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Biomedical subjects

D Alberti

Publications and source records attributed to D Alberti.

At least 55 records · Page 3Linked to original sources
PubMed1997

Long-term progression of chronic renal insufficiency in the AIPRI Extension Study. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.

The Angiotensin-converting-enzyme Inhibition on Progressive Renal Insufficiency (AIPRI) Study showed that the ACE inhibitor benazepril provides protection against loss of renal function in patients with chronic renal insufficiency (CRI) caused by various renal diseases. As a result of unexpectedly low mortality in the placebo group, there was a substantial imbalance in mortality during the course of this study (8 patients on benazepril vs. 1 on placebo). The aim of the extension study was to follow-up the patients from the AIPRI core study until autumn 1996, focusing on CRI progression and mortality. Data collection was post hoc. Patients were treated according to investigators' usual practices, without knowledge of the core study trial medication or (initially) the core trial results. A new primary efficacy parameter was defined as the time from the start of core study treatment to the occurrence of the first event in the combined composite end-point of dialysis, renal transplantation or death related to renal disease. Serial serum creatinine levels and all-cause mortality were also recorded. The median total follow-up for core + extension periods was 6.6 years. Many patients from both treatment groups (64% on benazepril and 61% on placebo) received ACE inhibitors during follow-up. In the intention-to-treat analysis of the core + extension data, only 79 of 300 patients from the benazepril group, compared to 102 of the 283 patients from the placebo group needed dialysis or renal transplantation, or died related to renal disease (P < 0.013, log-rank test). The mortality imbalance seen in the core trial was not evident with the longer follow-up (25 deaths in the benazepril and 23 in the placebo group, before dialysis). These data clearly demonstrate a long-term beneficial effect in patients randomized to take benazepril during the core study, but because treatment during the extension period was not randomized, the results of this intention-to-treat analysis need to be interpreted with care.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.

BACKGROUND: Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases. METHODS: In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-line serum creatine concentration or the need for dialysis. RESULTS: At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with base-line urinary protein excretion above 1 g per 24 hours. Benazepril was not effective in patients with polycystic disease. Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group. CONCLUSIONS: Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.

Adult↗
PubMed1996

Microemulsion formulation of cyclosporine in pediatric liver transplantation.

The oral bioavailability of Sandimmun can be impaired by cholestasis, external biliary diversion, and diarrhea. We report two cases of pediatric liver transplant recipients who experienced chronic rejection and diarrhea secondary to proximal bowel resection. These conditions resulted in poor oral absorption of Sandimmun; the children were converted to the new oral microemulsion formulation Neoral, which significantly improved oral absorption, allowing intravenous cyclosporine weaning and patient discharge. Comparative pharmacokinetic studies were performed in both cases, and the relative Neoral/Sandimmun bioavailabilities were 32.9 and 5.4, respectively. Accordingly, Neoral may constitute to good alternative to ensure the effectiveness of oral cyclosporine administration, particularly in liver-transplanted children with severe cholestasis or shortened small bowel.

Administration, Oral↗
PubMed1996

Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Northern Italian Cooperative Study Group.

AIMS: To identify the prognostic factors possibly related to end-stage renal failure development. SUBJECTS AND METHODS: The prognostic factors affecting chronic renal failure progression were analysed in 456 patients who had participated in a formal, multicentre, prospective randomized trial aimed at verifying the role of protein restriction in slowing down or halting the progression of chronic renal failure. The 24-month follow-up foreseen by the protocol was completed by 311 patients and 69 reached an end-point. An inductive analysis on patient survival was made by using the Cox proportional hazard regression model, using a stepwise procedure in order to select only those factors which are significantly associated with survival. For each individual risk factor, a univariate descriptive analysis of survival was performed using the Kaplan-Meier technique. RESULTS: Underlying nephropathy, baseline plasma creatinine, proteinuria, and plasma calcium were all shown to be related to end-stage renal failure onset. Hypertensive patients (mean blood pressure > 107 mmHg) had a worst cumulative renal survival but the degree of proteinuria was even more important as a prognostic factor of renal death than hypertension. The cumulative renal survival of patients whose proteinuria decreased during the trial follow-up was better than those of patients without changes. However, the interaction between baseline lying mean blood pressure and proteinuria was not significant. CONCLUSIONS: Only primary renal disease and proteinuria were related to renal survival, being baseline plasma creatinine confounding factor. By blocking the possible causal role of proteinuria and hypertension, end-stage renal failure could be prevented in a significant percentage of patients.

Adolescent↗
PubMed1996

Leucovorin modulation of 5-iododeoxyuridine radiosensitization: a phase I study.

Evidence for clinically significant radiosensitization by the halogenated pyrimidine 5-iododeoxyuridine (IdUrd) continues to accumulate. In vitro radiosensitization has been demonstrated in human colon tumor cell lines following exposure to 1-10 micrometer. Coadministration of leucovorin (LV) increases radiosensitization, which correlates directly with increased IdUrd DNA incorporation. Clinical data regarding proliferation rates and thymidine kinase levels in tumors versus normal tissues suggest selective incorporation of IdUrd into gastrointestinal tumors may occur. The objectives of this Phase I study were: (a) to assess the feasibility of LV modulation of IdUrd radiosensitization by determining the maximum tolerated dose (MTD) of IdUrd plus LV; and (b) to perform correlative laboratory studies to investigate the potential of IdUrd plus LV to increase radiosensitization in vivo. Seventeen patients with unresectable or recurrent gastrointestinal adenocarcinomas received a 14-day course of continuous i.v. infusion of IdUrd prior to initiation of radiotherapy. Two additional 14-day infusions of IdUrd with LV were given during the course of radiotherapy (60 Gy in 6 weeks). The initial dose of IdUrd was 250 mg/m2/day and was escalated in subsequent patients to 400 and 600 mg/m2/day. The LV dose remained fixed at 250 mg/m2/day. Leukopenia was the dose-limiting toxicity, and 400 mg/m2/day was the MTD for this trial. At the MTD, the mean +/- SD steady-state plasma concentration of IdUrd during the infusion, measured by high-performance liquid chromatography, was 0.66 +/- 0.23 micrometer. There was no significant influence of LV on IdUrd DNA incorporation in peripheral blood granulocytes as measured by high-performance liquid chromatography. Based on toxicity data and correlative laboratory studies, a meaningful increase in radiosensitization would not be achieved with the IdUrd infusion schedule and dose of LV investigated compared with IdUrd alone.

Adult↗
PubMed1995

Hypertension as a factor in chronic renal insufficiency progression in polycystic kidney disease. The Northern Italian Cooperative Study Group.

The aim of this study was to evaluate the role of blood pressure in the progression of chronic renal failure (CRF) in polycystic kidney disease, by analysing the behaviour of 74 affected patients, out of 456 CRF patients with various underlying nephropathies enrolled in a multicentre, formal prospective trial aimed at clarifying the role of protein restriction in retarding CRF progression. Because no difference was found between the patients on a low protein and those on a controlled protein diet, an inductive analysis was made by separating all of the patients into fast progressive or slowly progressive CRF groups. Hypertensive patients were defined as those with a mean resting blood pressure of more than 107 mmHg; of the 62 polycystic patients who completed the study or who reached an end point, 41 patients were hypertensive and 21 normotensive (10 of whom were pharmacologically controlled). The results of the stratified analysis, taking into account the degree of renal function deterioration and the underlying disease, showed a significant relationship between hypertension and CRF progression only in patients with polycystic kidney disease.

Adolescent↗
PubMed1995

Induction and maintenance of monocyte cytotoxicity during treatment with liposomes containing muramyl tripeptide despite tachyphylaxis to the cytokine response.

Monocyte-mediated cytotoxicity (determined in a 72-h111In release assay) and the circulating levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 1beta, IL-6, IFN-gamma, C-reactive protein, and beta2-microglobulin were determined in 14 melanoma patients treated with multilamellar vesicle liposomes containing muramyl tripeptide phosphatidylethanolamine, 4 mg twice a week for 12 weeks. Monocyte-mediated cytotoxicity increased 24 h after the first infusion in 9 of 14 patients and had reached maximum levels (mean, 44% +/- 8) in all patients by the sixth week; similar values were observed at the 12th week. Once increased in vivo, peripheral blood monocyte cytotoxicity was not susceptible to any further increase after a subsequent in vitro incubation of the monocytes with liposomes. However, the peripheral blood monocytes which were not cytotoxic in vivo were activated by in vitro incubation with liposomes and not by medium. TNF-alpha and IL-6 peaked 2 h after the first infusion and returned to baseline values at 24 h; they were not significantly increased by subsequent treatments. The induction of fever in patients, observed 2 h after the first infusion, correlated with TNF-alpha and IL-6 levels. Similarly, C-reactive protein levels also increased at 24 h, but only after the first dose. No increase in beta2-microglobulin and IL-1beta levels was observed, and IFN-gamma was never detected in serum. Two patients experienced stable disease lasting 7 and 12 months, and 12 patients progressed. These results show that multilamellar vesicle muramyl tripeptide phosphatidylethanolamine administration activates monocyte cytotoxicity and cytokine production (TNF-alpha, IL-6). Chronic treatment with multilamellar vesicle muramyl tripeptide phosphatidylethanolamine results in tachyphylaxis in terms of cytokine secretion but not cytotoxicity. There was no difference between the maximum cytotoxicity levels obtained in vivo and those obtained in vitro using the same agent. A better understanding of immunoregulation is required for a rational application of this and related immunotherapies.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1994

Phase I clinical trial of intravenous L-buthionine sulfoximine and melphalan: an attempt at modulation of glutathione.

PURPOSE: A phase I dose-escalation trial of intravenous (IV) L-buthionine-SR-sulfoximine (BSO) with melphalan (L-PAM) was performed to determine the toxicity and biologic activity of BSO, administered as a short infusion every 12 hours, and the combination of BSO plus L-PAM. PATIENTS AND METHODS: Twenty-eight patients with refractory malignancies received 30-minute infusions of BSO every 12 hours for 6 to 10 doses in week 1 followed in week 2 by either IV L-PAM (15 mg/m2) alone or BSO as in week 1 with L-PAM. Patients received the combination in week 5 (course no. 2) if they received L-PAM alone during week 2 and vice versa. BSO doses ranged from 1.5 g/m2 to 13.104 g/m2. RESULTS: The only toxicity observed with BSO infusions was occasional nausea/vomiting. Evaluation of 23 paired courses (L-PAM plus BSO v L-PAM) showed significantly (P < .001) greater leukopenia and thrombocytopenia with L-PAM plus BSO. No other significant toxicity was noted. Measurement of intracellular glutathione (GSH) levels in peripheral mononuclear cells (PBLs) of all patients receiving BSO showed a consistent, non-dose-dependent, linear decrease in GSH with repeated BSO doses. Maximal GSH depletion (40% of baseline values, absolute values 200 to 250 ng/10(6) PBLs) was noted after the sixth BSO dose; extended BSO dosing schedules beyond six total BSO doses did not further deplete GSH. Evaluation of gamma-glutamylcysteine synthetase (GCS) activity showed marked inhibition near the end of each infusion with near complete recovery of GCS activity before the next BSO dose. The pattern of GCS inhibition mirrored the plasma BSO concentrations with peak values (level 6, 4 to 8 mmol/L L,R+L,S BSO) observed at the end of the infusion with a rapid decrease in plasma concentrations with an estimated half-life (t1/2) of less than 2 hours. Differential elimination of the R+S stereoisomers was observed. Analysis of L-PAM pharmacokinetics showed marked interpatient variability and a significant decrease in total-body clearance (P = .01) and volume of distribution (P = .03) in courses with L-PAM plus BSO as compared with L-PAM alone. CONCLUSION: This study shows that BSO alone and in combination with L-PAM can be safely given to patients, but that a schedule of short infusions every 12 hours does not result in GSH depletion less than 30% of baseline values.

Adult↗
PubMed1994

Phase I trial of 3-hour infusion of paclitaxel with or without granulocyte colony-stimulating factor in patients with advanced cancer.

PURPOSE: We conducted a phase I trial of a 3-hour infusion of Taxol (paclitaxel; Bristol-Myers Squibb Co, Princeton, NJ) to identify the maximum-tolerated dose of Taxol as a 3-hour infusion with and without granulocyte colony-stimulating factor (G-CSF) support. MATERIALS AND METHODS: Thirty-five patients with advanced, untreatable malignancies were treated with a 3-hour infusion of Taxol once every 3 weeks. Groups of three patients were entered at escalating dose levels of Taxol in a traditional phase I design in each of two parallel arms: arm A, without G-CSF, and arm B, with G-CSF. Patients assigned to the G-CSF arm received G-CSF 5 micrograms/kg/d subcutaneously starting on day 2 for 9 to 14 days. All patients were pretreated with dexamethasone, diphenhydramine, and ranitidine, and were monitored continuously for cardiac arrhythmias during the first treatment. RESULTS: Dose-limiting myelosuppression with Taxol without G-CSF was observed at the 250-mg/m2 dose level. The dose-limiting toxicity for Taxol with G-CSF was peripheral neuropathy at the 300-mg/m2 dose level. One of 35 patients (2.8%) had a grade 3 anaphylactic reaction at 250 mg/m2. No clinically significant cardiac arrhythmias were documented. Twenty-seven of 111 courses (24%) were associated with grade 3 arthralgias or myalgias requiring narcotics for pain control. Taxol plasma concentrations declined in a triexponential fashion, with a final elimination half-life of 10 to 12 hours. The peak Taxol plasma concentrations and total area under the curve (AUC) increased with increasing doses of Taxol, although this increase appeared to be somewhat nonlinear. CONCLUSION: The maximum dose of Taxol recommended for phase II and III studies, when administered as a 3-hour infusion alone and with G-CSF support, is 210 mg/m2 and 250 mg/m2, respectively. No increased incidence of hypersensitivity reactions or other side effects were observed, with the possible exception of arthralgias and myalgias. If ongoing trials demonstrate that a 3-hour infusion is as efficacious as a 24-hour infusion, we conclude that with proper monitoring and premedication, high-dose Taxol can be safely administered in the outpatient setting.

Aged↗
PubMed1994

A phase I trial of 3-hour infusions of paclitaxel (Taxol) with or without granulocyte colony-stimulating factor.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a novel antitubulin agent derived from the bark of the Pacific yew tree, may be one of the most active single agents in our chemotherapy armamentarium. Concern over acute hypersensitivity reactions has resulted in an administration schedule consisting of a 24-hour infusion. We conducted a phase I trial of a 3-hour infusion of paclitaxel to determine whether a 3-hour infusion could be administered with relative safety, and to identify the maximal tolerated dose with and without granulocyte colony-stimulating factor (G-CSF) support. Thirty-five patients with advanced, untreatable malignancies received a 3-hour infusion of paclitaxel once every 3 weeks. Groups of three patients were entered at escalating dose levels in a traditional phase I design consisting of two parallel arms: arm A (without G-CSF) and arm B (with G-CSF). Dose levels of paclitaxel ranged from 210 mg/m2 to 300 mg/m2. Patients assigned to the G-CSF arm received 5 micrograms/kg/d subcutaneously starting on day 2. All patients were pretreated with dexamethasone, diphenhydramine, and ranitidine, and were monitored continuously for cardiac arrhythmias during the first treatment. The dose-limiting toxicity for paclitaxel without G-CSF was myelosuppression at the 250 mg/m2 dose level and with G-CSF was peripheral neuropathy at the 300 mg/m2 dose level. The mean absolute neutrophil count at the 250 mg/m2 dose level when administered with and without G-CSF support was 4,500/microL and 840/microL, respectively. Neuropathy appeared to be dose related and somewhat cumulative. One patient who previously received cisplatin developed a severe grade III peripheral neuropathy at the 300 mg/m2 dose level, which left her unable to use her hands and wheelchair bound; the peripheral neuropathy slowly resolved to a grade I level. Twenty-seven of III courses (24%) were associated with grade III arthralgias or myalgias, requiring narcotics for pain control. Prednisone was empirically started in 10 patients and found to be helpful in the control of these symptoms. One of 35 (2.9%) patients had a grade III anaphylactic reaction. No clinically significant cardiac arrhythmias were observed. Two previously treated patients (one with breast cancer and one with ovarian cancer) had a partial response. The maximum tolerated dose of paclitaxel administered as a 3-hour infusion was 210 mg/m2 without G-CSF and 250 mg/m2 with G-CSF.(ABSTRACT TRUNCATED AT 400 WORDS)

Drug Hypersensitivity↗
PubMed1994

[Locoregional complications of stomas. Therapeutic approach].

Principal local complications of ostomies are examined. Etiologic factors and possibilities of treatment are analyzed. These pathologies are often extremely troublesome and their resolution very difficult, unless appropriate therapy is established and, when possible, causal factors removed. However, because of the particular problems of these patients it would be better for them to be assisted by a specialized staff, in qualified centers.

Adult↗
PubMed1994

[Functional and esthetic results of surgery of leg varices].

An experience of 1240 patients suffering from varicose veins of the lower limbs and operated from December 1987 to October 1992, is reported. In order to obtain an objective valuation of functional and aesthetic results, a table with subjective symptoms and clinical and instrumental signs was filled in, before the surgical operation. The correction of anatomic and functional defects and the results so obtained were evaluated by filling in another table after the operation and comparing the postoperative to the preoperative situation. We gave different scores to each parameter considered according to the results obtained and the overall result was obtained by adding up all the different scores for each parameter. In 73.6% of the patients we registered the maximum score, 15 (excellent result), in 1.9% of the patients the score obtained was 10 (sufficient result) and in the remaining 24.5% of the patients the score was variable from 14 to 11 (good result).

Adult↗
PubMed1994

[Varicocele and infertility: clinical framework and therapeutic approach].

A diagnostic-therapeutic protocol which can be used in patients affected with varicocele, in order to obtain a complete clinical study of them and try to improve functional results of therapy, is described. The aims of this protocol are: precise diagnosis of venous refluxes, examination of testicular functionality, detection of possible associated pathologies which can cause infertility, establishment of correct indication to hormonal postoperative therapy. The rapid surgical correction of venous stasis, the treatment of prostatic phlogosis, often concomitant, and, in selected patients, the use of hormonal therapy, can improve functional results in the treatment of this pathology.

Adolescent↗
PubMed1994

[Systems of cerebral monitoring and protection in extracranial carotid surgery].

The main methods for cerebral monitoring and protection during surgical operations of extracranial carotid are examined, analyzing for everyone advantages and limits. Particularly, the authors discuss benefits and disadvantages of cerebral monitoring using somato-sensorial evoked potentials (EP) associated with the measurement of the stump pressure in patients in which general anaesthesia was performed, comparing this method to the monitoring of patients operated using locoregional anaesthesia. The results obtained allow us to say that EP are a very good method for cerebral monitoring and that, if they are not pathological, also with stump pressure values lower than 40 mmHg, a shunt is not necessary.

Aged↗
PubMed1993

[Surgical alternatives in the treatment of perforated duodenal ulcer].

The therapy of perforated gastroduodenal ulcer is still discussed, especially today that good drugs and new surgical devices are available for the treatment of this disease. The authors try to establish a valid protocol for the diagnosis and the therapy of patients affected with this disease.

Clinical Protocols↗
PubMed1993

[Acute cholecystitis in videolaparoscopy].

The authors describe their experience in 15 cases of acute cholecystitis treated with laparoscopic cholecystectomy in emergency. Only in one patient, affected with an abscess of the upper right abdominal space, a laparotomy was performed. The results were excellent. The 14 patients treated with laparoscopic cholecystectomy were quickly discharged from the hospital (on an average 4 days after the surgical treatment) and the convalescence period was very short (range 10-15 days). In the patient treated with laparotomic cholecystectomy the postoperatory period was regular.

Acute Disease↗
PubMed1993

Hepatic tumor and tumor-like lesions in childhood.

Tumors of the liver are rare in infancy and childhood. Some are peculiar to the pediatric age, e.g., hepatoblastoma, infantile hemangioendothelioma, mesenchymal hamartoma, embryonal rhabdomyosarcoma. This review is based upon personal experience with a series of 32 cases. On the basis of the histological features it is proposed that focal modular hyperplasia (FNH) and mesenchymal hamartoma be considered as tumor-like lesions rather than true neoplasms. A few benign epithelial lesions (FNH, adenoma) were associated with inborn error of metabolism. In half of the patients, hepatocellular carcinoma (HCC) developed in perinatally hepatitis B virus (HBV)-infected children. HCC developed in a noncirrhotic liver in a single patient, in whom HBV-DNA integration had occurred.

Carcinoma, Hepatocellular↗