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Biomedical subjects

L Giuliani

Publications and source records attributed to L Giuliani.

At least 73 records · Page 4Linked to original sources

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↗

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)

Adult↗

Differential distribution of phenol and catechol sulphotransferases in human liver and intestinal mucosa.

Phenol and catechol sulphotransferases were studied with p-nitrophenol and dopamine as substrates in the mucosa of the ileum and colon obtained from 6 subjects and also in the liver from 6 subjects. The ileum and colon were from the same donor. The kinetics of phenol and catechol sulphotransferases were studied in each tissue specimen. The maximum velocity of reaction (Vmax) for phenol sulphotransferase (in pmol X min-1 X mg-1; mean +/- SD) was 165 +/- 28 (ileum), 79 +/- 42 (colon) and 1,361 +/- 370 (liver), whereas Vmax for catechol sulphotransferase was 489 +/- 75 (ileum), 198 +/- 93 (colon) and 39 +/- 23 (liver). Phenol sulphotransferase is the predominant pathway in the liver, whereas catechol sulphotransferase is the predominant pathway in the intestine. The ileum catalysed the sulphation of p-nitrophenol and dopamine at a higher rate than the colon. The Michaelis-Menten constant (Km) for phenol sulphotransferase (in mumol/l; mean +/- SD) was 0.96 +/- 0.11 (ileum), 1.00 +/- 0.19 (colon) and 0.84 +/- 0.07 (liver), whereas Km for catechol sulphotransferase was 17.8 +/- 2.8 (ileum), 18.2 +/- 3.4 (colon) and 21.4 +/- 1.2 (liver). Km values of hepatic phenol or catechol sulphotransferases are not different from those of intestinal enzymes. Previous work has shown that 2-naphthol sulphotransferase obeys non-Michaelis-Menten kinetics in the human intestinal mucosa [Pharmacology, 1988;43:411]. Here, we show that 2-naphthol is sulphated by at least two enzymes in human intestine.

Aged↗

First experience with the Lithoring in the management of urinary stones.

The Lithoring Multi-One is a lithotripter recently developed in Italy. Its main features are (1) spark gap generator with large ellipsoid, with tunable power for treatments with or without analgesia; (2) localization by fluoroscopy and ultrasounds without moving the patient; (3) isocentric variation of shock wave window, and (4) multifunctional table. It can treat both urinary and biliary stones. The first 50 patients were treated without anesthesia with an average of 1,700 shock waves at 19.2 kV. 37 patients had stones larger than 1 cm. 13 patients had ureteral stones. Two patients had complete staghorn stones. The disintegration rate was 97.9%, the overall stone-free rate at 3 months' follow-up was 83.3%, and the retreatment rate was 1.29 treatments for patients. No complication occurred.

Anesthesia↗

Zoladex with or without flutamide in the treatment of locally advanced or metastatic prostate cancer: interim analysis of an ongoing PONCAP study. Italian Prostatic Cancer Project (PONCAP).

Since March 1987, 304 evaluable patients with stage C and D prostate cancer have been entered into a prospective trial comparing Zoladex and Zoladex plus flutamide. To date, there has been no significant difference in over-all and progression-free survival between the 2 treatment groups. However, combined treatment produced a higher response rate (particularly in stage D patients) and a more rapid normalization of abnormal prostatic acid phosphatase levels. In addition, more prompt relief of bone pain was evident in the Zoladex plus flutamide group. However, significantly more side-effects were associated with combined treatment. These findings should be considered with caution because they form an interim analysis, and follow-up time is short. The results do suggest, however, that there is no particular advantage in using a combination of Zoladex plus flutamide compared to adding flutamide on failure of treatment with Zoladex alone.

Aged↗

Flexible antegrade and retrograde nephroscopy: review of 50 cases.

50 cases of flexible instrumentation of the intrarenal collecting system are reviewed. 28 were performed by retrograde flexible ureterorenoscopy. The introduction was carried out by combining hydraulic dilation, rigid ureterorenoscopy and a working sheath. 22 cases were performed through a percutaneous route. The indications were both diagnostic (filling defects and/or hematuria) and therapeutic (caliceal stone and/or fragments). The success rate was high in the diagnostic cases (20 of 24), but lower in the therapeutic cases (13 of 26). The complication rate was extremely low and the postoperative course was always uneventful. Flexible instruments offer a very good chance to explore the intrarenal collecting system. Both transureteral and percutaneous flexible nephroscopies are feasible and effective procedures. A laser can be used well in this area.

Adult↗

[Extracorporeal lithotripsy using the Lithoring multi-one, a third generation lithotripter].

The Lithoring multi-one is a lithotripter recently developed in Italy. Its main features are: (1) spark gap generator with large ellipsoid with tunable power for treatments with or without analgesia (2) localization by fluoroscopy and ultrasounds without moving the patient (3) isocentric variation of shock wave window (4) multi-functional table. It can treat both urinary and biliary stones. Herein we described (1) the experimental in vitro studies, including those carried out by intentionally changing the direction of the blast path during the treatment (2) the experimental in vivo studies on pigs which demonstrated a rate of side effects favourably comparable with that of other spark gap lithotripters (3) the clinical experience on urinary stones which started in May, 1989. The first 50 patients were treated without anaesthesia with an average of 1700 shock waves at 19.2 Kv. 37 patients had stones larger than 1 cm. 13 patients had ureteral stones. Two patients had complete staghorn stones. The disintegration rate was 97.9 percent, the overall stone-free rate at 3 months follow-up was 83.3 percent and the retreatment rate was 1.29 treatments for patients. No complication occurred.

Adult↗

A rational postoperative follow-up with carcinoembryonic antigen, tissue polypeptide antigen, and urinary hydroxyproline in breast cancer patients.

Breast cancer patients (n = 224) aged 28 to 81 were postoperatively followed up with serial determinations of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and urinary hydroxyproline (OHP). The clinical usefulness of these tumor markers to diagnose and monitor distant metastases was compared with that of the imaging techniques commonly used to monitor breast cancer patients (bone scanning [BS], liver echography [LE], chest radiograph, and skeletal radiograph). So far, 23 patients withdrew from the study, and distant metastases occurred in 33 patients. In 91% of the metastatic patients, constant elevation or progressive increase in serum CEA and/or TPA levels were the first pathologic findings of the relapse. Of the remaining 168 nonrelapsed patients, 122 were followed up longer than 24 months (43 +/- 17 months; mean +/- SD). In these 122 patients the false-positive results of CEA, TPA, and OHP were 0.8%, 2.4%, and 0%, respectively, when used simultaneously with clinical examination and the common laboratory examinations. BS and LE are the only imaging techniques that showed such a high sensitivity to be suitable in the postoperative follow-up of breast cancer patients. Nevertheless, because BS has a low specificity and is not harmless, it should be performed at longer intervals than tumor markers. Eventually, in the relapsed patients, TPA and OHP well reflected the response to treatment better than CEA and prevented useless radiologic examinations.

Adult↗

Valpromide is a poor inhibitor of the cytosolic epoxide hydrolase.

The effect of the antiepileptics valpromide and sodium valproate on the cytosolic epoxide hydrolase was studied in human fetal liver, kidneys and adrenals and from human adult liver and kidneys. Trans-stilbene oxide was used as substrate. Valpromide (10 mM) lowered the activity of the epoxide hydrolase to one half of the control in all organs studied. Sodium valproate (10 mM) was less powerful as an inhibitor than valpromide; however, it exerted a significant inhibition in all tissues studied.

Anticonvulsants↗

Distribution of 2-naphthol sulphotransferase and its endogenous substrate adenosine 3'-phosphate 5'-phosphosulphate in human tissues.

The activity of sulphotransferase towards 2-naphthol and the concentration of its endogenous substrate, adenosine 3'-phosphate 5'-phosphosulphate (PAPS), have been measured in five specimens of human liver, lung, and kidney, and the mucosa from the ileum and the ascending, descending and sigmoid colon. The activity of 2-naphthol sulphotransferase (mean nmol.min-1.mg-1 protein) was 1.82 (liver); 0.034 (kidney); 0.19 (lung); 0.64 (ileum); 0.47 (ascending colon); 0.50 (descending colon); 0.40 (sigmoid colon). The concentration of PAPS (mean nmol.g-1 wet tissue) was 22.6 (liver); 4.8 (kidney); 4.3 (lung); 12.8 (ileum); 8.1 (ascending colon); 7.5 (descending colon); 6.2 (sigmoid colon). The concentration of PAPS and the activity of 2-naphthol sulphotransferase were higher in the liver than in the extrahepatic tissues. There was significant difference between ileum and ascending colon, both the activity of sulphotransferase and the concentration of PAPS being higher in the former. 2-Naphthol sulphotransferase activity and the concentration of PAPS have consistent distribution patterns. Differences between the tissues studied were more marked for sulphotransferase than for its endogenous substrate.

Adenine Nucleotides↗

Neoadjuvant or definitive alternating chemotherapy and radiotherapy for infiltrating bladder cancer.

Thirty-two patients with infiltrating bladder cancer were treated with transurethral resection followed by one course of alternating chemoradiotherapy before radical cystectomy (group A, 20 patients) or two courses as definitive procedure (group B, 12 patients). One course consisted of: cisplatin 20 mg/m2 i.v. and 5-fluorouracil 200 mg/m2 i.v. for 5 consecutive days, the first and the fourth weeks; radiotherapy 20 Gy in 10 fractions in the second and third weeks. At the seventh week the same integrated therapy was restarted in group B. All 32 patients were evaluable for toxicity after the first course: no grade IV toxicity was observed. Significant increase in hematological toxicity was observed in 12 patients who received the second course of chemoradiotherapy: two patients had grade IV toxicity, and five patients had grade III. Fifteen patients of group A underwent radical cystectomy: 40% had a pathological (p) complete response (CR) and 13.3% a partial response Five patients in group A did not receive either the second course of therapy or cystectomy because of age (three patients), vascular obliteration (one patient) and enteritis (one patient). Actuarial disease-free survival in group A is 78% at 21 months. All patients of group B obtained clinical (c) CR and all but one have no evidence of disease at a median follow-up of 10 months (range 6-13). The high pCR and cCR obtained in patients of group A and group B, respectively, appears promising. A longer follow-up and a larger number of patients is required to determine the role of this integrated treatment.

Adjuvants, Pharmaceutic↗

Profile of drug-metabolizing enzymes in human ileum and colon.

Six patients (4 women and 2 men, age between 60 and 90 years), subjected to right hemicolectomy, were gut donors. The mucosa was isolated from the last portion of the ileum and the first portion of the colon. Tissue specimens were free from pathological changes. The activities of the enzymes of phase I (NADPH cytochrome c reductase, ethoxycoumarin O-deethylase, aminopyrine N-demethylase, microsomal epoxide hydrolase, cytosolic epoxide hydrolase, glutathione reductase and glutathione peroxidase) and the enzymes of phase II (glutathionetransferase, glucuronyltransferase, acetyltransferase, thioltransferase, sulphotransferase and glyoxalase) were measured in the microsomal or cytosolic fractions obtained from ileum and colon mucosa. The activity in the ileum was higher than in the colon for NADPH cytochrome c reductase (p less than 0.05) and cytosolic epoxide hydrolase (p less than 0.001) (phase I enzymes), and glutathionetransferase (p less than 0.02), sulphotransferase (p less than 0.05) and glyoxalase (p less than 0.02) (phase II enzymes). The other enzymes had similar activities in two mucosa. The distribution pattern of drug metabolizing enzymes cannot be considered as a single pattern in human ileum and colon because of the observed enzyme-dependent differences.

Aged↗

Characterization of sulphotransferase in human ileum and colon.

The kinetics of sulphotransferase (ST) were studied at varying concentrations of 2-naphthol or adenosine 3'-phosphate-5'-phosphosulphate (PAPS) in specimens of ileum and colon mucosa obtained from 6 subjects. When 2-naphthol was the variable substrate the enzyme obeyed non-Michaelis-Menten kinetics. The enzyme kinetic profile consists of two phases: one at higher and the other at lower activity for 2-naphthol. The maximum velocity of reaction (Vmax, mean +/- SD; pmol/min.mg protein) of the high-affinity phase was 403 +/- 82 (ileum) and 216 +/- 42 (colon) (p less than 0.01). Vmax for the low-affinity phase was 669 +/- 105 (ileum) and 415 +/- 84 (colon) (p less than 0.01). Km (mean +/- SD) of the high affinity phase was 0.034 +/- 0.004 (ileum) and 0.025 +/- 0.001 mmol/l (colon) (NS) and that of the low-affinity phase was 0.101 +/- 0.013 (ileum) and 0.095 +/- 0.014 mmol/l (colon) (NS). At varying concentrations of PAPS the enzyme obeyed Michaelis-Menten kinetics. Vmax (mean +/- SD) was 995 +/- 163 (ileum) and 520 +/- 114 (colon) pmol/min.mg protein (p less than 0.02). Km was 0.096 +/- 0.008 (ileum) and 0.079 +/- 0.012 mmol/l (colon) (NS). The ST of ileum differs from that of colon for Vmax only.

Adult↗

Painless extracorporeal shock wave lithotripsy for outpatients: a new option.

Extracorporeal shock wave lithotripsy is becoming the most common procedure for the treatment of renal and ureteral stones. The introduction of a new generator and a new hemi-ellipsoid for the Dornier HM-III lithotripter improves patient comfort and requires no general or peridural anesthesia, thus making it easier to perform this procedure on an outpatient basis.

Adolescent↗

In situ or retrograde manipulation of ureteral stones: still a controversy?

A series of 365 patients with ureteral stones is reviewed. ESWL, ureterorenoscopy, basket extraction and open surgery were alternatively used according to the stone and to the increasing experience in minimally invasive techniques. The overall success rate of in situ ESWL varied between 79 and 90% according to the localization of the stone and no difference was noted between patients treated with the original HM III Dornier lithotriptor and patients treated with the upgraded HM III with low pressure and large ellipsoid for painfree ESWL. Also the retreatment rate did not differ significantly (38 vs 42%). Ureterorenoscopy, carried out as first approach or after ESWL failure, was successful in 80.4% of the cases. Basket extraction was successful only in 32.3% of the cases. In situ ESWL, in one or two sessions, without anaesthesia and without hospital stay, is a good solution for roughly 80% of ureteral stones. Retrograde manipulation with or without ureterorenoscopy, requiring anaesthesia and hospitalization, should be reserved to failures of in situ ESWL.

Adolescent↗

Development of the glucuronyltransferase and sulphotransferase towards 2-naphthol in human fetus.

The activity of the microsomal glucuronyltransferase (GT) was measured in 34 fetal and 27 adult human livers with 2-naphthol as substrate. The average (+/- SD) enzyme activity was 0.07 +/- 0.07 nmol/min/mg protein (fetal) and 7.98 +/- 4.19 nmol/min/mg protein (adult) livers. The adult to fetal ratio of the GT activity was 114. The activity of the cytosolic sulphotransferase (ST) was measured with 2-naphthol as substrate in 30 fetal and 23 adult livers. ST activity (mean +/- SD) was 0.18 +/- 0.12 nmol/min/mg protein (fetal) and 0.63 +/- 0.22 nmol/min/mg protein (adult). The adult to fetal ratio of the ST activity was 3.5. The postnatal development of GT is more marked than that of ST. In the fetal livers, the rate of 2-naphthol sulfation correlated (p less than 0.01) with the rate of 2-naphthol glucuronidation, whereas they did not correlate in the adult livers. No relationship was observed between the activity of the GT or ST and gestational age. The correlation existing between ST and GT in human fetus might suggest that the two enzymes are under a common developmental pattern which seems to be independent of gestational age. The activity of the GT with morphine as substrate was measured in 25 fetal and 29 adult livers and found to be 0.23 +/- 0.20 nmol/min/mg protein (fetal) and 1.85 +/- 0.98 nmol/min/mg protein (adult). Thus, the adult to fetal ratio of morphine glucuronidation was 8.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Estramustine phosphate (estracyt) following androgens in men with refractory stage D2 prostate cancer.

Twenty-two orchiectomized men with progressive stage D2 prostate cancer were treated with a 3-week cycle of estramustine phosphate (EMP: from day 3 to day 21) and androgen priming (from day 1 to day 4). A partial response according to the NPCP-USA criteria was shown in 4 of 20 evaluable patients. Median progression-free survival of all patients was 24 weeks (range, 4-48) and median survival, 42 weeks (range, 4-112). Although in two cases treatment had to be stopped due to a marked increase in bone pain, no life-threatening side effects were observed. The androgen sensitivity of tumors was supported by the occurrence of increase in prostatic phosphatase and in bone pain in most patients. In this group of patients, androgen priming did not seem to potentiate the effectiveness of EMP, our results being comparable to those previously reported using EMP alone.

Aged↗

Cytosolic epoxide hydrolase in humans: development and tissue distribution.

Cytosolic epoxide hydrolase activity was measured towards trans-stilbene oxide in 41 human adult livers, in 40 fetal livers, in 17 placentas and in fetal and adult lungs, kidneys and gut. The cytosolic epoxide hydrolase activity was measurable in all specimens investigated. The rate of formation of trans-stilbene glycol (pmol/min per mg protein, mean +/- SD) was 55.2 +/- 89.6 (fetal liver). 303.2 +/- 73.2 (adult liver) and 18.8 +/- 13.1 (placenta) In the fetal extrahepatic tissues, the cytosolic epoxide hydrolase activity was 70.0 +/- 9.4 (adrenals), 47.6 +/- 7.2 (gut), 69.4 +/- 22.5 (kidneys) and 43.2 +/- 19.2 (lungs) pmol/min per mg protein, whereas in the adult tissues it was 131.2 +/- 63.1 (kidneys), 27.8 +/- 20.3 (intestine), 8.5 +/- 2.8 (lungs) and 7.2 +/- 4.2 (urinary bladder) pmol/min per mg protein.

Adult↗