[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.

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.

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.

Beta-endorphins ACTH and cortisol in CSF and plasma of HIV infected patients.

Interactions between HPA (Hypothalamic-pituitary-axis) and immune system seem to involve the EPO (endogenous opioid peptides) system, as shown by some recent findings. Possible relationships between beta-endorphin (beta-End) synthesis and severity rate of immunodeficiency have been studied in 48 HIV Ab positive patients, at different stages of infection. A statistically significant decrease in the beta-End synthesis was observed in these patients, as compared to a control group of 19 healthy subjects, but this decrease was not related to the CD4+T lymphocytes number. Plasmatic levels modifications of HPA-related peptides were not observed in the IVC1 CDC group.

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.

Chromosome locations of human EMX and OTX genes.

We have determined the chromosomal localization of four human homeobox-containing genes, EMX1, EMX2, OTX1, and OTX2, related to Drosophila genes expressed in the developing head of the fly. Murine homologs of these genes are expressed in specific nested domains in the developing rostral brain of midgestation embryos. DNAs from a panel of 19 rodent-human hybrids, each carrying one or a few human chromosomes such that most human chromosome regions were represented, were tested for the presence of the four gene loci by filter hybridization to radiolabeled probes. Regional chromosomal localization was determined by similarly testing DNAs from hybrid mapping panels for each of the candidate chromosomes. Finally, fluorescence in situ hybridization of cosmid clones for these loci refined the locations, two of which were in the vicinity of previously mapped orphan homeobox genes and two of which were near each other. OTX2, the earliest and most widely expressed gene, maps to chromosome region 14q21-q22; the OTX1 locus maps to 2p13; EMX2 maps to 10q26.1; and EMX1, the most narrowly and lately expressed, maps to 2p14-p13. Thus, these homeobox-containing genes involved in brain development are not linked to any of the four HOX clusters on 7p15-p14, 17q21-q22, 12q12-q13, and 2q31. However, the OTX1 and EMX1 loci may be closely linked on or near 2p13, prompting speculation that a clustered gene structure could have functional significance, as is presumably the case for the HOX clusters.

[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)

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.

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.

[Syndrome X and surgical stress. A clinical case]. / Sindrome X e stress chirurgico. Caso clinico.

The syndrome X is a clinical disease characterised by anginous pain with the absence of significant and angiographically visible stenosis of the coronary tree. D. P. M., a 61-year-old woman suffering from biliary lithiasis, underwent cholecystectomy. During the immediate postoperative period, the patient showed difficulty in regaining consciousness and there were electrocardiographic signs of extensive anterior ischemia; prior to the operation only a 1st degree atrio-ventricular block and a positive history of occasional precordial pain had been reported. On the 2nd postoperative day the patient complained of violent retrosternal pain irradiated to the left shoulder. Given that the signs of ischemia had regressed, various instrumental tests were performed: echocardiogram, cycloergometric test, dipyridamole test, cold pressure test, Holter's dynamic ECG, all of which were within the normal; moreover, selective coronarography did not reveal significant stenosis of the coronary tree. The patient was therefore diagnosed as suffering from syndrome X. In the light of the present case, the authors conclusion may be summarised as follows: the diagnosis of syndrome X, which is by definition not easy, may sometimes become critical, as in the present case, since rapid intervention would have enabled prophylactic therapy to be performed to combat surgical stress.

Evidence of chromosomal fragile sites in schizophrenic patients.

Chromosomal fragility and other chromosomal abnormalities were frequently observed in subjects with neuropsychiatric disorders, such as fragile X syndrome, autism or schizophrenia, but only for the first one the fragility is accepted to be associated to a specific pathology, so that it is used as a diagnostic marker. In this study the authors analyzed 50 schizophrenic males, searching for the rare fragile sites or other aberrations with the method suitable for fra(X) detection. Chromosomes from schizophrenic patients resulted more fragile than those from normal controls, especially chromosome 9. The authors discuss the implications of a possible association of these data with the aetiopathogenesis of schizophrenic syndrome.

[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)

Expression of selected human HOX-2 genes in B/T acute lymphoid leukemia and interleukin-2/interleukin-1 beta-stimulated natural killer lymphocytes.

Although the key role of human homeobox (HOX) genes in development is well established, their function in adult cells is still under scrutiny. We have analyzed, in normal adult blood cell subpopulations, acute lymphoid leukemia (ALL) cells lines, and primary blasts, the RNA expression of all HOX-2 cluster genes (5'-2.5, 2.4, 2.3, 2.2, 2.1, 2.6, 2.7, 2.8, 2.9, 3') and nine genes in the HOX-1, -3, and -4 cluster by Northern blotting, RNAse protection, and/or reverse transcriptase polymerase chain reaction (RT-PCR). The analyzed HOX-1, -3, and -4 genes were never expressed in all tested cell populations. Natural killer (NK) cells activated in interleukin-2 (IL-2)/IL-1 beta-treated cultures exhibit a gradually increasing, abundant expression of three HOX-2 genes (2.2, 2.6, 2.8), while three other genes (2.3, 2.1, 2.7) are expressed at a lower level at late culture times. However, no HOX-2 gene is expressed in quiescent lymphocytes (NK, B and T [T-cell receptor (TCR) alpha/beta, gamma/delta lymphocytes, thymocytes] cells), granulocytes, and monocytes. In B- and T-ALL cell lines, HOX-2 genes are expressed according to different patterns: (1) widespread transcription (seven of nine genes, including 2.3 and 2.6) in the Peer line bearing the TCR gamma/delta; (2) expression of 2.5, 2.2, and 2.6 in the SEZ 627 line, which derives from an HTLV-1+ T-helper leukemia; (3) transcription of 2.3 and 2.6 in both the T-ALL CEM line and four B-ALL lines (interestingly, CALLA- B-ALL lines are constantly 2.3/2.6 RNA+); (4) no HOX-2 gene expression was detected in one T- and two B-ALL lines. Primary blasts from five T- and five pre-B-ALL showed selective expression of one or more HOX-2 genes, namely 2.5, 2.2, 2.6, and 2.7. Our data are compatible with the hypothesis that selected HOX-2 genes play a role in the IL-2/IL-1 beta-induced activation and/or proliferation of normal NK lymphocytes and possibly in the oncogenetic process of some T- and B-ALL.

Endocrine abortion in assisted reproduction technologies (ART).

Luteal function, endometrial receptivity, endometrial prolactin and glycoprotein secretions, blastocyst-secreted immunomodulant factors and embryo quality are nowadays considered the main determinants involved in embryo implantation control. The endometrial factors are progesterone-dependent. Out of 128 cycles of ART (AIH-IU, GIFT, IVF-ET), performed in 67 women at the Dept. of Obstetrics and Gynaecology of Parma during the period 1986-1991, 31 conceptions were obtained (pregnancy rate: 24.21%), 7 of which miscarried (abortion rate: 22.58%). According to these data, ART high abortion rate is possibly connected with poor luteo-endometrial function and poor embryo quality. Controlled ovarian hyperstimulation is thought to inhibit embryo implantation after IVF-ET by decreasing endometrial receptivity. Such a situation can be treated either by exogenous progesterone administration or by tubal techniques (GIFT, TET) performed in non-tubal infertility. Both strategies showed to better endometrial receptivity. A delayed intrauterine embryo transfer at blastocyst stage, when cocultures allow to, is supposed to raise the implantation rate in tubal infertility by enhancing embryo selection and endometrial receptivity. This paper also reports preliminarily on the predictive value of beta-HGC and estradiol levels, as well as of endometrial thickness, on early pregnancy outcome.

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.

Adrenocorticotropic hormone, beta-endorphin, cortisol, growth hormone and prolactin circulating levels in nineteen athletes before and after half-marathon and marathon.

Circulatory levels of ACTH, beta-endorphin (beta-Ep), prolactin (PRL), growth hormone (GH) and cortisol were evaluated in 19 volunteers athletes 48 h, 1 h before and soon after an international marathon (Romaratona 1988) and a national half-marathon. ACTH, beta-Ep and cortisol levels 48 h and 1 h before the half-marathon were similar, whereas 1 h before the marathon they were significantly elevated (p less than 0.01). Presumably the stress produced by the expectancy of the race induce a significant increase of the hormones of the hypothalamus-pituitary-adrenal axis in the very competitive marathon (Romaratona 1988). Moreover a remarkable increase of ACTH, beta-Ep, GH, PRL and cortisol circulating levels has been observed in the athletes after both runs, but in a different extend in relation not only to the duration and intensity of the muscular work but also to the agonistic effort: thus the hormonal increase was higher after the international marathon run than after the national half-marathon.

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.

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.