Study and implementation of a performance set of indicators for the nurse manager in a frailty hospital.

INTRODUCTION: Hospitals are known to be the most complex entities to manage. In fact, the main problem in healthcare are the expensive needs with limited resources. During the last years the complexity of the nurse manager role has gradually changed from assistance to management. However, nowadays the methods for quantifying the nurse managers' skills and performance are not available. The aim of this study is to implement a method to assess and measure the skills of the nurse managers. An innovative indicator to globally evaluate the features, the professional skills and their performance is described. METHODS: The authors started with an interview with the directors of all the nurses as the top experts of the nurse managers' technical skills. The purpose of this step was to understand what were the features of a valuable nurse manager. The methods identified three different aspects (qualitative, quantitative and relational) that were transformed in a single indicator. These parameters also enable to identify the strengths and weaknesses of each professional. An important implication of this score is the possible improvement of loss-making skills. RESULTS: A total of 18 centres, with their nurse managers, were evaluated in this study. All the results confirmed the judgment of the Healthcare Professions Structure Manager. CONCLUSIONS: This assessment method, validated with these tests, evaluated the nurse manager's ability to deal with personnel, resources and patients and to quantify his/her organizational and welfare performances. It is useful for planning actions that allow nurse managers to improve their skills.

Metal ion regulation of gene expression. Fur repressor-operator interaction at the promoter region of the aerobactin system of pColV-K30.

Transcription of the iron-controlled aerobactin operon of the enterobacterial plasmid pColV-K30 is negatively regulated through the interaction of a Fe2+-binding repressor (the Fur protein) with operator sequences within the promoter region of the operon. The DNA sequences essential for interaction with the repressor were located by site-directed mutagenesis of specific regions within the 31 base-pair protected by the repressor from DNase I nicking. Occupation of two contiguous repressor-binding sites appears to be required for the complete repression of the system. Contacts of the Fur repressor with the corresponding operator sequences were analyzed with hydroxyl radical footprint and methylation protection experiments. These indicate that DNA-protein contacts approach a symmetrical mode and take place at all sides of the DNA helix.

Treatment of an aneurysm of the celiac artery arising from a celiomesenteric trunk. Report of a case.

INTRODUCTION: Visceral artery aneurysms (VAA) are rare, frequently present as a life-threatening emergency and are often fatal. The celiacomesenteric trunk (CMT), a common origin of the celiac trunk (CT) and the superior mesenteric artery (SMA) from abdominal aorta, is quite rare. Aneurysms that involve this celiomesenteric anomaly are even rarer and in the last 32 years have been reported in only 20 cases in the literature. PRESENTATION OF CASE: We describe a case with 30mm aneurysm arising from a CMT. In general, an aneurysm that is 20mm or greater in size is considered to be significant enough to warrant treatment. Abdominal VAA sometimes can be treated with low-invasive procedures: our patient required open surgical repair with the celiac artery replanted on to the aorta. DISCUSSION: The clinical course was complicated only by an increase of hepatic cytolysis enzymes, and by a low output pancreatic fistula, treated conservatively. The patient was discharged on the fifteenth postoperative day. One month after discharge, imaging revealed a good patency of all reconstructed arteries. In the subsequent 36-month follow-up period, the patient reported no clinical episodes. CONCLUSION: Our finding of a very rare case of a celiomesenteric anomaly with a concurrent aneurysm is extremely rare (20 cases in word literature in the last 32 years). The feasibility of the endovascular approach for aneurysms originating from the common celiomesenteric trunk depends mainly on aneurysmal location, diameter and neck size. In case of specific unfit anatomy, a careful surgical treatment can ensure the best results.

Peptide neurotoxins, small-cell lung carcinoma andneurological paraneoplastic syndromes.

Peptide neurotoxins isolated from the venom of snakes, spiders and snails have represented invaluable tools for the identification and characterisation of membrane ion channels and receptors in vertebrate cells, including human neurons. We here report on the use of these toxins for the characterisation of membrane ion channels and receptors expressed by one of the most aggressive human cancers, small-cell lung carcinoma. This tumour shares many properties with other neuro-endocrine cell types, including the ability of firing action potentials and release hormones in a calcium-dependent manner. Toxins such as alpha-bungarotoxin and omega-conotoxins, among others, have been successfully used to characterise neuronal nicotinic receptors and voltage-dependent calcium channels, respectively, in human small-cell lung carcinoma cells. These receptors and ion channels are not only crucial for the growth of this specific tumour, but also represent autoantigens against which cancer patients build an autoimmune response. Although the aim of this autoimmune response is eventually the destruction of the cancer cells, the circulating antibodies cross-react with similar ion channels and receptors present in normal neurons or other cells, causing a number of different paraneoplastic diseases, the best characterised of which is the Lambert-Eaton myasthenic syndrome. Conotoxin-based radioimmunoassays have become an invaluable tool for the diagnosis and follow up of these paraneoplastic disorders and could represent a step forward in the early diagnosis of small-cell lung carcinoma itself.

Calcium channel subtypes contributing to acetylcholine release from normal, 4-aminopyridine-treated and myasthenic syndrome auto-antibodies-affected neuromuscular junctions.

1 Acetylcholine release at the neuromuscular junction relies on rapid, local and transient calcium increase at presynaptic active zones, triggered by the ion influx through voltage-dependent calcium channels (VDCCs) clustered on the presynaptic membrane. Pharmacological investigation of the role of different VDCC subtypes (L-, N-, P/Q- and R-type) in spontaneous and evoked acetylcholine (ACh) release was carried out in adult mouse neuromuscular junctions (NMJs) under normal and pathological conditions. 2 omega-Agatoxin IVA (500 nM), a specific P/Q-type VDCC blocker, abolished end plate potentials (EPPs) in normal NMJs. However, when neurotransmitter release was potentiated by the presence of the K(+) channel blocker 4-aminopyridine (4-AP), an omega-agatoxin IVA- and omega-conotoxin MVIIC-resistant component was detected. This resistant component was only partially sensitive to 1 micro M omega-conotoxin GVIA (N-type VDCC blocker), but insensitive to any other known VDCC blockers. Spontaneous release was dependent only on P/Q-type VDCC in normal NMJs. However, in the presence of 4-AP, it relied on L-type VDCCs too. 3 ACh release from normal NMJs was compared with that of NMJs of mice passively injected with IgGs obtained from patients with Lambert-Eaton myasthenic syndrome (LEMS), a disorder characterized by a compromised neurotransmitter release. Differently from normal NMJs, in LEMS IgGs-treated NMJs an omega-agatoxin IVA-resistant EPP component was detected, which was only partially blocked by calciseptine (1 micro M), a specific L-type VDCC blocker. 4 Altogether, these data demonstrate that multiple VDCC subtypes are present at the mouse NMJ and that a resistant component can be identified under 'pharmacological' and/or 'pathological' conditions.

Lipid hydroperoxide induced mitochondrial dysfunction following acute ethanol intoxication in rats. The critical role for mitochondrial reduced glutathione.

It has been found that acute ethanol (EtOH) intoxication of rats caused depletion of mitochondrial reduced glutathione (GSH) of approximately 40%. A GSH reduction of similar extent was also observed after the administration to rats of buthionine sulphoximine (BSO), a specific inhibitor of GSH synthesis. Combined treatment with BSO plus EtOH further decreased mitochondrial GSH up to 70% in comparison to control. Normal functional efficiency was encountered in BSO-treated mitochondria, as evaluated by membrane potential measurements during a complete cycle of phosphorylation. In contrast a partial loss of coupled functions occurred in mitochondria from EtOH- and BSO plus EtOH-treated rats. The presence in the incubation system of either GSH methyl monoester (GSH-EE), which normalizes GSH levels, or of EGTA, which chelates the available Ca2+, partially restores the mitochondrial phosphorylative efficiency. Following EtOH and BSO plus EtOH intoxication, the presence of fatty-acid-conjugated diene hydroperoxides, such as octadecadienoic acid hydroperoxide (HPODE), was detected in the mitochondrial membrane. Exogenous HPODE, when added to BSO-treated mitochondria, induced, in a concentration-dependent system, membrane potential derangement. The presence of either GSH-EE or EGTA fully prevented a drop in membrane potential. The results obtained suggest that fatty acid hydroperoxides, endogenously formed during EtOH metabolism, brought about non-specific permeability changes in the mitochondrial inner membrane whose extent was strictly dependent on the level of mitochondrial GSH.

Zidovudine-induced experimental myopathy: dual mechanism of mitochondrial damage.

Myopathy often complicates Zidovudine (AZT) treatment in patients with acquired immunodeficiency syndrome (AIDS). The pathogenesis of the myopathy is controversial, since clinical phenomena intrinsic to AIDS may interfere per se with the onset of the myopathy. In the present work we investigated the in vivo effect of AZT in an animal model species (rat) not susceptible to HIV infection. Histochemical and electron microscopic analyses demonstrated that, under the experimental conditions used, the in vivo treatment with AZT does not cause in skeletal muscle true dystrophic lesions, but rather mitochondrial alterations confined to the fast fibers. In the same animal models, the biochemical analysis confirmed that mitochondria are the target of AZT toxicity in muscles. The effects of AZT on mitochondria energy transducing mechanisms were investigated in isolated mitochondria both in vivo and in vitro. Membrane potential abnormalities, due to a partial impairment of the respiratory chain capability observed in muscle mitochondria from AZT-treated rats, closely resemble those of control mitochondria in the presence of externally added AZT. mtDNA deletion analysis by PCR amplification and Southern blot analysis did not show any relevant deletion, while mtDNA depletion analysis demonstrated a significant decrease in mtDNA in AZT-treated rats. The present findings show that AZT causes damage to mitochondria by two mechanisms: a short-term mechanism that affects directly the respiratory chain, and a long-term mechanism that alters the mitochondrial DNA thus impairing the mitochondrial protein synthesis. In addition, the ultrastructural observations indicate that the fiber types are differently affected upon AZT treatment, which poses a number of questions as to the pathogenesis of this myopathy.

Neuropsychological outcome of survivors of out-of-hospital cardiac arrest.

Thirty patients resuscitated from out-of-hospital cardiac arrest (15 with and 15 without postanoxic coma on admission) underwent a clinical examination and neuropsychological testing. In order to assess quality of life, they were compared to two matched control groups; 15 patients with previous myocardial infarction and 15 healthy subjects. None of the survivors showed severe neurologic impairment, and all had returned to self-sufficient physical activity. However, the behavior rating scale scores were significantly worse in patients with postanoxic coma. The processing ability linked to memory was significantly worse in the postanoxic coma group. Mood disorders were also observed in this group, but they did not have pathological significance. The remarkably low incidence of neurologic and psychological sequelae in these resuscitated patients, particularly in those with early clinical evidence of severe cerebral damage, is an encouraging result that supports the therapeutic systems development and efforts in the management of out-of-hospital cardiac arrest.

In progress identification of radon prone areas: Toscana and Veneto.

Two studies aimed at defining radon prone areas in Toscana and Veneto, based on indoor measurements, are merged in this paper to extract the key points for a possible general methodology. In territorial units, the geometric mean (GM) and standard deviation (GSD) are evaluated from empirical data and the fraction of dwellings above the reference level (RL) is derived according to a log-normal model. In Toscana the sampling base is made of nearly 1,000 measurements (dwellings and kindergartens), apportioned according to the lithological classes (22) of the region. In Veneto 1,230 measurements in dwellings of the upper part of the region (estimates are given for the south), have been assigned to 6 x 5 km2 sequential units of the territory: the detection floor has been considered and results are referred to the regional mean dwellings condition with respect to the floor. Empirical GM and GSD values are corrected to increase statistical power based on two different methods. Maps of the percentages of dwellings with more than 200 Bq x m(-3) are presented. Areas with magmatic rocks in southern Toscana and northern parts of Vicenza and Belluno provinces in Veneto clearly emerge with more than 10% of dwellings above 200 Bq x m(-3). Efforts are required to establish proper confidence limits for estimates and to trace radon maps upon an administrative basis.

[Jejunal mucosectomy as a preliminary technique of pancreatico-jejunal anastomosis]. / La mucosectomia digiunale come momento preliminare dell'anastomosi pancreatico-digiunale.

The Authors describe mucosectomy as a preliminary technique to pancreatico-jejunal anastomosis. The removal of the last few centimeters of the jejunal mucosa enhances the perfect adhesion of the loop to the pancreatic parenchyma. Results seem to confirm theory: in our experience, "telescopic" technique associated with mucosectomy and somatostatin administration prevented so far anastomotic leakages.

Nefopam or clonidine in the pharmacologic prevention of shivering in patients undergoing conscious sedation for interventional neuroradiology.

The aim of this randomised, double-blind study was to investigate the usefulness of intravenous nefopam, clonidine or placebo in preventing shivering in patients undergoing conscious sedation for interventional neuroradiological procedures. A total of 101 patients were prospectively enrolled and assigned to one of three groups to receive nefopam, clonidine or placebo. The overall incidence of intra-operative shivering was significantly lower in patients treated with nefopam than in those treated with clonidine or placebo (2/32 (6%) vs. 11/38 (29%), p < 0.02; 2/32 (6%) vs. 24/31 (77%), p < 0.0001, respectively). The number of patients who required ephedrine infusions to maintain a mean arterial pressure of 100 mm Hg was higher in the clonidine group than in the nefopam and placebo groups (18/38 (47%) vs. 5/32 (17%), p < 0.05; 18/38 (47%) vs. 6/31 (19%), p < 0.05, respectively). We found that both nefopam and clonidine significantly lowered the rate and severity of shivering during interventional neuroradiological procedures. Fewer patients in the nefopam group than in the other two groups required vasoactive drugs.

Inactivation properties of human recombinant class E calcium channels.

The electrophysiological and pharmacological properties of alpha(1E)-containing Ca(2+) channels were investigated by using the patch-clamp technique in the whole cell configuration, in HEK 293 cells stably expressing the human alpha(1E) together with alpha(2b) and beta(1b) accessory subunits. These channels had current-voltage (I-V) characteristics resembling those of high-voltage-activated (HVA) Ca(2+) channels (threshold at -30 mV and peak amplitude at +10 mV in 5 mM Ca(2+)). The currents activated and deactivated with a fast rate, in a time- and voltage-dependent manner. No difference was found in their relative permeability to Ca(2+) and Ba(2+). Inorganic Ca(2+) channel blockers (Cd(2+), Ni(2+)) blocked completely and potently the alpha(1E,)/alpha(2b)delta/beta(1b) mediated currents (IC(50) = 4 and 24.6 microM, respectively). alpha(1E)-mediated currents inactivated rapidly and mainly in a non-Ca(2+)-dependent manner, as evidenced by the fact that 1) decreasing extracellular Ca(2+) from 10 to 2 mM and 2) changing the intracellular concentration of the Ca(2+) chelator 1. 2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA), did not affect the inactivation characteristics; 3) there was no clear-cut bell-shaped relationship between test potential and inactivation, as would be expected from a Ca(2+)-dependent event. Although Ba(2+) substitution did not affect the inactivation of alpha(1E) channels, Na(+) substitution revealed a small but significant reduction in the extent and rate of inactivation, suggesting that besides the presence of dominant voltage-dependent inactivation, alpha(1E) channels are also affected by a divalent cation-dependent inactivation process. We have analyzed the Ca(2+) currents produced by a range of imposed action potential-like voltage protocols (APVPs). The amplitude and area of the current were dependent on the duration of the waveform employed and were relatively similar to those described for HVA calcium channels. However, the peak latency resembled that obtained for low-voltage-activated (LVA) calcium channels. Short bursts of APVPs applied at 100 Hz produced a depression of the Ca(2+) current amplitude, suggesting an accumulation of inactivation likely to be calcium dependent. The human alpha(1E) gene seems to participate to a Ca(2+) channel type with biophysical and pharmacological properties partly resembling those of LVA and those of HVA channels, with inactivation characteristics more complex than previously believed.

Fur (ferric uptake regulation) protein and CAP (catabolite-activator protein) modulate transcription of fur gene in Escherichia coli.

A fusion between the fur (ferric uptake regulation) gene, known to mediate negative regulation of iron absorption in Escherichia coli, and lacZ was constructed in vitro. beta-Galactosidase levels of cells harboring this fusion were under the control of sequences contained in a 185-bp DNA fragment located upstream of the fur structural gene. The fusion was prepared in multicopy (pVLN102 plasmid) and low-copy-number states, the latter constructed as a lambda phage lysogen carrying a fur'-'lacZ insert. DNase I footprinting experiments with purified Fur protein, performed on a 250-bp restriction fragment carrying the promoter region of the fusion, showed the presence of a single Fur-protected site overlapping the -10 region of a potential promoter sequence. Examination of the DNA sequences located upstream of the fur gene revealed a possible binding site for the catabolite-activator protein (CAP). beta-Galactosidase synthesis of E. coli cells harboring the fusion were measured in fur, crp and cya genetic backgrounds and compared with the corresponding levels in wild-type strains. The data obtained indicate a moderate autoregulation of fur expression by its gene product and also a significant stimulation by the cAMP-CAP system. Transcription start sites were mapped by primer-extension experiments with total RNA obtained in vivo from cells harboring pVLN102. The results show that transcription of the fur gene is initiated from at least two different sites separated by 6 bp, which appear to originate from two overlapping promoters sensitive to catabolic activation.

Membrane potential of hepatic mitochondria after acute cocaine administration in rats--the role of mitochondrial reduced glutathione.

Cocaine hepatotoxicity may be mediated by oxidative damage, possibly involving mitochondrial injury. The effect of an acute dose of cocaine in rats on the mitochondrial level of reduced glutathione, nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), important determinants in cellular defense against oxidative stress, was investigated. Under these conditions, the extent of lipid peroxidation was assessed as thiobarbituric acid reactive substances formation and the energy transducing capability of the inner mitochondrial membrane was evaluated by membrane potential measurements. Female Wistar albino rats were given an acute 50 mg/kg intraperitoneal dose of cocaine and, 6 hours later, hepatic and mitochondrial biochemical analyses were made. Rats administered intraperitoneally, 7.5 hours before the sacrifice, a specific inhibitor of glutathione synthesis, L-buthionine-(S,R)-sulphoximine, either alone or in combination with cocaine, underwent in parallel the same determinations. Cocaine intoxication did not impair mitochondrial functions, although a significant increase of lipid peroxidation occurred. By contrast the combination of L-buthionine-(S,R)-sulphoximine with cocaine induced a severe derangement of mitochondrial functional efficiency, a large depletion of reduced glutathione, and a further enhancement of lipid peroxidation. The mitochondrial functional anomalies were largely restored by the use of cyclosporin A, ethyleneglycotetraacetic acid (EGTA) and glutathione methylmonoester. A nonspecific calcium dependent inner membrane permeabilty transition (pore opening) accounted for the partial loss of mitochondrial coupled functions at a period of cocaine intoxication when no cell damage occurred. The level of mitochondrial glutathione played a critical role in protecting inner membrane functional integrity against cocaine-induced oxidative stress.

Iron-induced oxidant stress leads to irreversible mitochondrial dysfunctions and fibrosis in the liver of chronic iron-dosed gerbils. The effect of silybin.

Hepatic iron toxicity because of iron overload seems to be mediated by lipid peroxidation of biological membranes and the associated organelle dysfunctions. However, the basic mechanisms underlying this process in vivo are still little understood. Gerbils were dosed with weekly injections of iron-dextran alone or in combination with sylibin, a well-known antioxidant, by gavage for 8 weeks. A strict correlation was found between lipid peroxidation and the level of desferrioxamine chelatable iron pool. A consequent derangement in the mitochondrial energy-transducing capability, resulting from a reduction in the respiratory chain enzyme activities, occurred. These irreversible oxidative anomalies brought about a dramatic drop in tissue ATP level. The mitochondrial oxidative derangement was associated with the development of fibrosis in the hepatic tissue. Silybin administration significantly reduced both functional anomalies and the fibrotic process by chelating desferrioxamine chelatable iron.

Relationship between free iron level and rat liver mitochondrial dysfunction in experimental dietary iron overload.

The concentration of total iron in the hepatic tissue and mitochondria from rats fed a 2.5% carbonyl iron supplemented diet progressively increased up to 40 days, then reached nearly a steady-state. By contrast the level of free iron (desferrioxamine-chelatable) exhibited a transient but significant increase at 40 days of treatment, only in this period of treatment the induction of lipid peroxidation and the resulting mitochondrial abnormalities in calcium transport was observed too. The enhancement of the energy dissipating mitochondrial calcium cycling was found to be associated with a significant decrease of endogenous mitochondrial ATP content. As to the pathophysiological mechanism for hepatocellular injury in iron overload, these results indicated that the transit pool of free iron may play a critical role in initiating organelle dysfunctions, at least in this experimental model of iron overload.

N-acetylcysteine inhibits in vivo nitric oxide production by inducible nitric oxide synthase.

This in vivo study evaluates the effect of N-acetylcysteine (NAC) administration on nitric oxide (NO) production by the inducible form of nitric oxide synthase (iNOS). NO production was induced in the rat by the ip administration of 2 mg/100 g lipopolysaccharide (LPS). This treatment caused: (1) a decrease in body temperature within 90 min, followed by a slow return to normal levels; (2) an increase in plasma levels of urea, nitrite/nitrate, and citrulline; (3) the appearance in blood of nitrosyl-hemoglobin (NO-Hb) and in liver of dinitrosyl-iron-dithiolate complexes (DNIC); and (4) increased expression of iNOS mRNA in peripheral blood mononuclear cells (PBMC). Rat treatment with 15 mg/100 g NAC ip, 30 min before LPS, resulted in a significant decrease in blood NO-Hb levels, plasma nitrite/nitrate and citrulline concentrations, and liver DNIC complexes. PBMC also showed a decreased expression of iNOS mRNA. NAC pretreatment did not modify the increased levels of plasma urea or the hypothermic effect induced by the endotoxin. The administration of NAC following LPS intoxication (15 min prior to sacrifice) did not affect NO-Hb levels. These results demonstrate that NAC administration can modulate the massive NO production induced by LPS. This can be attributed mostly to the inhibitory effect of NAC on one of the events leading to iNOS protein expression. This hypothesis is also supported by the lack of effect of late NAC administration.

'Free' iron, as detected by electron paramagnetic resonance spectroscopy, increases unequally in different tissues during dietary iron overload in the rat.

'Free' iron concentration, as determined by electron paramagnetic resonance (EPR) spectroscopy, and lipid peroxidation (LPO), as determined by thiobarbituric acid test, were assessed in the lung, heart, liver, spleen, brain and kidney of rats subjected to experimental iron overload. Two tests, Desferal- and NO-available iron, were used to measure 'free' iron and gave comparable results. The most pronounced accumulation of 'free' iron was observed in liver, kidney and spleen. Differences between control and iron loaded animals increased during the initial 90 days of treatment. Between 90 and 180 days 'free' iron concentration reached a steady state level, or even decreased, as in the case of liver. Lipid peroxidation level, measured in the organs of both treated and matched controls, did not give any significant difference during the initial 90 days of treatment. A significant augmentation was observed in liver, kidney, spleen and heart at 180 days. The results of the present research show that, under conditions of moderate siderosis, the occurrence of LPO is partially related to the level of 'free' iron.

Antioxidant activity of silybin in vivo during long-term iron overload in rats.

BACKGROUND & AIMS: Hepatic iron toxicity may be mediated by free radical species and lipid peroxidation of biological membranes. The antioxidant property of silybin, a main constituent of natural flavonoids, was investigated in vivo during experimental iron overload. METHODS: Rats were fed a 2.5% carbonyl-iron diet and 100 mg.kg body wt-1.day-1 silybin for 4 months and were assayed for accumulation of hepatic lipid peroxidation by-products by immunocytochemistry, mitochondrial energy-dependent functions, and mitochondrial malondialdehyde content. RESULTS: Iron overload caused a dramatic accumulation of malondialdehyde-protein adducts into iron-filled periportal hepatocytes that was decreased appreciably by silybin treatment. The same beneficial effect of silybin was found on the iron-induced accumulation of malondialdehyde in mitochondria. As to the liver functional efficiency, mitochondrial energy wasting and tissue adenosine triphosphate depletion induced by iron overload were successfully counteracted by silybin. CONCLUSIONS: Oral administration of silybin protects against iron-induced hepatic toxicity in vivo. This effect seems to be caused by the prominent antioxidant activity of this compound.