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Biomedical subjects

L Giuliani

Publications and source records attributed to L Giuliani.

At least 19 recordsLinked to original sources
PubMed1995

[Colorectal carcinoma in the elderly. Assessment of prognostic factors].

Between 1976 and December 1992 a total of 80 patients aged 80 or over underwent surgery for colorectal cancer at the Surgical Clinic of Pisa University. Twelve patients died, 18 presented non-lethal complications and 48 had a normal postoperative recovery. The type of surgery did not appear to be correlated with mortality. Urgency, associated with the advanced stage of cancer (according to Duke's classification modified by Aster-Coller), was the factor which most severely influenced mortality. A marked prognostic improvement can be obtained by an early diagnosis and careful evaluation of the patient's overall conditions.

Age Factors↗
PubMed1992

Interindividual variability in the N-sulphation of desipramine in human liver and platelets.

1. The activity of N-sulphotransferase (N-ST) with desipramine (DMI) as substrate was measured in 118 human liver specimens, in platelets obtained from 105 subjects, in 12 specimens of human ileum and colon mucosa and in five specimens of human kidney and lung. 2. N-ST activity ranged between 5.71 and 157 pmol min-1 mg-1 protein in human liver and between 0.27 and 17.3 pmol min-1 mg-1 protein in human platelets. 3. Probit analysis was compatible with a unimodal distribution of the data from both liver and platelets. 4. The frequency distribution histograms of N-ST were asymmetric, with a positive skew in data from both liver and platelets. The mode, median and mean of N-ST were 16.4, 30.2 and 40.4 pmol min-1 mg-1 protein in liver, and 2.12, 3.61 and 3.82 pmol min-1 mg-1 protein in platelets, respectively. After logarithmic transformation of N-ST activity, the frequency distribution histogram was symmetric for data from both liver and platelets. 5. In extrahepatic tissues, the average (+/- s.d.) N-ST activity (pmol min-1 mg-1 protein) was 22.2 +/- 22.8 (ileum), 20.9 +/- 26.9 (colon), 12.4 +/- 5.5 (renal cortex), 9.3 +/- 2.8 (renal medulla) and 4.2 +/- 1.1 (lung). N-ST is widely distributed in the body and the intestine is the extrahepatic tissue with the highest N-ST activity.

Adult↗
PubMed1992

Histamine N-methyl transferase: inhibition by drugs.

1. Histamine N-methyl transferase activity was measured in samples of human liver, brain, kidney, lung and intestinal mucosa. The mean (+/- s.d.) rate (nmol min-1 mg-1 protein) of histamine N-methylation was 1.78 +/- 0.59 (liver, n = 60), 1.15 +/- 0.38 (renal cortex, n = 8), 0.79 +/- 0.14 (renal medulla, n = 8), 0.35 +/- 0.08 (lung, n = 20), 0.47 +/- 0.18 (human intestine, n = 30) and 0.29 +/- 0.14 (brain, n = 13). 2. Inhibition of histamine N-methyl transferase by 15 drugs was investigated in human liver. The IC50 for the various drugs ranged over three orders of magnitude; chloroquine was the most potent inhibitor. 3. The average IC50 values for chloroquine were 12.6, 22.0, 19.0, 21.6 microM in liver, renal cortex, brain and colon, respectively. These values are lower than the Michaelis-Menten constant for histamine N-methyltransferase in liver (43.8 microM) and kidney (45.5 microM). Chloroquine carried a mixed non-competitive inhibition of hepatic histamine N-methyl transferase. Some side-effects of chloroquine may be explained by inhibition of histamine N-methyl transferase.

Adult↗
PubMed1991

Distribution of UDP-glucuronosyltransferase and its endogenous substrate uridine 5'-diphosphoglucuronic acid in human tissues.

The activity of UDP-glucuronosyltransferase (UDPGT) and the concentration of its endogenous substrate, 5'-diphosphoglucuronic acid (UDPGA), have been measured in human liver, kidney, lung and intestinal mucosa. The activity of UDPGT was tissue- and substrate-dependent. The liver/kidney and liver/intestine ratios for UDPGT varied over one order of magnitude with three substrates. The highest activity of UDGPT in extrahepatic tissues was in the kidney, with 1-naphthol as substrate; it was about half of the hepatic activity. The concentration (mumol.kg-1) of UDPGA was 279 (liver), 17.4 (kidney), 19.3 (intestinal mucosa) and 17.2 (lung), it was at least 15-fold higher in liver than the other tissues, and the concentration in kidney, lung and intestinal mucosa was similar. The kinetics of UDPGT in a liver homogenate at varying concentrations of UDPGA and fixed concentration of 1-naphthol, ethinyloestradiol, and morphine was also measured. The apparent kM for UDPGT depended upon the chemical nature of the UDPGA-acceptor substrate; average values of kM were 63, 300, and 700 mumol.l-1 for 1-naphthol, ethinyloestradiol and morphine respectively. These values are, respectively, lower, similar to and higher than the hepatic concentration of UDPGA. Under certain circumstances UDPGA may be the limiting factor in the in vivo glucuronidation of drugs by extrahepatic tissues.

Adult↗
PubMed1991

Monotherapy with nilutamide, a pure nonsteroidal antiandrogen, in untreated patients with metastatic carcinoma of the prostate. The Italian Prostatic Cancer Project.

A total of 26 previously untreated patients with metastatic carcinoma of the prostate received the pure nonsteroidal antiandrogen nilutamide as a single agent. Objective response rate was 38.5 +/- 18.7% (95% confidence interval). Median progression-free survival and median survival were 9 and 23 months, respectively. Of 13 patients with progression on antiandrogen 5 showed an additional objective response to a second-line endocrine treatment. The drug was generally well tolerated, except for 2 patients who discontinued treatment because of moderate gastrointestinal symptoms. Approximately a third of the patients complained of decreased adaptation to darkness. An electroretinogram and dark adaptation test revealed the presence of functional damage and visual complaints reversed in all patients on cessation of therapy. The other most frequent side effects were slight nausea (26.9% of the patients) and alcohol intolerance (19.2%). A nonsignificant increase in testosterone levels was shown within 1 month of treatment, after which the levels remained stable. Approximately half of the sexually active men claimed maintenance of libido and sexual potency during treatment. A slightly significant increase in hemoglobin was observed during the long term, suggesting the occurrence of a trophic effect by androgens on erythropoiesis. The results indicate that nilutamide as a single agent has an acceptable toxicity and a moderate activity, and may maintain sexual interest in a discrete number of cases. Whether monotherapy with nonsteroidal antiandrogens offers a valid option in the palliation of advanced disease remains to be seen in comparative prospective trials.

Androgen Antagonists↗
PubMed1991

Evaluation of serum CA15-3 determination with CEA and TPA in the post-operative follow-up of breast cancer patients.

The usefulness of post-operatively serial serum CA15-3 determination with CEA and TPA was evaluated in a group of 285 breast cancer patients. In particular, the CA15-3 sensitivity to 'early' diagnosis and monitoring of the response to treatment of breast cancer relapses, was compared with those of the two other markers in order to define the most suitable association. Moreover, in a group of 169 non relapsed patients with a prolonged follow-up (40 +/- 8 months; mean +/- s.d.) CA15-3 specificity was investigated. During post-operative follow-up in 27 (10%) patients, distant metastases occurred. In most of them, elevated values of one or more tumour markers were the first pathological sign and CA15-3, CEA and TPA sensitivity to 'early' diagnosis of metastases were 46%, 7% and 63% respectively. When each tumour marker was considered in combination, CA15-3-CEA-TPA association showed a higher sensitivity (87%) than both CA15-3-TPA (83%) and the CEA-TPA (70%). Serum CA15-3 increase preceded the certain sign of metastases 2.7 +/- 2.6 months (mean +/- s.d.). Shortly before appearance and during treatment of distant metastases, constant elevation and/or progressive increase in serum CA15-3 values occurred in all evaluated patients except three in whom isolated elevated values were found as well. In 24 (14%) of 169 non relapsed patients with prolonged follow-up (40 +/- 8 months; mean +/- s.d.) high serum CA15-3 values occurred. In 16 of these 24 patients, an isolated elevated value was found, while four (2.3%) or the eight remaining ones with constant elevation and/or progressive increase were falsely suspected of metastases. In this group of non relapsed patients, chronic liver failure, diabetes and/or hepatic steatosis were the reasons more commonly responsible for the CA15-3 increase. In metastatic patients, no organ-specificity was shown either by CA15-3 or by CEA and TPA. In these patients serum TPA values showed the highest sensitivity and paralleled clinical and/or instrumental signs better than the CA15-3 and even more than CEA values. These data indicate that in the post-operative follow-up of breast cancer patients, TPA is the most useful tumour marker and TPA-CA15-3 the most suitable association. Contemporaneous measurement of serum CEA levels only slightly increases sensitivity and positive predictive value of TPA-CA15-3 combination.

Adult↗
PubMed1991

Interindividual variability in the glucuronidation and sulphation of ethinyloestradiol in human liver.

1. Glucuronidation and sulphation of ethinyloestradiol (EE2) was studied in human liver. Microsomal glucuronyltransferase activity was measured in 110 livers whose donors were 71 women and 39 men. Enzyme activity ranged between 12.6 and 242 pmol min-1 mg-1 protein, i.e. over a 19-fold range and the mean (+/- s.d.) glucuronyltransferase activity was 96.8 +/- 47.9 pmol min-1 mg-1 protein. 2. Cytosolic sulphotransferase activity was measured in 138 livers whose donors were 90 women and 48 men. Enzyme activity ranged between 14.4 and 98.2 pmol min-1 mg-1 protein, i.e. over a 7-fold range, and the mean (+/- s.d.) sulphotransferase activity was 43.7 +/- 18.6 pmol min-1 mg-1 protein. 3. Human liver glucuronyltransferase and sulphotransferase activities showed a unimodal distribution pattern. Enzyme activities were neither sex-related nor age-dependent. Sulphotransferase activity did not correlate with glucuronyltransferase activity (n = 80) suggesting that the two enzymes are independently regulated. The ratio of specific glucuronyltransferase to sulphotransferase activity ranged between 0.15 and 8.0 (mean +/- s.d., 2.44 +/- 1.51) and was unimodally distributed.

Adult↗
PubMed1991

Thiol methyltransferase in humans: development and tissue distribution.

Thiol methyltransferase (EC 2.1.1.9, TMT) activity was measured with 2-mercaptoethanol in the microsomal fraction of 12 placenta and 31 fetal and 33 adult liver specimens. TMT activity (nmol/min incubation/mg protein; mean +/- SD) was 0.61 +/- 0.25 (placenta), 0.74 +/- 0.45 (fetal liver), and 4.51 +/- 2.29 (adult liver). TMT activity was also measured in extrahepatic tissues and it was about one order of magnitude lower in fetal lungs, kidney and intestine as compared with the fetal liver. A similar distribution pattern was also observed in adult tissues except that in the kidney TMT activity was one third of the hepatic one. Studies of enzyme kinetics showed that fetal and adult hepatic TMT obeyed non-Michaelis-Menten kinetics when 2-mercaptoethanol was the varying substrate. Average values of Km for the higher and lower affinity phases were 0.03 and 14.05 mmol/l, respectively (fetal liver) and 0.005 and 14.57 mmol/l, respectively (adult liver). This paper shows that TMT develops prenatally and its distribution pattern is consistent with that of other microsomal enzymes, being preferentially associated with the liver both in the human fetus and in adult subject.

Adult↗
PubMed1991

Thiopurine methyltransferase in humans: development and tissue distribution.

Thiopurine methyltransferase (EC 2.1.1.67, TPMT) was studied with 6-mercaptopurine as substrate in the cytosolic fraction from 18 human fetal liver, 16 placental and 22 adult liver specimens. TPMT activity (pmol x min-1 x mg-1; mean +/- SD) was 33.2 +/- 15.8 (fetal liver), 19.5 +/- 11.1 (placenta) and 105 +/- 57.1 (adult liver). Fetal liver activity of TPMT is one third that in adult liver suggesting that this enzyme is well developed in the mid-gestational human fetus. The distribution of TPMT seems to be ubiquitous both in the fetus and adult subject. The kidney is an important site of methylation as suggested by the renal activity of TPMT (197 +/- 70 pmol x min-1 x mg-1) which is twice as high as the hepatic one. Fetal and adult hepatic TPMT obey nonmichaelian kinetics. Two phases, one with lower and one with higher affinity for 6-mercaptopurine, were observed. The average Km for the high affinity phase was 0.12 mmol/l (fetus) and 0.13 mmol/l (adult), whereas the Km for the lower affinity phase was 1.79 mmol/l (fetus) and 1.42 mmol/l (adult). This paper shows that TPMT develops before the second trimester of gestation in human fetus, that it has an ubiquitous distribution in the human fetus and adult subjects and the kinetic pattern of this enzyme is consistent in fetal and adult liver.

Adolescent↗
PubMed1991

Conjugation of benzoic acid with glycine in the human fetal and adult liver and kidney.

The rate of hippuric acid formation was measured in the homogenates obtained from 26 specimens of human adult liver, 9 specimens of human mid-gestational fetal liver, 5 specimens of human adult kidney and 11 specimens of human mid-gestational fetal kidney. The average (pmol/min/mg tissue +/- SD) rate of hippuric acid formation was 322 +/- 99 (adult liver), 7.6 +/- 3.6 (fetal liver), 284 +/- 117 (adult kidney) and 6.4 +/- 6.7 (fetal kidney). One third of the fetal livers and kidneys studied were inactive in the formation of hippuric acid. These findings indicate that the conjugation of carboxylic acid with glycine is poorly developed in the mid-gestational human fetus. The kinetics of the formation of hippuric acid were studied in 3 fetal and adult livers and also in 3 fetal kidneys and in 3 specimens of the cortex and medulla of adult kidneys. The transformation of the data into Eadie-Hofstee plots generated straight lines in fetal and adult livers and kidneys. The Michaelis-Menten constant for the formation of hippuric acid (mean +/- SD, mM) was 43.4 +/- 6.6 (adult liver), 27.3 +/- 10.1 (fetal liver), 33.3 +/- 6.1 (adult renal cortex), 34.7 +/- 11.3 (adult renal medulla) and 15.3 +/- 3.5 (fetal kidney). The maximum velocity of the reaction (mean +/- SD, pmol/min/mg tissue) was 204 +/- 47.8 (adult liver), 6.0 +/- 1.3 (fetal liver), 199 +/- 40.7 (adult renal cortex), 24.2 +/- 16.9 (adult renal medulla) and 6.4 +/- 1.8 (fetal kidney). The inhibitory effect of 8 drugs containing a carboxylic acid group on the rate of hippuric acid formation was studied in 3 adult livers. Salicylic acid and diflunisal were the most powerful as inhibitors. Ibuprofen, furosemide and sodium valproate were weak inhibitors, whereas ketoprofen, naproxen and captopril did not inhibit the formation of hippuric acid. The IC50 values (mean +/- SD) of salicylic acid and diflunisal on the rate of hippuric acid formation were 0.19 +/- 0.05 and 1.18 +/- 0.19 mM, respectively.

Acyltransferases↗
PubMed1991

Human liver sulphotransferase and UDP-glucuronosyltransferase: structure-activity relationship for phenolic substrates.

1. Human liver sulphotransferase and UDP-glucuronosyltransferase were studied with phenol, methyl-, ethyl-, propyl-, butyl-, phenyl-, nitro-, amino-phenols and hydroxybenzoic acids as substrates. 2. The Michaelis-Menten constants (Km) and the maximum velocities of reaction (Vmax) of sulphotransferase and UDP-glucuronosyltransferase for each substrate were measured. 3. The Km values for sulphotransferase varied over 5000-fold whereas they varied over 25-fold for UDP-glucuronosyltransferase. 4. Sulphotransferase and UDP-glucuronosyltransferase have different structure-activity relationships with phenolic substrates.

Adult↗
PubMed1991

Methylation of captopril in human liver, kidney and intestine.

1. The methylation of captopril was studied in the microsomal fraction from 20 human liver, 12 kidney, and 14 intestinal mucosa specimens. 2. The hepatic methyltransferase activity (mean +/- SD) was 477 +/- 204 pmol/min per mg. Renal and intestinal methyltransferase activities were 3 and 8 times lower, respectively, than hepatic activity. 3. The kinetics of methyltransferase with captopril as substrate were studied in four specimens of liver, kidney and intestine. The maximum velocities of reaction (mean +/- SD; pmol/min per mg) were 697 +/- 219 (liver), 456 +/- 120 (renal cortex), 264 +/- 77 (renal medulla) and 101 +/- 28 (ileum mucosa). Km values (mean +/- SD; mM) were 5.2 +/- 2.3 (liver) 4.3 +/- 1.7 (renal cortex) 4.1 +/- 1.5 (renal medulla) and 5.3 +/- 2.0 mM (ileum mucosa). Vmax is subjected to a marked tissue dependence whereas Km is similar in all tissues. 4. Liver is the primary site of captopril methylation whereas the intestine plays only a minor role. Kidney may contribute substantially to the hepatic methylation of captopril.

Adult↗
PubMed1991

Anandron (RU 23908) in metastatic prostate cancer: preliminary results of a multicentric Italian study.

Between March 1986 and March 1987, 48 patients with stage D prostate carcinoma were entered into a multicentric pilot study using the pure nonsteroidal antiandrogen nilutamide (Anandron--RU 23908) at the dose of 100 mg t.i.d. as the only therapy until disease progression or the occurrence of toxicity. Minimum follow-up was 15 months. Median age of patients was 72 (56 to 83) and median initial Performance Status (PS) was 1 (0 to 3). Of the 48 patients, 29 were untreated, while 19 patients were progressing following treatment by orchiectomy, LHRH analogs, or other endocrine therapies. According to the National Prostatic Cancer Project (NPCP) criteria, 43 patients were evaluable for response. Overall best response in untreated patients was partial response (PR), 41.6%; stationary disease (SD), 54.1%; 73.6% of pretreated patients achieved SD. Median progression-free survival and overall survival in untreated patients were 325 and 696 days, respectively, and 174 and 447 days, respectively, in pretreated patients. The more common side effects were G.I. toxicity (65%), hemeralopia (27%), and alcohol intolerance (6.2%). Results of this study suggest that Anandron may be a safe and effective treatment for patients with advanced prostatic cancer.

Aged↗
PubMed1991

Dopamine sulphotransferase is better developed than p-nitrophenol sulphotransferase in the human fetus.

The distribution patterns of two forms of sulphotransferase were studied in human adult and fetal tissues. One form was studied with p-nitrophenol as substrate and it is referred to as 'TS'. The other form was studied with dopamine as substrate and it is referred to as 'TL'. The activities of TS (pmol X min-1 X mg-1; mean +/- SD) were 1,077 +/- 293 (adult liver; n = 6), 97.8 +/- 26.4 (fetal liver; n = 8); 38.0 +/- 12.8 (adult kidney; n = 5), 28.5 +/- 21.5 (fetal kidney; n = 8); 78.9 +/- 21.3 (adult lung, ex-smokers; n = 5), 83.0 +/- 23.1 (adult lung, smokers; n = 5), 25.8 +/- 10.0 (fetal lung; n = 8), 140.8 +/- 18.9 (ileum; n = 5), 68.6 +/- 30.7 (ascending colon; n = 5), 28.6 +/- 10.8 (fetal gut; n = 8), 23.9 +/- 14.5 (placenta; n = 5). The adult to fetal ratios for TS were 11.0 (liver), 1.3 (kidney), 3.1 (lung) and 2.6 (gut). The activities of TL were 28.9 +/- 17.4 (adult liver; n = 6), 97.2 +/- 52.3 (fetal liver; n = 8); 10.3 +/- 4.7 (adult kidney; n = 5), 37.7 +/- 29.9 (fetal kidney; n = 8); 79.6 +/- 18.8 (adult lung, ex-smokers; n = 5), 76.3 +/- 23.7 (adult lung, smokers; n = 5), 98.2 +/- 55.0 (fetal lung; n = 8); 391.2 +/- 37.3 (ileum; n = 5), 161.5 +/- 66.0 (ascending colon; n = 5), 200.6 +/- 137.1 (fetal gut; n = 8), 21.8 +/- 13.6 (placenta; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Radical extensive surgery for renal cell carcinoma: long-term results and prognostic factors.

We studied 200 consecutive patients with renal cell carcinoma who underwent radical nephrectomy and extensive lymphadenectomy. Of the patients 25% already had distant metastasis at operation. Higher T stages tended to be associated with positive nodes (p less than 0.01) and distant metastasis (p less than 0.001). However, in patients with stage N0M0V0 tumors we found no statistically significant difference in survival in relationship to the T stage of the disease (5-year survival: stage T1 80%, stage T2 68% and stage T3 70%). Of all patients 10% had positive nodes without distant metastases and no venous spread of the tumor, and the 5-year survival rate was 52%. The 5-year survival rate of patients with distant metastases was 7%. Patient survival in the presence of a vena caval tumor thrombus is similar to that of patients with distant metastases. Based on our results the different stages in disease progression may be classified as having a good prognosis--intracapsular tumors (stages T1 to T2, N0M0V0) and tumors with involvement of perirenal fat (stage T3N0M0V0), an intermediate prognosis--tumors with nodal metastases alone (stages T1 to T3, N1 to 2, M0V0) and a poor prognosis--tumors with venous invasion and/or distant metastases. Histological grading and size of tumor can be used to assess prognosis but are not more accurate than pathological staging.

Adult↗