Biomedical subjects

A Torri

Publications and source records attributed to A Torri.

At least 19 recordsLinked to original sources

PubMed2002

Atorvastatin increases HDL cholesterol in hypercholesterolemic patients. Evidence of a relationship with baseline HDL cholesterol.

BACKGROUND AND AIM: It has been reported that atorvastatin increases high-density lipoprotein cholesterol (HDL-C) more in patients with low than in those with high baseline HDL-C levels. This may have a biological explanation, but also suggests a statistical artifact known as the regression to the mean. METHODS AND RESULTS: Atorvastatin 10 mg/day led to a 4% increase in HDL-C after two months in 67/121 patients with hypercholesterolemia (55%), who had lower baseline HDL-C levels than the patients in whom HDL-C did not increase. In the patients with baseline HDL-C below the median, HDL-C significantly increased whereas no change was observed in patients with baseline HDL-C above the median. The correlation coefficient between pre- and post-treatment HDL-C was 0.84, thus suggesting a regression to the mean. However, the regression artifact did not entirely explain the increase in HDL-C in patients with low baseline HDL-C or the lack of an increase in those with high baseline HDL-C. The adjusted mean increase was 5.4% in patients with low pretreatment HDL-C, and 2.4% in the patients with high pretreatment HDL-C. Multiple regression analysis with the changes in HDL-C as the dependent variable showed that baseline HDL-C and the changes in serum triglycerides independently contributed to the change in HDL-C levels. CONCLUSIONS: Atorvastatin 10 mg/day increases HDL-C more in patients with low pretreatment HDL-C levels, an effect that seems to be related to the hypotriglyceridemic activity of the drug.

Adult↗

PubMed2001

An approach to the identification of potent inhibitors of influenza virus fusion using parallel synthesis methodology.

Structure-activity studies associated with the salicylic acid-derived inhibitor of influenza fusion, BMY-27709, were examined using a parallel synthesis approach. This SAR survey led to the discovery of potent influenza inhibitory activity in a series of aromatic amides and thioamides derived from 1,3,3-trimethyl-5-hydroxycyclohexylmethylamine. Select compounds were characterized as inhibitors of the H1 subtype of influenza A viruses that act by preventing the pH-induced fusion process, thereby blocking viral entry into host cells. In a plaque-reduction assay, the most potent inhibitors displayed EC(50) values of 0.02-0.14 microg/mL.

Amines↗

PubMed2001

Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia.

BACKGROUND: Simvastatin 40 to 80 mg/d has been found to increase high-density lipoprotein cholesterol (HDL-C) levels significantly more than atorvastatin at equipotent doses (ie, 20-80 mg/d). Data on the effects of lower doses of the 2 drugs on HDL-C levels are conflicting. OBJECTIVE: The purpose of this study was to investigate the effects of simvastatin 20 mg/d and atorvastatin 10 mg/d on HDL-C levels in patients with hypercholesterolemia. METHODS: Patients with primary hypercholesterolemia (total cholesterol [TC] >250 mg/dL) who were not taking any lipid-lowering agents and who were following a low-fat diet were randomized to receive 1 of 2 treatments: simvastatin 20 mg/d or atorvastatin 10 mg/d. Serum TC, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and HDL-C levels were measured using standard methods after 2 months of therapy. In a secondary analysis, lipids and lipoprotein cholesterol were measured after 1 year in patients who continued treatment. RESULTS: Of the 240 patients enrolled (108 men and 132 women; age range, 23-77 years, mean [SEM] 56.7 [0.69]), 235 completed the study. After 2 months of therapy, TC, LDL-C, and serum TG levels decreased significantly versus baseline in both groups (P < 0.001), with no significant differences between treatment groups. HDL-C levels increased by 9.0% (P < 0.001 vs baseline) in the simvastatin group and by 4.3% (P < 0.02) in the atorvastatin group. The difference between the 2 groups in the percentage increase in HDL-C was statistically significant (P < 0.05). In 113 patients who continued treatment, HDL-C levels at 1 year were still significantly higher than baseline levels in the simvastatin group (6.3%, P = 0.034), but not in the atorvastatin group (2.8%, P = 0.587). CONCLUSIONS: The findings from this study suggest that the HDL-C-increasing effect of simvastatin 20 mg is significantly greater than that of atorvastatin 10 mg. Since increasing HDL-C levels is thought to lower the risk for atherosclerosis and coronary heart disease, these results warrant further investigation.

Adult↗

PubMed2000

Salicylamide inhibitors of influenza virus fusion.

Structural variation of the quinolizidine heterocycle of the influenza fusion inhibitor BMY-27709 was examined by several topological dissections in order to illuminate the critical features of the ring system. This exercise resulted in the identification of a series of synthetically more accessible decahydroquinolines that retained the structural elements of BMY-27709 important for antiviral activity. The 2-methyl-cis-decahydroquinoline 6f was the most potent influenza inhibitor identified that demonstrated an EC50 of 90 ng/mL in a plaque reduction assay.

Animals↗

PubMed1999

Identification of a 3 kb Alu-mediated BRCA1 gene rearrangement in two breast/ovarian cancer families.

Most of the hereditary breast cancers are attributed to constitutive alterations of either BRCA1 or BRCA2 genes; nonetheless, germline mutations of these genes in 'high risk' families are found less frequently than expected from linkage data. Recent findings suggest that major genomic rearrangements of the BRCA1 gene might account for at least some of the apparently mutation negative cases. We studied 60 affected probands belonging to families with a strong history of breast and/or ovarian cancer who scored negative for BRCA1 gene mutations by PTT and SSCP analysis. DNA was analysed by the Southern blotting procedure using three different restriction enzymes, and two probes obtained by RT-PCR of the 5' and 3' BRCA1 coding sequence. A 3 kb deletion encompassing exon 17 and causing a frameshift mutation was identified in two independently ascertained families. RT-PCR and long-range DNA PCR were employed to characterize the rearrangement that was finally shown to be the result of a recombination between two very similar Alu repeats. This type of mutation is not identified by the conventional methods of mutation detection which are based on PCR amplification of single exons. Therefore, further search for gene rearrangements is needed to better define the proportion of 'high risk' families that might be explained by gross genomic alterations of the BRCA1 gene.

Alu Elements↗

PubMed1999

Lowering effects of four different statins on serum triglyceride level.

OBJECTIVES: The main effect of statins is the decrease of serum level of low-density lipoprotein (LDL) cholesterol, due to the inhibition of intracellular cholesterol biosynthesis which brings about an upregulation of LDL receptors. A minor effect is the decrease of serum triglycerides. The present study was undertaken to verify whether all statins are effective in reducing serum triglycerides and whether their effect on triglycerides is related to the LDL cholesterol lowering activity. METHODS: Of 197 hypercholesterolaemic patients on stable low-fat low-cholesterol diet, 49 were put on atorvastatin 10 mg per day, 48 on fluvastatin 40 mg per day, 50 on pravastatin 20 mg per day and 50 on simvastatin 10 mg per day. RESULTS: After 2 months, mean percentage change in serum triglycerides and LDL cholesterol resulted to be significantly different among the four treatment groups, whereas the ratio between the percentage decrease in serum triglycerides and that of LDL cholesterol (Deltatriglyceride/DeltaLDL cholesterol ratio) was not significantly different. Only baseline serum triglycerides resulted to be significantly associated with Deltatriglycerides/DeltaLDL cholesterol ratio. All statins are then effective in decreasing triglyceride levels. CONCLUSION: The lack of a significant difference in Deltatriglycerides/DeltaLDL cholesterol ratio among the treatment groups suggests that the more effective the statin is in decreasing LDL cholesterol, the more it will also be in decreasing serum triglycerides.

Adult↗

PubMed1999

Elevated urinary norepinephrine in interstitial cystitis.

OBJECTIVES: To measure urinary catecholamines and determine the extent to which they may be elevated in urine from patients with interstitial cystitis (IC). METHODS: Random urine samples from patients with IC (n = 111) and urine from normal volunteers (n = 92) were acidified on collection (voided and catheterized specimens) and assayed for catecholamine (norepinephrine or normetanephrine) by enzyme-linked immunosorbent assay. Creatinine levels in these urine samples were also measured. RESULTS: Analysis of the data indicated that patients with IC had a higher urinary level of the neurotransmitter norepinephrine compared with the measured levels in the urine of normal volunteers (89.1 +/- 58.3 versus 54.9 +/- 37.1 microg/g creatinine, P <0.05). The metabolite normetanephrine was similar in the urine samples from these two groups. Urine from patients with bladder outlet obstruction (n = 11) did not have elevated amounts of urinary norepinephrine. The norepinephrine levels were not statistically different in the urine samples from patients with symptomatic and asymptomatic IC. The elevated urinary levels in patients with IC did not decrease after treatment with sodium pentosanpolysulfate (Elmiron), heparinoids, dimethyl sulfoxide, or combinations of these during 1 to 15 months of treatment. CONCLUSIONS: Norepinephrine was found to be elevated in the urine from patients with IC compared with urine from normal controls. This would be consistent with increased sympathetic (adrenergic) activity from the bladders of patients with IC or possibly from increased adrenal activity, since stress is associated with symptom increase in some patients with IC. Norepinephrine levels did not decrease with treatment nor did they differ between symptomatic and asymptomatic patients at the time of urine collection.

Adult↗

PubMed1998

Accuracy of calculated serum low-density lipoprotein cholesterol for the assessment of coronary heart disease risk in NIDDM patients.

OBJECTIVE: To evaluate the accuracy of LDL cholesterol calculated with Friedewald's equation in the assessment of cardiovascular risk in NIDDM patients. RESEARCH DESIGN AND METHODS: The calculation of LDL cholesterol according to Friedewald's formula was compared with the measurement of LDL cholesterol separated by ultracentrifugation in 151 NIDDM patients with fairly good metabolic control (HbA1c < or =10%) and in 405 nondiabetic subjects. RESULTS: Measured and calculated LDL cholesterol was found to be well correlated in both diabetic (r = 0.95) and nondiabetic (r = 0.97) subjects. Compared with measured LDL cholesterol, the calculated LDL cholesterol differed by > or =10% in 34% of samples from diabetic patients and in 26% of samples from nondiabetic subjects (chi(2) = 3.885, P < 0.05). The percentage of error increased when the serum triglyceride (TG) level was > or =200 mg/dl (2.26 mmol/l) and when the ratio of VLDL cholesterol to TG was <0.20 or >0.29 in both groups of subjects. Although the percentage of error from calculated LDL cholesterol was greater in diabetic than in nondiabetic subjects because of the greater prevalence of hypertriglyceridemia in the former group, the misclassification of coronary heart disease risk, according to the cutoff points of the National Cholesterol Education Program (NCEP), was similar in the two groups (25% in diabetic and 22% in nondiabetic subjects). In both groups of patients, the misclassification of coronary heart disease risk was higher when calculation of LDL cholesterol produced values near the cutoff points. CONCLUSIONS: Although accuracy in the estimation of LDL cholesterol is less than ideal, Friedewald's equation seems to be of value in the correct assignment of coronary heart disease risk classes in the great majority of diabetic as well as nondiabetic subjects. Caution must be exercised for subjects in whom calculated LDL cholesterol is close to the cutoff points of the NCEP guidelines.

Cholesterol, LDL↗

PubMed1997

Association of alcohol consumption with HDL subpopulations defined by apolipoprotein A-I and apolipoprotein A-II content.

OBJECTIVE: To investigate the relationship between alcohol intake and serum level of high-density lipoprotein (HDL) subfractions defined on the basis of their apolipoprotein A-I and A-II content (LpA-I and LpA-I: A-II). DESIGN: Observational study. SETTING: Institute of Internal Medicine and Medical Physiopathology, IRCCS Maggiore Hospital, University of Milan. SUBJECTS: One hundred healthy males with a mean age of 42 +/- 11.1 y, selected among blood donors. RESULTS: Both LpA-I and LpA-I:A-II were significantly higher in men drinking more than 30 g a day of alcohol than in non-drinkers (LpA-I: difference between means 6.5 mg/dL, 95% C.I. 1.14-11.9; LpA-I:A-II difference between means 11.5 mg/dL, 95% C.I. 0.52-22.5). The association of alcohol consumption with LpA-I and LpA-I:A-II levels was independent from age, body mass index, physical activity, serum triglycerides and diet composition. CONCLUSIONS: Alcohol consumption is associated with an increase of serum levels of both LpA-I and LpA-I:A-II particles and this may, at least in part, explain the reduced cardiovascular morbidity observed in subjects drinking moderate amounts of alcoholic beverages. SPONSORSHIP: Supported by grants from Ricerca Corrente Ospedale Maggiore di Milano IRCCS, Milan Italy.

Adult↗

PubMed1997

Biodistribution of indocyanine green in a porcine burn model: light and fluorescence microscopy.

BACKGROUND: Infrared-excited fluorescence of intravenously administered indocyanine green (ICG) is being used as a method of early determination of burn depth. METHODS: Fluorescence microscopy and tissue fluorescence were recorded in a porcine burn model and correlated to burn severity and age. RESULTS: Recently placed superficial burns show significant fluorescence compared with adjacent normal tissue as a result of a strong inflammatory reaction in the superficial dermis with minimal vascular occlusion. The magnitude of the inflammatory reaction decreases with time. For deeper burns, vascular occlusion prevents transport of ICG into the burn and the intensity of ICG fluorescence in burn eschar is negligible. CONCLUSION: The intensity of ICG fluorescence measured at the surface of the wound for burns of similar age was shown to decrease exponentially with the depth of the burn. The enhanced fluorescence of partial-thickness burns is attributable to increased permeability, and the decreased signal associated with deeper injuries is attributable to vascular occlusion. These results suggest that it is possible to differentiate burns that will heal spontaneously with minimal granulation from those that will not by measuring the intensity of ICG fluorescence.

Animals↗

PubMed1997

Molecular mechanism underlying the action of a novel fusion inhibitor of influenza A virus.

In the initial stages of influenza virus infection, the hemagglutinin (HA) protein of influenza virus mediates both adsorption and penetration of the virus into the host cell. Recently, we identified and characterized BMY-27709 as an inhibitor of the H1 and H2 subtypes of influenza A virus that specifically inhibits the HA function necessary for virus-cell membrane fusion (G.-X. Luo, R. Colonno, and M. Krystal, Virology 226:66-76, 1996). Studies presented herein show that the inhibition is mediated through specific interaction with the HA protein. This binding represses the low-pH-induced conformational change of the HA protein which is a prerequisite for membrane fusion. In an attempt to define the binding pocket within the HA molecule, a number of drug-resistant viruses have been isolated and characterized. Sequence analyses of the HA gene of these drug-resistant viruses mapped amino acid changes responsible for drug resistance to a region located near the amino terminus of HA2. In addition, we have identified inactive analogs of BMY-27709 which are able to compete out the inhibitory activity of BMY-27709. This finding suggests that inhibition of the HA-mediated membrane fusion by this class of compounds is not solely the result of binding within the HA molecule but requires specific interactions.

Animals↗

PubMed1994

Estimation of cardiovascular risk: total cholesterol versus lipoprotein profile.

The complete lipoprotein profile is thought to give more information about the individual risk of coronary heart disease than total cholesterol alone. Although total cholesterol has a low sensitivity in the correct assessment of the risk of coronary heart disease, it may be of value in screening programs because of its low cost. In this study of 5,335 subjects, total cholesterol gave a different assessment of coronary heart disease risk (United States National Cholesterol Education Program guidelines) in 25% of subjects than the complete lipoprotein profile. Differences in risk assignment were mainly accounted for by high- and low-density lipoprotein-cholesterol (Friedewald equation). The calculated low-density lipoprotein-cholesterol was highly correlated with the value measured with a mixed ultracentrifugation and precipitation procedure. However, calculated values gave estimates of coronary heart disease risk which were 20% different from those from measure values. In 200 subjects in whom the lipoprotein profile was assessed three times in 1 year, the total cholesterol low-density lipoprotein-cholesterol varied by more than 30 mg/dl (0.78 mmol/l) in 52% and 50%, respectively, triglycerides by more than 30 mg/dl (0.34 mmol/l) in 75%, and high-density lipoprotein-cholesterol by more than 15 mg/dl (0.39 mmol/l) in 34%. Compared with the mean of the measurements, the single measurement of total cholesterol misclassified 48% of subjects, low-density lipoprotein-cholesterol 60%, high-density lipoprotein-cholesterol 12%, and 28%. We conclude that total cholesterol alone may be misleading in the assignment of coronary heart disease risk. Calculation of low-density lipoprotein-cholesterol, although less accurate than desirable, is the only way of evaluating this in clinical practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

[Ulcer and hepatic cirrhosis. Epidemiologic and clinical correlations].

Peptic ulcer has been reported with increased frequency in patients with liver cirrhosis, its prevalence ranging form 5% to 20%. The aim of the present study is twofold: 1) to define the frequency of peptic ulcer in chronic liver disease in a large sample of cirrhotic patients, 2) to investigate the epidemiological and clinical features of a group of subjects affected by both peptic ulcer and liver cirrhosis. Two years of admission have been retrospectively investigated to define the frequency of peptic ulcer in chronic liver disease. In 237 subjects affected by both cirrhosis and peptic ulcer, epidemiological and clinical data were collected. Peptic ulcer was present in 16% of cirrhotic patients. There were no differences between ulcer subjects who drank and those did not. A linear positive correlation between smoking habit and frequency of ulcer disease has been found in the words. A positive history for peptic ulcer was described in a little subgroup of the studied sample, suggesting a low importance of the genetic factor in the pathophysiological pattern of ulcer disease in chronic hepatitis.

Adult↗

PubMed1990

[A clinico-endoscopic study on cicatrization of lesions and prevention of recurrences in patients with liver cirrhosis and peptic ulcer].

Seventy-four and five cirrhotic patients with acute peptic ulcer were respectively treated with H2-blockers and cytoprotective drugs for 4-6 weeks; after this period 49 (62.2%) healed and 14 (17.7%) did not heal after further 2 months with the same therapy. In order to observe the effectiveness of H2-blockers in preventing peptic ulcer recurrences, 77 cirrhotic patients were followed-up for a mean period of 12 months (range 3-48 months) after ulcer scarring; 51.2% under H2-blockers maintenance treatment and 54.8% who took antiacid in case of need, relapsed. The therapeutical response, as regards short-term treatment in cirrhotic patients, seems not to differ from the usual outcome of the general ulcer population; on the contrary, the relapses, also during a maintenance therapy, appears increased.

Adult↗

PubMed1989

Clinical response and survival according to estrogen receptor levels after bilateral ovariectomy in advanced breast cancer.

Estrogen receptor levels were determined at the time of ovariectomy in 71 premenopausal women with advanced breast cancer. Three groups of estrogen receptor concentration were established: less than 10 fmol/mg cytosol protein (group 1), between 10 and 25 fmol/mg cytosol protein (group 2), and more than 25 fmol/mg cytosol protein (group 3). The frequency of clinical response to ovariectomy was low in group 1 (17.4%), high in group 3 (79.4%), and intermediate in group 2 (35.7%). Median survival was poor in group 1 (18.5 months) and better in groups 2 (33.0 months) and 3 (32.5 months). These results were independent of disease stage and neoplastic localization.

Adult↗

PubMed1988

Complete remission after ovariectomy for advanced breast cancer correlated with estrogen receptor status and urinary androgen excretion.

Our previous work showed urinary androgen excretion (A) as well as estrogen receptor (ER) to predict clinical response and survival after ovariectomy for advanced breast cancer. We here compare the complete responders with the partial responders to ovariectomy. The likelihood of CR (55% of responders) rather than PR was not strongly dependent on the location of metastases or on the ER/A status (though as noted previously there were no responses at all in the ER-/A- group), but CR did appear to increase survival.

Androgens↗

PubMed1987

Urinary androgens and tumor estrogen receptor as predictors of ovariectomy response and of survival in advanced breast cancer.

Estrogen receptor (ER) status and urinary androgen (A) concentration were simultaneously determined in 50 premenopausal patients submitted to bilateral ovariectomy for advanced carcinoma of the breast. When both the hormonal parameters were positive (ER+ A+), the response to castration was favorable in 87.5% of the cases, with a survival rate of 39% at 5 years. No patient responded to the therapy when both the parameters were negative (ER- A-); none of them was alive at 5 years. An intermediate response (more than 50%) and survival rate at 5 years (more than 20%) was obtained in the group of patients with at least one of the two parameters positive (ER+ A-, or ER- A+). These responses were independent of the topography of neoplastic localizations and the length of the disease-free interval.

Adult↗

PubMed1986

Unusual DNA structures in the adenovirus genome.

More than 80% (approximately 29 kilobase pairs) of the adenovirus serotype 2 genome was surveyed for the presence of unusual DNA conformations. Seven recombinant DNAs containing the largest HindIII fragments of AD2 DNA were analyzed for the presence of negative supercoil-dependent S1 nuclease-sensitive sites. Four plasmids each contained a specific site of S1 nuclease sensitivity whereas the other three showed no reaction. Further investigation was focused on a plasmid containing one of the positively reacting fragments (fragment C) which contained the major late promoter at coordinate 16.4 on the genome; three serotypes (Ad2, Ad7, Ad12) were studied. Fine mapping studies revealed the S1-sensitive sites to be a small region (approximately 6 base pairs) located at the TATA box of the major late promoter in all three cases. Other determinations (supercoil relaxation, T7 gene 3 product sensitivity, bromoacetaldehyde reactivity, anomalous gel mobility, the influence of negative superhelical density on nuclease sensitivity) led to the conclusion that the B-helix deformation was not due to a previously recognized DNA conformation (left-handed Z-DNA, cruciform, bent DNA), but may be accounted for by the homopurine X homopyrimidine nature of this region.

Acetaldehyde↗