Biomedical subjects

D Alberti

Publications and source records attributed to D Alberti.

At least 73 records · Page 4Linked to original sources

PubMed1993

Phase I trial of mitoxantrone and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with advanced solid malignancies.

PURPOSE: To determine the maximally tolerated dose (MTD) and pharmacokinetics of high-dose mitoxantrone and document the toxicities and side effects of mitoxantrone when administered with GM-CSF. PATIENTS AND METHODS: Twenty-three patients with advanced solid tumors were entered into a phase I and pharmacokinetic study. Mitoxantrone was administered at doses of 12, 21, 28, 32, 37, and 48 mg/m2 on day 1; GM-CSF (5 micrograms/kg once or twice daily) was administered on days 2 to 14. Therapy was repeated every 3 weeks. Dose escalation continued in sets of three patients until the dose limiting toxicity (DLT) was observed. The DLT was based on hematologic, non-hematologic, and cardiac toxicity, and delay of therapy by more than 1 week due to toxicity. Plasma samples were assayed for mitoxantrone concentrations using high performance liquid chromatography (HPLC). RESULTS: Twelve patients required either mitoxantrone dose reductions or delays. DLT of neutropenia was observed at a mitoxantrone dose of 48 mg/m2/day. Therefore, we conclude the MTD was 37 mg/m2/day. Myelosuppression appeared to be cumulative. Two patients were withdrawn from the study due to a drop in left ventricular ejection fraction (LVEF). Two of 23 patients experienced a partial response. The mean area under the curve (AUC) and peak mitoxantrone levels increased linearly with dose; triexponential elimination of mitoxantrone was observed. No statistically significant correlation was observed between either peak mitoxantrone level or AUC and duration of absolute neutrophil count (ANC) < 500/mm3. CONCLUSION: The use of GM-CSF allows administration of mitoxantrone at a dose greater than three times that given in standard therapy; treatment is well tolerated. Further studies are needed to determine whether mitoxantrone has cumulative cardiac or hematologic toxicity.

Adult↗

PubMed1993

Hypertension and chronic renal insufficiency: the experience of the Northern Italian Cooperative Study Group.

There is general agreement that hypertension is a prognostic index of the progression of chronic renal insufficiency (CRI), although it remains to be clarified whether this is related to the hypertension per se, or to the underlying disease and the level of CRI. In an attempt to clarify this important point, an inductive analysis was made of the behavior of blood pressure values and their relationship to the progression of CRI in 456 patients (pts) who participated in a multicenter prospective formal randomized trial, designed to compare the effects of a restricted and a controlled protein diet on CRI progression. An analysis was also made (on the population as a whole and by separating the pts into fast progressive and slowly progressive groups) of the type and frequency of the antihypertensive drugs used, the number and type of drugs used in association, and their possible relationship to the progression of CRI. Of the 456 enrolled pts, 406 (89%) were defined as hypertensive at entry (mean blood pressure > 107 mm Hg); 324 out of the 380 pts (85.3%) who completed the 24-month follow-up or reached an end point were treated with antihypertensive drugs. There was a significant difference at entry between the supine blood pressure values of the pts with fast progressive CRI (182 pts), and those of the pts with slowly progressive CRI (198 pts). During the follow-up period, no significant differences were observed between the two groups. There was no difference in the blood pressure levels reached with the different drugs used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Phase I clinical trial of carboplatin and 41.8 degrees C whole-body hyperthermia in cancer patients.

PURPOSE: To evaluate the biologic interactions and toxicities of carboplatin combined with 41.8 degrees C whole-body hyperthermia (WBH) for 60 minutes in a phase I clinical trial. PATIENTS AND METHODS: Thirty assessable patients with cancer refractory to conventional therapy were treated. During induction therapy, patients received WBH alone in week 1, WBH plus carboplatin in week 2, and carboplatin alone in week 5. Carboplatin dose was escalated (three patients per group) as follows: 100, 150, 200, 250, 300, 350, 400, 480, and 575 mg/m2; three additional patients were entered at 480 mg/m2. Carboplatin was administered at target temperature. RESULTS: Comparisons of the mean/median WBC and platelet nadirs for carboplatin alone and carboplatin plus WBH demonstrated no enhancing effect by WBH. Toxicities including nausea and/or vomiting, as well as myelosuppression, were within acceptable limits, allowing for escalation to a dose of 575 mg/m2; three of three patients at this dose level experienced grade 4 myelosuppression with no associated infection or bleeding. No renal toxicity was observed. Analysis of platinum in plasma ultrafiltrate and urine showed only slight effects of WBH on the pharmacokinetics and renal excretion of platinum. Responses included the following: lung--minor response (200 mg/m2); gastrointestinal neuroendocrine--complete response (CR) (400 mg/m2); pancreatic--partial response (PR) (480 mg/m2); small bowel--PR (575 mg/m2); ovarian--CR, two patients (575 mg/m2), with marker data suggesting WBH enhancement of carboplatin cytotoxicity. Another three patients experienced clinical improvement after WBH plus carboplatin, but progression with carboplatin alone (lung, 400 mg/m2; gastrointestinal neuroendocrine, 480 mg/m2; melanoma, 480 mg/m2). CONCLUSION: We conclude that carboplatin with WBH is well tolerated even at conventional carboplatin doses. Clinical results are consistent with preclinical predictions of an increased therapeutic index for this combination, which encourages future clinical studies.

Adult↗

PubMed1993

Therapeutic strategies in the surgical management of pancreatic neoplasms in the elderly.

The clinical records of all consecutive patients aged 65 and older undergoing surgical treatment for pancreatic neoplasms between January 1980 and January 1992 were reviewed in order to establish a clinical trial based on the morbidity and mortality rates related to the different surgical procedures. In early diagnosed neoplasms, in patients in good general condition, even in the geriatric age a radical surgical procedure is preferred. In other cases, a palliative surgical procedure has to be performed if possible, namely a bilio-digestive anastomosis, associated if necessary with a gastro-enteric anastomosis.

Aged↗

PubMed1993

[Varicose veins in pregnancy: physiopathology and therapeutic approach].

The Authors examine the endocrinological, mechanical and constitutional factors which are involved in the pathogenesis of varicose veins in pregnancy. Discussing the results of their experience (328 pregnant patients observed, 158 of which affected with various degrees of varicose veins) they suggest a protocol of treatment in the different situations in order to obtain an improvement of the clinical conditions and, if necessary, postpone a surgical operation after delivery, so avoiding useless risks during the pregnancy.

Adult↗

PubMed1993

[Surgical staplers in surgical emergencies. Our experience].

This study describes the use of staplers during surgical treatment performed in emergency from January 1980 to December 1991. For the different, possible operations, some technical notes are examined and results reported. The advantages and risks related to the use of these devices are analysed.

Colectomy↗

PubMed1993

[Giant ovarian dermoid cyst in prepubertal age. Report of a case].

We report a case of a very large (size cm 33 x 41) dermoid cyst in the right ovary in a 11 year old child, causing a complete atrophy of the remaining right ovarian parenchyma and ipsilateral salpinx. Sonography and CT allowed us to diagnose this disease and also showed an associated ureterohydronephrosis. The patient underwent a surgical operation during which a right ovarosalpingectomy was performed. A rapid regression of the ureterohydronephrosis was observed and the patient was discharged from the hospital six days after operation.

Abdomen↗

PubMed1993

The anastomotic aneurysms.

The authors describe their experience of anastomotic aneurysm diagnosis and treatment. They are classed into two groups: slowly growing anastomotic aneurysms, which are the most common; and rapidly growing anastomotic aneurysms, which are more infrequent. A follow-up is proposed in order to detect this involvement early, in election. Urgent diagnostic timing is also proposed. Moreover an analysis is made of criteria to follow in their therapy and indications to surgical treatment. In the period from January 1988 to October 1992 we observed 413 patients and 876 anastomosis or arterial sutures in election, discovering 27 anastomotic aneurysms whereas in 6 cases we had patients who were affected with rapidly growing anastomotic aneurysms. These were urgently operated, whereas of the 27 patients with slowly growing anastomotic aneurysms, 22 were operated and in 5 cases we preferred to check them by a close follow-up.

Anastomosis, Surgical↗

PubMed1993

[Surgery vs PTA in sub-inguinal atherosclerosis].

The authors describe their experience in the treatment of arterial occlusive disease of the lower limbs in the femoro-popliteal and tibioperoneal districts, by surgery (proximal or distal femoro-popliteal by-pass or segment by-pass) and Percutaneous Transluminal Angioplasty (PTA), analyzing indications, advantages, limits and complications of the two methods. Immediate and after one and three year results of surgical by-pass and PTA are compared. On the whole, in the patients in which we performed a surgical by-pass, we obtained slightly better results. Anyway, in the second stage of the arterial occlusive disease and in patients affected with short arterial stenosis and/or obstructions, PTA represents the best treatment.

Aged↗

PubMed1993

[Role of the second look in ovarian neoplasia].

The indications for the execution of a second look in patients affected with ovarian cancers and the possible benefits of this procedure, related to the stage of the neoplastic disease, are examined. The second look, at first largely used in patients in which had been performed adjuvant chemotherapy with drugs containing platinum and with no evidence of residual disease, has been later strongly criticized and the effective usefulness of this invasive procedure discussed. At the moment, we think that the indications for its execution are still large because with the second look it is also possible to put into the abdomen a catheter which can be used for locoregional chemotherapy and there is now the opportunity to perform this procedure also in video-laparoscopy.

Adnexa Uteri↗

PubMed1992

Clinical and biologic effects of combination therapy with gamma-interferon and tumor necrosis factor.

Tumor necrosis factor (TNF) and gamma-interferon (gamma-IFN) are cytokines with synergistic biologic and antiproliferative effects in vitro and in mouse models. The biologic effects of the combination of TNF and gamma-IFN, however, have not been studied well in humans. A Phase I trial was conducted of TNF and gamma-IFN therapy in 24 patients with advanced malignancies to determine the tolerability of the combination and the biologic effects of TNF and gamma-IFN in vivo. Both TNF and gamma-IFN were administered as 30-minute intravenous infusions three times per week. Doses of TNF ranged from 25 to 100 micrograms/m2; all patients received 100 micrograms/m2 of gamma-IFN. Dose-limiting toxicity consisted primarily of orthostatic hypotension and constitutional symptoms. The maximum tolerated dose level (MTDL) of 50 micrograms/m2 of TNF and 100 micrograms/m2 of IFN-gamma was less than the maximum tolerated dose (MTD) observed in previous Phase I trials of gamma-IFN and TNF alone. Biologic responses were studied in seven patients treated at the MTDL. Serum interleukin-2 receptor levels and neopterin secretion were enhanced significantly 24 hours after therapy (P = 0.002); enhancement of monocyte Fc receptor levels had borderline statistical significance (P = 0.07). With the exception of the mean fluorescent intensity on monocytes positive for histocompatibility antigen HLA-DR (P = 0.03), HLA Class I and II cell surface protein expression was not increased. The combination significantly enhanced indoleamine dioxygenase activity and serum beta 2-microglobulin expression (P less than 0.04) but not 2',5'-oligoadenylate synthetase activity, bactericidal function, or chemiluminescence. These results were compared retrospectively with those observed in previous Phase I trials of gamma-IFN and TNF alone. The combination of TNF and gamma-IFN significantly increased urinary kynurenine levels more than either TNF alone or gamma-IFN alone. Given the limitations inherent in any retrospective analysis, however, the enhancement in the other biologic parameters measured at the MTDL during this trial did not differ significantly from the changes observed at the MTD of either TNF or gamma-IFN alone. It was concluded that the combination of TNF and gamma-IFN, when administered at the MTDL of the combination, does not offer any enhancement in biologic responses over either agent alone.

2',5'-Oligoadenylate Synthetase↗

PubMed1992

A phase I trial of 5-fluorouracil, leucovorin, and dipyridamole given by concurrent 120-h continuous infusions.

A phase I trial of 5-fluorouracil (FUra) and leucovorin (LV) given with and without dipyridamole (DP) by concurrent 120-h continuous infusion was performed in 27 patients with advanced solid malignancies, 8 of whom had previously received FUra. The LV and DP doses were fixed at 500 mg/m2 daily and 7.7 mg/kg daily, respectively, whereas the FUra dose was escalated. Level 3 (450 mg/m2 FUra daily) represented the maximum tolerated dose for both FUra/LV+DP and FUra/LV. Dose-limiting stomatitis (greater than or equal to grade 3 or grade 2 occurring during the infusion) was encountered in 75% of the first courses given at level 4 (600 mg/m2 daily). Stomatitis was observed in 44/78 (56%) courses. Diarrhea was infrequent and mild. DP infusions were complicated by mild to moderate headache, which was controlled with narcotic analgesics, and mild to moderate nausea/vomiting. FUra-related toxicity was not enhanced by DP administration. Limited pharmacokinetic sampling at levels 3 and 4 revealed mean steady-state FUra concentrations of around 1.0 microM with infusions of FUra/LV+DP. Among three paired courses given with and without DP, no statistically significant difference was found in the total body clearance of FUra (P = 0.44). One partial response was seen in a patient with metastatic gastric carcinoma. For phase II trials, we recommend that concurrent 120-h continuous infusions of FUra (450 mg/m2 daily) and LV (500 mg/m2 daily) be given with and without DP (7.7 mg/kg daily) every 21 days.

Adult↗

PubMed1992

Progressive cardiac failure following orthotopic liver transplantation for type IV glycogenosis.

Orthotopic liver transplantation (OLT) has been proposed to treat patients with type IV glycogenosis because of early progressive cirrhosis. Reports have shown absence of disease progression in other organs after OLT and even regression of cardiac amylopectin infiltration in one case. We describe a 15-month-old child in whom a liver transplant was performed for type IV glycogenosis. There were no clinical signs of extrahepatic disease before OLT. Nine months later, the patient developed progressive cardiac insufficiency and died from cardiac failure. Because of massive amylopectin deposits, decreased myofibrils in cardiac cells, and exclusion of other causes of cardiac failure, death was attributed to amylopectionosis. Our observation contrasts with the Pittsburgh experience and suggests that cardiac amylopectionosis may progress after OLT.

Amylopectin↗

PubMed1992

Factors affecting chronic renal failure progression: results from a multicentre trial. The Northern Italian Cooperative Study Group.

In order to evaluate the prognostic factors concerning the rate of progressive deterioration of renal function, we made an inductive analysis of the behaviour of 456 patients in a multicentre, formal prospective trial aimed at clarifying the possible role of protein restriction in retarding the progression of chronic renal insufficiency (CRI). The main clinical and laboratory findings in patients whose plasma creatinine (PCr) levels doubled in comparison with baseline randomization values or who needed dialysis within 24 months after onset of the study were compared with those of the other patients. In addition, independently of the assigned diet, we tested the main variables that might affect CRI progression (sex, systolic and diastolic blood pressure, change in body weight, hematocrit, calcium-phosphate product, proteinuria, protein catabolic rate, total cholesterol and triglycerides). We used multiple regression analyses and also plotted the mean values of these parameters in each patient against an estimate of the deterioration of chronic renal failure based on the difference between the final and the initial reciprocal of the PCr and the creatinine clearance (CCr) levels. A descriptive analysis of the behaviour of PCr in the three CRI groups and in the four underlying diseases groups was made. PCr levels at entry, underlying disease and proteinuria were prognostic factors for CRI progression. The increase in PCr was 0.0102 mg/dl/month in patients with nephrosclerosis, 0.0203 mg/dl/month in interstitial nephropathy, 0.0360 mg/dl/month in glomerulonephritis and 0.0704 mg/dl/month in polycystic kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Twenty-four-hour activity of felodipine extended release in chronic stable angina pectoris.

To investigate the antiischemic efficacy and duration of action of the dihydropyridine calcium antagonist felodipine, 15 patients with stable exertional angina were enrolled in a double-blind, crossover study comparing 2 doses (5 and 10 mg) of felodipine extended release (ER) and placebo given once daily for 1 week. Bicycle exercise tests were repeated at the end of each treatment period 4 and 24 hours after dosing. Four hours after dosing with both felodipine doses, only 5 patients discontinued the exercise test because of greater than 2 mm of ST-segment depression, whereas 10 continued until exhaustion (p less than 0.01 vs placebo). Compared with placebo, total exercise time was increased by 19% (p less than 0.001), with no difference between doses. After 24 hours, exercise duration was prolonged up to physical exhaustion in 6 patients taking felodipine 10 mg (p less than 0.05 vs both placebo and felodipine 5 mg); moreover, 11 patients taking 10 mg and 5 taking 5 mg increased time to 1 mm of ST depression greater than or equal to 15% compared with exercise time during the placebo test. Mean time to 1 mm of ST depression at 24 hours was increased by 8% with 5 mg and by 18% with 10 mg (p less than 0.001 vs placebo; p less than 0.01 between doses). Total exercise time at 24 hours was increased with both doses (p less than 0.001), with greater efficacy with the 10-mg dose (p less than 0.05 vs 5 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Prospective, randomised, multicentre trial of effect of protein restriction on progression of chronic renal insufficiency. Northern Italian Cooperative Study Group.

A multicentre, prospective trial was organised to clarify the role of protein restriction in the progression of chronic renal insufficiency (CRI). 456 adult patients were assigned either a low-protein diet (0.6 g/kg body weight daily; n = 226) or a "normal" controlled-protein diet (1.0 g/kg daily; n = 230) and were stratified into three groups (A-C) with increasing baseline plasma creatinine concentrations. Each patient was followed up for 2 years or until an endpoint (a doubling of the baseline plasma creatinine or a need for dialysis) was reached. The difference between the diet groups in cumulative renal survival defined by these endpoints (27 low-protein, 42 controlled-protein) was of borderline significance (p less than 0.06). The difference in renal survival between the low-protein and controlled-protein diet groups was of borderline significance in group A (0 vs 4 endpoints), significant in group B (10 vs 21 endpoints; p less than 0.025), and not significant in group C. There were no differences among the diet groups or subgroups in mean plasma creatinine concentrations, creatinine clearance, the slope of the plasma creatinine reciprocal, or mean blood pressures. Compliance was good in the controlled-protein group but poor for the low-protein diet: the difference in protein intake between the groups was substantially less than that required by the protocol. However, there was no correlation between the progression of renal failure and protein catabolic rate. These findings offer little, if any, support to the hypothesis that protein restriction retards CRI progression: careful medical care and a "normal" controlled protein intake also allow very slow progression of CRI.

Actuarial Analysis↗

PubMed1991

Biological and clinical effects of intravenous tumor necrosis factor-alpha administered three times weekly.

Tumor necrosis factor (TNF) is a cytokine with pleiotropic biological and antitumor effects in vitro and in mouse models. The immunological effects of the molecule as a single agent, however, have not been well studied clinically. We conducted a Phase I trial of TNF in 53 patients with advanced malignancies in order to determine the biological and clinical effects of TNF when administered as a 30-min i.v. infusion three times/week. Dose levels of TNF ranged from 5 to 275 micrograms/m2; doses of TNF were escalated between patient groups. The most common clinical toxicities of TNF consisted of rigors, anorexia, headache, and fatigue. Dose-limiting toxicity consisted of hypotension, fatigue, and nausea. Four patients treated at the maximally tolerated dose of 225 micrograms/m2 received dexamethasone to determine whether the toxicities of TNF could be ameliorated. No significant differences in hypotension or subjective symptomatology were observed in those patients receiving dexamethasone and those who did not or between injections in which dexamethasone was administered and when it was not. One patient with colorectal carcinoma treated with 50 micrograms/m2 had a partial response lasting about 9 months. Biological responses were evaluated in 8 patients treated at the maximally tolerated dose before therapy and 24 h afterward. TNF significantly (P less than 0.05 for all) enhanced serum beta 2-microglobulin, serum neopterin, and serum interleukin-2 receptor (Tac antigen) levels. Indoleamine 2,3-dioxygenase activity was also increased 24 h following the administration of TNF, although this increase was only of borderline statistical significance (P = 0.07). TNF did not enhance granulocyte bactericidal activity. The expression of cell surface proteins on monocytes, including HLA-DR, HLA-DQ, beta 2-microglobulin, and the Fc receptor, and serum interleukin-1 activity also were not significantly increased by the administration of TNF. Thus, in humans TNF caused biological response modulation with evidence of HLA Class I (beta 2-microglobulin) increase and T-cell (Tac antigen) and monocyte (neopterin) activation.

2',5'-Oligoadenylate Synthetase↗

PubMed1991

Phase I clinical trial of fazarabine as a twenty-four-hour continuous infusion.

A phase I trial of fazarabine (ara-AC, 1-beta-D-arabinofuranosyl-5-azacytosine, NSC 281272) administered as a 24-h continuous infusion was performed in 24 adults with solid tumor malignancies. The majority of patients had received prior marrow-suppressive therapy. Level 7 (54.5 mg/m2/h for 24 h) was the maximum tolerated dose since during 6 evaluable first courses, 2 episodes of grade 4 granulocytopenia and 3 episodes of grade 3 occurred. Moderate thrombocytopenia also occurred at level 7 with 3 episodes of grade 1 and 1 episode of grade 4 thrombocytopenia during 6 first course treatments. Minimal myelosuppression, principally leukopenia, was seen prior to level 7. The nadir WBC through 47 courses had a linear relationship with plasma steady-state concentrations of ara-AC. The only other toxicity noted was moderate nausea/vomiting, which did not appear to be dose related. Plasma steady-state concentrations of ara-AC were reached in all patients within 4-6 h and ranged from 1.1 microM (11 mg/m2/h for 24 h) to 7.5 microM (54.5 mg/m2/h for 24 h). The mean total body clearance of ara-AC for 47 courses, levels 1-7, was 592 +/- 147 (SD) ml/min/m2 which is similar to prior pharmacokinetic data from the 24-h and 72-h infusion trials of the Pediatric and Medicine Branches, respectively. There were no objective disease responses during the trial. The recommended adult phase II dose for a 24-h infusion of ara-AC is 45-50 mg/m2/h.

Adult↗