[State of emergency plans for massive influx of injured (PEMAF) in Italian hospitals. Pilot study]. / Stato dell'arte dei Piani di Emergenza per il Massiccio Afflusso di Feriti (PEMAF) negli ospedali italiani. Studio pilota.

Aim of this study is to assess the level of implementation of plans for the massive influx of injured (PEMAF) in Italian hospitals. An anonymous questionnaire was administered to a sample of 100 hospitals selected through the network of the Italian Society of Emergency Medicine (SIMEU). Each answer of the questionnaire was assigned a score, then reported on a scale of compliance (maximum 65 points, threshold 35 points). The average scores were analyzed by hospital's venue, level of activity and previous experience of managing a real emergency. Student's t-test was used to compare means. Thirty-two hospitals sent the questionnaire, representing 33% of those selected. Five were excluded for incomplete data. The data analyzed refers to 27 hospitals of various levels of complexity, from all around the country: 55.6% from the Northern Section, 22.2% from the Centre and 22.2% from the Southern section and the Islands; and only 55.6% are above the minimum threshold of compliance. The weakest PEMAF's area is the one related to the specific training of health workers, therefore the percentage of hospitals complying the requirements in this field is down to 37%. Ten hospitals (37%) had managed a real maxi-emergence in the past: belonging to such group of hospitals is associated with an average level of compliance significantly higher than the others (p < 0.005). Due to a limited percentage of responders, the study involved so far a too small amount of hospitals; happily, they were evenly distributed in the different sections of the Country; therefore it will be appropriate to obtain a larger compliance before reaching clear-cut conclusions, but it already appears that the most critical point is the lack of specific education to maxi-emergencies in the hospital personnel.

Relationship between the c-myb locus and the 6q-chromosomal aberration in leukemias and lymphomas.

Deletions of the long arm of chromosome 6 (6q-) are frequently found in hematopoietic neoplasms, including acute lymphoblastic leukemias, non-Hodgkin lymphomas and (less frequently) myeloid leukemias. The c-myb proto-oncogene has been mapped to region 6q21-24, which suggests that it could be involved in the 6q- aberrations. By means of in situ chromosomal hybridization on cells from six hematopoietic malignancies, it was demonstrated that the c-myb locus is not deleted, but is retained on band q22, which is consistently bordered by the chromosomal breakpoints in both interstitial and terminal 6q- deletions. The deletion breakpoints were located at some distance from the myb locus since no rearrangement of c-myb sequences was found. In one case, however, amplification of the entire c-myb locus was detectable. Furthermore, in all cases tested that carry 6q- deletions, myb messenger RNA levels were significantly higher than in normal cells or in malignant cells matched for lineage and stage of differentiation but lacking the 6q- marker. These results indicate that 6q- deletions are accompanied by structural and functional alterations of the c-myb locus and that these alterations may be involved in the pathogenesis of leukemias and lymphomas.

Highly efficient elimination of Philadelphia leukemic cells by exposure to bcr/abl antisense oligodeoxynucleotides combined with mafosfamide.

Synthetic oligodeoxynucleotides complementary to the break-point junction of bcr-abl transcripts selectively inhibit the proliferation of Philadelphia-positive leukemic cells, but residual leukemic cells persist in antisense oligodeoxynucleotides-treated cultures. Cyclophosphamide derivatives such as mafosfamide and 4-hydroperoxycyclophosphamide are used at high doses for purging of Philadelphia leukemic cells from marrows but such treatment can be associated with delayed engraftment and prolonged cytopenias. To develop a more effective procedure that might optimize the killing of leukemia cells and the sparing of normal hematopoietic progenitor cells, a 1:1 mixture of Philadelphia leukemic cells and normal bone marrow cells was exposed to a combination of a low dose of mafosfamide and bcr-abl antisense oligodeoxynucleotides and assayed for growth ability in clonogenic assays and in immunodeficient mice. Bcr-abl transcripts were not detected in residual colonies, and cytogenetic analysis of individual colonies revealed a normal karyotype. Normal but not leukemic hematopoietic colonies of human origin were also detected in marrows of immunodeficient mice 1 mo after injection of the treated cells. Our results indicate that a combination of a conventional chemotherapeutic agent and a tumor-specific antisense oligodeoxynucleotide is highly effective in killing leukemic cells and in sparing a much higher number of normal progenitor cells as compared with high-dose mafosfamide treatment. This offers the prospect of a novel and more selective ex vivo treatment of chronic myelogenous leukemia.

Quality in emergency departments: a study on 3,285,440 admissions.

INTRODUCTION: A multi-centre study has been conducted, during 2005, by means of a questionnaire posted on the Italian Society of Emergency Medicine (SIMEU) web page. Our intention was to carry out an organisational and functional analysis of Italian Emergency Departments (ED) in order to pick out some macro-indicators of the activities performed. Participation was good, in that 69 ED (3,285,440 admissions to emergency services) responded to the questionnaire. METHODS: The study was based on 18 questions: 3 regarding the personnel of the ED, 2 regarding organisational and functional aspects, 5 on the activity of the ED, 7 on triage and 1 on the assessment of the quality perceived by the users of the ED. RESULTS AND CONCLUSION: The replies revealed that 91.30% of the ED were equipped with data-processing software, which, in 96.83% of cases, tracked the entire itinerary of the patient. About 48,000 patients/year used the ED: 76.72% were discharged and 18.31% were hospitalised. Observation Units were active in 81.16% of the ED examined. Triage programmes were in place in 92.75% of ED: in 75.81% of these, triage was performed throughout the entire itinerary of the patient; in 16.13% it was performed only symptom-based, and in 8.06% only on-call. Of the patients arriving at the ED, 24.19% were assigned a non-urgent triage code, 60.01% a urgent code, 14.30% a emergent code and 1.49% a life-threatening code. Waiting times were: 52.39 min for non-urgent patients, 40.26 min for urgent, 12.08 for emergent, and 1.19 for life-threatening patients.

Chromosome locations of the MYB related genes, AMYB and BMYB.

The MYB related loci, AMYB and BMYB, were localized to specific human chromosome regions by Southern blot analysis of their segregation patterns in a panel of rodent-human hybrid DNAs using radiolabeled AMYB and BMYB probes. The AMYB locus was present in hybrids retaining the chromosome region 8cen----8q22 and was absent in hybrids which had lost this chromosome region. The presence of the BMYB locus in rodent-human hybrids correlated with, and only with, chromosome region Xq13. Chromosomal in situ hybridization refined the localization of AMYB to region 8q22-23 and confirmed the localization of BMYB to region Xq13. Chromosome region 8q22 is involved in recurrent translocations in malignant lymphoma and in acute myeloid leukemia (AML-M2); therefore AMYB is a candidate for involvement in such translocations. A region on Xq13 is also involved in chromosomal abnormalities in acute myeloid leukemia and myelodysplasias.

Evolutionary conservation of the EPS8 gene and its mapping to human chromosome 12q23-q24.

We have previously isolated the coding sequence for a novel substrate for tyrosine kinases, eps8, from NIH3T3 fibroblasts. Eps8 was phosphorylated in vivo by several receptor tyrosine kinases (RTKs) and, upon overexpression, was able to enhance EGFR-mediated mitogenic signaling in NIH3T3 cells. To gain understanding of eps8 function as well as its role in normal and neoplastic proliferation, we cloned the human eps8 coding sequence and studied expression of the human RNA and protein, evolutionary conservation, and chromosomal location. In addition to a previously identified SH3 domain, the predicted amino acid sequence of human eps8 revealed a non-random distribution of prolines, clustered in a way to suggest SH3-binding sites and a putative PH domain. Eps8 was expressed in all epithelial and fibroblastic lines examined and in some, but not all, hematopoietic cells. An essential function of eps8 in cell growth regulation was underscored by its conservation during evolution, where eps8-related sequences were detected as early as in Saccharomyces cerevisiae. Finally, the human EPS8 locus was mapped to chromosome 12q23-q24.

Establishment from an adult leukemic patient of two novel precursor B cell lines with different growth modality.

Two novel cell lines, PC-53 and PC-53A were established from an adult ALL patient, at third relapse and in the terminal accelerated phase respectively. Both lines displayed the phenotype of B-cell precursors (CD19+, CD38+, CD20-, cytoplasmic-mu-, immunoglobulin gene rearrangement), identical to the freshly isolated blast cells. Chromosomal analysis showed a prominent 45-XX karyotype, including three marker chromosomes. No chromosome 8 abnormalities were detectable, consistently with a non-rearranged c-myc locus. Both cell lines were EBV-negative. Growth stimulation by autologous supernatant was observed for PC-53 cells during the first 4 months in culture, whereas it was much less evident for PC-53A cells. Thus, PC-53 and PC-53A cells represent a useful tool to investigate the mechanisms involved in the clonal expansion of B-cell precursors.

Phenotypic and phoniatric findings in mosaic cri du chat syndrome.

We report on mosaic 46,XY/46,XY,del(5)(p15) cri du chat syndrome. The clinical findings are compared with those compiled from a literature survey. A phoniatric evaluation was performed and compared with that of a cri du chat patient without mosaicism previously observed by the authors.

Effects of caloric restriction and exercise on B-endorphin, ACTH and cortisol circulating levels in obesity.

B-Endorphin (B-Ep), ACTH and cortisol circulating levels, before and after a two months therapy with a hypocaloric diet and an increase in physical exercise, were measured by RIA in 17 obese female subjects. After therapy, the body weight excess fell from 56.6 +/- 22.2% to 38.6 +/- 22.1% (p less than 0.01). Plasma levels of B-Ep decreased from 18.3 +/- 12.5 fmol/ml to 6.4 +/- 3.5 fmol/ml (p less than 0.01); those of ACTH from 46.8 +/- 22.8 pg/ml to 31.2 +/- 11.6 pg/ml (p less than 0.01); and those of cortisol from 15.9 +/- 4.6 micrograms% to 10.3 +/- 2.5 micrograms% (p less than 0.01). The reduction of the elevated plasma B-Ep levels found in obese subjects is related principally to the diet therapy. Thus, as shown in experimental animals, excessive feeding results in an increased hypothalamic-pituitary secretion of B-Ep.

Hyperendorphinemia in obesity is not related to the affective state.

In seventy-two patients affected by hyperphagic obesity and forty age-matched, normal weight volunteers we performed a psychological assessment, through various mental tests, and evaluated the beta-endorphin (B-Ep), ACTH and cortisol circulating levels, in basal condition and following an overnight short dexamethasone suppression test (DST). The hormones were measured by radioimmunoassay either directly in the serum (cortisol) and the plasma (ACTH), or after affinity gel column chromatography (B-Ep). In obese subjects B-Ep levels in basal conditions were four times greater than in normal weight controls and showed significantly less reduction after DST. ACTH and cortisol levels, in contrast, were in the normal range and were suppressed following dexamethasone as was also true in the control group. Psychological evaluation on M.M.P.I. (Minnesota Multiphasic Personality Inventory) revealed a trend toward hypochondria, depression, hysterias, psychoasthenia and schizophrenia. However, no significant correlation has been found between M.M.P.I. clinical scale scores and circulating levels of B-Ep and cortisol either in basal conditions or after DST. In conclusion, these data do not support the hypothesis that abnormalities of the hypothalamus-pituitary-adrenal axis in hyperphagic obesity are related to affective disorders.

Hyperendorphinemia in obesity and relationships to affective state.

Eight obese patients (exceeding ideal body weight by 50% or more) with no endocrinological or metabolic disorders and 8 healthy, age-matched, normal-weight volunteers were submitted to an overnight short dexamethasone (DXM) suppression test and to a psychological assessment through various psychometric scales. Plasma B-Endorphin (B-EP), B-Lipotropin (B-LPH), ACTH and cortisol concentrations were evaluated in basal conditions, as well as 9 and 17 hours after late night administration of 1 mg DXM in both groups. All hormones were measured by radioimmunoassay, either directly in the plasma (ACTH and cortisol) or after silicic acid extraction and Sephadex G-75 column chromatography (B-LPH and B-EP). In obese patients, plasma B-EP levels in basal conditions were three times higher than in normal weight controls and remained unaltered by DXM suppression. ACTH and B-LPH, in contrast, were within the normal range and were significantly reduced by DXM. In 3 of the 8 patients, plasma cortisol concentrations at 17 hours post-DXM were greater than 50 ng/ml indicating an early escape from the suppression. Psychometric evaluations revealed a prevalence of depressive personality in obese patients. These data indicate an hypersecretion of B-EP in obese patients, which is only partially dependent on hypothalamic control.

Genetic alteration in gastrointestinal cancer. A molecular and cytogenetic study.

We examined 16 cases of gastrointestinal cancer, of which 11 were from the colon, 1 from the rectum, and 4 of gastric origin, cytogenetically for expression and for loss of heterozygosity (LOH) on chromosome 18 using Deleted Colon Cancer (DCC) gene. LOH on chromosome 18 with DCC probe was detected in 7 out of 11 cases of colon, in 4 out of 4 cases of gastric and in 1 case of rectum cancer. In all gastrointestinal tumors the expression of DCC gene was absent, while it was present in normal tissue. We also found rearrangements of chromosomes 18 (10 cases) and 17 (9 cases), leading respectively to deletions of long and short arms. Other additional abnormalities were observed involving chromosomes 5, 6, 15 and 19. The data recorded in our series differ from other authors' data in three respects: a high incidence of pseudodiploid chromosome number, rearrangements of chromosome 19 and 15, and involvement of DCC gene in the development of gastric cancer, as well as in colorectal cancer as previously reported.

Multiple genetic lesions in solid tumors: relevance to diagnosis, prognosis, and molecular mechanisms.

In recent years, significant progress has been made in identifying characteristic chromosomal and molecular rearrangements associated with several solid tumors. Most solid tumors studied have been found to be characterized by recurrent chromosomal abnormalities that are specific to histologic types. We have studied primary specimens of malignant melanoma, gastrointestinal cancer, renal carcinoma, lung and ovarian cancer, by cytogenetic and molecular means, and we discuss the genetic alterations found. Brief descriptions of the potential clinical utility, and biological relevance changes in these disorders are also discussed.

Cytogenetic, molecular and phenotypic characterization of the newly established renal carcinoma cell line KJ29. Evidence of translocations for chromosomes 1 and 3.

The established non papillary human renal carcinoma cell line (RCC) KJ29 was submitted to a multiparametric characterization to evaluate its potential use for in vitro and in vivo studies. The cell line grows in vitro as monolayer as well as cell suspension. Cytogenetic analysis has shown a modal chromosome number of 50 with some marker chromosomes, including rearrangements of chromosomes 1 and 3. The antigenic phenotype is characterized by co-expression of cytokeratin and vimentin, as well as expression of urothelium differentiation antigens, low levels of class II MHC antigens and no class I antigens. A differential expression of the VLA-3 integrin heterodimer has been detected between the adherent and non adherent cell population. The cell line which is highly tumorigenic in athymic mice displays expression of erb B-2 and c-met oncogenes and high expression of cell-cycle related and Ha-ras 1 genes.

[The role of the endogenous opioid system in the pathogenesis of polycystic ovary syndrome: the altered neuroendocrine regulation of GnRH-LH is corrected after clomiphene therapy]. / Il ruolo del sistema oppioide endogeno nella patogenesi della sindrome dell'ovaio policistico: l'alterata regolazione neuroendocrina di GnRH-LH si corregge dopo terapia con clomifene.

To investigate whether inappropriate LH secretion in Polycystic Ovary Syndrome (PCO) was related to a reduction of inhibitory opioid control on the GnRH-LH system, 23 women affected by PCO (12 obese, BMI: 37.1 +/- 3.9 and 11 non obese, BMI: 21.5 + 2.4) and 19 fertile women (10 obese, BMI: 38.8 + 1.8 and 9 non obese, BMI: 20.1 + 1.5) were studied. Plasma levels of Beta-Endorphin (B-Ep) in basal condition and LH and FSH serum levels following acute administration of naloxone (0.1 mg/kg e.v.) were evaluated in the PCO and control groups. Moreover, in order to investigate whether the neuroendocrine abnormalities in PCO are a primary hypothalamic defect or secondary to an inappropriate feedback of gonadal steroids, the LH response following Naloxone administration was evaluated again after two months of clomiphene therapy (50 mg p.os ones a day for 5 days). The women affected by PCO had increased LH/FSH ratio, testosterone levels (P < 0.001, P < 0.01) and significantly decreased T/E2 ratio, SHBG levels compared to the normal women (P < 0.01, P < 0.001). B-Ep plasma levels in PCOs OB and PCOs nOB (6.13 + 1.2 Pmol/L, 4.8 + 0.4 Pmol/L) were similar to those observed in obese and non obese control women (7.2 + 2.5 Pmol/L, 4.2 + 1.3 Pmol/L), respectively. In the PCO and control groups naloxone induced a significant increase of FSH and LH levels. Thus the area under the curve of LH and FSH was significant higher after naloxone, than following saline infusion both in PCO (P < 0.01, P < 0.05) and controls (P < 0.001, P < 0.001). However, in PCO the post naloxone FSH increase was similar to that found in fertile women, while the LH increase post naloxone was lower than that observed in controls (50 + 32.4% vs 101.6 + 36.7%; P < 0.01). Particularly in PCO with LH/FSH ratio equal or higher than 3, no significant variation of LH levels was found after naloxone. Moreover the LH increase post naloxone was similar in PCO OB (46 + 19.8%) and in PCO nOB (49.9 + 13.1%), correlated negatively with LH basal levels (P < 0.02), LH/FSH (P < 0.005), E1/E2 (P < 0.005) and was independent of T/E2, BMI and duration of the disease. Following clomiphene treatment, the LH response after naloxone was significantly higher than that observed before treatment (from 9.4 + 4.2 mUI/ml to 16.5 + 3.9 mUI/ml, P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

[Insulin resistance in obese and non-obese patients with polycystic ovary syndrome. Possible role in the pathogenesis of the disease]. / L'insulinoresistenza nelle pazienti con sindrome dell'ovaio policistico (PCOs) obese e non obese. Possibile ruolo nella patogenesi della malattia.

The pathogenesis of Polycystic Ovary Syndrome (PCOs) is not well known till now. Previous reports indicated an hyperinsulinemia and insulin resistance in obese and non obese PCOs. However the role of hyperinsulinemia in PCOs pathogenesis is not completely understood. In this study we evaluated the glycemic and insulinemic response to OGTT in 21 women suffering from PCOs (13 obese and 8 normal weight) and in 16 fertile women as a control group (8 obese and 8 normal weight). All tested women showed normal glycemia before and after OGTT. Basal insulinemia in PCOs was similar to that observed in control group. Mean insulinemic levels following OGTT in obese control group and in PCOs were significantly higher than those observed in normal women (p < 0.05). Insulin area under curve (AUC) following OGTT in non obese PCOs was significantly higher than that observed in non obese control women (72442.13 +/- 18668.9 mUI/ml/h versus 53710.8 +/- 83365 mUI/ml/h; p = 0.02), but lower than that observed in obese PCOs (192793 +/- 49421; p < 0.001). In obese PCOs insulin AUC was significantly higher than that observed in obese control group (138836.8 +/- 28800.9; p = 0.012). Insulin AUC was positively related to BMI in control group (p < 0.001) but not in PCOs. In PCOs group insulin AUC was positively related to hirsutism degree (p = 0.032) and circulatory levels of T (p = 0.044), LH (p < 0.001) and E1 (p = 0.026).(ABSTRACT TRUNCATED AT 250 WORDS)

Cushing's disease and prolonged spontaneous remission. Clinical case.

We describe a case of prolonged spontaneous remission of Cushing's disease lasting since 1986 and documented both clinically and biochemically. This case confirms previous sporadic observations based mainly on clinical findings and indicates that spontaneous remission of Cushing's disease, although rare, may exist. The Authors outline that in some cases of Cushing's disease it could be convenient to adopt a conservative policy with frequent outpatient reviews in order to observe the natural course of the disease, particularly when the clinical findings are mild and the original lesion is not recognized with the available technology.

11p13 deletion and reduced RBC catalase in a patient with aniridia, glaucoma and bilateral Wilms' tumor.

A rare case of a one-year-old child with Wilms' tumor, aniridia and glaucoma is described, in whom bone marrow chromosome analysis showed the presence of an interstitial microdeletion on the short arm of chromosome 11, presumably involving the p13 band. Research of the enzyme activity of RBC catalase showed a 40% reduction. This finding is compatible with the loss of the 11p13 band which contains the gene coding this enzyme. 11p13 deletion in Wilms' tumor and 13q interstitial deletion in retinoblastoma provide a rare case of prezygotic chromosome abnormality, which may be considered to have a determinant role in the tumor etiopathogenesis.

C-MYB activation and the pathogenesis of ovarian cancer.

We have detected the expression of the MYB proto-oncogene in ovarian cancer. This oncogene was thought to be expressed in a tissue-specific manner in cells of hematopoietic lineage. Total RNA from three established cell lines and four human primary ovary cancers was examined by Northern and Southern blot, RNAse protection, in situ hybridization and cytogenetic analysis. A 3.8 kb RNA transcript was present in one human primary cell culture which is the same size as that found in the immature myeloid HL60 cell line. No expression was detected in normal ovary tissue. Southern blot analysis of DNA from five ovarian tumors indicated that this gene is not rearranged. Chromosomal analysis of three samples show many abnormalities in two cases and a normal karyotype in another one. The presence of MYB transcript in ovarian cancer suggests that MYB may play a specific role in the pathogenesis of this disease.

[Plasma levels of beta-endorphin and ACTH and serum levels of cortisol in different stages of arterial hypertension before and after clonidine therapy]. / I livelli plasmatici di beta-endorfina e di ACTH ed i livelli sierici di cortisolo in diversi stadi della ipertensione arteriosa, prima e dopo terapia con clonidina.

Beta-endorphin (B-Ep), ACTH plasma levels and cortisol serum levels have been evaluated by RIA, in 27 patients suffering from essential blood hypertension and in 20 healthy control subjects. The study was repeated in the hypertensive group after clonidine treatment for 15 days. B-Ep plasma levels were normal in the I stage of hypertension and did not show any significant difference in relation to the severity and duration of hypertension. ACTH and cortisol circulating levels in the hypertensive patients were in normal range. The increase of B-Ep plasma levels in the II and III stage of the hypertension is not modified by the reduction of blood pressure values; therefore it is unlikely linked to the elevated blood pressure, but probably to the vascular complications. Moreover, the results obtained after clonidine treatment seem to exclude that the hypotensive action of the drug is mediated by increment of B-Ep circulating levels.