Multidimensional Evaluation of Endogenous and Health Factors Affecting Food Preferences, Taste and Smell Perception.

OBJECTIVE: This study, by taking a holistic approach, investigates the relationships between taste, smell sensitivity and food preference with prognostic (endogenous and health) factors including age, gender, genetic taste markers, body mass, cigarette smoking, and number of drugs used. DESIGN: Cross sectional study. SETTING: Northern Italy. PARTICIPANTS: 203 healthy subjects (160 women/43 men; mean age: 58.2±19.8 years) were examined. MEASUREMENTS: Individual taste sensitivity was determined by saccharose, sodium chloride, acetic acid and caffeine solutions and by 6-n-propylthiouracil (PROP) responsiveness test. Olfactory sensitivity has been assessed by «Sniffin' Sticks¼. Four tag Single nucleotide polymorphisms (SNPs) in regions of interest were genotyped. Factor analysis and multivariate regression were performed for scaling food preferences and screening prognostic factors, respectively. RESULTS: Increasing age is associated with decreased responsiveness to NaCl (P=0.001), sweet solutions (P=0.044), and smell perception (P<0.001). Concerning the food preferences, elderly like the "vegetables" and "fruits" but dislike "spicy" more than younger. Regarding number of drugs taken, there is a significant negative effect on smell perception (P<0.001). In addition, drugs reduce both the "vegetables foods" score (P=0.002) and the "milk-product foods" score (P=0.027). With respect to Body Mass Index (BMI), only a significant effect was shown, on sweet perception (P=0.006). Variation in taste receptor genes can give rise to differential perception of sweet, acid and bitter tastes. No effect of gender and smoking was observed. CONCLUSIONS: Our study suggested that age, genetic markers, BMI and drugs use are the factors which affect taste and smell perception and food preferences.

Radio-frequency thermal ablation of liver metastases with a cooled-tip electrode needle: results of a pilot clinical trial.

The aim of this study was to evaluate feasibility, safety, and effectiveness of radio-frequency (RF) thermal ablation, performed by using a cooled-tip electrode needle, in the treatment of liver metastases. Twenty-nine patients (20 males and 9 females; age range 43-77 years) with one to four hepatic metastases 1.1-4.8 cm in diameter (mean 2.9 +/- 0.8 cm) from previously resected intra-abdominal primary malignancies were treated. All patients were excluded from surgery and had partial or no response to chemotherapy. Radio-frequency ablation was performed by using a 100-W generator and 17-gauge, dual-lumen, cooled-tip electrode needles with a 2- to 3-cm exposed tip. Exposure time was 12 min for each needle insertion. Findings at spiral CT were used to assess the therapeutic response. A total of 127 insertions were performed (mean 2.4 +/- 1.7 insertions/lesion) during 84 treatment sessions (mean 1.6 +/- 0.7 sessions/lesion) in absence of major complications. Complete tumor response (i. e., unenhancing area of thermal necrosis larger than the treated tumor) was seen in 41 (77 %) of 53 lesions, including 33 (87 %) of 38 lesions 3 cm or less in diameter. After a mean follow-up period of 6.5 +/- 2.1 months (range 3-9 months), recurrence of the treated lesion was seen in 5 (12 %) of the 41 cases. New metastatic lesions appeared in 7 patients. Two patients died after 6 and 8 months, respectively. Of the 27 patients still in follow-up, 14 are currently free of disease. Radio-frequency thermal ablation with a cooled-tip electrode needle is a safe and effective local treatment for hepatic metastases 3 cm or less in greatest dimension.

Effect of aging and sex on the [3H]-paroxetine binding to human platelets.

Since there exist conflicting results with regard to the possible effect of aging on platelet [3H]-imipramine binding, taken as a peripheral marker of the serotonin (5-HT) transporter, we reinvestigated this matter by comparing the binding of the more selective ligand [3H]-paroxetine in 20 aged and 23 young subjects. The results showed that neither the maximum binding capacity nor the dissociation constant (Kd) were significantly different in the two groups. When the subjects were compared according to sex, the young females revealed a statistically significant lower Kd than the males, while the contrary was true for the aged females. The Kd was significantly and negatively correlated to age in males. In addition, a significant age x gender interaction was also observed. Therefore, the sex of a subject would seem to provoke significant age-related changes in the Kd of [3H]-paroxetine binding to platelet membranes. This might indicate modifications in the 5-HT transporter that could form the basis of a sex-related difference in vulnerability to disorders, such as depression, where a dysfunction at this level is hypothesized.

Disappearance of skin lipofuscin storage and marked clinical improvement in adult onset coeliac disease and severe vitamin E deficiency after chronic vitamin E megatherapy.

A case of adult onset coeliac disease with IgA and severe vitamin E deficiencies, associated with cerebellar impairment and peripheral neuropathy, is described. Nerve conduction velocities, BAERs and SEP were altered. Brain nMR showed cortical atrophy mainly in the frontal and parietal regions. At ultrastructural examination, nerve biopsy showed a severe nerve fiber loss with presence of lipofuscin. Lipofuscin has been also found in skin and muscle biopsy. Duodenal biopsy showed villar atrophy with criptae hypoplasia. IgA, Apo A1 lipoprotein and cholesterol were decreased. Serum level of vitamin E was not detectable and its amount did not increase after an oral loading (2 g bolus). Parenteral vitamin E administration (900 mg/day) was able to normalize the plasma values only after 6 months of chronic administration of the drug in coincidence with a significant improvement of clinical and neurophysiological signs, and disappearance of lipofuscin storage in the skin biopsy.

[Short term assessment of anthropometric indices and metabolic parameters in obese subjects treated with acarbose]. / Valutazione (a breve termine) del comportamento degli indici antropometrici e dei parametri bioumorali in soggetti obesi trattati con acarbosio.

Acarbose represents the first of a new class of oral antidiabetic drugs: the alpha-glucosidases inhibitors. This drug in fact delays the production of monosacchtarides inhibiting the alpha-glucosidases of the small bowel, that are responsible of digestion of complex polysaccharides and sucrose. In patients with insulin dependent diabetes mellitus (IDDM) acarbose, significantly reduces the postprandial blood glucose levels, and improves the symptoms associated with nocturnal hypoglycaemia reducing the daily insulin dosage. Furthermore acarbose ameliorates the glycemic control of obese patients when associated with hypocaloric diet. The aim of our study has been to value the effectiveness of acarbose 300 mg/day for 12 weeks in patients affected by moderate obesity (30 < - BMI < 40) and with impaired glucose tolerance (IGT). We have studied 12 patients, 6 have been treated with acarbose and hypocaloric diet, while the other 6 have been treated only with diet, these last formed the control group. Before and after the treatment, anthropometric indexes and haematologic parameters have been observed. Patients treated with acarbose presented a significative decrement of body weight, BMI, fat free mass, fat mass and of basal and peak glycaemic values after oral glucose tolerance test (OGTT). Serum lipid values, insulin levels during OGTT and blood pressure presented a not significative improvement. Gastrointestinal symptoms such as flatulence and borborygmus have been reported only in the patients treated with acarbose. The incidence of these reactions usually decreases with time.

Treatment of large HCC: transcatheter arterial chemoembolization combined with percutaneous ethanol injection versus repeated transcatheter arterial chemoembolization.

PURPOSE: To compare the efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection (PEI) versus repeated TACE in the treatment of large hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty-three patients with cirrhosis and a large HCC (main tumor, 3.1-8.0 cm in diameter with no more than two daughter nodules) were enrolled in a prospective, randomized study. Twenty-six patients underwent a single TACE session followed by PEI (TACE-PEI group), whereas 27 patients underwent two to five TACE sessions (TACE group). Both groups of patients were similar with regard to liver function. Follow-up ranged from 8 to 39 months. RESULTS: Complete therapeutic responses were higher (P < .05) and tumor recurrences during follow-up were lower (P < .05) in the TACE-PEI group than in the TACE group. Patients in the TACE-PEI group survived longer than those in the TACE group, although the difference was not significant (P > .1). The rates of survival without recurrence were better in the TACE-PEI group than in the TACE group (P < .05). CONCLUSION: Use of a single TACE session combined with PEI is more effective than repeated TACE in the treatment of large HCC.

Treatment of small hepatocellular carcinoma with percutaneous ethanol injection. Analysis of prognostic factors in 105 Western patients.

BACKGROUND: Percutaneous ethanol injection (PEI) has been used in the Far East for treating small, unresectable hepatocellular carcinoma (HCC). To clarify when treatment with PEI may be best indicated for Western patients with HCC, the authors performed a retrospective analysis of the clinicopathologic factors influencing prognosis. METHODS: From December 1987 to August 1994, 105 patients with cirrhosis with HCC received PEI as the sole anticancer treatment. Eighty-two patients had uninodular tumors smaller than 5 cm, and 23 patients had multiple lesions (2-4) smaller than or equal to 3 cm each. All patients were in Child-Pugh class A (n = 64) or B (n = 41). Survival was analyzed according to patient- and tumor-related factors by means of the Kaplan-Meier method. RESULTS: The estimated survival rates of all 105 patients were 96% at 1 year, 86% at 2 years, 68% at 3 years, 51% at 4 years, 32% at 5 years, and 24% at 6 years. Survival was not affected by sex, age, etiology of cirrhosis, or hepatitis B surface antigen or anti-hepatitis C virus positivity, but depended on Child-Pugh class (P = 0.006) and presence of ascites (P = 0.009). Patients with a pretreatment alpha-fetoprotein level of 200 ng/ml or less had a better prognosis than patients with an alpha-fetoprotein level higher than 200 ng/ml (P = 0.007). Patients with unmodular HCC of 3 cm or less had significantly better long term survival (P = 0.04) than patients with uninodular HCC of 3.1-5 cm or with multinodular tumors. Tumor grade according to Edmondson and Steiner and tumor volume, in contrast, did not significantly influence prognosis (P > 0.1). CONCLUSIONS: For Western patients with HCC treated with PEI, the prognosis was highly dependent on the severity of the underlying cirrhosis. Treatment with PEI is best indicated for patients with uninodular tumors of 3 cm or less in greatest dimension and an alpha-fetoprotein level lower than 200 ng/ml.

Modulation of hemostatic balance with antithrombin III replacement therapy in a case of liver cirrhosis associated with recurrent venous thrombosis.

Patients with liver failure can present both thrombotic and hemorrhagic complications because of the deficiency in coagulation factors and inhibitors (protein C and S, antithrombin III) and impairment of fibrinolytic balance. Here we report the case of a 63-year-old man with liver cirrhosis, recurrent thrombosis, and features of low-grade consumption coagulopathy, showing severe antithrombin III deficiency (about 30% of normal values). Treatment with antithrombin III (2000 U/day) and low doses of heparin (5000 U b.i.d.) was successful in modulating the coagulation system toward an antithrombotic effect. After discharge from hospital the ambulatory treatment with antithrombin III concentrates (2000 U twice a week) allowed the attainment of antithrombin III activity of about 60% and prevented the patient from recurrence of venous thrombosis.

Oral doxifluridine in elderly patients with metastatic colorectal cancer: a multicenter phase II study.

BACKGROUND: Cancer chemotherapy in elderly patients is an important and under-researched area. Doxifluridine is a fluoropyrimidine derivative and is activated to 5-fluorouracil by uridine phosphorylase, which is more highly expressed in malignant cells. Because of the high bioavailability and low toxicity of oral doxifluridine we conducted this phase II trial to evaluate the feasibility, toxicity and activity of a home therapy with oral doxifluridine in elderly metastatic colorectal cancer patients. PATIENTS AND METHODS: Forty-three elderly metastatic colorectal cancer patients entered the study: their median ECOG performance status was 1 (0-2) and median age 74 years (69-83), the predominant site of metastasis was liver and all but one of the patients had received no previous chemotherapy. Doxifluridine was given orally at the initial daily total dose of 2250 mg for 4 consecutive days every week. The daily dose was reduced to 1500 mg if toxicities greater than grade 2 (WHO) occurred. RESULTS: Forty-two patients are evaluable for toxicity: treatment was well tolerated, with the most common side effect being diarrhea, severe in 7 (17%) patients (6 grade 3 and 1 grade 4). Thirty-six patients are evaluable for response and 2 complete and 3 partial responses have been observed (response rate 14%; 95% confidence limit interval 5%-29%). CONCLUSIONS: This study demonstrates that a home therapy with oral doxifluridine in elderly advanced colorectal cancer patients is feasible, with a relatively low rate of toxicity, and has moderate activity, comparable to that of intravenous 5-fluorouracil. Therefore, this treatment may be considered for the management of advanced colorectal cancer in the elderly.

Interindividual variability in the concentrations of albumin and alpha-1-acid glycoprotein in patients with renal or liver disease, newborns and healthy subjects: implications for binding of drugs.

The concentrations of human plasma albumin (HPA) and alpha-1-acid glycoprotein (AAG) were measured in the serum obtained from 84 healthy subjects, 56 umbilical cords, 41 patients with renal failure, 65 patients maintained on chronic hemodialysis and 46 patients with liver cirrhosis. Severity of liver dysfunction was assessed with the use of Pugh et al. [1973] classification. Of the cirrhotic patients, 12, 22 and 12 patients were classified as mild, moderate and severe liver dysfunction, respectively. The coefficient of variation of AAG was greater than HPA in all groups of subjects, and the variability of HPA and AAG is increased in patients compared to healthy subjects. As the liver dysfunction progresses, HPA concentration decreases whereas, the average AAG concentration is not changed in mild, moderate and severe liver dysfunction. The coefficients of variation for HPA and AAG in moderate and severe liver disease is over twice those for healthy subjects. The concentration of HPA is normally distributed in all groups of subjects, with the exception of the cord serum. The frequency distribution of AAG was normal in healthy subjects whereas, it was asymmetric, being positively skewed, in newborn, in renal and liver patients. The wide interindividual variability and the not-normal frequency distribution of AAG in liver or renal patients make its mean of little value in defining a group. Neither HPA nor AAG correlated with the clearance of creatinine in renal patients. In liver disease, HPA and AAG did not correlate with GPT and GOT activities, prothrombinic activity and bilirubin concentration. HPA did not correlate with AAG in any group.

The effect of ageing on plasma albumin and plasma protein binding of diazepam, salicylic acid and digitoxin in healthy subjects and patients with renal impairment.

1. Plasma albumin concentration was measured in 118 healthy subjects (aged between 18 and 87 years), in 95 renal patients with creatinine clearances between 15 and 50 ml min-1 (aged between 14 and 79 years) and in 101 uraemic patients maintained on chronic haemodialysis (aged between 27 and 83 years). 2. There was a significant (P less than 0.001) negative correlation between albumin concentration and age in healthy subjects, but no correlation in patients with low creatinine clearance or in uraemic patients. 3. The ex vivo plasma binding of diazepam (1 microM), salicylic acid (2 mM) and digitoxin (37 nM) was studied in groups of age-selected young and aged healthy subjects in patients with low creatinine clearance and in patients with uraemia. The unbound fractions of diazepam and salicylic acid were about double in old compared with young healthy subjects whereas they were similar in young and old patients with lowered creatinine clearance. In uraemic patients, ageing did not affect the binding of salicylic acid whereas the unbound fraction of diazepam was slightly but significantly greater in elderly subjects. The unbound fraction of digitoxin was independent of age in both healthy subjects and in those with renal disease. 4. Decreased plasma binding of diazepam and salicylic acid was partially corrected by extensive dialysis of plasma. The lower plasma binding of diazepam and salicylic acid associated with ageing may be ascribed to the effects of endogenous displacers and to hypoalbuminaemia. The influence of these two factors appears to be drug-dependent.

Conjugation pathways in liver disease.

1. The activities of microsomal glucuronyltransferase and thiomethyltransferase, and those of cytosolic sulphotransferase, acetyltransferase, glutathione transferase and thiomethyltransferase were measured in abnormal (cirrhosis and chronic hepatitis) and normal livers. 2. Glucuronyltransferase and sulphotransferase were investigated with 2-naphthol and ethinyloestradiol as substrates. p-Aminobenzoic acid, benzo(a)pyrene-4,5-epoxide and 2-mercaptoethanol were the substrates of acetyltransferase, glutathione transferase and thiomethyltransferase, respectively. 3. Enzyme activities are expressed as nmol min-1 incubation mg-1 protein and the averages (+/- s.d.) are given. With 2-naphthol as substrate, the glucuronyltransferase activity was 6.55 +/- 4.10 (abnormal liver, n = 33) and 7.81 +/- 4.02 (normal liver, n = 26) (NS); whereas sulphotransferase activity was 0.28 +/- 0.18 (abnormal liver, n = 35) and 0.68 +/- 0.43 (normal liver, n = 26) (P less than 0.01). Glucuronyltransferase activity towards ethinyloestradiol was 102.5 +/- 56.9 (abnormal liver, n = 30) and 107 +/- 59.9 (normal liver, n = 26) (NS), whereas sulphotransferase activity was 57.2 +/- 36.0 (abnormal liver, n = 35) and 122 +/- 67.6 (normal liver, n = 28) (P less than 0.01). Acetyltransferase activity was 0.84 +/- 0.83 (abnormal liver, n = 35) and 3.84 +/- 1.65 (normal liver, n = 26) (P less than 0.01). Glutathione transferase activity was 0.83 +/- 0.68 (abnormal liver, n = 35) and 2.90 +/- 1.59 (normal liver, n = 25) (P less than 0.01) and thiomethyltransferase activity was 1.00 +/- 0.69 (abnormal liver, n = 34) and 3.99 +/- 1.49 (normal liver, n = 25) (P less than 0.01). 4. Liver disease lowers the activities towards the substrates studied of sulphotransferase, acetyltransferase, glutathionetransferase and thiomethyltransferase but not that of glucuronyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic effectiveness and tolerance of 5-aminosalicylic acid in short term treatment of patients with ulcerative colitis at a low or medium phase of activity.

The therapeutic effectiveness and tolerance of 5-aminosalicylic acid (5ASA), compared with Salazosulphapyridine (SASP) in treatment of ulcerative colitis have been evaluated in 86 patients with the disease at a low or medium phase of activity. After a treatment of six weeks, an improvement was noted in 63.6% (5ASA) and 61.3% (SASP) of these patients. However in no case was a complete remission of the disease observed on the basis of endoscopic inspection. In patients with pancolitis the improvement was lower (37.5% with 5ASA, 40% with SASP). The only side-effect was gastric intolerance, which occurred in 18.1% of the 5ASA and in 19% of the SASP patients. In conclusion we can assume that 5ASA and SASP largely overlap each other as regards both therapeutic effectiveness and occurrence of side-effects.

[Efficacy and tolerability of 5-aminosalicylic acid in the short-term treatment of ulcerative rectocolitis during the mild or moderate stage]. / Efficacia e tollerabilità dell'acido 5-aminosalicilico nel trattamento a breve termine della rettocolite ulcerosa in fase di attività lieve o media.

The aim of the study was to compare the efficacy and side-effects of 5-ASA and SASP in the treatment of active ulcerative colitis. An improvement was seen in 71.4% (5-ASA) and 70.3% (SASP) but there were no complete remissions. The incidence of improvements was only 36.3% (5-ASA) and 37.5% (SASP) in pancolitis. The side-effects appeared in 14.2% (5-ASA) and 21% (SASP).

Plasma protein binding of frusemide in liver disease: effect of hypoalbuminaemia and hyperbilirubinaemia.

The binding of frusemide was studied in the plasma of 20 healthy subjects and 45 patients with liver disease. The unbound percentage (mean +/- s.d.) of frusemide was 1.64 +/- 0.21 healthy subjects) and 2.24 +/- 0.79 (patients) (P less than 0.01). By grouping the patients on the basis of plasma albuminaemia and bilirubinaemia four clusters namely: 'normal concentrations of albumin and bilirubin' (A), 'hyperbilirubinaemia and normal albumin concentration' (B), 'hypoalbuminaemia and normal bilirubin concentration' (C) and 'hypoalbuminaemia and hyperbilirubinaemia' (D) were defined. The unbound percentage of frusemide was 1.80 +/- 0.36 in (A); 2.44 +/- 1.05 in (B); 2.23 +/- 0.38 in (C); 2.76 +/- 0.77 in (D). The figure for healthy volunteers was not different from A, whereas it was significantly lower than those for B and D (P less than 0.01) and for C (P less than 0.05). A lowered binding of frusemide was associated with hypoalbuminaemia or hyperbilirubinaemia.

Plasma protein binding of ethinyloestradiol: effect of disease and interaction with drugs.

The protein binding of ethinyloestradiol (EE2) was investigated in the plasma from 14 healthy volunteers, 10 patients with hyperbilirubinemia, 10 patients with liver cirrhosis and 10 patients with renal failure. Binding assay was performed by equilibrium dialysis at 37 degrees C. The unbound fraction (mean +/- SD) of EE2 was 1.17 +/- 0.12 (volunteers), 2.74 +/- 0.77 (hyperbilirubinemics; p less than 0.001) 1.51 +/- 0.31 (cirrhotics; p less than 0.01) and 1.44 +/- 0.11 (renal failure; p less than 0.001). Studies with isolated albumin and alpha-1-acid glycoprotein showed that albumin is the major plasma protein to bind EE2. Warfarin (75 microM) and diazepam (75 microM) increased by 5.0% and 3.0%, respectively, the unbound fraction of EE2 when albumin concentration was 15 microM. Under similar conditions, digitoxin did not modify the binding of EE2. At therapeutic concentrations, warfarin and diazepam did not affect the binding of EE2 in plasma.

Plasma protein binding of alpidem in healthy volunteers, in neonates and in liver or renal insufficiency.

The binding of alpidem, a new anxiolytic drug, has been studied in plasma from 6 healthy subjects, 12 patients with renal failure, 12 patients with liver cirrhosis and 12 chronic uraemics maintained on haemodialysis, as well as in 12 serum samples from the placental cord, to represent the situation in the newborn. The unbound fraction was 0.61% (healthy volunteers), 1.31% (newborns), 0.86% (cirrhotic patients), 0.72 (patients with renal failure), 0.70% (before haemodialysis) and 0.79% (after haemodialysis). Binding in the volunteers was significantly different from that in neonates and cirrhotics only. Alpidem became bound to isolated albumin (45 g.l-1) and alpha 1-acid glycoprotein (0.75 g.l-1) to 97.2% and 97.1%, respectively. The bound fraction of the drug in a mixture of two proteins was 99.1%. For alpidem, it appears that alpha 1-acid glycoprotein may balance the effect of any decrease in the albumin concentration.

Plasma protein binding of zolpidem in liver and renal insufficiency.

Similar degree (65-66%) of binding of zolpidem (0.1 microgram/ml) was found with physiological concentrations of isolated human albumin (40 g/l) or alpha-1-acid glycoprotein (1 g/l). Zolpidem binding was studied in plasma from 6 healthy subjects, 12 patients with renal failure, 12 patients with liver cirrhosis and 12 chronic uremics maintained on hemodialysis as well as in 12 serum samples from the placental cord. The unbound fraction (mean +/- s.e.m.) was 8.1 +/- 0.2% (healthy volunteers), 10.8 +/- 0.4% (renal failure), 11.3 +/- 0.7% (liver cirrhosis); 14.9 +/- 1.0% (before hemodialysis); 9.8 +/- 0.4% (after hemodialysis) and 13.2 +/- 0.9% (placental cord). All values, except those after hemodialysis, were significantly different (Dunnett's test) from those of the volunteers. Hemodialysis significantly increased the binding of zolpidem in plasma. The kinetics of protein binding of zolpidem were investigated in plasma samples from 3 healthy subjects. The average number of binding sites was 1.83 x 10(-7) mol per gram protein and the average association constant was 4.49 x 10(5) M-1.

Plasma protein binding of clonazepam in hepatic and renal insufficiency and after hemodialysis.

The plasma protein binding of clonazepam was investigated in healthy volunteers, cirrhotic patients, chronic uremic patients maintained on hemodialysis, and patients with reduced renal function. Each group consisted of six subjects. The unbound fraction of clonazepam (mean +/- SEM) was 13.9 +/- 0.2% in volunteers. 17.1 +/- 1.0% in cirrhotic patients, 1.56 +/- 0.5% before and 12.2 +/- 0.4% after hemodialysis in chronic uremic patients, and 16.0 +/- 0.7% in patients with poor renal function. The figure for the healthy subjects was significantly different from that of cirrhotic patients only. Binding of clonazepam to albumin and alpha 1-acid glycoprotein was also studied. Clonazepam bound preferentially to albumin.