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Biomedical subjects

L Ferrari

Publications and source records attributed to L Ferrari.

At least 91 records · Page 5Linked to original sources

In vivo measurement of attenuation.

We propose a new technique for the in vivo measurement of attenuation. The method is conceptually simple and can also be easily implemented on a real-time ultrasound unit. The technique is suggested by an analysis of the propagation of a Gaussian pulse in a medium which has frequency-dependent attenuation as well as dispersion (frequency-dependent velocity). If the medium has a loss factor which can be described by H(f) = exp(-eta[f]pX), where f is the frequency and O less than or equal to p less than or equal to 2 (valid for tissues and other objects of interest), then the pulse retains its Gaussian shape, shifting only its centre frequency and bandwidth. This suggests that by measuring the mean frequency of the reflected rf waveform in a window which is moved in depth we can obtain an estimate of the attenuation. Here we describe a particular hardware implementation of this technique which we have completed (based on measurement of zero-crossings) and present some preliminary in vivo measurements.

Humans

New anthracycline analogs in advanced breast cancer.

To test the activity and toxicity of new anthracycline analogs, a series of Phase II disease-oriented studies were performed in women with advanced breast cancer previously untreated with doxorubicin. All drugs were administered every 3 weeks, and the doses in mg/m2 were as follows: doxorubicin and epirubicin 75 i.v., esorubicin 35 i.v., idarubicin 13 i.v. and 45 p.o. When epirubicin was tested vs doxorubicin, both response rate (13 of 21 or 62% vs 11 of 21 or 52%) and median response duration (11 months vs 13 months) were comparable. In 24 patients, esorubicin yielded complete plus partial response in 21% with a median duration of 15 months. In 27 patients given idarubicin intravenously the response rate was 11% for 4 months and the corresponding findings when the drug was administered orally to 25 women were 24% for 8 months. Acute toxic manifestations were lower following treatment with all three analogs compared to doxorubicin. Cardiac toxicity, as documented by echocardiography, systolic time interval and left ventricular ejection fraction was virtually absent following therapy with epirubicin and idarubicin. After a median cumulative dose of 600 mg/m2 for doxorubicin-treated women there was a significant fall in LVEF compared to basal values. Similar findings were observed after a median cumulative dose of 210 mg/m2 for esorubicin. We conclude that epirubicin is as effective as doxorubicin but comparatively less toxic when administered at the same dose schedule. At the doses and schedules utilized in this study, esorubicin and idarubicin resulted less active in breast cancer.

Adult

Long-lasting suppression of prolactin secretion and rapid shrinkage of prolactinomas after a long-acting, injectable form of bromocriptine.

Since Corenblum reported in 1975 the first documented reduction of tumor size in two patients with macroprolactinoma, evidence has accumulated that bromocriptine causes shrinkage of PRL-secreting adenomas in most patients. Recently a long-acting form of bromocriptine (bromocriptine LA) was developed. A single dose of 50 mg i.m. decreases basal and sleep-related PRL secretion in normal subjects for 28 days. We treated 13 patients (8 women, 5 men) with PRL secreting tumors (5 macroadenomas and 8 microadenomas) with a single dose (50 mg) of bromocriptine LA. In the 5 patients with macroprolactinomas plasma PRL levels decreased markedly within 12 hours, reaching normal levels in only one patient. In all patients the suppression of PRL secretion lasted at least 28 days and the tumor size was reduced by 20% to 59% within 21 days after the injection. Visual fields improved in all 3 patients with abnormal vision prior to the injection. In one patient with bitemporal hemianopsia an almost normalization of the visual field was noted 24 hours after bromocriptine LA administration. In 7/8 patients with microprolactinomas plasma PRL levels decreased to within the normal range within 12 hours after the administration of bromocriptine LA. The normalization of PRL secretion lasted for at least 28 days. Menses resumed in all 6 women 7 to 41 days after the injection, galactorrhea disappeared in all 4 patients, and libido and potency become normal in both men with microprolactinomas. Patients treated with bromocriptine LA reported only short-lasting (1 hour - 2 days) mild or moderate adverse effects, consisting of dizziness (4 patients) and nausea (4 patients). Long-acting bromocriptine should be considered as the initial management for patients with PRL-secreting tumors. The use of bromocriptine LA could also overcome the compliance problems that occur in many patients soon after the initiation of oral bromocriptine therapy.

Adolescent

Phase II study of doxorubicin versus epirubicin in advanced breast cancer.

Doxorubicin and its epimerized analog epirubicin were tested at a dose of 75 mg/m2 given iv every 3 weeks to 42 patients with advanced breast cancer, 23 of whom were in relapse from prior cyclophosphamide, methotrexate, and 5-FU (CMF) chemotherapy. The median cumulative dose was 540 mg/m2 (range, 225-650) for doxorubicin and 565 mg/m2 (range, 150-600) for epirubicin. Complete plus partial response was documented in 11 of 21 patients (52%) following doxorubicin and in 13 of 21 patients (62%) following epirubicin. The median observation period was 22 months (range, 14-30); the median duration of response and the median survival were superimposable. Doxorubicin and epirubicin exhibited a superior response rate in previously untreated patients [six of eight (75%) vs eight of 11 (73%)] compared to those previously given CMF with or without endocrine therapy [five of 13 (38%) vs five of ten (50%)]. Vomiting, mucositis, and leukopenia were documented less frequently following administration of epirubicin as compared to doxorubicin. Regarding cardiac evaluation, no significant differences were evident between the two drugs. However, a significant fall in the left ventricular ejection fraction was documented in women who received doxorubicin following a cumulative dose greater than 550 mg/m2. Following completion of doxorubicin therapy at cumulative doses of 580 and 562 mg/m2, two women developed left ventricular failure at 6 and 14 months, respectively. Epirubicin appears to be an effective drug for the treatment of breast cancer and, given at equal doses, is less toxic than doxorubicin.

Adult

Cisplatin administered as a continuous 5-day infusion: plasma platinum levels and urine platinum excretion.

Total and filterable platinum in plasma were monitored for seven courses (five patients, 25 mg/m2/day) using continuous 5-day infusions and one 30-minute infusion at a similar dose level (120 mg/m2). Maximum filterable (non-protein-bound) platinum levels (0.1-0.3 mg/L) for the extended infusions were ten to 40 times lower than that for the short-term infusion (4.0 mg/L). Filterable drug exposure as measured by the area under the [Pt]filterable-time curve is greater for the extended infusions (9.6 mg X hr/L) than that for the short-term infusion (4.8 mg X hr/L). Renal excretion of cisplatin (% of dose excreted/24-hour period after the beginning of the infusion) was measured for four courses of continuous 5-day infusions and for the 30-minute infusion. Urine excretion rates were lower for the continuous infusion (5%-8% of dose/24-hour period during the infusion) compared to the short-term infusion (33% of dose/24-hour period after the beginning of the 30-minute infusion).

Cisplatin

[Antiglobulin test using an immunoenzyme method].

An enzyme-linked antiglobulin test (ELAT) is described. All reagents are commercially available. The antiglobulin reagent is a monoclonal anti-IgG conjugated with alkaline phosphatase. The substrate (p-nitrophenylphosphate) is stable and innocuous. The procedure requires long incubations, particularly between red cells and the enzyme-conjugated antibody. However most of the time actively spent by the technician is consumed by washing procedures (LAV). These may be avoided by using density gradient centrifugation (CSG). ELAT is significantly more sensitive than agglutination, using either washing or gradient centrifugation (P = 0.002 and P = 0.0005, respectively). Moreover ELAT-CSG is significantly more sensitive than ELAT-LAV (P = 0.03). CSG yields better reproducibility and probably avoids some of the spontaneous elution of the primary and/or secondary antibody which may occur during washing.

Alkaline Phosphatase

Monoclonal gammopathy (IgM-k) in a patient with Burkitt's type lymphoblastic lymphoma.

We report a Burkitt's type lymphoblastic lymphoma (B-LL) case characterized by an abnormal IgMk immunoglobulin secretion and referred to us on February 12, 1982. The diagnosis has been histologically documented and the pathological stage of the disease (IV B) was determined according to the diagnostic criteria usually employed for the non-Hodgkin's lymphoma (NHL). Serum proteins were determined by electrophoresis and immunodiffusion. The review of the literature has allowed us to ascertain that the presence of a monoclonal IgM peak can be associated with NHL, particularly with those of B cell type and in adult subjects. Up to now, only six IgM B-LL secreting cases have been described. The biological and prognostic significance of this elevated Ig secretion is uncertain; therefore it may be important for the future to evaluate, in B-LL this immunological parameter.

Adolescent

Phase I study with 4'-deoxydoxorubicin.

4'-Deoxydoxorubicin (dxDx), a new doxorubicin analogue, was administered intravenously on a 3-week schedule to 73 patients affected by advanced malignant neoplasms. Sixty-five patients, treated with eight dose levels ranging from 10 to 45 mg/m2, were evaluable. The dose-limiting toxicity was myelosuppression, mainly leukopenia. About one third of the patients complained of vomiting which was almost always mild. Minimal hair loss was also documented in about 40% of patients. No hepatic or renal toxicity was observed. Transient and aspecific electrocardiographic changes were recorded in 6% of patients after 1 h and in 3% after 24 h from drug injection. Left ventricular ejection fraction was decreased in two patients after a cumulative dose of 90 mg/m2. One patient died with cardiorespiratory insufficiency and his initial cardiovascular disease might have been aggravated by dxDx. No changes in myocardial function parameters were documented in 18 patients who reached higher cumulative doses, i.e. greater than or equal to 100 mg/m2 and greater than or equal to 200 mg/m2. The highest total dose administered in this study was 340 mg/m2. Therapeutic activity was observed with doses ranging from 25 to 45 mg/m2. Partial response was documented in pancreatic, colon, anal and breast carcinomas as well as in non-Hodgkin's lymphoma. Minor response was observed in prostatic, thyroid, and renal carcinomas as well as in chronic lymphocytic leukemia. The maximum tolerated dose was assessed to be between 40 and 45 mg/m2. A Phase II trial is ongoing utilizing the dose of 35 mg/m2 every 3 weeks.

Adolescent

Phase I study of 4-demethoxydaunorubicin.

4-demethoxydaunorubicin (4-dm DNR), a new analog of daunorubicin, was tested at an every 3-week dose schedule in 63 evaluable patients with various forms of disseminated malignancy. Utilizing the intravenous (i.v.) route of administration, the maximum tolerated dose (MTD) was 15-18 mg/m2; with the oral route the MTD was 60 mg/m2. Myelosuppression represented the dose-limiting factor, and leukopenia was more often observed than thrombocytopenia. However, leukopenia was more frequently detected following i.v. administration while vomiting represented the most frequent toxic sign after oral administration. Loss of hair was moderate with either route of administration and comparatively less frequent and pronounced than that observed after doxorubicin (DX) and its analog 4'-epi-doxorubicin (4'-epi-DX). Aside from transient aspecific electrocardiographic changes recorded in 30% of patients, no cardiac toxicity was documented. Tumor response was documented in seven patients with malignant lymphomas, breast cancer, melanoma and carcinoma of uterine cervix. Two out of the seven responders achieved prolonged complete remission and four were resistant to doxorubicin. 4-dm DNR appears to be an analog worth further clinical trials.

Administration, Oral

Morphological, immunohistological and clinical findings in renal amyloidosis: correlations with prognosis in 16 patients.

Sixteen patients affected by renal amyloidosis (A.) and submitted to renal biopsy have been studied by light microscopy and immunofluorescence. Clinical manifestations at observation and follow up have been reviewed. Survival was 32% at ten years, lower than all other nephropathies except rapidly-progressive glomerulonephritis. Primary A. had a significantly worse survival rate than secondary A. An observation up to 6 years after biopsy allowed us to isolate a group of patients with a steady good renal function: this group is characterized by: a longer mean duration of nephropathy before observation, a lower incidence of nephrotic syndrome (NS), absence of renal failure at time of biopsy, a higher incidence of increased mesangial areas at light microscopy, a lower percentage of glomerular capillary walls thickening, a higher incidence of amyloid deposits on vessels but not on glomerular capillaries, a definite more elevated presence of Ig and C3 over mesangium and glomerular capillary walls. The possible role of the last findings is discussed.

Adolescent

[The incidence and variation of transferable antibiotic-resistance in Salmonella strains isolated in Modena in the years 1975-1977 (author's transl)].

The antibiotic-resistance of 450 strains of Salmonella isolated by the Microbiology Unit of the hospital of Modena during the years 1975-1977 was examined. During the study, the following antibiotics were assayed: ampicillin, kanamycine, tetracycline, chloramphenicol, streptomycin, sulfonamides, trimethoprim, tobramycin, gentamicin and nalidixic acid. The transfer capacity of antibiotic-resistance was measured by the double conjugation of E. coli K-12. During the period studied, a remarkable reduction was noted in those strains with multiple resistance (3 or more elements) decreasing from 72.9% in 1975 to 23.5% in 1977. These phenomena are due to the decrease of the serum-type wien during the years under study. Antibiotic-resistance demonstrated itself most frequently to streptomycin and tetracycline; and chloramphenicol-resistance showed the highest transfer capacity (97.2%).

Anti-Bacterial Agents

[Treatment with antilymphocyte globulin (ALG) and evolution of renal transplant: observations of 42 cases].

42 necrokidney transplants, performed in Renal Unit of "Niguarda - Ca' Granda" Hospital in Milan, since 1972, have been examined. Hystocompatibility score and previous transfusions and/or pregnancies apparently did not correlate with three months transplants survival. Our patients have been separated into two groups according to treatment with or without ALG: the group treated with ALG showed a better percentage survival of the kidney at three months a lower incidence of rejection episodes during the same period. The usefulness of ALG treatment is reaffirmed; we consider that a better prognosis at three months probably means a more favorable clinical course.

Adolescent