Could shared decision making affect staying in hospital? A cross-sectional pilot study.

BACKGROUND: Shared Decision Making (SDM) is an approach where clinicians and patients share the best available evidence to make decision and where patients opinions are considered. This approach provides benefits for patients, clinicians and health care system. The aim of the present study is to investigate the patients' perception of their participation in treatment choices and to identify the possible influences of variables in decision aids and therapeutic choices. Furthermore the present study evaluates the impact of SDM on the length of hospital stay and the health expenditure in Piemonte, an Italian region. METHODS: A cross-sectional study was performed in 2016. The patients were selected after hospitalization to clinical and surgical units at the Rivoli and Susa Hospital. Data were collected through the questionnaire and the Hospital Discharge Registers. STROBE guidelines for observational studies were used. A descriptive analysis was conducted. Frequencies and percentages of the categorical variables were reported. Statistical analyses were performed using t-test, chi-square test and Mann-Whitney test. RESULTS: The final sample was made of 174 subjects. More than half of the sample reported a SDM approach. Female gender (p = 0.027) and lower age (p = 0.047) are associated with an increased possibility to report SDM. Receiving "good" or "excellent" information, having their own request fulfilled and their opinions took into account by healthcare professionals, were all found to be predictors for an approach recognized as SDM (p ≤ 0.05). The perception that healthcare professionals spent a proper amount of time with the patients and used an understendable language are factors increase the chance of a "shared" decision process (p ≤ 0.05). The patients trust in the information given by the healthcare professional is not affecting their perception about the decision making process (P = 0.195). No significant difference where recorded in length of stay and hospital expenditure. CONCLUSIONS: The data show the role played by different dimension of the patients-clinician relationship and that the strongest determinant of a perceived shared decision making approach are healthcare professional-depending.

Dentigerous cyst in primary dentition: a case report.

Dentigerous cyst is a developmental odontogenic cyst, which apparently develops by accumulation of fluid between the reduced enamel epithelium and the tooth crown of an unerupted tooth. There is usually no pain or discomfort associated with the cyst unless there is acute inflammatory exacerbation. Management of dentigerous cyst in primary dentition needs special consideration regarding the preservation of the developing permanent tooth buds. Here, we report a case of dentigerous cyst in primary dentition in a 10-year-old male patient and its management.

The possible role of free fatty acids in the pathogenesis of cholesterol gallstones in man.

The lipid composition of hepatic and gallbladder bile was examined in 20 patients with cholesterol gallstones and in 20 control subjects. Lipid fractions other than bile salts, phospholipids and cholesterol were found to be present, i.e., sterol esters, non-identified fractions and, above all, free fatty acids. The latter probably originated from biliary phospholipids via activity of phospholipases, present in the gallbladder wall. No significant difference in amount and pattern of free fatty acids and phospholipids was found in hepatic bile between patients with gallstones and controls. On the contrary, we observed relevant differences in the lipid composition of gallbladder bile. In this way, we consider that the bile becomes lithogenic inside the gallbladder as a consequence of release of free fatty acids, particularly if these are constituted by saturated chains. In fact, these can compete with cholesterol in the solubilization in biliary micelles. On the other hand, free fatty acids can be directly toxic for the gallbladder wall and produce a cholecystitis.

Free fatty acids: a stimulus for mucin hypersecretion in cholesterol gallstone biles.

The concentration of free fatty acids, phosphatidylcholine and lysophosphatidylcholine, and the fatty acid composition as well as the levels of the mucins, analyzed by an improved GLC method, were examined in ten biles from patients with cholesterol gallstones (pathological biles) and in ten control biles. In pathological biles the amounts of free fatty acids and phosphatidylcholine, were significantly higher (8.99 +/- 1.09) vs. 2.75 +/- 0.62 micrograms/mg) and lower (6.62 +/- 0.71 vs. 21.91 +/- 3.86 micrograms/mg), respectively, than in control biles, indicating that a relationship exists between the two lipid fractions. Lysophosphatidylcholine concentrations remained unchanged in the two groups (1.02 +/- 0.55 micrograms/mg in pathological biles vs. 1.32 +/- 0.57 micrograms/mg in control biles). The increased levels of free fatty acids were directly correlated (r = 0.73, P less than 0.05) with biliary hypersecretion of mucus glycoproteins. Acetylglucosamine and acetylgalactosamine were significantly higher in pathological biles than in control biles (1.91 +/- 0.67 vs. 0.60 +/- 0.13 microgram/mg). The nucleating potency of the increased amounts of mucins, coupled with lowered levels of phosphatidylcholine, might play a very important role in stone formation and precipitation.

Saturated dicarboxylic acids as products of unsaturated fatty acid oxidation.

Upon chemical, radiation-induced or enzymatic oxidation, cis-polyunsaturated fatty acids, i.e., C18:2(n-6), C18:3(n-3), C20:2(n-6), C20:3(n-6), C20:3(n-3), C20:4(n-6), C20:5(n-3), C22:2(n-3), C22:4(n-6), C22:6(n-3), were found to generate saturated short and medium-chain length dicarboxylic acids, which can be regarded as a distinctive feature of the particular double bonds positions in the polyunsaturated fatty acid molecule. Two different dicarboxylic acids, which were unambiguously quantified by GC-MS, were produced from a single fatty acid: one deriving from the oxidative splitting at the level of the first double bond in the molecule, the other being two-carbon-atoms lower homologous. Formation of dicarboxylic acids occurred also from triacylglycerols and phospholipids containing cis-polyunsaturated fatty acids. In this case, following oxidation, the diacids remained covalently bound to the starting molecule and transesterification was necessary for identification. Being extremely stable and easily detectable compounds, dicarboxylic acids may be considered potential markers of oxidative attack to both free and esterified unsaturated fatty acids.

Dynamics of lipid oxidation and antioxidant depletion in Mediterranean fish stored at different temperatures.

Numerous changes occur post-mortem in fish, affecting its chemical composition and nutritional quality. In the present paper we describe the effect of storage on ice or at -30 degrees C or -80 degrees C on 10 species of Mediterranean fish. Water and lipid soluble antioxidants, lipid pattern and products of oxidative attack on lipids, proteins and DNA were quantified for 7 consecutive days on homogenates of fish light muscle. The earliest events were oxidation of ubiquinol and vitamin C, which disappeared almost completely within 48 hours. Ubiquinol oxidation gave rise to an initial increase of ubiquinone, which peaked at the second day: thereafter ubiquinone itslef decreased, more rapidly and to a greater extent than vitamin E. The decrease in antioxidants was accompanied by significant oxidative damage to lipids, proteins and DNA. TBARS significantly increased beginning from the third day of storage in all species and were linked to a significant reduction in the n-3 PUFA of triglycerides (TG) and phospholipid fractions (PL). A remarkable elevation of protein carbonyls and 8OHdG occurred approximately 24 hours later than PUFA oxidation. For SOD, GPX and GSH significant depletions occurred for all species only at 6th or 7th day, but the final values were always higher than 50% compared to the initial ones. Deep-freezing of the same species at -30 degrees C and -80 degrees C for up to 12 months did not significantly affect the levels of enzymatic antioxidants, the redox couple GSH/GS-SG, n-3 and n-6 PUFA of TG and PL fractions of the light muscle. The only antioxidants, which at -30 degrees C and -80 degrees C appeared to be degraded after 6 and 12 months were ubiquinol and vitamin C. As expected their degradation was higher at -30 degrees C than at -80 degrees C. In fact the average decrease for ubiquinol at -80 degrees C was 42% at 6 and 12 months respectively, whereas at -30 degrees C the decrease was 61% and 87% For vitamin C the average decrease at -80 degrees C was 36% and 67% at 6 and 12 months respectively, and at -30 degrees C it was 61% and 82%. Vitamin E was considerably more stable than ubiquinol and vitamin C. The relative stability of the antioxidants, with the exceptions of ubiquionols, vitamin C and, to a certain extent, vitamin E, was accompanied by a very limited increase in oxidation products. In addition no significant hydrolysis of TG and PL fractions were observed throughout the storage time. The dynamics of lipid, protein and DNA oxidation is discussed in the light of depletion of the various antioxidant systems.

Identification of tyrosinase inhibitors in cultures of Pityrosporum.

Lipid fractions capable of inhibiting the dopa-tyrosinase reaction in vitro were isolated by thin-layer chromatography from submerged cultures of Pityrosporum supplemented with oleic acid or vaccenic acid. Analysis of these fractions by gas chromatography-mass spectrometry revealed the presence mainly of C(9) and C(11) dicarboxylic acids. Standard dicarboxylic acids from C(8) to C(13) were capable of inhibiting tyrosinase in vitro to varying extents. Enzymatic kinetic studies showed that they act as competitive inhibitors of tyrosinase. These observations suggest that dicarboxylic acids could be used in the treatment of people with hyperpigmentary disorders.

Induction of hyphae in cultures of Pityrosporum by cholesterol and cholesterol esters.

The effect of cholesterol and cholesterol esters on Pityrosporum cultures has been studied. A mixture of 0.25% to 2.0% of cholesterol:cholesteryl stearate:glyceryl monostearate (2.0:1.5:2.0) added to Bacto Yeast Morphology Agar plus oleic acid was able to induce hyphae in cultures of both Pityrosporum orbiculare and P. ovale. This result is discussed with respect to the cholesterol effect on cell membranes and to the occurrence of cholesterol and cholesterol esters in the scaling patches of Pityriasis versicolor.

Growth requirements and lipid metabolism of Pityrosporum orbiculare.

The yeast, Pityrosporum orbiculare, isolated from lesions from lesions of tinea versicolor, grows in vitro only if fatty acids from the C12 to C24 series are added to the culture medium. Except for elaidinic and nervonic acids, all saturated and unsaturated fatty acids tested support growth. P. orbiculare can synthesize various lipid fractions containing both saturated and unsaturated fatty acids from a single fatty acid. Glucose and asparagine stimulate growth but exogenous vitamins do not.

Effect of dicarboxylic acids on lentigo maligna.

Dicarboxylic acids from C8 to C14 are competitive inhibitors of tyrosinase in vitro, and here, the effect of a cream containing 15% azelaic acid (C9) on 3 cases of lentigo maligna is described. The lesions were treated for 90 days, with remarkable clinical and histological effect, maintained for up to 2 yr after cessation of treatment. Progress during treatment of one case was additionally monitored by electron microscopy, which revealed progressive elimination of abnormal melanocytes both basally and suprabasally, and their replacement by essentially normal cells engaged in normal melanogenesis. There was also progressive diminution in the general disorganization of the epidermis, and disappearance of lymphocyte response. It is concluded that dicarboxylic acids have a direct inhibitory and cytotoxic effect on abnormally active or structurally disordered melanocytes in lentigo maligna, but further investigations are required to establish their precise mode of action. Similar application of dicarboxylic acids to normal skin affects only a small proportion of melanocytes, suggesting that some phasic factor, or individual states of activity, may be concerned in their susceptibility.

Lipoxygenase activity of Pityrosporum in vitro and in vivo.

Lipid peroxidation has been investigated both in cultures of Pityrosporum supplemented with different lipid classes and in skin surface lipids from patients affected with pityriasis versicolor. Thin-layer chromatography (TLC) and 2 spectrophotometric methods were used: the indirect thiobarbituric acid test and the direct N,N-diethyl-1,4-phenylene-diammonium sulfate (DEPD) test. The coupling of the DEPD test with the TLC technique performed by different eluent systems allowed the detection of the specific lipoperoxides deriving from the oxidation of the different lipid classes. In the cultures, Pityrosporum was capable of peroxidating not only unsaturated free fatty acids, but also unsaturated triglycerides, cholesterol, and squalene. A similar lipid peroxidation was observed in patients with pityriasis versicolor in skin lipids from areas positive for fungal hyphae and spores and fluorescent under the UV lamp (366 nm). The lipoperoxide values were significantly higher (p less than 0.05) than in skin lipids from normal controls. Hyphae and spore-negative areas of patients with pityriasis versicolor, whether apparently normal or achromic, showed no evidence of a significant lipid peroxidation and neither did skin areas of patients with pityriasis alba. Though further investigations are necessary, it seems reasonable to suggest, in analogy with other biologic systems, that the presence in skin lipids of a significant amount of highly reactive and cytotoxic lipoperoxides may play a role in the pathogenesis of skin alterations in pityriasis versicolor, including damage to melanocytes and resulting achromia.

Imbalance in the antioxidant pool in melanoma cells and normal melanocytes from patients with melanoma.

In order to evaluate the free radical defense systems of melanocytes and their possible correlation with melanoma, we have studied in cultured normal human melanocytes (20), normal melanocytes from melanoma patients (15), and melanoma cells (40) the fatty acid pattern of membrane phospholipids as a target of peroxidative damage and the superoxide dismutase and catalase activities, vitamin E, and ubiquinone levels as intracellular antioxidants. Cells were cultured in the same medium and analyzed at III or IV passage. Compared to the values obtained in normal human melanocytes, melanoma cells showed on average: a) higher levels of polyunsaturated fatty acids, b) increased superoxide dismutase and decreased catalase activities, higher vitamin E, and lower ubiquinone levels. Among the normal melanocytes from melanoma patients studied, two groups were differentiated: a) cultures (7) with enzymatic and non-enzymatic antioxidants level similar to those of normal human melanocytes; b) cultures (8) with antioxidant patterns similar to those observed in melanoma cells. Polyunsaturated fatty acids were also increased in the latter group. The results indicate that in melanoma cells and in a percentage of normal melanocytes from melanoma patients, an imbalance in the antioxidant system can be detected that can lead to endogenous generation of reactive oxygen species and to cellular incapability of coping with exogenous peroxidative attacks. These alterations could be correlated with the malignant transformation of cells and with the progression of the disease.

Ultrastructural observations on the effect of 4-hydroxyanisole on normal human melanocytes in tissue culture.

Riley's classic 1970 experiment showing a specific cytotoxic effect of 4-hydroxyanisole (4-OHA) on tissue-cultured melanocytes of black guinea pig ear skin was repeated on normal human melanocytes, and the results were examined by electron microscopy. In dispersed tissue culture, no specific toxic effect on human melanocytes was observed following equally timed exposures to similar (10(-3) M) or even higher (10(-2) M) concentrations of the drug; plasma membrane, nucleus, and cytoplasmic organelles, including melanosomes were unaffected. The same applied to melanocytes of whole epidermis exposed for 5 hr to the same concentrations of 4-OHA in culture medium. Melanocytes of PUVA treated skin similarly exposed for up to 24 hr to 10(-2) and 10(-3) M 4-OHA, likewise exhibited no evident morphological damage at the ultrastructural level. The discrepancy of results between guinea pig and man could have a variety of explanations, one of which could be due to a possible relatively low level of active tyrosinase in the human melanocytes (Riley believes the cytotoxic effect of 4-OHA to be due to the fact that it acts as a substrate for tyrosinase, toxic intermediates being liberated as a result). However, the lack of effect on the PUVA-activated melanocytes indicates that this cannot be the entire explanation.

Effect of dicarboxylic acids on Harding-Passey and Cloudman S91 melanoma cells in tissue culture.

Clinically, dicarboxylic acids have a cytotoxic effect on the abnormally hyperactive and malignant epidermal melanocyte, and diacids from C8 to C13 have been shown to inhibit mitochondrial oxidoreductases. Here, their effect on the growth kinetics and ultrastructure of murine melanoma cells in culture is examined. Cultures of Harding-Passey and Cloudman S91 melanoma cells were exposed to single doses of the disodium salts of C12, C9, and C6 (which does not significantly inhibit mitochondrial enzymes) dicarboxylic acids at concentrations of 10(-3) M to 10(-1) M. With C12 and C9, viability and cell proliferation over 3 days were significantly affected by concentrations greater than 10(-2) M. With exposure to C6 at 10(-1) M and to medium to which NaCl was added to produce equal osmolarity, the effect was much less. Electron microscopy of cells exposed to C9 at 10(-1) M for 1 h and 6 h revealed massive swelling of mitochondria with destruction of cristae, but plasma and nuclear membranes and membranes of endoplasmic reticulum were intact. Similar damage was not seen with C6 at 10(-1) M nor with equiosomolar NaCl. The results confirm (1) the cytotoxicity of dicarboxylic acids for malignant melanocytes, and (2) that the mitochondrion is a prime target for their action.

Effect of L-carnitine on cultured murine melanoma cells exposed to azelaic acid.

The cytotoxic effect of azelaic acid on murine melanoma cells in culture is due, at least in part, to an antimitochondrial action. We investigated the possibility that the addition of carnitine to the medium may increase the transport of azelaic acid into the mitochondria and thereby increase its cytotoxic effect. Using mitochondrial cross-sectional area measured from electron micrographs as a criterion for mitochondrial damage, we found that the addition of L-carnitine to the culture medium had no effect either alone or with a low (10(-3) M) concentration of azelaic acid. At a high concentration (5 X 10(-2) M) azelaic acid caused swelling and disruption of the mitochondria to such an extent that this was not increased by carnitine. At 10(-2) M azelaic acid, however, some swelling of the mitochondria occurred which was significantly increased by the addition of carnitine. This indicates that carnitine-mediated transport of the diacid into the mitochondria had occurred. We conclude that carnitine may reduce the time or concentration needed for azelaic acid to have a toxic effect on the malignant melanocyte.

Increased sensitivity to peroxidative agents as a possible pathogenic factor of melanocyte damage in vitiligo.

To examine the sensitivity of vitiligo melanocytes to external oxidative stress, we studied enzymatic and non-enzymatic anti-oxidants in cultured melanocytes of normal subjects (n = 20) and melanocytes from apparently normal skin of vitiligo patients (n = 10). The activity of superoxide dismutase and catalase and the intracellular concentrations of vitamin E and ubiquinone were evaluated in cultures at the fourth or fifth passage. In addition, cells were exposed to various concentrations of a peroxidizing agent, cumene hydroperoxide (CUH, 0.66-20 microM), for 1 and 24 h. Compared to normal melanocytes, vitiligo melanocytes showed normal superoxide dismutase and significantly lower catalase activities and higher vitamin E and lower ubiquinone levels. At the concentration used, CUH did not significantly affect cell number or viability of melanocytes after either period of culture. On the contrary, vitiligo melanocytes were susceptible to the toxic effect of CUH after 24 h of continuous treatment at concentrations greater than 6.6 microM. The degree of CUH toxicity correlated strictly with the anti-oxidant pattern, defined as the ratio between vitamin E concentration and catalase activity, suggesting that the alteration in the antioxidants was the basis for sensitivity to the external oxidative stress. Our results demonstrate the presence of an imbalance in the anti-oxidant system in vitiligo melanocytes and provide further support for a free radical-mediated damage as an initial pathogenic event in melanocyte degeneration in vitiligo.

Mechanism of antitumoral activity of catechols in culture.

Cell lines Raji and K 562, lacking tyrosinase, and two melanotic human melanoma cell lines (IRE 1 and IRE 2), were exposed to concentrations from 5 X 10(-3) M to 10(-5) M of different phenols which are substrates of tyrosinase, i.e. l-dopa, dopamine, hydroquinone, terbutylcatechol, and of phenols which are not substrates of the tyrosinase, i.e. resorcinol, butylated hydroxyanisole and hydroquinone dimethyl ether. Cultures were carried out in the presence or in the absence of oxygen radical scavenger enzymes superoxide dismutase, catalase and peroxidase. The stability of each substance in culture medium was assayed by high performance liquid chromatography (HPLC). Results showed that: catechols which are substrates of tyrosinase decompose fully after 24 hr in medium; they are equally toxic for melanoma and non-melanoma cell lines; their toxicity increases when they are preincubated in medium for 24 hr and 48 hr before addition of cells; their toxicity is significantly reduced by addition of scavenger enzymes; on the contrary, phenols not substrates of tyrosinase are stable in medium and their toxicity is not reduced by scavenger enzymes. It is concluded that tyrosinase does not play a major role in catechol toxicity in vitro, which is probably due to some products of catechol decomposition, especially oxygen radicals, acting outside the cells.

Antimitochondrial effect of saturated medium chain length (C8-C13) dicarboxylic acids.

In isolated rat liver mitochondria, respiration was competitively inhibited by medium chain length (C8 to C13) dicarboxylic acids to different extents: the higher the number of carbon atoms up to C12, the greater the inhibition. In particular, experiments on submitochondrial particles showed that the competitive inhibition concerned the following enzymes: NADH dehydrogenase, succinic dehydrogenase and reduced ubiquinone: cytochrome c oxido-reductase. These results tend to confirm the suggestion that the melanocytotoxic effect of dicarboxylic acids, which are also competitive inhibitors of tyrosinase, may be primarily due to an antimitochondrial effect rather than being tyrosinase-dependent.

Activity of azelaic acid on cultures of lymphoma- and leukemia-derived cell lines, normal resting and stimulated lymphocytes and 3T3 fibroblasts.

Azelaic acid (C9- -dicarboxylic acid) is a competitive inhibitor of tyrosinase and some oxidoreductase in vitro, and in vivo has a beneficial effect on lentigo maligna and malignant melanoma. A definite cytotoxic effect in cultures of malignant melanocytes was also reported. In order to establish if the cytotoxic effect of the diacid is exerted equally in the absence of tyrosinase, lymphoma- and leukemia-derived cell lines were cultured for 72 hr with 10(-3) M, 10(-2) M and 5 X 10(-2) M C9 disodium salt. Normal resting lymphocytes, lymphocytes activated by phytohemoagglutinin, and mouse Balb/c 3T3 fibroblasts were also tested to study a possible effect of azelaic acid on DNA synthesis and cell duplication. At 10(-3) M C9 had no effect on the viability of all the cells tested; at 10(-2) M and 5 X 10(-2) M, C9 2Na had a 50-80% cytotoxic effect on lymphoma- and leukemia-derived cell lines, while at the same concentrations it was not toxic to normal lymphocytes, either resting or stimulated, or to 3T3 fibroblasts. The experiments on cellular incorporation of (1-9 14C) azelaic acid showed that the radiocarbon uptake was two to three times higher for lymphoma- and leukemia-derived cell lines than for lymphocytes, either resting or stimulated, or 3T3 fibroblasts. Biochemical analysis revealed that the diacid underwent beta-oxidation in all the cell cultures. Fractionated centrifugations of 3T3 fibroblasts cultured in the presence of radiolabelled azelaic acid (2 X 10(-4) M) plus cold C9 2Na (10(-2) M), showed that the radioactivity was mainly concentrated in the cytoplasm. The results, being similar to those obtained by adding azelaic acid to cultures of melanoma cells, suggest that the cytotoxic effect of azelaic acid may be due to interference with mitochondrial oxido-reductase enzymes, rather than with tyrosinase. The difference in reaction between lymphoma- and leukemia-derived cell lines and normal or stimulated lymphocytes, and 3T3 fibroblasts, could be explained on the basis of a different degree of permeability of the cell membrane, and/or to a possible different sensitivity of reaction of mitochondrial functions. A similar argument could be used to explain the absence of an effect of dicarboxylic acids upon normal as compared with hyperactive or malignant melanocytes in vivo.

Skin surface lipids in HIV sero-positive and HIV sero-negative patients affected with seborrheic dermatitis.

Skin surface lipids of patients affected with seborrheic dermatitis both HIV sero-negative (C group) and HIV sero-positive (B group) have been studied by capillary Gas chromatography-Mass spectrometry (GC-MS) in comparison with normal age matched controls (A group) to determine whether, among the three groups of individuals, there were qualitative and quantitative changes in lipid class composition and in the fatty acid and alcohol components of lipid fractions. With regard to percent composition of skin surface lipid fractions, no significant differences were found between HIV sero-positive and HIV sero-negative patients with seborrheic dermatitis. The observed significant reduction of total lipids (micrograms/sq cm) in the sites affected with the disease in comparison with controls was associated with a slight but significant decrease of squalene (P less than 0.05) and with a corresponding increase of cholesterol and cholesterol esters (P less than 0.05). These abnormalities in lipid fractions and total lipids were not observed in the uninvolved skin of subjects with seborrheic dermatitis. Fatty acid and alcohol patterns of skin lipid fractions were not significantly different among the three groups of individuals.