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Biomedical subjects

J Sastre

Publications and source records attributed to J Sastre.

At least 145 records · Page 8Linked to original sources
PubMed1993

Molecular cloning and sequence of the cynomolgus monkey apolipoprotein A-II gene.

A clone containing the coding region for cynomolgus monkey (Macaca fascicularis) apolipoprotein A-II has been isolated from a cynomolgus genomic DNA library. The gene spans 1.4 kilobases (kb). The complete nucleic acid sequence of the apolipoprotein A-II gene has been determined, establishing that the gene is interrupted by three intervening sequences of 170, 273 and 394 bp, respectively. The open reading frame encodes a protein of 100 amino acids, and shows 94% sequence similarity with its human equivalent. Both apolipoproteins have identical signal peptide. A noticeable feature is the substitution of mature human Cys-6 for Ser. This change explains the existence of cynomolgus apolipoprotein A-II as a monomer and may have important consequences in the kinetics of this apolipoprotein.

Animals↗
PubMed1993

Ifosfamide in advanced epidermoid head and neck cancer.

A total of 37 men with epidermoid head and neck cancer whose disease had recurred following primary treatment (surgery and/or radiotherapy) received first-line chemotherapy with ifosfamide at i.v. doses of 3 g/m2 given daily on 3 consecutive days in combination with mesna (600 mg/m2 x 3 oral daily doses on days 1-3) every 3 weeks. In all, 7 patients showed a partial response and 2 patients achieved a complete response, for an overall objective response rate of 26% (9 of 35 eligible patients; 95% confidence interval, 12.5%-43%). Excluding the 5 early nontoxic deaths observed during the first 3 weeks of therapy, the objective response rate was 30% (9 of 30 patients; 95% confidence interval, 15%-49.5%). Responses were seen in lung metastases (2 patients), lymph nodes (2 patients), skin (3 patients), and cases of local recurrence (5 patients). The median duration of responses was 3 months (range, 2-5 months). The main side effects of ifosfamide were alopecia (83% of patients), emesis (80%), granulocytopenia (23%), and mild mucositis (20%). Two poor-risk patients suffered severe CNS complications that were probably related to treatment. Three patients died due to chemotherapy-related complications (2 patients with CNS toxicity and 1 patient with granulocytopenic sepsis). In conclusion, ifosfamide appears to be an active drug in epidermoid head and neck cancer and merits further evaluation in this disease.

Adult↗
PubMed1993

Anticardiolipin antibodies in autoimmune thyroid disease.

IgG and IgM anticardiolipin antibodies were assayed by an ELISA technique in 69 patients with autoimmune thyroid disease (ATD) and compared with 43 patients with thyroid disease of no autoimmune aetiology (non-ATD) and 72 healthy controls. IgG anticardiolipin antibodies were detectable in 3 of 41 patients with Graves' disease, in 4 of 28 patients with Hashimoto's thyroiditis, in 5 of 43 non-ATD patients and in 3 of 72 normal subjects (differences not significant). IgM antibodies were measurable in 3 patients with Graves' disease, in 1 patient with Hashimoto's thyroiditis, in 1 non-ATD patient and in 2 normal subjects (differences not significant). Patients with anticardiolipin antibodies did not exhibit a higher titre of thyroglobulin or thyroid microsomal antibodies than patients without anticardiolipin antibodies. There was no relation between IgG or IgM anticardiolipin antibody levels and the thyroid function status, the serum concentration of thyroid hormones or thyrotrophin levels. Neither was there any correlation between anticardiolipin antibody levels and age, sex, previous treatments or time of disease progress. Our results suggest that there is no association between anticardiolipin antibodies and ATD.

Adolescent↗
PubMed1993

Influence of recombinant human erythropoietin treatment on cortisol responses to insulin-induced hypoglycemia in CAPD patients.

The effect of chronic treatment with recombinant human erythropoietin (rHuEPO) on pituitary-adrenal axis responses to stress in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The purpose of this study was to assess the influence of rHuEPO treatment on corticotropin (ACTH) levels and cortisol responses to insulin-induced hypoglycemia in CAPD patients. Nine clinically stable and well-nourished patients (age 19-59 years) treated with subcutaneous rHuEPO, 34-208 U/kg BW/week, during 6-25 months were studied. Nine patients matched for age, sex, and duration of CAPD and not previously treated with rHuEPO were studied as the control group. Crystalline insulin (0.1 U/kg BW) was injected IV to the fasting subjects. Blood samples were collected before and 15, 30, 60, 90, and 120 minutes after insulin administration. In all blood samples serum cortisol and glucose concentrations were assessed. There were no statistically significant differences between both groups in hematocrit values and blood hemoglobin concentrations. Insulin administration induced a decrease in glucose levels that reached a nadir at 30 minutes in both groups (1.8 +/- 0.1 mmol/L in the rHuEPO group vs 2.1 +/- 0.2 mmol/L in the control group). After hypoglycemic stimuli cortisol levels clearly rose in rHuEPO-treated patients reaching a peak of 720 +/- 71 nmol/L at 60 minutes. However, in the control group the cortisol peak, which was not different from that observed in the rHuEPO group (676 +/- 44 nmol/L), occurred at 90 minutes. The areas under the secretory curve of cortisol did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

[Magnesium. New perspectives].

We reviewed the literature on the Mg++ cation with special attention on the clinico-therapeutical, physiopathogenic, and biochemical aspects. We extended the survey to some pathologies such as cardiovascular diseases and diabetes mellitus, given our understanding that a deficiency of this ion may constitute a primary cardiovascular risk factor. The dissociation present between the levels of intracellular and serum Mg++ is shown, since it may invalidate results that follow. We place special emphasis on the necessity to treat certain pathologies with magnesium salts and to quantify, with successive studies, the amount to administer.

Animals↗
PubMed1992

Outbreak of hypersensitivity pneumonitis among mushroom farm workers.

Between April 1982 and August 1985, seven cases of mushroom worker's lung (MWL), a form of hypersensitivity pneumonitis, were diagnosed among workers at one mushroom farm in Florida. The cases suffered from episodic shortness of breath, cough, fever and chills, myalgia, malaise, and difficulty breathing. Pulmonary function testing revealed restrictive ventilatory impairment and reduced diffusing capacity; chest radiographs exhibited diffuse interstitial pulmonary infiltrates. The seven cases occurred among workers from different farm operations, suggesting that workers throughout the farm were exposed to the disease causing agent(s). Six of the affected workers left employment at the farm in order to remain free of symptoms. The other affected worker was able to continue working at the farm, but only by remaining in a maintenance shop which was physically separated from the rest of the farm facilities. An industrial hygiene survey demonstrated that farm workers from every work area were exposed to organic dust constituents suspected of causing MWL, but no specific antigens were identified as the cause of the cases. Of the remaining workers who participated in a cross-sectional respiratory morbidity survey at the farm, approximately 20% of the more heavily exposed workers reported occasionally experiencing symptoms consistent with MWL. Approximately 10% of the workers had below normal spirometry test results, but interpretation was hampered by the diverse racial makeup of the population and lack of an adequate comparison group. No abnormalities consistent with either acute or chronic MWL were seen on the chest radiographs. Serologic tests demonstrated that almost all workers had been exposed to antigens capable of causing MWL, but the results were not associated with health status. At the time of the cross-sectional survey, no workers were found to be suffering acute respiratory problems consistent with MWL.

Adult↗
PubMed1992

Effect of aging on glutathione metabolism. Protection by antioxidants.

The free radical theory of aging suggests that oxygen free radicals may be involved in the aging process. Thus, changes in antioxidant mechanisms may occur with aging. Since glutathione is one of the most effective antioxidant systems in the cell, its metabolism may change with aging. In this chapter we describe experiments which show the involvement of glutathione in the aging process and which provide a rationale for the administration of antioxidants to old organisms to protect them against some of the changes that occur with aging.

Aging↗
PubMed1992

Effect of aging on metabolic zonation in rat liver: acinar distribution of GSH metabolism.

The effect of age on the glutathione antioxidant system and its acinar distribution in rat liver was studied. GSH/GSSG ratio in blood and liver was lower in old than in young rats. Hepatic glutathione peroxidase and glutathione S-transferase activities were higher in old than in young rats, whereas hepatic gamma-glutamyl transpeptidase activity was lower in old than in young rats. Glutathione reductase and glucose-6-phosphate dehydrogenase activities did not change with age in rat liver. Total glutathione levels and glutathione peroxidase activity were higher in periportal than in perivenous areas of young rats, but this heterogeneous distribution did not occur in old rats. No change with age was found in hepatic zonation of glutathione reductase and glucose-6-phosphate dehydrogenase.

Aging↗
PubMed1992

Progressive loss of antiemetic efficacy during subsequent courses of chemotherapy.

The maintenance of the antiemetic efficacy of a combined protocol (intravenous methylprednisolone, oral thiethylperazine and oral amitriptyline) during six consecutive courses of adjuvant FAC chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) was analysed in 107 female breast cancer patients who completed the six planned courses of treatment. A continuous decrease in complete (no vomiting episodes) and major protection rate (0-2 vomiting episodes) was evident during chemotherapy. Complete protection rate decreased from 62.6% in the first course to 48.6% in the sixth (P less than 0.05, chi 2 test). The respective figures for major protection rate were 76.6% and 58% (P less than 0.01, chi 2 test). These data, together with other from the literature, should be taken into consideration when reviewing the overall results of current antiemetic trials, which usually only mention the results obtained in the first course of chemotherapy.

Adult↗
PubMed1992

Intravenous and oral magnesium supplementations in the prophylaxis of cisplatin-induced hypomagnesemia. Results of a controlled trial.

The effects of oral and intravenous magnesium supplementation on cisplatin (CDDP)-induced hypomagnesemia were investigated in 41 patients treated with 100 mg/m2 CDDP. Patients were randomly allocated to receive no magnesium supplementation, intravenous magnesium supplementation (magnesium sulphate, 3 g before each CDDD administration) or oral magnesium supplementation (magnesium pidolate, 2 g orally every 8 hours on days 2 to 21 of each CDDP course) during the first 4 courses of CDDP treatment. Patients in both supplementation arms showed significantly higher magnesium levels than control patients from the second course on (oral magnesium arm) or from the third course on (intravenous magnesium arm). Three of the 9 patients (33%) in the intravenous magnesium arm and 4 of the 9 (44%) in the oral magnesium arm developed hypomagnesemia after the fourth course of CDDP, compared with 9 of the 10 (90%) unsupplemented patients. There were no magnesium-related side effects in patients on intravenous magnesium supplementation. Two patients treated with oral magnesium developed mild gastrointestinal symptoms (emesis and diarrhea), probably from magnesium therapy. Our study showed that both intravenous and oral magnesium supplementations appear to be safe and efficacious in the prevention of CDDP-induced hypomagnesemia. Since patients were not completely protected, and since the analysis was limited to the first four courses of chemotherapy, additional studies are needed to determine the best schedule of magnesium supplementation, especially in patients who receive more than four courses of CDDP chemotherapy.

Administration, Oral↗
PubMed1992

Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration.

We have studied the effect of exhaustive concentric physical exercise on glutathione redox status and the possible relationship between blood glutathione oxidation and blood lactate and pyruvate levels. Levels of oxidized glutathione (GSSG) in blood increase after exhaustive concentric physical exercise in trained humans. GSSG levels were 72% higher immediately after exercise than at rest. They returned to normal values 1 h after exercise. Blood reduced glutathione (GSH) levels did not change significantly after the exercise. We have found a linear relationship between GSSG-to-GSH and lactate-to-pyruvate ratios in human blood before, during, and after exhaustive exercise. In rats, physical exercise also caused an increase in blood GSSG levels that were 200% higher after physical exercise than at rest. GSH levels did not change significantly. Thus, both in rats and humans, exhaustive physical exercise causes a change in glutathione redox status in blood. We have also found that antioxidant administration, i.e., oral vitamin C, N-acetyl-L-cysteine, or glutathione, is effective in preventing oxidation of the blood glutathione pool after physical exercise in rats.

Animals↗
PubMed1992

Growth hormone responses to pituitary and hypothalamic stimuli in CAPD patients treated with recombinant human erythropoietin.

Several alterations of growth hormone (GH) secretion have been described in patients with chronic renal failure. The effect of chronic treatment with recombinant human erythropoietin (rHuEPO) on GH secretion in uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The purpose of this study was to assess the GH responses to both direct and hypothalamic stimuli in CAPD patients chronically treated with rHuEPO. Eight clinically stable and well-nourished patients (age 19-59 yr) treated with subcutaneous rHuEPO, 96.5 +/- 72.1 U/kg/week, during 6-25 months were tested with GH-releasing hormone (GHRH, 100 micrograms iv in bolus). Insulin-induced hypoglycemia (0.1 U/kg iv in bolus) and clonidine (0.15 mg/m2 po) were used as indirect stimuli for GH release. Baseline concentrations of insulin-like growth factor I (IGF I) concentration was also determined. Five CAPD patients matched for age and sex and not previously treated with EPO were studied as a control group. There was no statistically significant difference in baseline IGF I concentrations in EPO treated patients in comparison with control group (2.6 +/- 0.7 vs 0.9 +/- 0.3 U/ml). GHRH administration was followed by a GH release in the treated group that did not differ significantly from that obtained in controls (peak: 10.6 +/- 3.7 vs 15.2 +/- 7.8 micrograms l, area under the curve [AUC]: 16.3 +/- 5.6 vs 24.0 +/- 11.4 micrograms.h/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[Primary empty sella turcica: clinical, radiological and hormonal evaluation].

A retrospective study of 33 patients diagnosed of primary empty sella turcica has been done. Main clinical feature was cephalea, which was present in 51.1% of cases. Diagnosis was done based in Neuroradiologic studies (CAT, Cisternography, Pneumocisternography, Nuclear Magnetic Resonance) finding sellar size being significantly smaller in cases studied after 1980. After Hypophyseal function study, 19 patients did not show any endocrinological disorders, in the other 14 (42.4%), hyperprolactinemia was the most frequent finding (7 patients, 23.3%). 17.8% of cases showed a lowered response of Growth Hormone to insulinic Hypoglycemia. In two cases Panhypopituitarism was found and in case Insipidus diabetes was diagnosed.

Adolescent↗