Health-related quality of life burden in scleroderma patients treated with two different intravenous iloprost regimens.

Systemic sclerosis (SSc)-related Raynaud's phenomenon (RP) and digital ulcers (DU) can impair health-related quality of life (HRQoL). The aim of our study was to estimate HRQoL in SSc patients treated with two different intravenous (IV) iloprost (ILO) regimens and in patients not treated with IV ILO. 96 consecutive SSc patients were enrolled in a pragmatic, prospective and non-randomized study, and divided into 3 groups: not requiring therapy with IV ILO (N=52), IV ILO once monthly (N=24) or IV ILO for 5 consecutive days every 3 months (N=20). Patients were followed up for three months. We assessed HRQoL using the generic preference-based questionnaire EQ-5D-5L. We conducted multiple regression analyses to estimate, in each treatment group, the mean general health (GH) and the mean utility index of the EQ-5D-5L, adjusting for possible confounders. The mean adjusted utility index and GH score, after three months' follow-up, were not different in the three groups: IV ILO was able to make patients requiring IV ILO similar to those not requiring it. Moreover, there was no difference in this model between the two ILO regimens (1 day monthly vs 5 consecutive days every 3 months). The two different IV ILO regimens (the most appropriate regimen was decided according to patients' characteristics and needs) were able to stabilize HRQoL in RP secondary to SSc non-adequately controlled by oral therapy.

Assessment of Salmonella survival in dry-cured Italian salami.

The inactivation of Salmonella during curing of Italian traditional pork salami was investigated. A total of 150 batches of ground raw meat (GRM) used for salami manufacturing by four producers were tested for Salmonella by real-time PCR followed by ISO 6579 cultural confirmation and MPN enumeration. Salami produced with Salmonella positive GRMs were re-tested at the end of their curing period. Aw, pH and NaCl content were also measured. Detection of Salmonella was performed testing both 25 and 50g of the samples. By Real-Time PCR 37% of the GRMs resulted positive, but cultural detection of Salmonella was obtained in 14% of the samples only. Salmonella enumeration ranged from 31 MPN/g to <1.3 MPN/g. The difference between testing 50g and 25g of the samples was statistically significant (p value≤0.01). In particular, ISO-50g detected Salmonella in 100% of all positive samples, vs. 62% of ISO-25g. Salami made of the contaminated GRMs were 29% Salmonella-positive, as most batches of salami produced with Salmonella-positive GRMs resulted negative after regular curing (20-48days). Overall, 13% of salami produced with Salmonella-contaminated GRMs were positive. They belonged to six batches, which turned out negative after prolonged curing ranging between 49 and 86days. Salmonella enumeration in salami ranged from 8.7 MPN/g to <1.3 MPN/g. Unlike GRMs, no significant difference was observed between the ISO-50g and the ISO-25g in detecting Salmonella in cured salami (p value: >0.05). The most common Salmonella serovars in GRMs were Derby (52%), Typhimurium monophasic variant 4, (Barbuti et al., 1993), 12:i:- (19%) and Stanley (10%). Salmonella Derby (56%), London, Branderup, Panama (13%, respectively) and Goldcoast (6%) were most frequent in cured salami. The study showed negative correlation between real-time CT values and cultural confirmation of Salmonella, as well as the importance of sample size for Salmonella detection. Among considered factors with possible effect on the occurrence of Salmonella in salami, statistical analysis revealed a role for aw in salami and for Salmonella load in GRMs, while pH and NaCl content did not significantly affect the probability of finding Salmonella in dry-cured salami in the context of this study. In particular the lower aw values due to longer curing were associated with lower Salmonella presence in traditional dry-cured salami.

Quality control of ultrasound transducers: analysis of evaluation parameters and results of a survey of 116 transducers in a single hospital.

PURPOSE: The aim of this study was to develop a quality control programme for ultrasound equipment and assess equipment performance at a single hospital. MATERIALS AND METHODS: We tested 116 transducers by means of a phantom; ultrasound quality control tests were done on parameters from B-mode images, and each parameter was rated according to a three-point score as good, sufficient or poor. RESULTS: Surface transducers showed worse performance in terms of image uniformity, with 7/55 (13%) transducers rated poor, and depth of penetration, with 24/55 (44%) transducers, rated sufficient or poor. The 3.5-MHz transducers showed worse performance in lateral resolution, with 18/48 (38%) rated poor, and particularly in focusing, with 40/48 (83%) classified as poor. In addition, the 3.5-MHz transducers proved less accurate in vertical distance accuracy than in horizontal distance, with 31/48 (64%) considered sufficient. No significant geometric distortions of masses were identified, although 4/116 (3%) transducers failed to visualise two masses. CONCLUSIONS: The first goal of an ultrasound quality control programme is to establish specific parameters to evaluate equipment performance and, should results be below recommended action levels, implement corrective measures.

Psychological consequences of the 1998 landslide in Sarno, Italy: a community study.

OBJECTIVE: This community study assessed the prevalence of post-traumatic stress disorder (PTSD) and the psychosocial consequences of the landslide which occurred in Sarno, Southern Italy, in May 1998. METHOD: A random sample (n=272) of the population living in the highest risk area of Sarno, and a control group recruited in a small town situated near the disaster area, but not affected by the event, were assessed 1 year after the disaster by standardized instruments. RESULTS: Of the subjects recruited in Sarno, 27.6% met DSM-IV criteria for PTSD; 59% subjects recruited in Sarno and 35% of the control group were identified as "probable cases" by the GHQ-30 (P<0.0001). Subjects recruited in Sarno had significantly higher scores on the four GHQ-30 subscales identified by factor analysis. CONCLUSION: This study emphasizes the negative impact of a natural catastrophic event on mental health, and the need for preventive interventions.

Inhibition of promotion and persistent nodule growth by S-adenosyl-L-methionine in rat liver carcinogenesis: role of remodeling and apoptosis.

The resistant hepatocyte model (initiation/selection) and the triphasic model (initiation/selection followed by phenobarbital, for a maximum of 16 weeks) were compared for their ability to generate enzyme-altered foci (EAF) and nodules in the liver of Wistar rats initiated by diethylnitrosamine. The effects of S-adenosyl-L-methionine (SAM) on the development of preneoplastic tissue was tested in these experimental models. In the absence of phenobarbital (PB), EAF and early nodules (EN) went through a phase of rapid growth, between 4 and 9 weeks after initiation, to a phase in which progressive decrease in number and size occurred. By the 26th week only a few remodeling EAF and nodules were found. In PB-treated rats a rapid increase in the percentage of liver occupied by EAF and EN, up to the 9th week after initiation, was followed by a period of slow growth (from the 9th to the 20th week) and then, after PB withdrawal (20th week), by a drop in the number and size of EAF and EN. However, at the 26th week actively growing nodules with a low tendency to spontaneous remodeling (persistent nodules) developed. EAF and EN showed a high DNA synthesis 5 weeks after initiation. Thereafter, progressive decline in DNA synthesis, coupled with remodeling and decrease in number of biochemical markers, was seen both in the absence and, even though to a lesser extent, in the presence of PB, indicating that preneoplastic lesions became increasingly insensitive to PB. Relatively few apoptotic bodies could be observed in EAF and EN during PB treatment. After PB withdrawal, decrease in growth potential was coupled with increase in apoptotic bodies. In contrast, in persistent nodules relatively high apoptosis occurred which partially counterbalanced high DNA synthesis. Administration of SAM for a maximum of 16 weeks, starting at the 4th week after initiation, caused a great decrease in number and size of EAF and EN, associated with inhibition of DNA synthesis, high cell death by apoptosis, high remodeling, and loss of biochemical markers, in preneoplastic lesions of both PB-treated and untreated rats. A 1-8-week SAM treatment, started after the development of persistent nodules, caused a great regression of nodular lesions, coupled with a sharp fall in DNA synthesis and increase in apoptosis. It is suggested that inhibition by SAM of the development of preneoplastic tissue is linked to a shift of the equilibrium between cell production and cell death in favor of cell death.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition by ethanol of rat liver plasma membrane (Na+,K+)ATPase: protective effect of S-adenosyl-L-methionine, L-methionine, and N-acetylcysteine.

(Na+,K+)ATPase activity of rat liver plasma membranes was evaluated in female rats feeding an ethanol containing diet for 46 days (total ethanol ingested, 59.7 g/100 g body wt). Determinations were performed at the end of ethanol treatment or at various times after stopping treatment. (Na+,K+)ATPase and 5'-nucleotidase activities exhibited a 8- and 1.4-fold decrease, respectively, at the end of ethanol ingestion. In contrast no modifications of Mg2+-ATPase activity were observed. There also occurred, in ethanol-treated rats, release of sorbitol dehydrogenase into the blood, fat accumulation in liver cells, and decrease in reduced glutathione (GSH) liver content. A decrease in (Na+,K+)ATPase activity was also found in plasma membranes isolated from hepatocyte suspensions after a 2-hr incubation with 50 mM ethanol or 1 mM acetaldehyde (ACA), in conditions that caused a great fall in hepatocyte GSH content but did not cause cell death. After the cessation of ethanol administration, there occurred a progressive recovery of (Na+,K+)ATPase activity, GSH and triacylglycerol content, and release of sorbitol dehydrogenase. These parameters reached control values 12 hr after ethanol withdrawal. S-Adenosyl-L-methionine (SAM), L-methionine, and N-acetylcysteine (NAC), given to rats during ethanol treatment, prevented the decrease in (Na+,K+)ATPase activity and GSH content. They also reduced steatosis and liver necrosis. The efficiency of these compounds decreased in this order: SAM, methionine, NAC. SAM accelerated the recovery of all parameters studied after ethanol withdrawal, and also protected (Na+,K+)ATPase activity and GSH content of isolated hepatocytes from the deleterious effect of ethanol. These SAM effects were prevented by 1-chloro-2,4-dinitro-benzene, a compound which depletes cell GSH. Treatment of isolated hepatocytes with [35S]SAM led to the synthesis of labeled GSH. The total amount and specific activity of labeled GSH underwent a significant increase, in the presence of 2 mM ethanol or 0.5 mM ACA, which indicates a marked stimulation of GSH synthesis by ethanol and ACA. These data indicate that ethanol intoxication may inhibit (Na+,K+)ATPase activity; an effect that does not seem to depend on cell necrosis. SAM, methionine, and NAC exert various degrees of protection toward ethanol-induced cell injury, which are related to the efficiency of these compounds in maintaining a high GSH pool.

Reversal by ribo- and deoxyribonucleosides of dehydroepiandrosterone-induced inhibition of enzyme altered foci in the liver of rats subjected to the initiation--selection process of experimental carcinogenesis.

The effect of dehydroepiandrosterone (DHEA) on the activity of NADPH-producing enzymes and the development of enzyme-altered foci has been investigated in the liver of female Wistar rats subjected to an initiating treatment (a necrogenic dose of diethylnitrosamine) followed, 15 days later, by a selection treatment [a 15-day feeding of a diet containing 0.03% 2-acetylaminofluorene (2-AAF), with a partial hepatectomy at the midpoint of this feeding]. At the end of the selection treatment all rat groups received, for 15 days, a basal diet containing, when indicated, 0.05% phenobarbital (PB) and/or 0.6% DHEA. The effect of DHEA on the activity of NADPH-producing enzymes was also studied in normal rats fed, for 15 days, a diet containing 0.6% DHEA and in their pair-fed controls. DHEA caused a 43-58% inhibition of glucose-6-phosphate dehydrogenase (G6PD) and, respectively, 338-420% and 21-24% increases in malic enzyme (ME) and isocitric dehydrogenase activities in all rat groups. This was coupled with a great fall in the production of ribulose-5-phosphate, while no change in NADP+/NADPH ratio occurred. Hepatocytes, isolated from DHEA-treated rats, exhibited a very low activity of hexose monophosphate shunt (HMS), which was not stimulated by methylene blue, an exogenous oxidizing agent that markedly stimulated HMS activity in control hepatocytes. DHEA caused a great fall in the percentage of liver occupied by gamma-glutamyltranspeptidase (GGT)-positive foci, in the rats subjected to the initiation-selection treatments. PB enhanced the development of these foci, an effect which was completely overcome by DHEA. In addition, focal cells no longer expressed a G6PD activity higher than that of surrounding liver in DHEA-treated rats, but exhibited a high histochemical reaction for ME. DHEA also caused a great fall in labelling index of GGT-positive foci. Starting at the end of 2-AAF feeding, a mixture of ribonucleosides (RNs) of adenine, cytosine, guanine and uracil and of deoxyribonucleosides (DRNs) of adenine, cytosine, guanine and thymine were injected i.p. every 8 h for 12 days to the rats subjected to the initiation-selection treatments plus PB. Rats were killed 3 days after the end of RN and DRN treatments. These treatments completely overcome the DHEA effect on the development of GGT-positive foci and DNA synthesis by the focal cells, without affecting G6PD activity of both whole liver and putative preneoplastic foci. Experiments with labeled nucleosides revealed that RNs and DRNs produced derivatives that were incorporated into liver DNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Decreased stimulation by 12-O-tetradecanoylphorbol-13-acetate of superoxide radical production by polymorphonuclear leukocytes carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase.

Polymorphonuclear leukocytes (PMNs) from individuals carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase (G6PD) exhibit a great decrease in this enzymatic activity and in hexose monophosphate shunt (HMS). 12-O-tetradecanoylphorbol-13-acetate (TPA) greatly stimulates HMS of normal PMNs, while it does not affect that of the deficient PMNs. Similarly, the stimulation of HMS by methylene blue is largely reduced in G6PD-deficient PMNs. These changes are paralleled by a 58% decrease in TPA-stimulated superoxide radical (O2-) formation by the deficient PMNs. G6PD activity is not detectable in the deficient PMNs incubated with dehydroepiandrosterone, and these cells show a near complete inhibition of O2- production. It thus seems that the low ability of G6PD-deficient PMNs in the production of O2- depends on the low NADPH generation by HMS in these cells. The decrease in TPA-stimulated O2- production suggests a reduced response of G6PD-deficient cells to promoting agents.

Variations of ornithine decarboxylase activity and S-adenosyl-L-methionine and 5'-methylthioadenosine contents during the development of diethylnitrosamine-induced liver hyperplastic nodules and hepatocellular carcinoma.

Liver ornithine decarboxylase (ODC) activity and content of S-adenosyl-L-methionine (SAM) and its catabolite 5'-methylthioadenosine (5'-MTA) were determined in the late stages of hepatocarcinogenesis. Wistar rats received one diethylnitrosamine dose, followed by a partial hepatectomy at the midpoint of a 15-day treatment with 2-acetylaminofluorene (2-AAF), and then by an 18-week phenobarbital (PB) treatment. Thirty-eight per cent of liver was gamma-glutamyltranspeptidase (GGT)-positive and no visible nodules and hepatocellular carcinomas developed 16 weeks after starting 2-AAF feeding. Hyperplastic nodules and hepatocellular carcinomas were found on weeks 24 and 56 respectively. On weeks 24 and 56 only approximately 10% of liver was occupied by GGT-positive foci. At all times studied the foci exhibited a low labeling index (LI), and liver ODC activity was near control values. By contrast, a high ODC activity and LI and a low SAM and 5'-MTA levels were found in hyperplastic nodules and neoplasia. These tissues exhibited a high 5'-MTA phosphorylase activity. SAM administration during PB treatment, caused a 25-36% fall of GGT-positive liver and prevented the development of hyperplastic nodules and hepatocellular carcinomas. This was coupled to a sharp increase of SAM and 5'-MTA liver contents. SAM and 5'-MTA inhibited hepatocyte DNA synthesis in vitro. The addition of 5'-MTA to the reaction mixture for the ODC assay strongly inhibited ODC activity. However, the preincubation of SAM with liver homogenates or hepatocytes, used to prepare crude ODC, was necessary to inhibit ODC activity by SAM. Adenine, an inhibitor of 5'-MTA-phosphorylase, enhanced inhibition of DNA synthesis and ODC activity by SAM and 5'-MTA. Thus, during a prolonged promoting treatment a selected population of GGT-positive foci appears to acquire a stable phenotype characterized by a high DNA and polyamine synthesis. The development of nodules and carcinomas is associated with low SAM and 5'-MTA contents and high ODC activity and LI. 5'-MTA accumulation, during SAM administration, is probably responsible for the inhibition of promotion by SAM.

Inhibition by dehydroepiandrosterone of liver preneoplastic foci formation in rats after initiation-selection in experimental carcinogenesis.

The effect of dehydroepiandrosterone (DHEA) on the development of liver preneoplastic foci was evaluated. The experimental protocol used initiation by diethylnitrosamine (DENA), followed by selective growth induced by partial hepatectomy (PH), in rats fed an N-acetylamino-fluorene (AAF)-containing diet, and followed by a standard diet with or without 0.05% phenobarbital (PB). DHEA (0.6%) was administered in the diet for 4 or 7 weeks after DENA injection (treatments A and B) or for 3 weeks after the end of AAF feeding (treatment C). On the 7th week after DENA injection, DHEA treatments A and C caused slight decrease of body weight and 40-60% increase in liver weight and cell size; number of nuclei per g of liver was not changed. The dietary treatment also caused a marked decrease of liver glucose-6-phosphate dehydrogenase (G6PD) activity and of the percentage of the gamma-glutamyltranspeptidase (GGT)-positive liver. PB increased G6PD activity and GGT-positive liver. This effect was oblated by DHEA treatments A and C. On the 7th week, the labeling index (LI) was low in surrounding liver, and high in GGT-positive foci. PB had an enhancing effect, while DHEA treatments A and C were inhibitory. G6PD was low at the end of DHEA treatment B, but it returned to normal values 4 weeks after the end of this treatment. At this time no effect of DHEA treatment B was observed on the extent of GGT-positive liver and LI.(ABSTRACT TRUNCATED AT 250 WORDS)