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Biomedical subjects

A Venturino

Publications and source records attributed to A Venturino.

At least 19 recordsLinked to original sources

Ultramicroscopic and biochemical changes in ram spermatozoa cryopreserved with trehalose-based hypertonic extenders.

The ability of a range of extenders to cryopreserve ram spermatozoa was tested. The extenders were modified by the inclusion of citrate, Tris buffer, trehalose, and EDTA. Ejaculates from three Pampinta rams were evaluated and pooled at 30 degrees C. The semen was diluted to contain 1 x 10(9) cells/mL, cooled to 5 degrees C, loaded into 0.25-mL straws, frozen and stored in liquid nitrogen. Evaluation was based on the hypoosmotic swelling test (HOS test), electron microscopy, and biochemical parameters such as lipid peroxidation and reduced and total glutathione levels, all measured after thawing. The HOS test indicated that the percentage of intact plasma membranes after freezing and thawing was significantly higher for the hypertonic extender containing trehalose (T), compared with an extender containing trehalose+EDTA (TE) or an isotonic Tris extender (B) (p < 0.05). Membrane evaluation by ultramicroscopy also indicated better sperm cryopreservation in extender T compared with the others, and there was a significant reduction in the number of damaged membranes (27%, p < 0.0002). The level of reduced glutathione was significantly higher after sperm cryopreservation in either hypertonic diluent (T and TE) with respect to the isotonic extender B, immediately after thawing (12%) and after a 3-h post-thawing thermotolerance test at 37 degrees C (17%, p = 0.007). Total glutathione levels did not show statistical differences among the extenders. After 3h post-thawing incubation at 37 degrees C, lipid peroxide levels in spermatozoa were statistically lower for T than TE (35%) or isotonic extender B (44%) (p = 0.002). Taken together these results indicate a reduction in the oxidative stress provoked by freezing and thawing when semen is cryopreserved in extender T. The antioxidant properties of extender T may be related to its effectiveness in membrane cryopreservation.

Animals↗

Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer).

BACKGROUND: First-line chemotherapy regimens suitable for elderly advanced breast cancer patients are still not defined. PATIENTS AND METHODS: Women with stage III or IV breast cancer aged > or =70 years were enrolled in a phase II study aimed to evaluate both activity and toxicity of weekly paclitaxel. Among 46 planned patients, at least 18 responses and not more than seven unacceptable toxic events are required for a favourable conclusion. Paclitaxel 80 mg/m(2) was administered weekly for 3 weeks every 28 days. RESULTS: Unacceptable toxicity occurred in seven out of 46 patients evaluated for toxicity [15.2%; exact 95% confidence interval (CI) 7.6% to 28.2%] and was represented by one case of febrile neutropenia, one case of severe allergic reaction and five cases of cardiac toxicity. Among 41 patients evaluated for response, a complete response occurred in two (4.9%) patients and a partial response in 20 (48.8%), with an overall response rate of 53.7% (exact 95% CI 38.7% to 67.9%). The median progression-free survival was 9.7 months (95% CI 8.5-18.7) and median survival was 35.8 months (95% CI 19-not defined). CONCLUSIONS: Weekly paclitaxel is highly active in elderly advanced breast cancer patients. Data on cardiovascular complications, however, indicate the need for a careful monitoring of cardiac function before and during chemotherapy.

Age Factors↗

Geriatric oncology: a clinical approach to the older patient with cancer.

Due to the ageing of the population and the sharp increase in life expectancy, cancer in the older person has become an increasingly common problem in the Western world. Although several authors have stressed that elderly cancer patients deserve special attention as a target group for research efforts, older aged patients are still less likely to be offered participation in clinical trials. The cellular and molecular mechanisms regulating the physiological process of ageing and senescence are far from understood, although inflammation is likely to play an important role, at least in some cancers. In addition, the relationship between ageing and cancer risk is also far from understood. One of the most intriguing aspects of ageing is how different the ageing process is from person to person; the basis for this variation is largely unknown. Population-based studies and longitudinal surveys have shown that comorbidity and physical and mental functioning are important risk factors; thus, a meaningful assessment of comorbidity and disability should be implemented in clinical practice. Modern geriatrics is targeted towards patients with multiple problems. Such patients are not simply old, but are geriatric patients because of interacting psychosocial and physical problems. As a consequence, the health status of old persons cannot be evaluated by merely describing the single disease, and/or by measuring the response, or survival after treatment. Conversely, it is necessary to conduct a more comprehensive investigation of the 'functional status' of the aged person. A geriatric consultation provides a variety of relevant information and enables the healthcare team to manage the complexity of health care in the elderly; this process is referred to as the Comprehensive Geriatric Assessment (CGA). The use of CGA is now being introduced into oncological practice. The definition of frailty is still controversial and represents a major issue of debate in clinical geriatrics. As the frail population increases, clinical trials in frail persons are needed. The usefulness of these trials requires a consensus as to the definition of frailty. Clearly, the management of older persons with cancer requires the acquisition of special skills in the evaluation of the older person and in the recognition and management of emergencies as well as experience in geriatric case management.

Age Factors↗

Cryopreservation and post-thawed fertility of ram semen frozen in different trehalose concentrations.

We evaluated freeze-thawing tolerance of heterospermic ram spermatozoa (Pampinta breed) in a base diluent (Tris, citric acid, fructose, egg yolk, glycerol) with the addition of different trehalose concentrations (0-400 mOsm). We chose sperm motility, acrosome integrity and hypo-osmotic swelling test as parameters to evaluate cryopreservation capacity. We obtained the best results for 50 and 100 mOsm trehalose-supplemented extenders, with values (referred to fresh semen values) of 65% for motility, 75% for acrosome integrity and 50% for hypo-osmotic swelling test, while freeze-thawing tolerance diminished significantly for 200 and 400 mOsm of the disaccharide. Fertility values measured at lambing were 47.1 and 44.6% (2 consecutive years), using semen cryopreserved in 100 mOsm trehalose-containing diluent, which is 2.5 times greater than those obtained with the base diluent (18.5 and 14.5%). We conclude that the membrane-protecting disaccharide trehalose confers a greater cryoprotective capacity to the base extender, when added up to 100 mOsm. This action is reflected in the different sperm membranes, the motile activity and in vivo fertility.

Acrosome↗

Thiols and polyamines in the potentiation of malathion toxicity in larval stages of the toad Bufo arenarum.

Treatment with exogenous spermidine enhanced acute malathion toxicity during larval development of the toad Bufo arenarum Hensel. The polyamine was rapidly incorporated in the larvae with a subsequent metabolization to putrescine and spermine, which were excreted to the media. Endogenous polyamine levels were not changed by either spermidine or malathion treatments. However, 0.5-mM spermidine modified malathion uptake and bioavailability increasing the concentration of the xenobiotic in the larvae. The amount of reduced thiols was decreased by both compounds, but the depletion was insufficient to induce cytotoxicity. The oxidative degradation of polyamines competes for the pool of reduced glutathione used in the conjugation of malathion in the larvae, thus leading to the reported potentiation of toxicity. Our results suggest that exposure to thiols-depleting agents may induce alteration of organophosphate degradation in amphibian larvae.

Animals↗

Effect of trehalose and EDTA on cryoprotective action of ram semen diluents.

To obtain better ram semen extenders for artificial insemination (AI), we developed effective trehalose-containing hypertonic diluents. The cryoprotective action of trehalose has been explained by its dehydrating activity and interaction with cell membranes. Accordingly, we tested the cryopreserving capacity of different combinations of a Salamon's modified plus trehalose extender with EDTA. Evaluations were based on the percentage of motile spermatozoa and acrosome integrity, measured after thawing and after a 4-h post-thaw resistance test at 37 degrees C. We conclude that the combination of trehalose plus EDTA confers the highest cryopreserving activity tested, not only for freeze-thawing but also for post-thawing resistance, possibly by removing calcium from the medium thereby preventing cation competition with trehalose for membrane-binding sites.

Animals↗

Is salvage chemotherapy for metastatic breast cancer always effective and well tolerated? A phase II randomized trial of vinorelbine versus 5-fluorouracil plus leucovorin versus combination of mitoxantrone, 5-fluorouracil plus leucovorin.

Metastatic breast cancer remains an incurable disease and the median overall survival has not significantly improved over the past two decades. Aims of the present randomized phase II trial were to analyse activity and toxicity of chemotherapies with single agent or with combination regimens in previously treated patients with advanced breast cancer. Ninety-nine eligible patients were randomized to receive the following chemotherapies: Arm A - vinorelbine 30 mg/m2 i.v. weekly; Arm B - leucovorin 100 mg/m2 i.v. followed by 5-fluorouracil 370 mg/m2 i.v. days 1 --> 5, q 28 days; Arm C - mitoxantrone 12 mg/m2 i.v. only day 1 + leucovorin 100 mg/m2 i.v. followed by 5-fluorouracil 370 mg/m2 i.v. days 1 --> 3, q 28 days. Patients characteristics are comparable in the three groups. The median number of chemotherapy courses administered was 7, 6 and 5 in arm A, B and C, respectively. Objective responses were 24%, 30% and 21% and the median duration of responses were 2, 2.5 and 5.5 months in the arm A, B and C, respectively. Median overall survivals were 9.5, 9 and 9 months in the three arms. No difference was noted comparing the survivals of responding or non responding patients. General toxicity was not mild, with 27.5% of patients experiencing WHO grade 3-4 toxicities. Our results are similar in the three groups of patients and comparable to those reported by other authors. Chemotherapy applied to patients with second or subsequent recurrence allow objective responses in a small percentage of patients. Moreover responders have a negligible prolongation of survival.

Adult↗

Formestane is feasible and effective in elderly breast cancer patients with comorbidity and disability.

Age is a major risk factor for solid tumors, including breast cancer. The majority of elderly breast cancer patients have oestrogen-dependent tumors, thus, tamoxifen is widely administered. However, it has been noted that tamoxifen-related thrombotic events are not exceptional. Due to the increasing prevalence of comorbidity, including vascular diseases, with age, such events are more frequently observed in the aged patients. Formestane, a selective steroidal aromatase inhibitor, may represent a therapeutic option after failure with tamoxifen, or in the presence of vascular diseases contraindicating its administration. The present report provides a new clinical experience on a consecutive series of 45 elderly breast cancer women affected by moderate to severe degree of comorbidity and disability measured by a Comprehensive Geriatric Assessment (CGA) scale validated on oncological patients. Formestane was given intramuscularly at the dose of 250 mg every 2 weeks. The study included 31 patients who had metastatic disease, and 14 who received formestane as an adjuvant treatment. Median age was 74 years (range 65-93), with nine patients > 80 years. Median ECOG Performance Status (PS) was one. The more frequent comorbidities observed in our series were arthrosis-arthritis (64.4% of patients), hypertension (44.4%), vascular diseases (35.5%), CNS diseases (28.8%). Twenty percent of patients presented at least one dependency in Activities of Daily Living (ADL) and 51.2% in Instrumental Activities of Daily Living (IADL). The treatment was well tolerated - only two patients interrupted formestane because of minor adverse reaction at the injection site and generalised itching. In particular Formestane was not responsible for any worsening of pre-treatment comorbidities, especially hypertension and vascular diseases. Objective responses (OR) were observed in 11.1% of advanced patients, while the disease was stabilised in 51.8% subjects. Median duration of OR was 12 months; median overall survival was 11 months. Among patients receiving formestane as adjuvant treatment, three relapsed, with a time to failure (TTF) of 12 months. Formestane is effective and minimally toxic in an elderly breast cancer population with comorbidities and disabilities measured by CGA.

Activities of Daily Living↗

Groundwater contamination by azinphos methyl in the northern Patagonic Region (Argentina).

Approximately 30 groundwater monitoring wells, under a fruit production field, in the Valley of the Neuquen River (Northern Patagonic, Argentina), to which different pesticides have been applied, were sampled eleven times between October 1995 and March 1997. Azinphos methyl was the main pesticide applied and it was detected with the highest frequency in groundwater wells during the period of intensive pesticide application in the Southern Hemisphere. Dimethoate, methidathion, fosmet, cipermethrin, carbaryl, propoxur, carbofuran, benomyl and carbendazim were also detected with lower frequency. The characteristic of the area under study was alkaline soil, with an organic matter content below 2.5% and texture sandy clay loam. The half life of azinphos methyl in soils was 166.2 days in the sun light for horizon A and 194.15 in the dark for horizon B. Leaching of azinphos methyl through the different soil horizons was minimum. On the basis of our lysimeter laboratory data, in which most of the pesticide was adsorbed into the soil column and only small quantities leachate, we inferred that the impact of azinphos methyl on groundwater would be minimal. However, field data indicates that there is a persistence of azinphos methyl in groundwater during the application season.

Argentina↗

Performance status and comorbidity in elderly cancer patients compared with young patients with neoplasia and elderly patients without neoplastic conditions.

BACKGROUND: Elderly people constitute a heterogeneous group and are at an increased risk for the development of cancer. It is not clear whether comorbid conditions and functional status influence clinical decisions and the pattern of referral in elderly cancer patients. The current study investigated functional status measured by Eastern Cooperative Oncology Group performance status, comorbid conditions, and medication taken as well as social environment in three series of patients grouped according to age and diagnosis. METHODS: A total of 593 patients were involved: 138 neoplastic patients age > 70 years with breast, colon, or prostate carcinoma, 177 neoplastic patients age < 70 years with the same types of pathology, and 278 elderly patients with nonneoplastic conditions. Patients with neoplastic disease were recruited from cancer centers; patients with nonneoplastic disease were recruited from either geriatric or general medicine departments. Differences in the distribution of variables were analyzed by univariate and bivariate analyses. RESULTS: No significant differences in social environment, marital status, or education were observed. Statistical differences were noted when comparing the distribution of comorbidities, performance status, and medication taken, elderly neoplastic patients presented in poorer condition compared with younger patients but in better condition compared with elderly patients with nonneoplastic disease. CONCLUSIONS: The overall better health of older cancer patients compared with those without cancer needs to be assessed further. It is possible that cancer is more likely to be diagnosed in healthier elderly, or that primary care providers are reluctant to refer for cancer care patients in poor general health. Studies of comorbidity, function, and social resources are necessary to establish the impact of cancer on survival and quality of life of older patients and to determine the social resources necessary for adequate care.

Activities of Daily Living↗

Lung cancer.

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Age Factors↗

Home care in the older person.

Life expectancy has progressively increased in Western countries over the last few decades. The number of individuals over age 65 also has increased. Home health care, as an alternative to hospital and ambulatory care, is currently one of the fastest growing sectors of the health care market and has met the favor of most patients and families.

Aged↗

Caring for the Older Cancer Patient: Comprehensive Geriatric Evaluation.

Elderly patients comprise almost half of daily adult oncology practice, but management guidelines based on data from clinical trials performed in the elderly are lacking. Comprehensive geriatric evaluation and the use of different outcome measures for trials of interventions in the elderly are needed to provide clinicians and patients the information required to make the best management decisions.

Journal Article↗

Phase II study of weekly mitoxantrone, 5-fluorouracil, and leucovorin in metastatic breast cancer.

A phase II study to test the toxicity and the efficacy of a weekly combination of Mitoxantrone, 5-Fluorouracil and L-Leucovorin (MFL) was carried out in 43 patients with metastatic breast cancer. Chemotherapy consisted of mitoxantrone 4 mg/m2, 5-fluorouracil 375 mg/m2, and L-leucovorin 100 mg/m2 on day 1, weekly. Patient characteristics were: median age 53 years (range 36-65); estrogen receptor (ER) status was known in 26 patients and of these 15 (57.7%) patients were ER-positive and 11 (42.3%) ER-negative. Of the 43 patients, 25 (58.1%) and 18 (41.9%) patients had received prior adjuvant chemotherapy and prior adjuvant endocrine treatment, respectively. MFL was administered to 22 (51.1%) patients as first line chemotherapy for advanced disease, while 21 (48.9%) patients had received 1 to 2 cytotoxic regimens for metastatic disease. The dominant sites of metastases were: soft tissue in 11 (25.5%) patients, bone in 8 (18.6%) patients and viscera in 24 (55.9%). All patients were assessable for toxicity: only 8 patients experienced WHO grade 3 leukopenia. Thrombocytopenia, diarrhea, stomatitis, and nausea/vomiting were negligible. Anemia and alopecia were not observed. Thirty-nine patients were assessable for response: overall response rate was 28.2% (complete response 7.7% and partial response 20.5%). Median duration of response was 12 months (range 6-34). Patients with no prior anthracyclines had a 42.1% response rate compared to 15% in patients who had received anthracyclines. Median overall survival of the 43 patients was 6 months (range 1-34). Weekly MFL is a well-tolerated and a moderately effective regimen for the treatment of metastatic breast cancer.

Adult↗

Histamine receptors in an experimental mammary carcinoma.

An experimental mammary carcinoma was induced in Sprague-Dawley rats by the ip administration of N-nitroso-N-methylurea (NMU) in three doses of 50 mg/kg. In order to study the expression of histamine receptors in these experimental tumors, the presence of specific binding sites for histamine was studied. Using [3H]-histamine as a radioligand, two specific binding sites were characterized on the cell membrane. The first site, of high affinity, Kd = 4 +/- 2 nM, was further characterized as an H2 type using [3H]-cimetidine and [3H]-tiotidine as radioligands and by displacement experiments with different histamine agonists and antagonists. The second one of low affinity, Kd = 35 +/- 14 nM, needs further characterization. The determination of cAMP levels showed that histamine and the H2 agonist dimaprit, produced a significant decrease in the nucleotide concentration 6 minutes after stimulation, in a response that was specifically abolished by H2 antagonists. Based on these results, we conclude that neoplastic cells from NMU induced tumors express H2 histamine membrane receptors which are coupled to a transductional pathway different from cAMP production, which may be involved in the regulation of tumor growth.

Animals↗