker selection and statistical methods on the accuracy of prediction of three different heritability traits in a reference population (RP) of 284 inbred accessions. Next, we investigated the size and the degree of relatedness with the progeny population (PP) of sub-sets of the RP that maximize the accuracy of prediction of phenotype across generations, i.e., for 97 F5-F7 lines derived from biparental crosses between 31 accessions of the RP. The extent of linkage disequilibrium was high (r 2 = 0.2 at 0.80 Mb in RP and at 1.1 Mb in PP). Consequently, average marker density above one per 22 kb did not improve the accuracy of predictions in the RP. The accuracy of progeny prediction varied greatly depending on the composition of the training set, the trait, LD and minor allele frequency. The highest accuracy achieved for each trait exceeded 0.50 and was only slightly below the accuracy achieved by cross validation in the RP. Our results thus show that relatively high accuracy (0.41-0.54) can be achieved using only a rather small share of the RP, most related to the PP, as the training set. The practical implications of these results for rice breeding programs are discussed.

Appropriateness of knee MRI prescriptions: clinical, economic and technical issues.

OBJECTIVES: Many studies show that a large portion of medical prescriptions for diagnostic examinations may be not useful for patient's management or unnecessary. Rapid technological advancement has made it possible for magnetic resonance imaging (MRI) to be increasingly used all over the world, particularly for musculoskeletal disorders. The aim of this study was to assess the appropriateness of the knee MRI prescriptions. MATERIALS AND METHODS: A panel of experts found standard clinical practice guidelines in the management of knee disorders. Secondly, the finalized set of guidelines chosen was compared with the data of 400 patients who underwent previous knee MRIs, which were then reported in a specific questionnaire prepared by the authors. The rate of appropriateness of knee MRI prescriptions was then calculated. RESULTS: Almost 21% of prescriptions were totally inappropriate, 18.8% were uncertain, and 60.2% could be considered totally appropriate. The most frequent prescription indication was for meniscal disorders that account for 26.8% of the total indications. CONCLUSIONS: Our results demonstrate that approximately 40% of the total prescriptions were totally inappropriate or uncertain and that most of these were made by general practitioners. In light of these results, the economic impact of inappropriate prescriptions on the Italian healthcare system has to be seriously considered.

Three-dimensional rotational angiography for craniotomy planning and postintervention evaluation of intracranial aneurysms.

PURPOSE: The authors evaluated the usefulness of three-dimensional rotational angiography (3DRA) in surgical planning and postoperative evaluation of cerebral aneurysms. MATERIALS AND METHODS: A total of 111 consecutive aneurysms in 100 patients (32 emergency referrals due to haemorrhage) were evaluated with 3DRA over a period of 3 years. The rotational study was always performed with a single injection of 20 cc of contrast agent in the afferent vessel after diagnostic cerebral angiography in the two orthogonal projections. Three-dimensional reconstructions were obtained for the pre- and postoperative assessment. RESULTS: Three-dimensional RA provides a virtual view of the surgical field with the same orientation required for the surgical approach and, compared with surgical findings, reliably defined location, orientation, morphology and relationship with parent vessels of the aneurysm in all cases. Postoperatively, it allowed better assessment of any residual lesion and of the relationship between surgical clips and parent vessels, compared with standard 2D angiography. CONCLUSIONS: 3DRA is a reliable method for preliminary assessment of cerebral aneurysms undergoing surgery. It provides multiple projections with a preview of the surgical field and study of lesion characteristics, which can help achieve faster and safer surgery. Compared with 2D angiography, the 3D model, with its multiple views, allows better assessment of postoperative outcomes. The method also significantly reduces the number of angiographic projections and therefore radiation and contrast-medium dose to the patient.

Chloroplast Microsatellite Diversity in Phaseolus vulgaris.

Evolutionary studies that are aimed at defining the processes behind the present level and organization of crop genetic diversity represent the fundamental bases for biodiversity conservation and use. A Mesoamerican origin of the common bean Phaseolus vulgaris was recently suggested through analysis of nucleotide polymorphism at the nuclear level. Here, we have used chloroplast microsatellites to investigate the origin of the common bean, on the basis of the specific characteristics of these markers (no recombination, haploid genome, uniparental inheritance), to validate these recent findings. Indeed, comparisons of the results obtained through analysis of nuclear and cytoplasmic DNA should allow the resolution of some of the contrasting information available on the evolutionary processes. The main outcomes of the present study are: (i) confirmation at the chloroplast level of the results obtained through nuclear data, further supporting the Mesoamerican origin of P. vulgaris, with central Mexico representing the cradle of its diversity; (ii) identification of a putative ancestral plastidial genome, which is characteristic of a group of accessions distributed from central Mexico to Peru, but which have not been highlighted beforehand through analyses at the nuclear level. Finally, the present study suggests that when a single species is analyzed, there is the need to take into account the complexity of the relationships between P. vulgaris and its closely related and partially intercrossable species P. coccineus and P. dumosus. Thus, the present study stresses the importance for the investigation of the speciation processes of these taxa through comparisons of both plastidial and nuclear variability. This knowledge will be fundamental not only from an evolutionary point of view, but also to put P. coccineus and P. dumosus germplasm to better use as a source of useful diversity for P. vulgaris breeding.

Development and use of chloroplast microsatellites in Phaseolus spp. and other legumes.

Chloroplast microsatellites (cpSSRs) provide a powerful tool to study the genetic variation and evolution of plants. We have investigated the usefulness of 39 primer pairs tagging cpSSR loci on a set of eight different genera of Leguminosae (Papilionoideae subfamily) and five species belonging to the genus Phaseolus. Thirty-six 'universal' primer pairs were retrieved from the literature, one was re-designed and a further two were designed de novo. The cpSSR loci analysed were highly polymorphic across the individuals examined. Twenty-seven primer pairs were polymorphic in the overall sample, 18 within Phaseolus, and 16 in both P. vulgaris and P. coccineus. Analysis of the plastome sequences of four Leguminosae species (obtained from GenBank) showed that in the loci targeted by universal primer pairs: (i) the originally tagged cpSSRs can be lost; (ii) other cpSSRs can be present; and (iii) polymorphism arises not only from differences in the numbers of cpSSR repeats, but often from other insertion/deletion events. Multilocus linkage disequilibrium analysis suggests that homoplasy is not a major problem in our dataset, and principal component analysis indicates intelligible relationships among the species considered. Our study demonstrates that this set of chloroplast markers provides a useful tool to study the diversity and the evolution of several legumes, and particularly P. vulgaris and P. coccineus.

Integrating self-referral for mammography into organised screening: results from an Italian experience.

OBJECTIVE: To compare self-referred screenees with respondents to invitation for main performance indicators of mammography screening. SETTING: First round of an organised, population-based screening programme in six districts of northern Italy. METHODS: The screening test was a two-view mammography. Eligible women aged 50-69 years were invited. Self-referred attendees were accepted if they were eligible for screening and had not yet been invited or had been invited >6 months before presentation. Age-specific performance indicators were compared with the calculation of their ratio and 95% confidence intervals (CIs). Total ratios were age standardised. In situ carcinomas were excluded. RESULTS: The eligible population was 183 542 women. There were 112 188 respondents to invitation and 20 280 self-referred attendees. Self-referral rate was inversely related to age. Performance indicators were as follows: recall rate, 5.6% for self-referred attendees vs 5.5% for respondents (ratio 1.02, 95% CI 0.96 to 1.08); total aspiration cytology rate, 37.3% vs 28.3% (1.37, 1.24 to 1.51); biopsy rate, 17.0 vs 12.6 x 1000 (1.51, 1.35 to 1.67); total detection rate, 10.7 vs 7.5 x 1000 (1.70, 1.48 to 1.94); detection rate of pT1 carcinoma, 7.0 vs 6.1 x 1000 (1.35, 1.14 to 1.59); detection rate of pT2-4 carcinoma, 3.5 vs 1.2 x 1000 (3.51, 2.75 to 4.43); false-positive rate, 4.5% vs 4.7% (0.93, 0.87 to 0.99); positive predictive value (PPV) of mammography, 19.1% vs 13.5% (1.59, 1.39 to 1.82); PPV of biopsy, 63.7% vs 60.6% (1.13, 0.98 to 1.29); detected:expected ratio, 5.02 vs 3.37 (1.49, 1.28 to 1.74). All differences were more pronounced among or restricted to women aged 50-54 years. CONCLUSIONS: Self-referred screenees were similar to respondents to invitation in main indicators of screening feasibility such as recall rate and PPV of biopsy, while showing important increases in detection rates and detected:expected ratios, especially among women aged 50-54 years.

Performance indicators of organized cervical screening in Romagna (Italy).

The availability of published data from organized cervical screening programmes in southern Europe is scant. In the Italian area of Romagna, a first round of organized screening (based on a 3-yearly Pap smear for women aged 25-64 years) was initiated between December 1995 and January 1997 and was completed in an average of 42 months (range 36-48 months). The target population included 305 478 women. Of these, 253 949 were eligible and received a personal letter of invitation. Age-specific screening performance indicators were calculated according to standard methods. The response rate within 6 months of invitation was 49.1% (n=124 621). The total participation rate including women who presented later was 61.7% (n=156 735). The recall rate was 35.2 per 1000 of participants (n=5514). Positive cytology results were distributed as follows: atypical squamous cells of un-determined significance/atypical glandular cells of undetermined significance (ASCUS/AGUS) 40.1%, low-grade squamous intraepithelial neoplasia (LGSIL) 48.6%, high-grade squamous intraepithelial neoplasia (HGSIL) 10.7% and carcinoma 0.7%. Compliance to colposcopy follow-up was 93.4% (n=5149). The biopsy rate was 52.4% (n=2696) of patients undergoing colposcopy. The detection rate was 4.5 per 1000 of participants (n=707) for CIN2-3 and 0.5 (n=75) for invasive carcinoma. The proportion of microinvasive carcinomas was 36.0% (n=27). The positive predictive value for CIN2-3/carcinoma was 5.8% for the cytology reports of ASCUS/AGUS, 7.6% for those of LGSIL, 76.5% for those of HGSIL, and 100.0% for those of carcinoma (80.4% for combined HGSIL/carcinoma). The ratio of observed to expected (or prevalent to incident) cases of invasive carcinoma was 2.35 (95% confidence interval (CI) 1.85-2.95). In conclusion, most early results of the programme were compatible with an acceptable performance.

Acute disseminated intravascular coagulation syndrome in cancer patients.

Hemostatic abnormalities are rather frequent in cancer patients either in hematological or in solid tumors. Acute disseminated intravascular coagulation (DIC) is a rare coagulopathy in cancer patients, but when it develops it becomes rapidly fatal. Between June 1988 and December 1992 we observed 8 cases of acute DIC occurring in gastric cancer (4 patients), breast cancer (3 patients) and high-grade non-Hodgkin lymphoma (1 patient). In 3 patients affected by gastric carcinoma, acute DIC was the first manifestation of the presence of the tumor, while in the other patients DIC occurred during the course of the disease. All the patients were treated with heparin, fresh frozen plasma and platelet support, but only in 1 patient was a short duration improvement of clinical conditions and coagulation tests recorded. Acute DIC can be the first manifestation of gastric tumors and the presence of the hemorrhagic syndrome associated with thrombocytopenia, hypofibrinogenemia and fibrin/fibrinogen degradation products should initiate a search for gastric carcinoma.

Biologic characterization of pleural metastases from lung adenocarcinoma: description of the new DV90 cell line.

AIMS AND BACKGROUND: The characterization of pleural metastases from lung adenocarcinoma is often limited to single biologic features. METHODS: The present paper describes the cellular kinetic parameters, as well as immunocytochemical, ultrastructural and genetic characteristics of the new DV90 cell line, established from the pleural effusion of a stage IV lung adenocarcinoma. RESULTS: The cell line has a diploid DNA content, a doubling time of 24 h and 7% cloning efficiency, it is tumorigenic in nude mice. Ultrastructural investigation revealed the typical features of lung adenocarcinoma; the diagnosis was confirmed by its immunohistochemical reactivity with a panel of monoclonal antibodies specifically capable of identifying adenocarcinoma cells. Genetic analysis revealed a 46 X, -Y, +8, der (6)t(6?)(q27;?) karyotype and hyperexpression of the protein codified by genes Her2/Neu and p53. CONCLUSION: The importance of multidisciplinary biologic characterization in identifying the origin and biological behavior of pleural metastases deriving from lung adenocarcinoma is discussed.

Etoposide, doxorubicin and cisplatin (EAP regimen) in advanced gastric cancer.

The treatment of advanced gastric cancer is unsatisfactory. The response rates for single chemotherapy agents: 5-fluorouracil, mitomycin-c, methotrexate, cisplatin, adriamycin, nitrosoureas and etoposide are approximately 10-25% and response duration ranges from 3 to 6 months. Complete responses with single agents are rare. Combination chemotherapy produces higher response rates, but these responses are short. Recently the combination of etoposide, adriamycin and cisplatin (EAP regimen) has been reported to produce results superior to what have been previously reported with other regimens. Twenty-four consecutive patients with locally advanced or metastatic gastric cancer (stage III-IV) were treated between June 1990 and December 1992 with the EAP regimen at our Department. Twenty-two patients were evaluable for response and toxicity. Objective responses were observed in 8 of 22 patients (response rate 36%; 95% confidence interval 17% to 59%). No clinical complete response was found. The median duration of the response was 7 months (range 2 to 22). Myelosuppression represented the primary toxicity associated with the EAP regimen. Grade 4 leukopenia was observed in 4 patients (18%). Grade 3-4 thrombocytopenia was registered in two patients, and grade 3 anemia was detected in 4 patients (18%). The median survival for all patients was 8 months and 12 months for the 8 responding patients. The EAP regimen seems to be an effective chemotherapeutic regimen, but cannot be considered the standard therapy for patients with locally advanced or metastatic gastric cancer, because of the high incidence of moderate to severe myelotoxicity and a response rate and duration of survival similar, but not superior, to those obtained using a less toxic schedule.

Patterns of Pap smear use in the Rimini area: an analysis of women's attitudes to the test.

The use of the Pap test is a method of the prevention of cervical cancer in our local division of the Sanitary Unit and has been studied with the help of a questionnaire which was completed by women who had adopted this test. The socioeconomic characteristics, level of education, occupation and general attitudes regarding the Pap test as well as how the women had acquired knowledge of the test, have all been examined. From an analysis of the answers, we have been able to trace a precise social, economic and cultural profile of the type of women who take advantage of this test. Principally, we are dealing with women aged 40-49 years, often with children, with a medium to low level of education, who are mainly housewives and white-collar workers. Very few elderly women present themselves for the Pap test. We have noticed that there is a direct decrease in the use of preventive methods, proportional to the increase in age. These results demonstrate that an erratic use of this preventive method, in the absence of an organized screening programme, seems only to involve women who are among those at less risk from cervical cancer.

Evaluation of NK and LAK cell activities in neoplastic patients during treatment with morphine.

The cytotoxic activity of Natural Killer (NK) and Lymphokine Activated Killer (LAK) cells in neoplastic patients with or without antalgic treatment was studied. NK cell activity was found reduced in untreated neoplastic patients when compared to healthy subjects. The atalgic treatment with morphine (orally or intrathecally administered) was able to significantly reduce the mean values of NK cell activity found in cancer patients. In three patients the cytotoxicity of NK cells significantly decreased during transfer from oral to intrathecal administration of morphine. In contrast to the NK cell function, the development of LAK cell activity significantly increased in neoplastic patients when compared to healthy controls. Further increments were obtained during treatment with morphine. The oral treatment with morphine was able to determine a higher induction of LAK cells than the intrathecal administration of the drug. Besides providing new knowledge on the effect of morphine on immune system our findings suggest that, in order to include neoplastic patients in clinical trials of adoptive immunotherapy with LAK cells and interleukin-2 (IL-2), the antalgic therapy with oral administration of morphine may represent a better solution than the intrathecal administration of the drug.