Assessing the risk of false-negative fine-needle aspiration cytology and of incidental cancer in nodular goiter.

OBJECTIVE: In cases of multinodular goiter with negative cytologic result, reasonable management options include surgical treatment, simple follow-up, or more recently introduced conservative therapies such as laser or radiofrequency ablation, and recombinant human thyroid-stimulating hormone-augmented radioiodine. For patients who are eligible for follow-up or nonsurgical treatments, the possibility that they may have an undiagnosed malignancy (false-negative [FN]-fine-needle aspiration cytology [FNAC] result or incidental thyroid cancer [ITC]) should be considered. The aim of our study was to assess the risk of malignancy in patients known to have presumably benign thyroid disease. METHODS: Surgical series of patients who underwent total thyroidectomy for benign disease between 2000 and 2010 at two Italian centers were reviewed. Patients with any preoperative suspicion of malignancy were excluded. RESULTS: Histologic examination revealed that 84 of 970 (8.6%) thyroidectomized patients had malignancy (5% ITC and 3.6% FN-FNAC), with 89.8% of ITCs having a diameter <10 mm, and 65.7% of FN-FNAC cancers having a diameter >30 mm. Sixty-seven thyroid malignancy patients (79.8%) had stage I disease (American Joint Committee on Cancer criteria). The risk of FN-FNAC increases with increasing size of the nodule, while the risk of ITC increases as nodule size decreases. CONCLUSION: The risk of malignancy in presumably benign thyroid disease cannot be overlooked, but can be minimized through skillfully performed ultrasonography (US) examination and FNAC. Once a patient with multinodular goiter is referred for follow-up or nonsurgical therapy, careful US surveillance is mandatory.

The risk factors for impulsivity-related falls among hospitalized older adults.

PURPOSE: Falls among older adults are a common, preventable problem associated with increased morbidity and mortality. Impulsivity is a known risk factor for older adult falls; however, there is a gap in evidence demonstrating the unique risk factors associated with impulsivity related falls (IRF). The research explored the association between seven fall risk factors and impulsivity related falls in hospitalized older adults in a community hospital. METHODS: This retrospective descriptive study analyzed the association between seven fall risk factors and IRF in hospitalized older adults. RESULTS: The sample (N = 233) included patients age 65 years and older who had a documented in-patient fall in 2008. Of the falls, 29.7% were classified as IRF. The mean age of patients with IRF was 78 years, with the median day of fall being Day 5 of hospitalization/rehabilitation admission. Logistic regression demonstrated that only inattention and cognitive impairment were significant risk factors for IRF. DISCUSSION: The incidence of IRF was 29.7%. Our findings also indicate that cognitive impairment and inattention are strongest predictors for IRF among usual risk factors. CONCLUSION: Early identification of the unique risk factors associated with IRF could improve identification and reduce fall rates among hospitalized older adults.

Clinical feasibility trial of a motion detection system for fall prevention in hospitalized older adult patients.

The purpose of this pilot study was to test the feasibility of a wireless 5-sensor, motion detection system (5S-MDS) with hospitalized older adults. Interventions to prevent hospital-based falls in older adults are important to reduce morbidity, mortality, and health care costs. Wearable motion sensors, which track and wirelessly transmit body movements, may identify human movement patterns that immediately precede falls, thus allowing early prevention. Descriptive feasibility study in which 5 hospitalized older adults were recruited to wear the 5S-MDS for 4 hours. Measurement included assessment of participant acceptance, skin integrity, and sensor accuracy. All 5 participants (mean age, 90.2 years) agreed that sensors were acceptable and skin integrity was maintained. The sensor data accurately reflected the patient movements. The 5S-MDS was feasible for 4 hours' use with hospitalized older adults. It has potential as an early warning system for falls.

A pilot study testing a fall prevention intervention for older adults: determining the feasibility of a five-sensor motion detection system.

Interventions to prevent hospital-based falls in older adults are critically important to reduce morbidity, mortality, and health care costs. The purpose of this pilot study was to test the accuracy and acceptability of a wireless five-sensor motion detection system (5S-MDS) for detecting falls. Wearable motion sensors, which measure and integrate movement in space, may identify human movement patterns that immediately precede falls, thus allowing prevention. However, sensors must be accurate, and older adults must find wearable sensors acceptable. This descriptive feasibility study recruited 5 healthy older adults (mean age = 69.6) who wore the 5S-MDS while performing 35 movement scenarios. All participants agreed the sensors were acceptable, and skin integrity was maintained for all. The 5S-MDS accurately reflected the patients' movements and was found acceptable to the older adults; thus, the 5S-MDS has potential as an early warning system for falls.

Contributing factors associated with impulsivity-related falls in hospitalized, older adults.

Impulsivity-related falls (IRFs) sustained by hospitalized, older adults can lead to critical adverse events. The purpose of this study was to determine whether 7 common fall risk factors contributed to the occurrence of IRF in hospitalized, older adults. This study found that 31% of falls were classified as IRF. Logistic regression indicated that inattention and mobility were contributors to IRF. Early identification of these 2 risk factors could improve identification of potential IRFs and reduce fall rates.

Evaluating the relationship between inattention and impulsivity-related falls in hospitalized older adults.

Impulsivity in older adults is poorly understood and there is limited literature on the relationship between impulsivity and falls. This retrospective study evaluated the relationship between of inattention and impulsivity related falls (IRF) in hospitalized older adults. The sample (N = 192) included patients 65 years and older with a documented in-patient fall in 2007. "Impaired judgment" was identified as the critical attribute of IRF. The Confusion Assessment Method item for inattention was extracted as the variable for inattention. Twenty-eight percent (28%) of falls were classified as IRF. A significant relationship was found between inattention on the shift prior to a fall and the fall being an IRF (Chi-square = 45.5, df = 1, p = .00, Phi = .54, p = .00). Early identification of older adults with impaired attention has potential to reduce IRF when nursing uses this assessment to implement additional safety interventions for hospitalized older adults.

Synthesis, structural characterization and antiproliferative and toxic bio-activities of copper(II) and nickel(II) citronellal N4-ethylmorpholine thiosemicarbazonates.

This paper reports the syntheses and characterization of ethylmorpholine substituted citronellal thiosemicarbazone copper(II) and nickel(II) metal complexes. The compounds were characterized through elemental analyses and spectroscopic (IR, UV-Vis, NMR, MS) methods. The X-ray analysis of the two complexes shows that both Ni and Cu derivatives present a square planar coordination, where the coordinating homologous donor atoms bind in trans to each other. The compounds were tested for their biological activity after determination of their octanol-saline partition coefficients, followed by their radical scavenging properties. Eventually the complexes were tested for their proliferation inhibition on human histiocytic lymphoma U937 cell line. The GI(50) values resulted to be 2.3microM for the copper derivative and 12.3microM for the nickel derivative.

Synthesis, characterization and deepening in the comprehension of the biological action mechanisms of a new nickel complex with antiproliferative activity.

Thiosemicarbazones are versatile organic compounds that present considerable pharmaceutical interest because of a wide range of properties. In our laboratory we synthesised some new metal-complexes with thiosemicarbazones derived from natural aldehydes which showed peculiar biological activities. In particular, a nickel complex [Ni(S-tcitr)(2)] (S-tcitr=S-citronellalthiosemicarbazonate) was observed to induce an antiproliferative effect on U937, a human histiocytic lymphoma cell line, at low concentrations (IC(50)=14.4microM). Therefore, we decided to study the interactions of this molecule with various cellular components and to characterise the induced apoptotic pathway. Results showed that [Ni(S-tcitr)(2)] causes programmed cell death via down-regulation of Bcl-2, alteration of mitochondrial membrane potential and caspase-3 activity, regardless of p53 function. The metal complex is not active on G(0) cells (i.e. fresh leukocytes) but is able to induce perturbation of the cell cycle on stimulated lymphocytes and U937 cells, in which a G(2)/M block was detected. It reaches the nucleus where it induces, at low concentrations (2.5-5.0microM), DNA damage, which could be partially ascribed to oxidative stress. [Ni(S-tcitr)(2)] is moreover able to strongly reduce the telomerase activity. Although the biological target of this metal complex is still unknown, the reported data suggest that [Ni(S-tcitr)(2)] could be a good model for the synthesis of new metal thiosemicarbazones with specific biological activity.

Complexes of 2-thiophenecarbonyl and isonicotinoyl hydrazones of 3-(N-methyl)isatin. A study of their antimicrobial activity.

Cobalt(II), nickel(II), copper(II) and zinc(II) complexes of 2-thiophenecarbonyl and isonicotinoyl hydrazones of 3-(N-methyl)isatin (HL(1) and HL(2), respectively) were synthesized and characterized, being the crystal structures of HL(1), HL(2) and [Ni(L(1))(2)].2CHCl(3) elucidated by X-ray diffraction techniques. The in vitro antimicrobial activity of all these compounds was tested against several bacteria and fungi. HL(1)and its complexes exhibited a strong inhibition of the growth of Haemophilus influenzae (MIC 0.15-1.50microg/mL) and good antibacterial properties towards Bacillus subtilis (MIC 3-25microg/mL). The minimal inhibitory concentration (MIC) was defined as the lowest concentration of compound inhibiting the growth of each strain. The antibacterial effectiveness was confirmed against a number of Gram positive bacteria, including methicillin-resistant Staphylococcus aureus. Yeasts and moulds showed a low susceptibility, except the dermatophyte mould Epidermophyton floccosum that is inhibited at concentrations ranging from 6 to 50microg/mL. In general, the antimicrobial activity of the thiophene derivatives was greater than that of the isonicotinic analogues.

Zinc complexes with cyclic derivatives of alpha-ketoglutaric acid thiosemicarbazone: Synthesis, X-ray structures and DNA interactions.

Six new cyclic ligands derived from alpha-ketoglutaric acid thiosemicarbazone (H(3)ct) and their zinc complexes have been synthesized and characterized by analytical and spectroscopic (IR and NMR) studies. The X-ray structures of ligands Me-H(2)ct(C) (1), Allyl-H(2)ct(c) (3) and of complex [Zn(Me-Hct(C))(2)(OH(2))(2)].2H(2)O (7) have been determined. In complex (7) the zinc atom lies on a twofold axis and is surrounded in a tetrahedral coordination by two water molecules and two carboxylic oxygen donor atoms from the ligand. DNA titration in the UV-visible region and thermal denaturation have been employed to determine the details of DNA binding for the studied compounds. Studies of nuclease activity have also been performed with all our compounds through a gel electrophoresis experiment using plasmid pBR322 showing that no DNA breakings take place. Tests in vitro on human leukemia cell line U937 have been carried out on cell growth inhibition where solubility of the compounds allowed the experiments.

Copper(II) and cobalt(III) pyridoxal thiosemicarbazone complexes with nitroprusside as counterion: syntheses, electronic properties, and antileukemic activity.

In this paper the syntheses of new pyridoxal thiosemicarbazone copper(II) and cobalt(III) complexes with nitroprusside as a counterion and tests on the antileukemic activity of three of these complexes toward human cell lines U937 and CEM are reported. Nitroprusside was chosen in order to test if its ability to release NO can increase the biological activity already shown by these complexes. The compounds were characterized by spectroscopic and magnetic methods and by single-crystal X-ray diffraction.

Copper(II) complexes with substituted thiosemicarbazones of alpha-ketoglutaric acid: synthesis, X-ray structures, DNA binding studies, and nuclease and biological activity.

New alpha-ketoglutaric acid thiosemicarbazone (H(3)ct) derivatives and their copper complexes were synthesized and characterized by analytical and spectroscopic (IR and NMR) methods. For two of the ligands, Me-H(3)ct and Allyl-H(3)ct, and for a complex, [Cu(Me-Hct)(OH(2))](n) x 2nH(2)O, the X-ray structures were also determined. In the latter the copper atom shows a 4 + 1 pyramidal coordination, a water oxygen appears in the apical position, and three of the basal positions are occupied by the SNO tridentate ligand and the fourth by a carboxylic oxygen of an adjacent molecule that gives rise to a polymeric chain. DNA binding constants were determined, and studies of thermal denaturation profiles and nuclease activity were also performed. Tests in vitro on human leukemia cell line U937 were carried out on cell growth inhibition, cell cycle, and apoptosis induction.

Synthesis, characterization and biological activity of copper complexes with pyridoxal thiosemicarbazone derivatives. X-ray crystal structure of three dimeric complexes.

A dimeric copper complex of the unsubstituted pyridoxal thiosemicarbazone (H(2)L), [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O, previously tested on Friend murine cell lines has been recently resynthesized to evaluate its behavior on different murine and human leukemic cell lines and has been compared, in vitro and in vivo, with its monomeric counterpart [Cu(H(2)L)(OH(2))Cl]Cl. On TS/A murine adenocarcinoma cell line in vitro, both compounds significantly inhibit cell proliferation at micromolar concentrations, although the dimeric compound is more active. Despite this cytotoxicity they lack in vivo activity on TLX5 lymphoma. The unsubstituted dimeric [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O induces apoptosis on CEM and U937 human cell lines, with IC(50) concentrations of 1.2 x 10(-5) and 6.7 x 10(-6) M, respectively, but it is inactive on K562. Moreover, it alters significantly the cell cycle of U937 and CEM lines and decreases the telomerase activity of U937. To verify if other dimeric copper complexes show relevant biological activity new complexes with N-substituted pyridoxal thiosemicarbazones have been synthesized and characterized using spectroscopic techniques. Three of them, namely [Cu(Me(2)-HL)Cl](2).6H(2)O (Me(2)-H(2)L=pyridoxal N1,N1-dimethylthiosemicarbazone) (1), [Cu(MeMe-HL)Cl](2)Cl(2).4H(2)O (MeMe-HL=pyridoxal N1,N2-dimethylthiosemicarbazone) (2), [Cu(Et-H(2)L)Cl](2)Cl(2).2H(2)O (Et-H(2)L=pyridoxal N1-ethylthiosemicarbazone) (3), were also characterized by X-ray diffractometry. These complexes are dimeric and all three present a square pyramidal coordinative geometry with the ligand showing an SNO tridentate behavior. Their biological activities have been tested in vitro on U937, CEM and K562 cell lines to ascertain their effectiveness in comparison to the corresponding unsubstituted complex [[Cu(HL)(OH(2))](2)]Cl(2).2H(2)O. Compound 1 shows weak proliferation inhibition on all three cell lines, but it does not induce apoptosis and it does not inhibit telomerase activity, compound 2 is not effective at low concentration and is toxic at higher doses; compound 3 inhibits CEM cell growth better than complex 1 but it does not exert any other biological effect.

Cu(II) complexes with heterocyclic substituted thiosemicarbazones: the case of 5-formyluracil. Synthesis, characterization, x-ray structures, DNA interaction studies, and biological activity.

Two new 5-formyluracil thiosemicarbazone (H(3)ut) derivatives, Me-H(3)ut (1) and Me(2)-H(3)ut (2), were synthesized by reacting thiosemicarbazides, mono- and dimethylated on the aminic nitrogen, with 5-formyluracil and were subsequently characterized. These ligands, treated with copper chloride and nitrate, afforded three complexes: [Cu(Me-H(3)ut)Cl(2)].H(2)O (3), [Cu(Me(2)-H(3)ut)Cl(2)].H(2)O (4), and [Cu(Me-H(3)ut)(NO(3))(OH(2))(2)]NO(3) (5). The crystal structures of these complexes have been determined by single-crystal X-ray diffraction. In 3 and 4, a similar pentacoordination is present; the copper atom is surrounded by the ligand SNO donor atoms and by two chloride ions. The structure of 5 consists of [Cu(Me-H(3)ut)(NO(3))(OH(2))(2)](+) cations and nitrate anions. The copper coordination (4 + 2) involves the SNO ligand atoms and a water oxygen in the basal plane; the apical positions are occupied by a second water oxygen and by an oxygen of a monodentate nitrate group. Two biochemical techniques, namely DNA titration in the UV-vis region and thermal denaturation, have been employed to probe the details of DNA binding of these compounds. Analysis of the results suggests that our compounds are able to interact with DNA by electrostatic and groove binding but not by intercalation. The compounds have been also tested in vitro on human leukemic cell line U937, but they are not able to inhibit significantly cell proliferation.

Synthesis, characterization and X-ray structures of new antiproliferative and proapoptotic natural aldehyde thiosemicarbazones and their nickel(II) and copper(II) complexes.

Synthesis and characterization of new thiosemicarbazones derived from natural aldehydes (1-9) have been investigated in order to develop a research program aimed at the development of compounds with antiviral, antibacterial, and antitumor properties. These substances contain both a chain with N and S nucleophilic centers with tuberculostatic activity, and an alkyl or terpenic moiety. In addition, a few nickel(II) and copper(II) complexes (10-18), derived also from the previously studied ligands, were synthesized and characterized by means of NMR and IR techniques. The trans-2-octenal N(1)-phenylthiosemicarbazone and its nickel complex were also characterized by X-ray diffractometry. Biological studies, performed with some of these compounds, have involved both inhibition of cell proliferation and apoptosis tests in vitro on human leukemia cell line U937 to deepen our knowledge on the way these substances interfere with biological processes in leukemic cells.

Synthesis, characterization and biological activity of two new polymeric copper(II) complexes with alpha-ketoglutaric acid thiosemicarbazone.

In this paper we describe the synthesis of new copper complexes with alpha-ketoglutaric acid thiosemicarbazone. The crystal structures of the two compounds: [Cu(H(2)ct)Cl](n) [(Cu(H(2)ct)Cl)(2)] (1) and [Cu(Hct)](n).3nH(2)O (2) (H(3)ct=alpha-ketoglutaric acid thiosemicarbazone) have been determined by X-ray and spectroscopic methods. In 1 two independent copper atoms are present. Cu(1), in a nitrogen- and oxygen-bridged polymer, is a six-coordinated (4+2), Cu(2), five coordinated (4+1), is a chlorine-bridged dimer. In 2 the copper atom presents a penta-coordination, polymeric chains form layers and the -CH(2)CH(2)COO(-) groups bridge copper atoms. In 1 a monodentate and in 2 a syn-anti bidentate bridging carboxylate are present. The biological properties of 1 and 2 and also of the free ligand (H(3)ct) were tested in vitro and compared on Friend erythroleukemia cells (FLC) and on human leukemia cell lines K562 and U937. On the FLC cells the free ligand does not inhibit cell growth, but increases the DNA synthesis; complex 1 inhibits cell proliferation and increases the DNA synthesis; complex 2 inhibits cell growth, but induces a decrement of DNA synthesis and increases the reverse transcriptase activity. Regarding the human cell lines, both complexes show proliferation inhibition through an apoptosis mechanism on cell line U937, while they have no effects on the K562 line.