Rethinking vulnerability in city-systems: A methodological proposal to assess "urban entropy".

This paper aims at proposing a possible alternative point of view to investigate the vulnerability of urban systems. The basic ideal refers to the possibility of thinking about vulnerability as deriving by the interactions of several risks that can affect the urban system and by the interactions among them. In this sense, it is possible to refer to an "integrated territorial risk". Considering the city as a complex and dynamic system that while evolving produce entropy is the main theoretical reference supporting this study. The loss of energy during the evolution of the system corresponds to some conditions of inefficiency that involve the whole system and, as such, this lost energy can be assumed as a "systemic entropy". Is it possible to measure the levels of this vulnerability of the urban system when it stays in ordinary conditions, namely not during stress states that modify the state of equilibrium of the system itself? It is possible to assess the production of this "internal entropy"? In order to answer to these questions in mind, this study aims at analyzing dyscrasias that can occur within the main components of the urban system in order to individuate possible strategies able both to mitigate the fragility of the urban system and to improve its resilience.

General and sex profile of women with partner affected by premature ejaculation: results of a large observational, non-interventional, cross-sectional, epidemiological study (IPER-F).

BACKGROUND: Couple distress is a crucial point in premature ejaculation (PE). PE has been associated with significant bother, interpersonal problems, and dissatisfaction with sexual intercourse for both men and their partners. OBJECTIVES: The primary objective of this study was to assess the effect of PE on female sexuality in female partners of men affected from PE. Secondary objectives were to assess the impact of PE on female sexual quality of life, to assess the presence of sexual problems of the male partner, and to evaluate the prevalence and characteristics of comorbidities. MATERIALS AND METHODS: Adult women aged 18 to 80 years old, sexually active, were randomly sampled from the patient lists of General Practitioners in Italy and were included in this observational, non-interventional, cross-sectional epidemiological study. Subjects were asked to fill: a general questionnaire regarding anthropometric data, lifestyle, marital status, education, occupation, economic conditions, general health status, comorbidities, and sexual habits; the Sexual Quality of Life Questionnaire-Female (SQoL-F); the Female Sexual Distress Scale (FSDS-R-PE); the Self-rating Depression Scale (SDS); and Self-rating Anxiety Scale (SAS). In addition, females reported about their partner's ejaculation time and the presence of sexual dysfunctions. RESULTS: A total of 3,104 women were included. Mean age was 45.1 years. Woman with PE partners presented a higher percentage of sexual dysfunction and reported more anxiety compared with female partners of men not affected from PE (42.69% vs. 20.56% and 30.95% vs. 15,34%, respectively). In addition, they referred more sexual dysfunction in their partners. Hypertension, hypercholesterolemia, arthritis, heart diseases, thyroid disease, a history of menopause, or hysterectomy resulted in significantly more prevalence in women with PE partners. DISCUSSION AND CONCLUSIONS: Female partners of PE patients present an increased prevalence of sexual distress, a reduced quality of sexual life, and an increased anxiety score when compared to women whose partners are not affected from PE.

Extensive study on physicochemical properties of polychlorinated biphenyls in a commercial ion trap mass spectrometer, relevance in analytical and environmental chemistry.

Polychlorinated biphenyls (PCBs) exist as 209 congeners, consisting of biphenyl molecules, where the number and substitution positions of halogen atoms are known to affect industrial uses, environmental transport mechanisms, distribution, fate, and toxicity. The complexity of the problem requires accurate physicochemical studies of an increasing number of congeners in order to understand the environmental and biological processes at play. This work presents a systematic study on the thermodynamic and kinetic properties of PCBs by quadrupole ion trap mass spectrometry. A clear relationship between structure and behavior of PCBs in mass spectrometry experiments has been observed. Overall data demonstrate that di-ortho congeners show lower thermodynamic stability and higher fragmentation rate than non/mono-ortho. Congeners follow different fragmentation mechanisms according to the number of chlorine atoms in ortho position of the biphenyl system. Experimental kinetic curves of mono/non-ortho and di-ortho congeners show a strong similarity with classical first-order kinetics curves; in particular, di-ortho congeners follow a first-order consecutive reaction, while mono/non-ortho follow a first-order parallel reaction. For each studied congener, the kinetic constant of reaction (fragmentation) has been determined. Data support environmental levels and biochemical transformations described in literature. The general picture of the PCB behavior inside a quadrupole ion trap provides the basis for the development of reliable and cost-effective analytical methods to the determination of ultra-low level trace of PCB congeners.

Effects of alpha1-blockers on urodynamic parameters of bladder outlet obstruction in patients with lower urinary tract symptoms suggestive of benign prostatic enlargement: a review.

α1-adrenergic receptors blockers (ABs) are recommended as first-line medical therapy in men with Lower Urinary Tract Symptoms suggestive of Benign Prostatic Enlargement (LUTS/BPE). Available ABs include: terazosin, doxazosin, tamsulosin, naftopidil, alfuzosin and silodosin. These agents have different profiles of selectivity for α1-adrenergic receptors subtypes. All these agents are efficacious in improving both storage and voiding LUTS. In recent years the efficacy of ABs in improving urodynamic parameters of bladder outlet obstruction (BOO) has been questioned. We reviewed literature evidences about the effects of available ABs on invasive urodynamic parameters of BOO in men with LUTS/BPE. The impact of ABs therapy on urodynamic parameters indicative of BOO has been evaluated for all currently approved drugs. Available data demonstrate improvements in terms of both free uroflowmetry and pressure-flow parameters. While the impact of ABs on maximum urinary flow is clinically modest, the improvement of detrusor pressure at maximum urinary flow is more robust. Only few studies exist that directly compare the urodynamic effects of a small number of ABs. According to these studies there are no differences among ABs in terms of urodynamic efficacy. Indirect comparison of ABs suggests greater effectiveness of silodosin in terms of detrusor pressure at maximum urinary flow reduction. Studies that stratified populations based upon the degree of obstruction at baseline demonstrated greater urodynamic changes in patients with baseline BOO with respect to the unobstructed patients. Globally, the quality of studies available is low and there is considerable heterogeneity among studies.

Integrated microfluidic device for single-cell trapping and spectroscopy.

Optofluidic microsystems are key components towards lab-on-a-chip devices for manipulation and analysis of biological specimens. In particular, the integration of optical tweezers (OT) in these devices allows stable sample trapping, while making available mechanical, chemical and spectroscopic analyses.

Long-term hemostatic effects of cholesterol-lowering therapy with atorvastatin.

This study assessed hemostatic effects of an HMC-CoA reductase inhibitor, atorvastatin, on different parameters in 32 hypercholesterolemic patients of both sexes. In the patients and in 25 control subjects, plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor (PAI-1), D-dimer, prothrombin fragment 1 + 2 (F1 + 2), total cholesterol, triglycerides and fibrinogen had been measured. All these parameters were evaluated in patients after 6 and 12 months of treatment with atorvastatin at a dosage of 20 mg/day. This treatment significantly lowered the total cholesterol level in all patients. Moreover, after 6 months of atorvastatin treatment, PAI-1 and F1 + 2, which were both increased at baseline, were significantly reduced. This reduction continued after 12 months. The present results show that a reduction of hemostatic abnormalities, which exist in hypercholesterolemia, may be another important effect of the atorvastatin therapy.

A novel mutation in the pendrin gene associated with Pendred's syndrome.

OBJECTIVE: Pendred's syndrome is an autosomal recessive disorder characterized by goitre, sensorineural deafness and iodide organification defect. It is one of the most frequent causes of congenital deafness, accounting for about 10% of hereditary hearing loss. It is caused by mutations in the pendrin (PDS) gene, a 21 exon gene located on chromosome 7. The aim of this study was to examine an Italian family affected with Pendred's syndrome at the molecular level. PATIENTS: Thirteen subjects belonging to a family from Southern Italy were evaluated for the clinical and genetic features of Pendred's syndrome. MEASUREMENTS: Exons 2-21 of the PDS gene were amplified from peripheral leucocytes by the polymerase chain reaction; mutation analysis was performed by single strand conformation polymorphism, direct sequencing and restriction analysis. RESULTS: The index patient had the classical triad of the syndrome and harboured two mutations in the PDS gene in the form of compound heterozygosity. He was found to be heterozygous for a cytosine to adenosine mutation at nucleotide 1523 in exon 13 and for a IVS 1001 + 1G --> A mutation. The former is a novel mutation which results in a change of 508 threonine to asparagine in the putative eleventh transmembrane domain. The latter mutation in the donor splice site has already been described in other patients and is thought to lead to aberrant splicing and premature protein truncation. Three subjects who were heterozygous for one mutation had normal phenotypes. Two subjects had sensorineural deafness and were heterozygous for a single mutation. Goitre was found only in patients with Pendred's syndrome and was absent in all other individuals, albeit residing in an iodine-deficient area. CONCLUSIONS: We have identified a novel mutation in the pendrin gene causing Pendred's syndrome, and confirm that molecular analysis is a useful tool for a definitive diagnosis. This is particularly relevant in cases such as in the subjects of our family in which the clinical features might be misleading and other genetics factors might be responsible for deafness.

Recurrent chondrosarcoma of the cranial base: a durable response to ifosfamide-doxorubicin chemotherapy.

The case of a 46-year old woman with recurrent chondrosarcoma of the cranial base, refractory to neurosurgical intervention and external radiotherapy is reported. She received five cycles of systemic chemotherapy utilizing ifosfamide and doxorubicin which resulted in a durable clinical and radiographic response lasting 52+ months. A review of the management options for recurrent chondrosarcoma of the cranial base is also presented.

Cyclin D1 and retinoblastoma susceptibility gene alterations in non-small cell lung cancer.

Among the major regulators of the G1 restriction point are cyclin D1 and the retinoblastoma gene product (RB). In non-small cell lung cancer (NSCLC), the cyclin D1 gene is amplified/over-expressed in almost 50% of cases, and RB is inactivated in 6-32% of cases. It is of interest to evaluate concurrently the alterations of both genes on the same series of NSCLCs, to investigate whether cyclin D1 and RB alterations are alternative pathways leading to inactivation of the G1 restriction point or if they can occur in the same tumor, possibly exerting an additive effect on cancer progression. We investigated a series of 57 NSCLCs, analyzing cyclin D1 and RB at the gene and protein levels by Southern blot, Northern blot and immunohistochemistry. The cyclin D1 gene was amplified in 18 cases, cyclin D1 immunoreactivity was seen in 25 tumors. Amplification and expression were significantly associated. RB immunohistochemical expression was absent in 9 of 42 informative cases. RB mRNA expression was low to absent in 9 of 45 informative cases, cyclin D1 amplification was associated with normal RB mRNA, and cyclin D1 over-expression was associated with normal RB immunoreactivity, supporting the hypothesis that alterations of cyclin D1 and RB are alternative mechanisms by which tumor cells may escape the G1 restriction point. A concurrent alteration of RB and cyclin D1 was seen in a small subset of NSCLCs. Abnormalities of cyclin D1 and/or RB at the gene and/or expression level were present in more than 90% of cases, stressing that cyclin D1 and/or RB alterations represent an important step in lung tumorigenesis.

Clinical and experimental evidence of inhibition of testosterone production by suramin.

The effect of suramin on testosterone production was evaluated in cancer patients, adult male rats, rat Leydig cells, and NCI-H295 human adrenal cancer cells. Testosterone plasma levels markedly decreased in 14 patients receiving suramin as a therapy for refractory cancer, and in 8 of them, the plasma LH and/or FSH levels increased beyond the normal range. The hCG stimulation test (5000 IU, im) was performed in 8 patients and induced an average 2.1-fold increase in testosterone levels over baseline values. Testicular histology after suramin treatment was available in 1 patient who died of progressive disease; this revealed atrophy of seminiferous tubules and reduced Leydig cells in the interstitium. A significant reduction in plasma testosterone was also observed in rats given 18 mg/kg suramin, ip, twice weekly for 8 weeks, whereas plasma LH and FSH levels did not change significantly. Cytohistochemistry of testes from suramin-treated rats showed a reduced number of 3 beta-hydroxysteroid dehydrogenase-positive cells within the interstitium compared to controls, and light microscopy revealed severe impairment of spermatogenesis. Suramin inhibited the production of testosterone by isolated rat Leydig cells as well as the conversion of pregnenolone to progesterone by the 3 beta-hydroxysteroid dehydrogenase enzyme extracted from rat testes, with 50% inhibitory concentrations (IC50 values) of 108.2 and 87.5 micrograms/mL, respectively. Furthermore, suramin reduced the release of testosterone into the culture medium of NCI-H295 adrenal cancer cells with IC50 values of 91.2 and 83.9 micrograms/mL after 6 and 12 days, respectively. These data provide the first evidence in patients that suramin treatment produces a marked reduction in the circulating levels of testosterone, a result that was also obtained in experimental models.

[Video-thoracoscopic pulmonary lobectomy. Our experience]. / Lobectomie polmonari videotoracoscopiche. Nostra esperienza.

Video-endoscopic surgery developed from laparoscopic removal of the gallbladder and can be used for treatment of certain disease processes of the chest. The major application of this technique is the performance of pulmonary resections (lobectomies and pneumonectomies). Video-thoracoscopic lobectomy requires general anesthesia with a double lumen intubation. After collapse of the involved lung, two intercostal incisions are performed (the first one in seventh space, mid axillary and the second one in fifth space, below the angle of the scapula) and an additional mini-thoracotomy (submammillary in the fifth space) is made. The lobar arteries, veins and bronchus are occluded with an automatic endoscopic stapling device. Seven cases of pulmonary neoplasms (stage I) have been treated by video pulmonary lobectomy (3 right lower lobectomies, 2 right upper lobectomies, 2 left lower lobectomies). Two procedures have been converted for an advanced neoplastic stage that required a radical pneumonectomy and an uncontrolled bleeding. This new procedure has the advantage of greatly reducing the pain and ventilatory disability associated with conventional open thoracic surgery.

Modifications of functional and physico-chemical properties of rat ileal plasma membranes.

A membrane fraction enriched with plasma membranes was isolated from rat ileal brush-border cells before and after five-day starvation of the animals. Cholesterol/phospholipid ratio of the standard cell membranes decreased highly significantly (0.42 to 0.18), as did the microviscosity of the membranes determined by polarization of fluorescence (0.187 to 0.142). Concomitantly, the specific activity of Na,K-ATPase in the basolateral membranes significantly increased (59 to 83 mumol ATP hydrolyzed per mg protein per min).

The influence of age and sex on nutritional parameters in subjects aged 60 years and over.

The nutritional assessment of the elderly shows several interpretative difficulties due to the lack of standard parameters. Moreover chronic age-related diseases can interfere with the physiological nutritional status. Anthropometric (triceps skinfold, arm muscle area, total body muscle mass, fat mass and Body Mass Index (BMI)), biochemical (serum prealbumin, transferrin, ceruloplasmin, total protein and albumin) and immunological (serum lymphocytes) parameters were measured in 583 out-patients aged 60 years or over selected on the basis of clinical and biochemical criteria and with BMI /= 75) for each sex. The F-test analysis for all anthropometric parameters except BMI showed significant differences with respect to age (P < 0.05) and sex (P < 0.05). Among biochemical parameters, prealbumin showed a significant difference for age (P < 0.05) and sex (P < 0.05) (males, 30.3 +/- 8.2; females, 29.1 +/- 7.5) while ceruloplasmin showed a significant difference for sex only (P < 0.05) (males, 40.9 +/- 9.3; females, 43.8 +/- 8.2). When the biochemical mean values obtained in this study were compared with those utilized in the daily routine of the hospital central laboratory, ceruloplasmin and prealbumin resulted in significantly higher (P < 0.05) while total protein and albumin were significantly lower values (P < 0.05).

Suramin inhibits bFGF-induced endothelial cell proliferation and angiogenesis in the chick chorioallantoic membrane.

The effects of suramin, an inhibitor of growth factor mitogenic activity, were evaluated on basic fibroblast growth factor (bFGF)-induced proliferation of bovine aortic endothelial cells and on angiogenesis in the chorioallantoic membrane (CAM) of chick embryos. The role of bFGF gene expression in endothelial cell growth was also investigated by using an antisense oligodeoxynucleotide to bFGF. The 4-fold increase in [3H]-thymidine uptake in endothelial cells in vitro upon stimulation with 10 ng ml-1 of bFGF was inhibited by suramin 300 micrograms ml-1. bFGF antisense oligomer (10 microM) reduced [3H]-thymidine incorporation in exponentially growing cells by 76%; this effect was reversed by bFGF 10 ng ml-1. In the CAM of chick embryos suramin 50 micrograms was a more potent inhibitor of angiogenesis than the combination of heparin 60 micrograms/hydrocortisone 50 micrograms; the mean value of the area with reduced vascularity was significantly larger in suramin-treated CAMs (2.4 cm2) than in heparin/hydrocortisone (0.6 cm2), while the reduction of vascular density was similar (- 35 and - 29% compared to controls, respectively), In conclusion, the effects of treatments with bFGF and bFGF antisense oligomer demonstrate that bFGF plays a relevant role in endothelial cell proliferation and may be the target of suramin since the drug is able to suppress basal and bFGF-induced endothelial cell growth; in addition to this, suramin is a more potent angiogenesis inhibitor in the CAM than the combination of heparin/hydrocortisone.

[Rationale for the use of bile salts after cholecystectomy: results of a controlled clinical study using tauroursodeoxycholic acid (TUDCA)]. / Razionale all'utilizzo dei sali biliari nel paziente colecistectomizzato: risultati di uno studio clinico controllato con l'impiego dell'acido tauroursodesossicolico (TUDCA).

Cholecystectomy causes alterations in bile composition. In particular it rises the proportion of highly detergent bile acids with the possible consequence of the manifestation of dyspepsia in a high percentage of patients: this is the well-known post-cholecystectomy syndrome. In this clinical trial we studied the activity and safety of tauroursodeoxycholic acid--TUDCA--(500 mg/die) in the prevention of dyspepsia in cholecystectomized patients, in comparison with no treated group. We enrolled 203 patients (101 TUDCA--group A--and 102 control-group B). The two groups were comparable for age (47.1 years in group A and 50.7 years in group B), sex (m/f: 28/73 and 37/65 in the two groups) and for other characteristics connected to surgical procedures. After operation all patients suffered from dyspepsia symptoms. In patients treated with TUDCA we registered a prompt regression in severity of symptoms when compared with no treated group: in fact we noted a significant difference only at the first control planned after one month from operation. No difference were registered at the other controls (two and three months after operation). Two patients in A and 3 in group B manifested adverse events. In conclusion, the treatment with TUDCA, a new hydrophilic bile acid, seems to contribute to the improvement of clinical course in cholecystectomized patients.

[Immediate reconstruction after radical mastectomy for breast carcinoma with a Becker-type expander prosthesis]. / Ricostruzione immediata dopo mastectomia radicale per carcinoma mammario con protesi-espansore tipo Becker.

In recent years, the breast has won importance from the female psychology point of view. After ablative surgery for cancer, the loss of the breast gives rise in the woman to a feeling of refusal of her new body shape. Reconstruction produces positive feelings in the patient. The best-used surgical technique for operable breast cancer is modified radical mastectomy. An immediate reconstruction of the missing breast is considered when the following conditions are fulfilled: desire for reconstruction, age of the patient, clinical and pathologic evaluation (tumor size-tumor grade-lymph-node status). After modified radical mastectomy with "en bloc" removal of axillary lymph nodes, an immediate reconstruction is performed by lining the surfaces with human fibrin glue (Tissucol) followed by the insertion of a prosthesis of appropriate size (Becker Expander Mammary Prosthesis-Type 1) in the subserratus-subpectoral position. Human fibrin lining reduces the incidence of capsular contracture and effusion production. A suction drain is placed in the axillary area and is removed after 5 days. The use of expanding-type prostheses means that the patient must return for further expanding. When the pathologic features are negative, the delayed nipple areola reconstruction is possible with the full-thickness skin grafts in the groin or in pre-existent appendectomy incision. By this procedure, adjuvant chemotherapy or radiation therapy can be performed if required. From 1987 to 1991 the procedure has been performed in 35 cases of mammary neoplasm (mean age 40 years) at INRCA Department of Surgery of Ancona). No evidence of adverse effect on the natural course of the breast disease for have been seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptive control with feedback strategies for suramin dosing.

Suramin, a drug used in the treatment of parasitic diseases, is currently being evaluated in clinical trials as an antineoplastic agent. The use of therapeutic drug monitoring and adaptive control with feedback in clinical trials of suramin was initially motivated by an association between acute neurologic toxicity and plasma suramin concentrations in excess of 350 micrograms/ml. We have prospectively examined the performance of both two- and three-compartment population pharmacokinetic models in controlling plasma suramin concentrations and have found that a three-compartment model best describes this drug. No correlation was found between the clearance of suramin and creatinine clearance, as had been previously hypothesized. The low systemic clearance of suramin and the number of parameters required to describe the three-compartment model suggest the need for a bayesian approach to the estimation of individual pharmacokinetics.

A pilot study of suramin in the treatment of progressive refractory follicular lymphomas.

Ten patients with progressive follicular lymphomas (seven with follicular mixed lymphomas, three with follicular, small cleaved cell lymphomas) with clinical indications for systemic therapy received parenteral suramin. Each had failed from one to six prior chemotherapeutic regimens and three had in addition received prior radiation therapy. All had measurable disease and nine of the ten had documented bone marrow involvement at the start of therapy. Suramin was administered at an initial infusion rate of 350 mg/m2/day, which was then modified on the basis of subsequent weekly plasma suramin concentrations in order to reach a final plasma concentrations of 250-350 micrograms/ml. Treatment cycles were repeated at eight week intervals. Nine of ten patients are evaluable for response. Five of nine evaluable patients achieved a partial remission as defined by a greater than 50% decrease in the sum of the product of all measurable lesions. Sites of response include: Peripheral (five patients) and central (four patients) adenopathy, disappearance of biopsy-proven skin involvement (one patient), malignant pleural effusions (one patient) and shrinkage of an enlarged spleen (two patients). Disappearance of B symptoms occurred in the one responder with these symptoms. Response duration varied from 3 to 9 months (mean 5.6 months) with time to subsequent systemic therapy varying from 5 to 12 months (mean 8 months). Drug related toxicity included the development of polyradiculopathy (one case), liver function abnormalities (three cases), thrombocytopenia (five cases), vortex keratopathy (two cases) and bacterial infection (two cases). We conclude that suramin has significant activity against follicular lymphomas refractory to standard chemotherapy and that its precise role in the treatment of lymphoproliferative neoplasms in general warrants further investigation.