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Biomedical subjects

A Riva

Publications and source records attributed to A Riva.

At least 181 records · Page 10Linked to original sources

High-dose epirubicin for untreated patients with advanced tumours: a phase I study.

In a phase I study, epirubicin was administered as an intravenous bolus at an initial dose of 105 mg/m2 in untreated patients with advanced tumours considered resistant to antineoplastic treatment. A 15 mg/m2 dose escalation was done every 3 patients if toxicity was below grade 3 or every 6 patients if at least 1 patient had grade 3 toxicity. 18 patients entered the study. The dose was (mg/m2): 105 (3 patients), 120 (3), 135 (3), 150 (6) and 165 (3). The maximally tolerated dose was 165 mg/m2. The dose-limiting toxicity was neutropenia. Other side-effects were nausea/vomiting (78%) and alopecia (100%). 4 patients stopped treatment because of a decrease in left ventricular ejection function, without clinical signs of cardiotoxicity. A complete response was observed in a patient with abdominal metastases from unknown origin at 105 mg/m2 and a partial response in 2 out of 7 patients with non-operable non-small cell lung cancer, at 135 and 150 mg/m2, respectively. The recommended dose for phase II trial is 135-150 mg/m2.

Adult↗

Phase II study of high-dose epirubicin in non-small cell lung cancer.

24 patients with measurable advanced non-small cell lung cancer (NSCLC) were treated with epirubicin 135-150 mg/m2 every 3 weeks. There were 6 partial responses. Randomised studies should reveal whether and how incorporation of epirubicin into combination chemotherapy can enhance outcome in advanced NSCLC.

Adult↗

Phase II feasibility study of high dose epirubicin-based regimens for untreated patients with small-cell lung cancer.

17 previously untreated patients with small cell lung cancer entered a phase II study testing the feasibility of incorporating high dose epirubicin (110 mg/m2, day 1) in combination regimens, including cyclophosphamide (1 g/m2, day 1), and etoposide (120 mg/m2, day 1) (courses 1, 3, 5) or cisplatin (60 mg/m2, day 1) and etoposide (120 mg/m2, days 1-4) (courses 2, 4, 6), every 3 weeks. Complete responders with limited or extensive disease received thoracic (40 Gy) and prophylactic cranial (30 Gy) irradiation. All patients were evaluable for toxicity and response. Myelosuppression and stomatitis were the dose-limiting side-effects. Maximum myelosuppression occurred as granulocytopenia and anemia, but a recovery by day 21 was observed in the majority of courses. Neutropenic fever occurred in 47 of 99 courses. Severe stomatitis was experienced in 25 courses and lasted generally 7-12 days. Acute cardiac toxicity was uncommon and represented by mild to moderate rhythm abnormalities. No change was noted in the mean QRS voltage on electrocardiogram (ECG) and no patient had a decline of greater than or equal to 20% in the cardiac ejection fraction and/or episode of overt heart failure at any stage of treatment. The overall objective response rate was 88%, with six (35%) complete and nine (53%) partial responses. With a median follow-up of 16 months, overall median survival was 13 months (range, 2-18+). This study demonstrates that epirubicin, at the present dose and schedule, is feasible in combination regimens and that cardiotoxicity is not dose-limiting and induced or enhanced by thoracic irradiation and/or cyclophosphamide.

Adult↗

Subcellular localization of blood group substances ABH in human salivary glands.

We investigated the subcellular localization of ABH antigens in human submandibular, sublingual, and buccal glands by applying a post-embedding immunogold method using monoclonal antibodies specific for A, B, and H antigens. In most glands the immunoreactivity was usually restricted to mucous cells, in which only secretory granules and sometimes Golgi cisternae were specifically labeled. A and B antigens were demonstrated only in the glands of type A, B, and AB subjects, while H antigen was visualized in glands from individuals of all blood types. Moreover, differences were observed in the relative distribution of ABH antigens, depending on the type of gland.

ABO Blood-Group System↗

Ultrastructure of human bulbourethral glands and of their main excretory ducts.

The endpieces of human bulbourethral (BU) glands, studied with SEM after removal of the connective tissue, consist of short, coiled tubules often dilated into alveoli. Immunohistochemical studies at the EM level have shown that the mucous cells of these glands have mucous droplets, which react to blood group antigens, suggesting that BU glands participate in the secretion of these antigens into the seminal plasma. The main excretory duct is lined by a stratified columnar epithelium consisting of six-seven cellular layers. Cells of superficial layers, that are endowed with typical secretory granules, seem to contribute some unknown components to the secretions of these glands.

ABO Blood-Group System↗

Fine structure of excretory ducts of human salivary glands.

Excretory ducts of human major salivary glands are lined by an epithelium consisting of principal cells and by a discontinuous row of basal cells. The principal cells are tall and columnar with mitochondria, large lipofuscin granules and a central nucleus. Just beneath the plasmalemma bordering the lumen, their cytoplasm contains a number of small granules and vesicles similar to those observed in cells of striated ducts. Both in TEM and SEM, these cells also show large apical protrusions devoid of cytoplasmic organelles that may represent a kind of apocrine secretion. The cytoarchitecture of the principal cells seems to be at variance with that of cells of striated ducts. First, the cell body remains unique and does not split into major basal processes. Second, these cells usually lack the long laminated basal folds, housing vertically aligned mitochondria, that are typical of striated ducts. Instead, below the smooth area occupied by the junctional complexes, the lateral cell surfaces are completely covered by a great number of short irregular processes. These organelle-free folds are apparently involved in the mechanism of ion transport since, at their level, there is a strong reactivity for the transporting enzyme K(+)-pNPPase. The basal cells, which are small and cuboidal, have a dense and filamentous cytoplasm. Their functional role is still uncertain.

Adult↗

Primary progressive cerebellar ataxia.

Thirty-two patients with primary progressive cerebellar ataxia were studied using MRI. This technique is better than CT in demonstrating atrophy of cerebellar structures as well as of brainstem and spinal cord. The differential diagnosis from other diseases particularly with multiple sclerosis is easier. The degree of ataxia correlated well with the degree of atrophy of cerebellum. However we could not see any correlation between the degree of atrophy and the onset and duration of the disease and no certain specific aspects could be demonstrated in the different groups examined.

Adult↗

[Systemic thrombolysis using streptokinase. Experiences at the Civic Hospital of Lugano in the framework of the ISIS-2 study].

With a small group of Swiss hospitals we had an opportunity of participating in ISIS-2, the major study on thrombolysis in acute myocardial infarction. Experience with our microcosm (Ospedale Civico Lugano) was compared with the macrocosm of the results of ISIS-2 in 17,187 randomized patients (in brackets). Mortality was 5.1% (7.8%) in our streptokinase group and 15.8% (12.8%) in our placebo group. In the ISIS-2 study the combination of thrombolytic therapy with streptokinase, and of antiplatelet therapy with aspirin, showed a reduction of approximately one third in acute mortality of myocardial infarction, stroke and reinfarction. Our experience confirms the reduced incidence of allergic side effects (3.5%), major bleeding (0.3%) and minor bleeding (2.9%) during or after thrombolytic therapy.

Administration, Oral↗

Ultrastructural observations on human sublingual gland.

That part of the human sublingual gland that corresponds in morphology to the conventional description of this organ presented in most histology texts (probably the major sublingual gland, in contradistinction to the aggregated small glands that compose the minor sublingual glands) was studied by electron microscopy. The gland is mixed, with slightly more mucous elements than seromucous ones. The mucous cells are arranged in tubules that usually are capped by seromucous demilunes. Seromucous cells also form occasional acini or may be scattered in the walls of the mucous tubules. The appearance of the mucous cells varies with the stage of the secretory cycle that they may be in. Their secretory droplets increase in number and progressively compress cytoplasmic organelles. Filamentous bodies also may be present. Based on secretory-granule substructure, four different kinds of seromucous cells can be recognized; these may be a morphological expression of asynchronous synthesis of different secretory proteins. The duct system is an abbreviated one compared to the other major salivary glands. The first duct segments, into which the mucous tubules drain, are similar to intercalated ducts. Larger ducts contain mitochondria-rich cells but lack the basal striations that characterize striated ducts. The paucity of typical striated ducts may be correlated with the elaboration of sodium-rich saliva by the human sublingual gland.

Adult↗

Concanavalin A binding sites on the surface of Drosophila melanogaster sperm: a fluorescence and ultrastructural study.

The distribution of alpha-D-mannose/alpha-D-glucose terminal residues in the plasma membrane of Drosophila melanogaster spermatozoon has been investigated by fluorescence and electron microscopy using concanavalin A (Con A) labeling. The results indicate the presence of distinct domains on the sperm surface. Intense binding of Con A to the plasma membrane is highly restricted to the acrosomal region and to the endpiece of the tail. In the former, Con A receptors are not homogeneously distributed, suggesting the presence of microdomains in the acrosomal area. The main part of the tail contains very few Con A binding sites, which are confined to specific areas of the membrane. The sperm surface overlying the nucleus is completely negative. The labeling pattern is unchanged after storage in the female before fertilization. A preliminary analysis of the surface of mature oocytes using fluorochrome-conjugated horseradish peroxidase indicates that D-mannose binding molecules are specifically associated with the chorion of the micropyle anterior part, which might therefore be the site of a preliminary interaction between egg and spermatozoon.

Animals↗

A granular cell in the proximal intercalated duct of human parotid and submandibular glands.

In human parotid and submandibular gland unusual granulated cells are observed at the acinar-intercalated duct junction. These cells, which show a well developed Golgi apparatus, greatly differ from the typical elements of the intercalated ducts mainly due to the presence of abundant secretory granules of unknown nature. A complex substructure distinguishes these granules from those of conventional ductal cells and from those of acinar cells as well. In addition, some differences exist in the morphology of the granules observed in parotid with respect to those of submandibular gland.

Adolescent↗

Markedly reduced levels of anthracycline-induced DNA strand breaks in resistant P388 leukemia cells and isolated nuclei.

DNA single-strand and double-strand breaks produced by doxorubicin and two anthracycline derivatives (4-demethoxy-daunorubicin and 4'-deoxy-4'-iododoxorubicin) were measured in doxorubicin-sensitive and -resistant P388 leukemia cell lines, using filter elution methods, and compared with cellular drug accumulation to account for major differences in their cytotoxic activities and cross-resistance. The increased cytotoxic potency of the two derivatives reflects at least in part the enhanced drug accumulation by cells that results from their increased lipophilicity. However, the level of protein-linked DNA breaks was not directly related to cellular accumulation of drug analogues. It is possible that enhanced cytotoxicity may also be the consequence of the greatly enhanced ability of analogues to cause DNA strand breaks. The resistant line showed only a modest degree of resistance to both anthracycline derivatives compared with the high degree of resistance to doxorubicin. Although for all the anthracyclines tested drug accumulation was reduced in the resistant line, this did not correlate with the degree of resistance. A differential sensitivity of resistant and parental cell lines to DNA cleavage activity was consistently found for all three drugs tested. However, in contrast to a lack of effect of doxorubicin, the derivatives caused appreciable DNA strand breakage in resistant cells. The enhanced ability of these analogues to break DNA in resistant cells is consistent with the slight cross-resistance with doxorubicin. DNA double-strand breaks produced in isolated nuclei from these cells paralleled the pattern found in whole cells, thus indicating that a nuclear alteration, presumably involving DNA topoisomerases, is associated with anthracycline resistance. Our findings strongly support the hypothesis that anthracycline resistance in these cell variants may be mediated by multiple mechanisms, involving alterations of plasma membrane and changes of nuclear enzymatic activities responsible for DNA strand breaks.

Animals↗

Quantitative ultrastructural approach to the study of the spatial relationships among cell organelles. I. Cytological organization of human exocrine epithelia.

Currently available morphometric methods provide useful information on the three-dimensional properties (such as volume, surface, etc.) of biological structures. These methods, however, do not reveal how the same structures are spatially organized within the cell. A sum of problems, which concern mainly the definition of shape and location of the sectioned structures, does not allow the three-dimensional representation of the organelle arrangement from a quantitative analysis of sections. Following a different approach, this study considers the topographic relationship between ten distinct subcellular structures: nucleus, Golgi, ribosomes, mitochondria, lysosomes, lipid droplets, secretory granules, and apical, lateral, and basal plasmalemma. The analysis of associations from 2 X 2 tables calculated for each pair of structures and the pattern of multiple associations obtained by clustering methods provide a useful description of the spatial relationship among different cell compartments. The results of the investigation carried out in parallel on seven human exocrine glands (pancreas, parotid gland, submandibular gland, lacrimal gland, ceruminous gland, ampulla of the vas deferens, and seminal vesicle) allow an immediate evaluation of the method and a comparative analysis of the cytologic organization of secreting cells of human exocrine glands.

Data Interpretation, Statistical↗

Cavernous sinus meningiomas: an MRI study.

The authors report their experience in examining cavernous sinus meningiomas with MRI. The advantages of this diagnostic method particularly in comparison with conventional neuroradiological techniques are described.

Carotid Artery, Internal↗