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Background: Head-split fractures are a subgroup of proximal humeral fractures in which the fracture line affects the articular surface. Limited data are available regarding outcomes and risk factors for failure following surgical treatment of this rare fracture type., Methods: Of 45 patients with head-split fractures identified, a total of 30 (67%) were included in this retrospective study, with a mean follow-up of 49 ± 18 months (range, 12 to 83 months). Of those 30, 24 were treated with open reduction and internal fixation (ORIF), 4 with reverse total shoulder arthroplasty (RTSA), and 2 with hemiarthroplasty. Subjective Shoulder Value, Simple Shoulder Test, Constant score, and biplanar radiographs were assessed. Fracture pattern, quality of reduction, eventual complications, revision procedures, and clinical failure (adjusted Constant score < 40) were analyzed, and risk factors for failure were calculated., Results: The overall complication rate was 83% (ORIF: 21 of 24 [88%]; RTSA: 3 of 4 [75%]; and hemiarthroplasty: 1 of 2 [50%]). The most common complications following ORIF were humeral head osteonecrosis (42%), malunion of the lesser tuberosity (33%), and screw protrusion (29%), whereas all complications following RTSA were related to tuberosity problems. Revision was performed in 7 of 24 (29%) of initial ORIF patients, and no revisions were performed in RTSA or hemiarthroplasty patients. Four patients (17%) who underwent primary ORIF underwent conversion to RTSA, and 3 patients (12.5%) had screw removal due to penetration. The overall clinical failure rate was 50% (ORIF: 12 of 24 [50%]; RTSA: 1 of 4 [25%]; and hemiarthroplasty: 2 of 2 [100%]). No significant association was found between preoperative factors and clinical failure. ORIF and primary RTSA showed higher average clinical outcome scores than primary hemiarthroplasty and secondary RTSA. In general, patients who required revision had worse Subjective Shoulder Value (p = 0.014), Simple Shoulder Test (p = 0.028), and adjusted Constant scores (p = 0.069)., Conclusions: Head-split fractures of the humerus treated with ORIF showed high complication and revision rates. RTSA resulted in comparable clinical outcomes and complication rates; however, the complications associated with RTSA were mostly related to tuberosity problems, which in this small series did not require revision. Therefore, RTSA may be the most predictable treatment option for head-split fractures in elderly patients., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete list of levels of evidence.

Introduction: Depression and anxiety symptoms are commonly experienced by women during pregnancy and may have negative consequences on mothers and newborns. Deterioration of sleep quality throughout pregnancy increases insomnia, which may lead to adverse outcomes including increased psychopathology in the perinatal period. Thus, identifying women at high risk of developing insomnia may have important clinical implications on maternal-fetal outcomes. Stress-related sleep reactivity is a well-established risk factor for future insomnia, depression, and anxiety in general adult samples. However, little is known of sleep reactivity and its relations to sleep and mood pathology in pregnancy. Therefore, we explored sleep reactivity in pregnant women and its relations to prenatal symptoms of insomnia, depression, anxiety, and suicidality., Method: Sixty-two pregnant women (mean age 33.6 ± 3 years, 20.6 ± 0.6 weeks of pregnancy) were evaluated during their routine visit at the Gynecological Unit of the University of Pisa, Italy, using the Insomnia Severity Index (ISI) for insomnia symptoms, the Ford Insomnia Response to Stress Test for sleep reactivity (FIRST), Edinburgh Postnatal Depression Scale (EPDS) for depressive symptoms, and the Zung Self Rating Anxiety Scale (SAS) for anxiety symptoms. Item #10 of the EPDS was used to assess for suicidality. Differences in means between women with high vs low stress-related sleep reactivity were calculated using t-test or Mann-Whitney U/Wilcoxon test. Linear/multiple regression analyses have been performed to study associations between variables., Results: Pregnant women with high stress-related sleep reactivity, relative to those with low reactivity, reported greater symptoms of insomnia (t = 6.5, 0.004) as well as higher rates of depression (62.0% vs 6.1%, p < 0.001), anxiety (55.1% vs 15.1%, p = 0.030), and suicidality (17.2% vs 3.0%, p = 0.025). Multivariate models revealed sleep reactivity to correlate independently with symptoms of insomnia, depression, and anxiety, when controlling for comorbid symptoms., Conclusions: In mid-pregnancy, women with high sleep reactivity report elevated symptoms of insomnia, depression, and anxiety, and are more likely to endorse suicidal ideation. As a prognostic marker of future insomnia and psychiatric illness, early detection of high prenatal sleep reactivity holds potential to prevent the development of sleep and mood pathology during pregnancy, thereby potentially improving maternal and child outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Irreparable rotator cuff tears are common conditions seen by shoulder surgeons, characterized by a torn and retracted tendon associated with muscle atrophy and impaired mobility. Direct fixation of the torn tendon is not possible due to the retracted tendon and lack of healing potential which result in poor outcome. Several treatment options are viable but correct indication is mandatory for a good result, pain improvement, and restoration of shoulder function. Patient can be treated either with a conservative program or surgically when necessary, by different available modalities like arthroscopic debridement, partial reconstruction, subacromial spacer, tendon transfer, and shoulder replacement with reverse prosthesis. The aim of this study was to review literature to give an overview of the available possible solutions, with indications and expected outcomes., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Introduction: Secondary repair of flexor tendon injuries remain a challenging procedure for hand surgeons. Usually, secondary reconstruction should be performed by staged approach. When the tendon and pulley integrity are intact, tenolysis may be the first surgical option. One-/two-stage tendon grafts are suggested when the integrity of flexor tendon is compromised. Active tendon implants (Brunelli prostheses) may represent an efficient option in patients with a poor prognosis, as well as whenever classical techniques fail. Due to lack of literature about this second-line treatment, the authors present the experience of two different orthopedic departments with the permanent active tendon implant., Materials and Method: Nineteen consecutive patients with failed previous flexor tendons repairs were treated with active tendon implants between 2000 and 2011. The functional outcome of the patients was examined with a mean follow-up of 5.6 years, using Strickland assessment and QuickDASH., Results: In 16 cases, the tendon implants were well tolerated and patients resulted satisfied with a QuickDASH score less than 33. Strickland score was fair to excellent in 10 patients. We registered adhesion complications in 3 cases., Conclusion: We can conclude that these prostheses represent an alternative to biological reconstructions and a potentially permanent procedure in complicated flexor tendon injuries., Level of Evidence: Multicentric case series, Level IV.

Study Objectives: According to the diathesis-stress model of insomnia, insomnia may develop in vulnerable individuals in response to stress. Resilience is a psychobiological factor that determines an individual's capacity to adapt successfully to stressful events and low resilience increases vulnerability for development of mental disorders. The aim was to explore resilience in subjects with insomnia and its relationship with the factors that contribute to its development and perpetuation., Methods: The study consisted of 58 subjects with Insomnia Disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and 38 good sleepers. Resilience Scale for Adults (RSA), Ford Insomnia Response to Stress Test (FIRST), Pre-sleep Arousal Scale (PSAS), and Difficulties in Emotion Regulation Scale (DERS) were administered while taking into account psychiatric symptoms. Differences in means between groups were assessed using t test or Mann-Whitney U /Wilcoxon test. Linear/multivariable regression analyses and mediation analyses were performed., Results: Subjects with insomnia (24 females, mean age 49 ± 2.1 years) had lower RSA and higher FIRST, DERS, and PSAS scores than good sleepers (22 females, mean age 47.2 ± 1.2 years). After controlling for anxiety/depressive symptoms, low resilience correlated with high stress-related sleep reactivity ( P = .004), pre-sleep cognitive hyperarousal ( P = .01) and emotion dysregulation ( P = .01). Emotion dysregulation mediated the relationship between low resilience and cognitive hyperarousal (Z = 2.06, P = .03)., Conclusions: Subjects with insomnia showed low resilience, which was related to high stress-related sleep reactivity, emotional dysregulation, and hyperarousal. If resilience helps to minimize the extent of pathogenesis in the developmental process, an early identification of vulnerable candidates should be useful for preventing insomnia development and maintenance., Commentary: A commentary on this article appears in this issue on page 709., (© 2018 American Academy of Sleep Medicine.)

Studies show that unhelpful cognitive processes play a role in insomnia, whereas interpersonal factors have been less studied in insomnia. Attachment theory can be used as a cognitive-interpersonal framework for understanding insomnia. Because attachment insecurity (vs security) is related to psychiatric disorders the objective was to study the attachment style in insomnia. To this aim sixty-four subjects with Insomnia Disorder (DSM-5) and 38 good sleepers were evaluate in a cross-sectional study with: Attachment Style Questionnaire (ASQ), Arousal Predisposition Scale (APS), Pre-Sleep Arousal Scale (PSAS) and Difficulties in Emotion Regulation Scale (DERS). Differences in means between groups were assessed using t-test or Mann-Whitney U/Wilcoxon test. Linear/multiple regression analyses were performed. Subjects with insomnia (mean age 47.1 + 13 yrs) presented an insecure attachment style and higher scores in all the scales (ASQ, APS, PSAS, DERS p < 0.0001) than good sleepers (mean age 48.2 + 14 yrs). After taking into account anxiety/depressive symptoms, insecure attachment was related to hyperarousal trait (p = 0.02), pre-sleep hyperarousal (p = 0.04) and emotion dysregulation (p = 0.002). In conclusion subjects with insomnia showed an insecure attachment which was related to hyperarousal trait, pre-sleep hyperarousal and emotion dysregulation. It may intervene in the trajectory of insomnia starting from predisposition to perpetuation. Clinical implications are discussed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Kidneys have an important role in the body. Any damage to kidney role can damage many organs of the body. Traditional Persian Medicine (TPM) or Iranian traditional medicine (ITM) is an ancient temperamental medicine with many literatures about kidney diseases and Avicenna (980-1025 AD) describes kidney diseases in details. This is a review study by searching of the most important clinical and pharmaceutical TPM textbooks such as The Canon of Medicine by Avicenna and scientific data banks using keywords such as "Hozal-e-Kolye", renal atrophy, tubular atrophy, kidney, chronic kidney disease, and end stage renal disease. This paper found that "Hozal-e-Kolye" in TPM texts is the same tubular atrophy in conventional medicine due to some similar symptoms between them. Lifestyle modification and use of proposed foodstuffs can be considered as a complementary medicine in addition to conventional treatments to manage these patients. TPM scholars prescribed some foodstuffs such as camel milk, sheep's milk and Ficus carica for this disease as a complementary management. This study aimed to explain HK (the same tubular atrophy considering their similar symptoms) and introduce some foodstuffs. It seems using of foodstuffs affecting tubular atrophy based on TPM literatures can has a role as a supplemental method in company with conventional medicine management.

Background: Bone marrow stem cells (BMSC) can participate to liver regeneration. However, conflicting results have been reported on this topic in patients undergoing liver resection., Aims: To assess the impact of liver resection extent and presence of underlying liver disease in modulating BMSC mobilization., Methods: We enrolled 29 patients undergoing liver resection of different extents, 5 surgical controls and 10 blood donors. Circulating CD133+ BMSC were measured by flow cytometry at different time-points after surgery. The hepatic commitment of mobilized BMSC was investigated by polymerase chain reaction. Liver specimens were collected during surgery for histopathological analysis. Hepatocyte growth factor and granulocyte-colony stimulating factor serum levels were measured by enzyme-linked immunosorbent assay., Results: BMSC mobilization was found in patients undergoing major liver resection, especially in the presence of underlying disease. Ductular reactions were noted in patients with chronic hepatopathy and the hepatic progenitor-like cells expressed CD133, NCAM, cytokeratin-19, and alpha-fetoprotein. Hepatocyte growth factor and granulocyte-colony stimulating factor levels increased following liver resection and the contemporaneous presence of liver disease was associated with their highest raise., Conclusions: Liver repair is mainly an endogenous process. BMSC become important in case of extensive resection, especially in the presence of underlying hepatopathy and hepatic progenitor-like cells activation. Hepatocyte growth factor and granulocyte-colony stimulating factor seem to be involved in the dynamics underlying hepatic regeneration and BMSC recruitment., (Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background/aims: Prognostic scores currently used in cirrhotic patients do not include thrombotic risk factors (TRFs). Predicting factors of portal vein thrombosis (PVT) development are still unknown. We wanted to describe TRFs as a function of liver disease severity using the MELD score and assess the role of local and systemic TRFs as predictors of PVT development in cirrhotic patients., Methods: One hundred consecutive patients with liver cirrhosis were included in the study. TRFs, D-dimers, MELD score, portal vein patency and flow velocity were evaluated in all subjects at baseline and every 6 months thereafter. Variables able to predict PVT development within 1 year were identified by means of multiple logistic regression., Results: The plasma levels of protein C and antithrombin were lower and the concentration of D-dimers was higher in patients with advanced disease. Plasma levels of antithrombin, protein C and protein S resulted significantly lower in PVT group at univariate analysis, but reduced portal vein flow velocity was the only variable independently associated with PVT development., Conclusions: Lower concentrations of natural coagulation inhibitors are frequently detected in patients with liver cirrhosis. A reduced portal flow velocity seems to be the most important predictive variable for PVT development in patients with cirrhosis.

Introduction: An integrated mental health surveillance program was developed by the department of occupational medicine at S. Chiara University Hospital in Pisa, Italy, in order to better assist and treat hospital staff suffering from psychiatric disorders in a preventive medical setting., Material and Methods: During the occupational medical surveillance of 4000 employees of S. Chiara Hospital in Pisa (Italy), 30 health care workers with psychiatric disorders were included in our program, which provided psycho-educational support and pharmacological treatment. Measures of effectiveness were: Clinical Global Impression (CGI scale) and a comparison between the average number of lost workdays due to mental illness before and after treatment., Results: At the end of the observation period there was a decrease in the CGI severity score with a improved CGI score ranging from 1 to 2 and a reduction in absenteeism, from an annual average of 36.70 to 25.10 lost workdays., Conclusion: Our outcome measures data seem to indicate that a preventive medicine setting can offer effective psychiatric support that is better accepted and tolerated by health care workers and that this approach may reduce absenteeism.

Objectives: Current treatment for small intestinal bacterial overgrowth (SIBO) is based on courses of broad-spectrum antibiotics. No data concerning SIBO recurrence are available. The aims of the present study were to investigate SIBO recurrence as assessed by glucose breath test (GBT) after antibiotic treatment and conditions associated to SIBO recurrence., Methods: Eighty consecutive patients affected by SIBO and decontaminated by rifaximin (1,200 mg per day for 1 wk) were enrolled. Diagnosis of SIBO was based on GBT. GBT was reassessed at 3, 6, and 9 months after evidence of GBT normalization. GBT positivity recurrence, predisposing conditions, and gastrointestinal symptoms were evaluated., Results: Ten (10/80, 12.6%), 22 (22/80, 27.5%), and 35 (35/80, 43.7%) patients showed positivity to GBT at 3, 6, and 9 months after successful antibiotic treatment, respectively. At multivariate analysis, older age (OR 1.09, 95% CI 1.02-1.16), history of appendectomy (OR 5.9, 95% CI 1.45-24.19), and chronic use of proton pump inhibitors (PPIs) (OR 3.52, 95% CI 1.07-11.64) were significantly associated to GBT positivity recurrence. All gastrointestinal symptoms significantly increased at 3, 6, and 9 months in patients with evidence of GBT positivity recurrence., Conclusions: GBT positivity recurrence rate was high after antibiotic treatment. Older age, history of appendectomy, and chronic use of PPIs were associated with GBT positivity recurrence. Patients with evidence of GBT positivity recurrence showed gastrointestinal symptoms relapse thus suggesting SIBO recurrence.

Protagonists of a new scientific era, stem cells are promising tools on which regenerative medicine relies for the treatment of human pathologies. Stem cells can be obtained from various sources, including embryos, fetal tissues, umbilical cord blood, and also terminally differentiated organs. Once forced to expand and differentiate into functional progenies, stem cells may become suitable for cell replacement and tissue engineering. The manipulation and/or stimulation of adult stem cells seems to be particularly promising, as it could improve the endogenous regenerative potential without risks of rejection and overcome the ethical and political issues related to embryonic stem cell research. Stem cells are already leaving the bench and reaching the bedside, despite an incomplete knowledge of the genetic control program driving their fate and plasticity. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy and acute or chronic hepatopaties. Nonetheless, critical aspects need to be further addressed, including the long-term safety, tolerability and efficacy of cell-based treatments, as well as their carcinogenic potential. Aim of this review is to summarize the state-of-the-arts on gastrointestinal and hepatic stem cells and on stem cell-based therapies in gastroenterology and hepatology, highlighting both the benefits and the potential risks of these new tools for the treatment and prevention of human diseases.

Objectives: Small intestinal bacterial overgrowth is defined as an abnormally high bacterial population level in the small intestine. Intestinal motor dysfunction associated with hypothyroidism could predispose to bacterial overgrowth. Luminal bacteria could modulate gastrointestinal symptoms and interfere with levothyroxine absorption. The aims of the present study were to assess the prevalence and clinical pattern of bacterial overgrowth in patients with a history of overt hypothyroidism and the effects of bacterial overgrowth decontamination on thyroid hormone levels., Methods: A total of 50 consecutive patients with a history of overt hypothyroidism due to autoimmune thyroiditis was enrolled. Diagnosis of bacterial overgrowth was based on positivity to a hydrogen glucose breath test. Bacterial overgrowth positive patients were treated with 1,200 mg rifaximin each day for a week. A glucose breath test, gastrointestinal symptoms, and thyroid hormone plasma levels were reassessed 1 month after treatment., Results: A total of 27 patients with a history of hypothyroidism demonstrated a positive result to the breath test (27 of 50, 54%), compared with two in the control group (two of 40, 5%). The difference was statistically significant (P < 0.001). Abdominal discomfort, flatulence, and bloating were significantly more prevalent in the bacterial overgrowth positive group. These symptoms significantly improved after antibiotic decontamination. Thyroid hormone plasma levels were not significantly affected by successful bacterial overgrowth decontamination., Conclusions: The history of overt hypothyroidism is associated with bacterial overgrowth development. Excess bacteria could influence clinical gastrointestinal manifestations. Bacterial overgrowth decontamination is associated with improved gastrointestinal symptoms. However, fermenting carbohydrate luminal bacteria do not interfere with thyroid hormone levels.

Recently, Tuscany regional government has promulgated (Regional law n. 464/07) guidelines for setting up suitable sanitary rooms for patients allergic to latex. These guidelines enforced the managers of the Tuscany Local Health Units to promote educational activities and a correct methodology for the safe management of both health workers and patients who need latex-free diagnostical and/or therapeutical procedures. An other Regional law (n.345/05) had previously enforced all the Tuscany Local Health Units managers to implement and update a Registry of every latex-allergic patients ever hospitalized in their own local facilities. Since 2002 a multi-disciplinary task force of health operators, lead by the Preventive Medicine Section, has been elaborating and implementing a plan for the safety of latex-allergic patients of the Pisa University Hospital, along with a Registry where each of these patients were recorded. Moreover, since 2005 under the responsabilities of the staff of the Preventive Medicine Section, another Registry has been implemented and updated. In this Registry all the Hospital employees who have been diagnosed a latex allergy, through the medical exams performed within the occupational medical surveillance activity, have been filed. In this study we report the results of this preventive activity both aimed at patients and heatlh operators safety.

Background and Aim: Kupffer cells are intrasinusoidal space located macrophages with phagocytic capacity. Interferons are cytokines with antiviral, antiproliferative and immunomodulatory activities which may influence the activity of Kupffer cells. Aim of this study was to evaluate Kupffer cell gene expression after interferon-alpha or interferon-gamma stimulation in order to investigate a link between these cytokines and macrophage activation., Methods: Rat Kupffer cells were cultured for 24 h and divided into three groups: unstimulated; stimulated with interferon-alpha and stimulated with interferon-gamma. After 8 h stimulation total RNA was extracted and processed according to Affymetrix protocols and hybridised on R34A microarray gene set. Data analyses was performed using Microarray Analysis Suite 5.0 software. Genes showing remarkably different expression in microarray analysis were confirmed by real-time PCR., Results: Nearly 4000 out of the 8800 genes represented in the array were expressed by Kupffer cells. Among these, interferon-alpha up-regulates 91 genes by over two-fold (antiviral, antigen processing and presentation, and tumour suppressor/proapoptotic genes) and down-regulates 72 genes by 50% or more. Interferon-gamma up-regulates 70 genes by over two-fold and down-regulates 78 genes by 50% or more. Most of the genes induced by interferon-alpha are also induced by interferon-gamma. Down-regulated genes include growth factors and genes involved in cell cycle/proliferation. Real-time PCR confirms the results of the array., Conclusion: Interferons directly target rat Kupffer cells and are involved in the regulation of a wide variety of genes. Their expression profile shed light onto molecular mechanism of Kupffer cells activation in specific pathways such as antiviral and antitumour processes.

Adult stem cells (ASC) have becoming a great domain of research by their promising interest for the regenerative medicine. For some years, the number of publications has been increasing, displaying the potential of ASC to differentiate in all tissue-lineages, challenging the previous dogma that ASC were restricted to give rise only to specific cells from their tissue of origin. Among the diversity of ASC, hematopoietic stem cells (HSC) have been the most studied and their use in the clinical setting is largely documented. Commonly, HSC have been harvested from the bone marrow, but for some years, two others sources, the peripheral blood and the umbilical cord blood have been introduced. All these HSC posses their own molecular characteristics and degree of maturity and represent a more or less good candidate to participate in the cellular-based tissue regeneration. We have reviewed the different parameters allowing to define which subset could be the more favorable such as the accessibility to the pool of HSC; the quantity of available cells; the tolerability of host-engraftment and the capacity of the cells to home correctly to the required site of damaged. Besides, recently, the molecular profiling of HSC has allowed identifying which subset posses the more promising characteristics.

The pattern of inhibition of cell proliferation and cytotoxicity in vitro by 1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (Naph-DNB) was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and the trypan blue (TB) dye exclusion assays in nine murine and human cell lines of different histologic origin. In our culture conditions Naph-DNB showed a good inhibiting activity against all cell lines tested, with IC(50)s varying within a narrow micromolar range of concentrations (2.0 +/- 0.2-14.3 +/- 2.3 microM). In particular, murine P388 (leukemia), human Jurkat (leukemia), A2780, PA-1 (ovarian carcinoma) and Saos-2 (osteosarcoma) cells showed the highest sensitivity to the inhibiting potential of Naph-DNB, while human A549 (non small cell lung cancer, NSCLC), MDA-MB-231 (breast cancer), HGC-27 (gastric cancer) and HCT-8 (colon carcinoma) were the least sensitive cell lines. Moreover, the analysis of cytotoxicity of Naph-DNB evaluated by the TB test showed that this compound was able to kill cells with IC(50)s ranging from 1.7 to 39.2 microM. The study of the induction of apoptosis was carried out by 4'-6-diamidine-2'-phenylindole (DAPI) staining of segmented nuclei, western blot of p53 protein and TdT-mediated dUTP-biotin nick end labeling (TUNEL) method, while the interaction with DNA was evaluated through the analysis of interstrand cross-link (ISCL) formation. Our data show that in all cell lines tested Naph-DNB was able to form ISCLs, to upregulate p53 oncosuppressor-protein and to induce apoptosis. Moreover, TUNEL analysis also suggested that Naph-DNB, similarly to other anticancer drugs, was able to block cells in the G (0)/ G (1) phase of the cell cycle. In conclusion our data suggest that Naph-DNB may be an effective novel lead molecule for the design of new anticancer compounds.

The inhibition of cell proliferation by 1,4-bis (1-naphthyl)-2,3-dinitro-1,3-butadiene (Naph-DNB) was evaluated in vitro against 4 cell lines (L1210/DDP, A2780/DX3, HCT-8/FU7dR, A549-T12) selected for their resistance to cisplatin, doxorubicin, 5-fluorouracil and taxol, and their wild-type counterparts. Naph-DNB is a novel anti-cancer compound obtained years ago within a research project of Organic Chemistry aimed at synthesizing 2,3-dinitrobutadiene derivatives. Because of its chemical structure, Naph-DNB was suggested to interact with nucleic acids, in particular DNA, and the other cellular macromolecules. This hypothesis made us consider Naph-DNB as a candidate for studies concerning its antitumour activity. We used the MTT assay to test the inhibition of cell proliferation after incubation of the cell lines with Naph-DNB for 72 h. For comparison, resistant and wild-type cell lines were also tested against those anticancer drugs used in vitro for their selection. In these culture conditions Naph-DNB retained its inhibiting activity against all resistant cells with IC50 values similar to those obtained in corresponding wild-type cell lines. Moreover, Naph-DNB was twice as effective as 5-fluorouracil against wild-type HCT-8 cells. Our previous findings about the interaction of Naph-DNB with DNA through the formation of interstrand cross-links suggested a mechanism of action similar to that of platinum/alkylating agents or topoisomerase inhibitors (intercalating agents). Our present data obtained by the K-SDS precipitation assay in A2780 and A549 cells showed that Naph-DNB is not able to form a stable topoisomerase-DNA complex as is the case for topoisomerase inhibitors. In conclusion, our results indicate that Naph-DNB is able to overcome some of the classical mechanisms of resistance selected by some anticancer drugs mainly used in clinical setting.

Within an overall ring-opening/ring-forming protocol, the (E,E)-4-methylthio-2-nitro-3-phenylsulfonyl-1-pyrrolidino-1,3-butadiene (7) [derived from the initial opening of 3-nitro-4-(phenylsulfonyl)thiophene (6) with pyrrolidine and silver nitrate in EtOH] is revealed to be an excellent precursor of nitro(phenylsulfonyl) derivatives of ring-fused aromatic (naphthalene, phenanthrene) or heteroaromatic (benzothiophene) compounds whose substitution pattern cannot be easily achieved by conventional methods. The key step is represented by a thermal electrocyclic rearrangement of (E,E)-1-aryl-4-methylsulfonyl-2-nitro-3-phenylsulfonyl-1,3-butadienes (9), which, thanks to proper geometric and electronic factors, occurs in unprecedentedly mild conditions and is followed by an irreversible, concerted syn beta-elimination of methanesulfinic acid to aromatize the newly formed cyclohexadienic ring.

The objective of this study was to investigate stay-on-therapy patterns over 3 years among patients prescribed different classes of antihypertensive drugs for the first time. A retrospective analysis of information recorded in the drugs database of the Local Health Unit of Ravenna (Italy) was carried out on 7312 subjects receiving a first prescription for diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II antagonists between 1 January and 31 December 1997. Patients were followed up for 3 years. All prescriptions of antihypertensive drugs filled during the follow-up periods were considered. The patients continuing or discontinuing the initial treatment, the duration of treatment, and the doses taken were all calculated, as well as main factors influencing the persistence rate. The drugs prescribed were predominantly ACE-inhibitors, followed by calcium channel blockers, diuretics, beta-blockers and angiotensin II antagonists. A total of 57.9% of patients continued their initial treatment during the 3-year follow-up period, 34.5% discontinued the treatment, whilst 7.6% were restarted on a treatment in the third year. Persistence with treatment was influenced by: age of patient (persistence rate increasing proportionately with advancing years), type of drug first prescribed (persistence rate higher with angiotensin II antagonists, progressively lower with ACE-inhibitors, beta-blockers, calcium channel blockers and diuretics), gender of patient (persistence was better in males), age of general practitioner (GP) (the younger the GP, the better the persistence rate) and gender of GP (better stay-on-therapy rate with male GP prescribing). In the case of patients treated continuously, mean daily dose increased progressively over the 3 years. With adequate markers, helpful data can be collected from prescription claims databases for the purpose of monitoring the persistence of patients in continuing their medication, and the quality of antihypertensive treatment in a general practice setting.

Static and dynamic stereochemistry of the hydrocarbon comprising a phenyl ring bearing two alpha-naphthyl substituents in the ortho positions, i.e., 1,2-di-(4-methyl-naphth-1-yl)-benzene 1, has been studied by a combination of variable temperature NMR, cryogenic HPLC, and MM calculations. Whereas in solution both syn (meso) and anti (chiral) forms were observed and the corresponding interconversion barrier was determined (Delta G(++) = 19.5 kcal mol(-1)), only the diastereoisomer anti was found to be present in the crystalline state (X-ray diffraction). When the molecule is rendered asymmetric by introduction of a nitro group in the phenyl ring as in 1,2-di-(4-methyl-naphth-1-yl)-4-nitrobenzene 2, the chiral syn and anti diastereoisomers are simultaneously present both in solution and in the solid state, albeit in different proportions. Cryogenic chromatography on a HPLC chiral stationary phase at 20 degrees C allowed the stereolabile diastereoisomers and the corresponding enantiomers to be separated.

Sixteen patients with RA (3 males, 13 females), diagnosed according to RA revised criteria, were selected and entered the study. They underwent six intra-articular injections of 750 mcg of SST14 at 15-day intervals. The thickness of the synovial membrane (SM) was measured with a 5-MHz linear sound with longitudinal and transversal scanning carried out on the upper patellar cavity. The contralateral knee was also assessed together with the injected knee in order to ascertain any systemic effect of the drug. A significant reduction of SM thickness was observed already at the first control (T3) in 14 out of 16 patients. At the 5th and 6th injections (T5 and T6) the reduction was still significant but to a lower extent. In 8 out of 16 cases a reduction of SM thickness was observed in the contralateral knee. Analysis of these data clearly shows that the intra-articular injection of SST14 is able to reduce the thickness of SM in patients with RA, and indicates that SST14 may directly reduce synovitis. This particularity has been detected in our work with a non-invasive technique such as the joint ultra-sound (US). In conclusion, our work confirms the efficacy of SST14 in the control of RA synovial hypertrophy and the reliability of US technique in the measurement of SM thickness.

19 patients with RA underwent six intraarticular injections of 750 micrograms of Somatostatin 14 in one knee at 15-day intervals. In all patients some clinical parameters were evaluated: articular function, pain on pressure, spontaneous pain, pain on movement, duration of morning stiffness. Also some laboratory parameters were examined: complete blood cell count, ESR and CRP. An overall and significant improvement of the symptomatology of the treated knee was seen in all patients especially after the 3rd infiltration and still more after the 5th. At follow up 3 months after the end of treatment 12 patients were controlled, 11 of these showed a persistence of the improvement. No side-effects were seen.

It is described a case of a Aicardi's syndrome: it is a question of a child observed for the first time when she was 3 months old in these was gived: alterations of the callosum corpus, and of the cerebellar vermis, ocular desed, epileptics convulsions and electroencephalographics alterations of ipsaritmic type.