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Biomedical subjects

J Sastre

Publications and source records attributed to J Sastre.

At least 109 records · Page 6Linked to original sources
PubMed1998

Specific IgE antibodies in the diagnosis of atopic disease. Clinical evaluation of a new in vitro test system, UniCAP, in six European allergy clinics.

A new immunoassay system utilizing new automatic instrumentation, new software for evaluation of data, and reagents updated for increased speed and accuracy was evaluated. Six clinical studies included 894 consecutive patients. Major symptoms were rhinoconjunctivitis, asthma, atopic dermatitis, and urticaria. The prevalence of inhalant allergy was 54-69%. Phadiatop, detecting atopic sensitization to common inhalant allergens, agreed with clinical diagnosis in 764/836 cases (91.4%). The clinical sensitivity and specificity were 93% and 89%, respectively. The clinical sensitivity and specificity of UniCAP specific IgE derived from 5170 comparisons with clinical diagnosis were 89% and 91%, respectively. Specific IgE measurements in UniCAP and in the Pharmacia CAP System agreed in 266/274 cases (97%). A comparison of the sensitivity and specificity of Pharmacia CAP System RAST in 1987 and with UniCAP specific IgE in 1995 showed equivalent performance without change of efficacy or degradation of IgE antibodies after 8 years. The systems were equivalent also in terms of measured values (r=0.96, slope=1.12), confirming the standardization of allergens and of assay calibration. UniCAP is an efficient laboratory system for routine diagnostic testing of allergy and a valuable tool for basic studies on allergens and antibodies.

Administration, Inhalation↗
PubMed1997

Eosinophils transcribe and translate messenger RNA for inducible nitric oxide synthase.

Because of the involvement of nitric oxide (NO) in inflammatory states such as parasitic and hypersensitivity disorders and the fact that eosinophils are one of the cell types implicated, we asked whether eosinophils were able to express mRNA specific to inducible NO synthase (iNOS) and iNOS protein and to secrete nitric oxide. iNOS protein was detected on eosinophil preparations by immunocytochemistry using iNOS mAb. Expression of iNOS protein was also detected by immunoblotting in human purified eosinophils and an eosinophilic leukemia cell line, Eol-3. Nitrite production was detected in the supernatant of human eosinophils and Eol-3 cells cultured for 24 h, and was completely inhibited in the presence of the NOS inhibitor N-methylester-L-arginine. iNOS cDNA was obtained by reverse transcription-PCR. After subcloning, sequencing of the 259-bp fragment from three different human eosinophils cDNAs revealed 97% identity with macrophage/monocyte iNOS. Our studies describe for the first time the presence of iNOS on eosinophil and a putative new role for this cell in inflammatory states such as asthma and parasitic disease.

Animals↗
PubMed1997

Liver intracellular L-cysteine concentration is maintained after inhibition of the trans-sulfuration pathway by propargylglycine in rats.

To study the fate of L-cysteine and amino acid homeostasis in liver after the inhibition of the trans-sulfuration pathway, rats were treated with propargylglycine (PPG). At 4 h after the administration of PPG, liver cystathionase (EC 4.4.1.1) activity was undetectable, L-cystathionine levels were significantly higher, L-cysteine was unchanged and GSH concentration was significantly lower than values found in livers from control rats injected intraperitoneally with 0.15 M-NaCl. The hepatic levels of amino acids that are intermediates of the urea cycle, L-ornithine, L-citrulline and L-arginine and blood urea were significantly greater. Ura excretion was also higher in PPG-treated rats when compared with control rats. These data suggest a stimulation of ureagenesis in PPG-treated rats. The inhibition of gamma-cystathionase was reflected in the blood levels of amino acids, because the L-methionine: L-cyst(e)ine ratio was significantly higher in PPG-treated rats than in control rats; blood concentration of cystathionine was also greater. Histological examination of liver and kidney showed no changes in PPG-treated rats when compared with controls. The administration of N-acetylcysteine (NAC) to PPG-treated rats reversed the changes in blood urea and in liver GSH. These data suggest that when liver L-cysteine production was impaired by the blockage of the trans-sulfuration pathway, the concentration of this amino acid was maintained mainly by an increase in protein degradation and by a depletion in GSH concentration that may spare L-cysteine.

Acetylcysteine↗
PubMed1997

A preliminary report of a phase II trial. UFT plus oral folinic acid as therapy for metastatic colorectal cancer in older patients. Spanish Group for the Treatment of Gastrointestinal Tumors (TTd Group).

The oral fluoropyrimidines have proved to be active in colorectal cancer in Japan and, recently, in the United States and Europe. Continuous oral administration simulates protracted fluorouracil (5-FU) continuous intravenous infusion. The purpose of this trial was to evaluate the tolerability and potential advantages of oral treatment for colorectal cancer in the elderly. The main inclusion criterion was age over 72 years. Patients were treated with UFT (tegafur plus uracil) 400 mg/24 hours (fixed doses) continuously plus folinic acid 45 mg/24 hours until toxicity. If grade 3 or 4 toxicity appeared, treatment was stopped until recovery. From September 1994 to November 1996, 126 patients were included. For the analysis in November 1996, 77 patients were evaluable for response, toxicity, and survival. The patients, including 34 women and 43 men, had a median age of 74 years (range, 72 to 82 years of age). The Karnofsky performance status was 60% to 80% for 41 patients and 90% to 100% for 36 patients. Liver metastasis was present in 48% of the cases, and 42% were locoregional and peritoneal. Toxicity was mild, with only one patient having grade 3 thrombocytopenia, 11 (14%) grade 3 or 4 nausea/vomiting, seven (9%) grade 3 or 4 diarrhea, and one grade 3 mucositis. Four patients (5%) had complete responses and nine (11.6%) partial responses, for an objective response rate of 16.9% (95% confidence interval, 9% to 27%). Twenty-two patients (28.6%) showed no change. The number of patients in whom disease did not progress (ie, patients with complete plus partial responses plus those with stable disease) was 35 (45.4%) (95% confidence interval, 34% to 57%). With a maximum follow-up of 24 months, the median actuarial survival is 14.4 months. The number without disease progression and the median survival in this preliminary analysis suggests that this schedule is a moderately effective, comfortable, treatment with only mild toxicity, that can be recommended for use in the elderly, and it warrants further study.

Aged↗
PubMed1996

Subungual hemorrhages. A primary manifestation of diabetes mellitus.

Subungual hemorrhages may be observed in a variety of systemic diseases and in some otherwise healthy persons. We describe three male patients who were referred because of toenail hemorrhages. Analytical investigations showed hyperglycemia in all the patients. Toenail bilateral hemorrhages were the first manifestation of previously undiagnosed type II diabetes mellitus in all cases. Ophthalmologic examination showed signs of background diabetic retinopathy in all three patients. The existence of retinopathy suggests that subungual hemorrhages might be due to microvascular involvement and could herald the presence of diabetes mellitus.

Aged↗
PubMed1996

Aging of the liver: age-associated mitochondrial damage in intact hepatocytes.

Mitochondrial damage may be a major cause of cellular aging. So far, this hypothesis had only been tested using isolated mitochondria. The aim of this study was to investigate the involvement of mitochondria in aging using whole liver cells and not isolated mitochondria only. Using flow cytometry, we found that age is associated with a decrease in mitochondrial membrane potential (30%), an increase in mitochondrial size, and an increase in mitochondrial peroxide generation (23%). Intracellular peroxide levels were also increased. The number of mitochondria per cell and inner mitochondrial membrane mass did not change. Gluconeogenesis from glycerol or fructose (mitochondrial-independent) did not change with age, whereas it did from lactate (mitochondrial-dependent). The change in the rate of gluconeogenesis was not accompanied by changes in any of the following parameters: phosphoenolpyruvate carboxykinase or pyruvate carboxylase activities or mitochondrial ATP/ADP or cytosolic NADH/NAD+ ratios. This was caused by a decreased rate of malate export (to 20% of the controls) from mitochondria. The impairment of the mitochondrial malate transporter is posttranscriptional because its expression in Xenopus oocytes using polyadenylated RNA from livers of young or old animals did not change. Ketogenesis from oleate also fell in hepatocytes from old rats. Our results show, for the first time in intact cells, a correlation between age-associated impairment of cell metabolism and specific changes in mitochondrial function and morphology, supporting the hypothesis that mitochondrial damage plays a key role in aging.

Aging↗
PubMed1996

Hypergastrinaemia in Cushing's syndrome: pituitary origin or glucocorticoid-induced?

OBJECTIVES: Several reports have shown an increase in serum gastrin levels in patients with Cushing's syndrome (CS). However, the actual origin of this hypergastrinaemia is not known. Two hypotheses have been proposed: concomitant ACTH and gastrin secretion by corticotrophic pituitary adenomas or hypergastrinaemia induced by hypercortisolism. DESIGN AND PATIENTS: We performed simultaneous, bilateral inferior petrosal sinus (IPS) sampling in nine patients with Cushing's disease (CD), proven by histological studies. In all of them, blood samples were taken from both IPS and a peripheral vein to measure plasma ACTH and serum gastrin. In addition, we measured peripheral serum gastrin levels after an overnight fast in 10 patients with CS (seven with pituitary tumours and three with adrenal tumours) before and after surgical treatment. RESULTS: Petrosal-peripheral and interpetrosal gradients of ACTH were higher than 2.0 and 1.4, respectively, confirming the pituitary origin of ACTH. Mean serum gastrin levels were 149.1 +/- 53.6 ng/l in peripheral vein, 183.4 +/- 71.7 ng/l in dominant IPS and 181.4 +/- 68.9 ng/l in non-dominant IPS. No significant differences in gastrin concentrations in these locations were found. Mean preoperative gastrin level in patients with CD was 194.6 +/- 47.9 ng/l, whereas in patients with adrenal tumours it was 247.3 +/- 125.9 ng/l. After surgical treatment, the gastrin levels decreased to 62.1 +/- 13.2 ng/l (P < 0.05) and 90.3 +/- 50.3 ng/l (NS), respectively. CONCLUSIONS: These results suggest that hypergastrinaemia is a common finding in patients with Cushing's syndrome. The lack of significant petrosal-peripheral gradient in individuals with Cushing's disease and the reduction in gastrin level following adrenal tumour resection argues against the hypothesis of a predominantly pituitary source of gastrin, suggesting a glucocorticoid related mechanism as an explanation for the hypergastrinaemia.

Adenoma↗
PubMed1996

Two consecutive phase II studies of oxaliplatin (L-OHP) for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines.

BACKGROUND: Oxaliplatin (L-OHP) is a platinum complex that possesses activity against human and murine cells in vitro and in vivo, including colorectal carcinoma-derived cell lines, and cells that have been selected for resistance to cisplatin. We report two consecutive phase II trials of L-OHP for treatment of patients with advanced colorectal carcinoma. PATIENTS AND METHODS: Fifty-eight patients were entered in study I, and 51 patients in study II. All of the patients had tumor progression when they were treated, prior to their enrollment, with a fluoropyrimidine-containing regimen. In both trials treatment consisted of L-OHP, 130 mg/m2, by i.v. infusion for two hours; the treatment was repeated every 21 days. RESULTS: Response to therapy: Study I: Fifty-five patients were assessed for response. The response rate was 11% (95% CI, 0.03-0.19). Study II: All 51 patients were assessed for response. The response rate was 10% (95% CI, 0.017-0.18). The overall response rate for the 106 evaluated patients was 10% (95% CI, 0.046-0.16). Times to disease progression in responders were 4, 4, 4.5+, 5, 5, 6, 6, 6, 6+, 9, and 13 months. The dose-limiting toxic effect was sensory peripheral neuropathy. The incidence of severe peripheral neuropathy grades was: Study I: grade 3, 23% of patients, and grade 4, 8% of patients. Severe neuropathy had a favorable course in all of the patients who had long-term neurologic follow-up. Diarrhea and myeloid impairment were minor. CONCLUSION: L-OHP produced modest, but definite antitumor activity in patients with advanced colorectal carcinoma who were previously resistant to chemotherapy including fluoropyrimidines. Toxicity is within acceptable limits of tolerance at the dose and schedule of oxaliplatin used in this trial.

Adult↗
PubMed1996

Mitochondrial glutathione oxidation correlates with age-associated oxidative damage to mitochondrial DNA.

Mitochondria may be primary targets of free radical damage associated with aging. We have found that mitochondrial glutathione is markedly oxidized with aging in rats and mice. The oxidized to reduced glutathione ratio rises with aging in the liver, kidney, and brain. The magnitude of these changes is much higher than that previously found in whole cells of any species previously studied. In the liver, this ratio (expressing GSSG as a percent of GSH) changed from 0.77 +/- 0.19% (n=5) in young rats to 2.47 +/- 1.25% (n=5) in old ones, i.e., 320% of the controls. In the brain and kidney, values for old rats were, respectively, 600 and 540% higher than those of young rats. A marked oxidation of mitochondrial glutathione also occurred in mice. Aging also caused an increase in 8-oxo-7,8-dihydro-2'-deoxyguanosine levels in mtDNA in rats and mice. Oral antioxidant administration protected against both glutathione oxidation and mtDNA damage in rats and mice. Finally, we have found a direct relationship between mtDNA damage and mitochondrial glutathione oxidation. This occurs both in rats (r=0.95) and in mice (r=0.98). This relationship, which has been observed for the first time in these studies, underscores the role of glutathione in the protection against free radical damage that occurs upon aging.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

Occupational asthma due to different spices.

We describe a 27-year-old subject who developed rhinitis and asthma symptoms 1 year after starting to prepare a certain kind of sausage. He was previously diagnosed as having allergy to coconut, banana, and kiwi and allergic rhinitis to horse, cat, dog, and cow. A positive immediate skin prick test (SPT) for paprika (dry powder of Capsicum annuum [Solanaceae]), coriander (Coriandrum sativum [umbelliferous]), and mace (shell of nutmeg, Myristica fragrans [Myristicaceae]) at a concentration of 10% (w/v) was obtained. SPT with other sausage ingredients, mites, pollens, and molds were negative. By ELISA, specific IgE antibodies to paprika, coriander, and mace were demonstrated. By ELISA-inhibition assays, a partial cross-reactivity was found among IgE-binding components from paprika and mace. The immunoblot analysis showed two IgE-reactive protein bands able to bind to IgE from mace of 20 and 40 kDa and two other bands from coriander extract of 50 and 56 kDa. No bands were detected from paprika extract. Specific bronchial inhalation challenges showed an immediate asthmatic reaction to extracts from paprika, coriander, and mace with a maximum fall in FEV1 of 26%, 40%, and 31%, respectively, with no late asthmatic reactions. In summary, we demonstrate that inhalation of dust from paprika, coriander, and mace can result in an IgE-mediated reaction to these spices. In this patient, occupational asthma was due to spices from botanically unrelated species.

Adult↗
PubMed1996

Allergy to cockroaches in patients with asthma and rhinitis in an urban area (Madrid).

Previous studies have established that cockroach allergens are important sensitizing agents in the induction of rhinitis and asthma principally in urban areas. This study was undertaken to assess skin test reactivity and specific IgE antibody reactivity to extracts of Periplaneta americana (P.a.), Blattella germanica (B.g.), B. orientalis (B.o.), and a fecal extract of B. germanica (FEB.g.) in a group of patients with rhinitis and asthma living in an urban area in Europe. We examined clinical characteristics and aerollergen sensitivities of 171 consecutive Madrid urban patients with rhinitis and asthma who met the criteria for the study. A comprehensive clinical evaluation was followed by skin prick test with common allergens and saline extracts of P.a., B.g., B.o., and FEB.g. and measurement of serum specific IgE antibody to cockroach extracts. The age of patients ranged from 7 to 68 years (mean 20.4 +/- 16). A total of 153 (90.5%) subjects were atopic and 19 (10%) were considered nonallergic. Pollen sensitivity (66.5%) was most prevalent, distantly followed by sensitivity to cockroach (25.7%), mite (20%), cat (15.5%), Alternaria alternata (14.5%), dog (14%), and food (2%). Skin test reactivity to cockroach extracts was 37 (21.6%) to B.o., 20 (11.6%) to P.a., 19 (11.1%) to B.g. and five (2.9%) to FEB.g. Twenty-one of these patients had rhinitis, 19 rhinitis and asthma, and one only asthma; 26 had perennial symptoms, while 16 had seasonal (spring) symptoms; three (1.7%) patients had only positive prick test to cockroach; all had perennial rhinitis and/or asthma. Eighteen (10.5%) patients had specific serum IgE (RAST 1 or 2) to B.o., 13 (7.6%) to P.a., and six (3.5%) to B.g. Eighty (46.7%) patients had visual evidence of cockroach infestation in their home, mostly B.o.; 31 had positive prick test to cockroach (P < 0.0003). The results indicate that sensitivity to outdoor allergens (pollen) is more prevalent than to indoor allergens. Cockroach sensitization is the most important indoor allergen in our area, and B.o. accounts for most cockroach sensitization.

Adolescent↗
PubMed1996

Growth hormone responses to growth hormone-releasing hormone and clonidine before and after erythropoietin therapy in CAPD patients.

Correction of anemia with recombinant human erythropoietin (rhEPO) in patients with end-stage renal disease has been associated with improvement of several abnormalities in hypothalamo-hypophyseal functions. The aim of the present work was to evaluate the growth hormone (GH) responses to GH-releasing hormone (GHRH) and clonidine stimulation, as well as the baseline concentrations of insulin-like growth factor I(IGF-I), before and after the correction of anemia with rhEPO in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Nine clinically stable patients (1 male, 8 female; mean age 55.4 years; mean duration of CAPD 14.1 months) were studied. Twelve normal volunteers were studied as controls. GHRH and clonidine stimulation tests were performed prior to starting rhEPO and again after partial correction of anemia with rhEPO therapy (60-130 U/kg/week, s.c., for 12 weeks). Blood samples for GH were collected during 2 h after GHRH (100 micrograms i.v. in bolus) or clonidine (0.15 mg/m2, p.o.) administration. In basal plasma samples IGF-I concentrations were also measured. Mean (+/- SEM) blood hemoglobin concentration rose from 5.32 +/- 0.25 to 7.22 +/- 0.25 mmol/l (p < 0.001) after rhEPO treatment. GH responses to GHRH were characterized by marked differences in single patients when compared with the control group. However, the GH peak and the area under the secretory curves (AUC) of GH responses in CAPD patients (9.89 +/- 4.01 micrograms/l and 15.06 +/- 6.02 micrograms.h/l, respectively) did not differ from those obtained in control subjects (14.58 +/- 3.25 microgram/l and 16.94 +/- 4.31 microgram.h/l, respectively). The study after correction of anemia showed an evident potentiation of GH values that reached statistically significant values at 60 and 90 min. GH AUC after rhEPO therapy rose to 25.61 +/- 9.25 micrograms.h/l (p = 0.01). In control subjects, clonidine administration was followed by a GH release that reached a maximum at 90 min (7.67 +/- 2.24 micrograms/l). However, CAPD patients exhibited a blunted response to clonidine both before (2.00 +/- 0.78 microgram/l) and after (2.78 +/- 0.76 microgram/l, NS) correction of the anemia with rhEPO. On the other hand, IGF-I concentrations after rhEPO therapy (32.05 +/- 5.52 nmol/l) were not significantly different from those found prior to starting therapy (38.13 +/- 8.44 nmol/l). In conclusion, these results suggest that correction of the anemia with rhEPO therapy potentiates GH responses to direct pituitary stimulation with GHRH although it is unable to restore the blunted response of GH to clonidine that is found in CAPD patients.

Adrenergic alpha-Agonists↗