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Biomedical subjects

A Costa

Publications and source records attributed to A Costa.

At least 325 records · Page 18Linked to original sources
PubMed1990

Cerebrospinal fluid corticotropin-releasing factor levels and stimulation test in dementia of the Alzheimer type.

Experimental findings have recently suggested a toxic role for glucocorticoids in hippocampus, the main brain target for the adrenocortical hormones. In this study, we explored the activity of the hypothalamus-pituitary-adrenal (HPA) axis in a group of patients with dementia of the Alzheimer's type (DAT) and in a control group of age-matched subjects. We measured the corticotropin-releasing factor (CRF) levels in cerebrospinal fluid (CSF) and evaluated the plasma cortisol response to a CRF stimulation test. While no differences were observed in the results of the CRF test for two groups, CSF CRF values in DAT patients were found to be significantly higher than in controls. Bearing in mind the bidirectional relationships between the neuroendocrine and immune systems and the changes in some immunological parameters reported in DAT, the possible role of HPA axis hyperactivity in the pathogenesis of primary dementia is discussed.

Aged↗
PubMed1990

Holoprosencephaly: prenatal diagnosis by sonography and magnetic resonance imaging.

Magnetic resonance (MR) imaging was performed on two women at the 33rd and 34th pregnancy week, respectively, after ultrasonographic detection of a brain malformation. Fetal neuromuscular blockade was induced by pancuronium bromide injected into the umbilical vein under continuous ultrasound (US) guidance. MR images supported the echotomographic diagnosis of holoprosencephaly, improving the image quality and offering additional information in such cases of difficult differential fetal diagnosis. Holoprosencephaly was finally confirmed by neonatal US and autopsy (case 1), US, CT and MR (case 2).

Adult↗
PubMed1990

ADP-ribosylation of proteins in brain regions of rats during postnatal development.

Post-translational modifications of chromatin-bound proteins play an important role in the regulation of eukaryotic gene expression. Processes such as acetylation, methylation, phosphorylation and ADP-ribosylation may alter the interaction of these proteins with DNA and consequently affect chromatin conformation and the binding of enzymes and other molecules involved in the regulation of gene expression. In the present study the process of ADP-ribosylation of chromosomal proteins (histone and non-histone proteins) in some rat brain regions during postnatal development was investigated; also the effect of epidermal growth factor (EGF) on this process in fetal brain slices was studied. It has been found that the process of ADP-ribosylation of total histones extracted from rat cerebral cortex and cerebellum at 1, 10 and 30 days of age, increases from 1 to 10 days of age (i.e. the period of maximal cell proliferation) and decreases thereafter, while the process of ADP-ribosylation of non-histone proteins (NHPs) sharply decreases during the same developmental period. The addition of EGF to fetal brain slices causes a significant increase of ADP-ribosylation of total histones (particularly of the histone H1 fraction) and also of NHPs and microsomal proteins. This result is in agreement with the effect of EGF as a mitogen factor, previously shown in astroglial cell cultures.

Adenosine Diphosphate Ribose↗
PubMed1990

Cell kinetics: an independent prognostic variable in stage II melanoma of the skin.

The prognostic role of cell kinetics (expressed as 3H-thymidine labelling index, 3H-TdR LI) was assessed on 145 patients with pathologic stage II melanoma subjected only to therapeutic lymph node dissection. The 3H-TdR LI determined on metastatic nodes was related to relapse-free survival and to survival. In particular, 3-year relapse-free survival was significantly different from patients with slowly and rapidly proliferating melanomas (40% vs 22%, P = 0.007), and this finding was consistently found for overall survival (68% vs 46%, P = 0.007). Moreover, in patients with high 3H-TdR LI tumours, the risk of relapse and death within the first year from lymphadenectomy was two-fold that of patients with low 3H-TdR LI tumours. Multiple regression analysis showed that 3H-TdR LI retained its prognostic significance on relapse-free and on overall survival even when the number of involved nodes and type of nodal metastases were considered. Present findings suggest that 3H-TdR LI can contribute to select high-risk stage II melanoma patients.

Adult↗
PubMed1990

Dementia of the Alzheimer type and hypothalamus-pituitary-adrenocortical axis: changes in cerebrospinal fluid corticotropin releasing factor and plasma cortisol levels.

The activity of the hypothalamus-pituitary-adrenocortical (HPA) axis was explored in 10 patients with dementia of the Alzheimer type (DAT) and in 11 age-matched controls, by measuring 1) corticotropin-releasing factor (CRF) levels in cerebrospinal fluid (CSF), 2) the circadian changes of plasma cortisol, 3) and 4) the plasma cortisol response to dexamethasone suppression test (DST) and to CRF stimulation test. CSF CRF levels in DAT were significantly higher than in controls and inversely related to the Mini Mental State (MMS) score. The patients also displayed increased morning (0800 h) plasma cortisol values, with higher mesor and amplitude in the circadian pattern. Dexamethasone resistance was shown by 6 of the 10 DAT subjects. Plasma cortisol response to CRF administration was similar in the two groups, except for the peak values, which in DAT patients were reached earlier than in controls. The present data suggest an overactivity of HPA axis in DAT; its possible role in the evolution of the disease is discussed.

Aged↗
PubMed1990

Induction and maintenance alpha-interferon therapy in myelofibrosis with myeloid metaplasia.

In 12 patients having myelofibrosis with myeloid metaplasia (MMM), recombinant- alpha interferon (r-alpha INF) was given for 16 weeks at an initial dose of 3 x 10(6) U/day as a cytoreductive agent. At the end of the 16th wk, Hb showed minor changes; WBC were reduced from 43 x 10(9)/l, range 6.4-69.4, to 16 x 10(9)/l, range 5-39 (p = 0.05); platelets decreased from 845 x 10(9)/l, range 215-1748, to 370 x 10(9)/l, range 96-730 (p = 0.005). 2 cases responded at the starting dose, while the effective dose was 5 x 10(6) U/d in the others. Minor changes in spleen size were noted, while no significant changes in bone marrow fibrosis occurred. After induction therapy, 3 patients were allocated to maintenance therapy (from 10 up to 34 months). To maintain platelet count lower than 500 x 10(9)/l, the required r-alpha-INF dose was constantly 10 MU/wk, while the same result was not achieved in 1 case with hydroxyurea, 1 g/die. The association with hydroxyurea, 500 mg/die, allowed reduction of the r-alpha INF dose to 6 MU/die in 1 other case.

Adult↗
PubMed1990

Cell kinetics of hepatic metastases as a prognostic marker in patients with advanced colorectal carcinoma.

Cell kinetics was determined, as 3H-thymidine labeling index (LI), in hepatic lesions from 36 patients with primary colorectal carcinoma: LI values ranged from 0.9% to 23.5% and were normally distributed. Cell kinetics was not related to sex or age of the patient, or to liver function. For clinical studies the median LI value of 10% was used to separate slowly and rapidly proliferating lesions. Univariate analysis showed that patients radically resected and with a low LI tumor have a longer disease-free interval and a better probability of 12-month survival than those non-radically resected and with a high LI tumor. When treatment and cell kinetics were taken into consideration, the probability of 12-month survival was 100% for patients with slowly proliferating and radically resected hepatic metastases. Patients with rapidly proliferating tumors, regardless of type of treatment, had the worst prognosis.

Adenocarcinoma↗
PubMed1990

Cancer chemoprevention. A review of ongoing clinical studies.

The mass of experimental data on various possibilities of inhibiting the carcinogenic process is growing rapidly. However, the biological complexity of carcinogenesis and the intrinsic limitations of the animal models make it often very difficult to identify the real potentially effective agents among the hundreds currently being proposed. In fact, more than 600 potentially chemopreventive agents have been identified and approximately 30 of them are presently being tested in humans. The great heterogeneity of these compounds (they belong to over 20 different classes of chemicals) might be a positive feature as it indicates that a variety of approaches is possible and that the options for selecting effective compounds will be numerous. In recent years, what could be called 'clinical chemoprevention' (that is controlled studies to evaluate in human subjects the efficacy of potentially chemopreventive agents) has developed considerably: according to American estimates 4 chemopreventive agents were tested clinically in 1981, 10 in 1985 and 18 in 1988. The number of reported preclinical investigations was 10 in 1985 and 75 in 1988. This rapid expansion has obviously led to some confusion in terminology and in the evaluation of primary results; at present there is still a need for further investigations to better define clinical chemoprevention and to differentiate it from chemotherapy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Neuropsychological changes in demented patients treated with acetyl-L-carnitine.

The study was carried out on 24 patients suffering from mild to moderate dementia. The diagnosis of dementia was made according to DMS III criteria. Patients with cerebrovascular pathologies were excluded by using Hachinski Ischaemic Score less than or equal to 4 and computerized tomography parameters. Patients with depression (Hamilton Rating Scale for Depression greater than or equal to 18) were excluded. All the patients, after a wash-out period of two weeks were treated on a simple blind method with acetyl-L-carnitine (No. = 12 patients) and piracetam (12 patients) by intravenous route (two weeks) followed by an oral one for further 10 weeks. A battery of clinical neuropsychological tests was applied to evaluate the cognitive, attentive and behavioural aspects. The results, analysed by non-parametric variance analysis (Friedman Test) show a statistically significant improvement of the behavioural profile, of attention and of psychomotricity in the patients treated with acetyl-L-carnitine. No significant improvement was found in the piracetam group.

Acetylcarnitine↗
PubMed1989

Plasma retinol level reduction by the synthetic retinoid fenretinide: a one year follow-up study of breast cancer patients.

Fenretinide (HPR) is a synthetic retinoid which has been shown to cause a reduction in the incidence of carcinogen-induced epithelial tumors in experimental animals, and it has been chosen to be tested as a chemopreventive agent in humans. A study on plasma concentrations of HPR, of its metabolite N-(4-methoxyphenyl)retinamide (MPR), and on its effects on endogenous retinol was performed in groups of 14 to 18 breast cancer patients who received p.o. daily doses of placebo or 100, 200, and 300 mg of HPR for 6 mo and subsequently 200 mg for an additional 6 mo. After the first 5 mo of treatment, there was a linear relationship between doses of HPR administered and HPR, MPR, and retinol levels. HPR and MPR levels increased with the increase in dose, whereas retinol levels decreased, and the reduction was statistically significant compared with the placebo group after all the doses tested. Plasma retinol binding proteins (RBP) decreased proportionally to retinol (r = 0.96). The effect of HPR on retinol and RBP occurred early, since retinol and RBP levels had already been decreased, compared with the initial levels, by 38% and 26%, respectively, 24 h after a 200-mg HPR dose. After 12 mo of treatment, in patients treated with 200 mg daily, the dose chosen for a chemopreventive trial, HPR and retinol levels were similar to those found at 5 mo, suggesting no drug accumulation and no further retinol reduction, whereas MPR levels were higher. Following interruption of treatment, as HPR decreased, retinol increased with a linear relationship between log levels (r = 0.78); after about 50 days, HPR was present in trace amounts, and retinol levels were in the range of those of the placebo group. These data show that HPR treatment lowers retinol and RBP plasma concentrations. This effect is related to HPR levels and is reversible on cessation of HPR administration.

Antineoplastic Agents↗
PubMed1989

Cell kinetics of solid tumors with time and its clinical implication.

The proliferative rate has been evaluated for several human tumor types as the fraction of cells in S-phase. The methodologies most often used are autoradiographic determination of 3H-thymidine incorporation and flow cytometric evaluation of DNA content. Cell kinetics determined on various solid primary tumors at the time of diagnosis is not related to pathologic stage but it is an indicator of clinical evolution of the disease similar or superior to other biologic and pathologic prognostic factors. In early disease, submitted to loco-regional treatment as a first-line therapy, the rate of cell proliferation provides prognostic information on relapse-free and overall survival. In this clinical situation, a different metastatic potential can be attributed to tumors with different proliferative rates. In more extensive disease, submitted to systemic treatment, proliferation indices generally influence overall survival, eventhough in responsive tumors a fast proliferative activity could be indicative of higher aggressiveness and remarkable chemosensitiveness. Proliferation indices of the metachronous metastatic lesions is increased over those of the primary tumors as a further evidence of the association between proliferative activity and disease progression.

Cell Division↗
PubMed1989

Cytoreductive effect of recombinant alpha interferon in patients with myelofibrosis with myeloid metaplasia.

In an attempt to reduce myeloproliferation, we administered recombinant alpha-2b interferon (r-alpha INF) to ten patients with myelofibrosis with myeloid metaplasia (MMM) in a hypercellular phase, as part of a phase II trial. Two patients experienced severe side effects and stopped treatment before completion of the first week. In the eight evaluable patients, r-alpha INF was given for 16 weeks at an initial dosage of 3 X 10(6) U/day, with monthly increments in the case of response failure, i.e. a decrease in WBC or platelet count of less than 25% of the initial value. Two cases responded at the starting dosage, while the effective dosage was 5 X 10(6) U/day in the others. At the end of the 16th week, Hb showed minor changes: from an initial value of 12.08 g/dl, range 8.3-17.3, to 11.6 g/dl, range 7.7-18 (P = 0.12); WBC were reduced from 54 X 10(9)/l, range 6.4-69.4, to 17.5 X 10(9)/l, range 5-39 (P = 0.09, 4/8 responses); platelets decreased from 775 X 10(9)/l, range 215-1748, to 403 X 10(9)/l, range 118-730 (P = 0.008, 8/8 responses). Minor changes in spleen size were also noted, while no significant changes in bone marrow fibrosis occurred. Influenza-like symptoms and fatigue were common side effects. In conclusion, r-alpha INF has a role as a non-leukemogenic cytoreductive agent in the therapy of MMM, especially for cases with thrombocytosis.

Adult↗
PubMed1989

Cell kinetic investigations in brain tumors studied by serial stereotactic biopsy.

Between July 1983 and July 1986, 109 consecutive patients affected by brain tumors and selected for stereotactic biopsy underwent in vitro investigation of cell kinetics. The potential proliferative activity of these different neoplasms, evaluated as in vitro 3H-thymidine labeling index (LI), has been determined in 46 mature astrocytomas, 19 anaplasic astrocytomas, 25 glioblastomas, 5 cystic craniopharyngiomas, 6 metastatic tumors, 4 primary C.N.S. lymphomas, 3 pineal germinomas and one choroid plexus papilloma. The relevance of LI on prognosis has been evaluated in 35 patients affected by glial tumors with adequate follow-up longer than 2 years. This retrospective study allowed us to demonstrate the prognostic value of LI in mature astrocytoma and anaplasic astrocytoma series. The feasibility of LI determination by in vitro procedure has been demonstrated also in non-neuroectodermal tumors. In craniopharyngioma the LI investigations allowed to demonstrate a peculiar topographic arrangement of cells in S phase.

Adolescent↗