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Biomedical subjects

H Vázquez

Publications and source records attributed to H Vázquez.

12 recordsLinked to original sources

Pharmacokinetics of a F(ab')2 scorpion antivenom in healthy human volunteers.

This paper presents the first study of F(ab')2 scorpion antivenom pharmacokinetics in humans. We have studied the pharmacokinetics of an antiscorpion venom preparation (Alacramyn) in eight human healthy volunteers. The fabotherapic was administered as a 47.5 mg i.v. bolus. Blood samples were drawn at 0, 5, 15, 30, 45, 60, 90, 120, 180 and 360 min after antivenom administration. Subsequently, the volunteers made seven visits to the hospital. Four of them at 24 h intervals, one at day 10, and one at day 21. We measured antivenom plasmatic concentrations using a specific high sensitivity ELISA method for F(ab')2. The time course of F(ab')2 in serum of seven subjects was well described by a lineal combination of three exponential components; a four exponential component model was necessary to fit the eighth subject. The most significant antivenom pharmacokinetic parameters determined were: AUC(infinity)=596.9 (369.3, 891.2) mg h l(-1); V(c) = 3.1 (2.3, 4.3)l; V(ss) = 15.4 (12.8, 39.9)l; MRT = 250.0 (218.8, 310.2) h; CL = 96.6 (58.0, 139.2) ml h(-1); t(1/2,tau1) (also called t(1/2,alpha)) = 0.25 (0.13, 0.37) h; t(1/2,tau(z)) (corresponding to the slowest component) = 161.3 (141.0, 212.0) h.

Adolescent↗

Antibodies to human recombinant tissue transglutaminase may detect coeliac disease patients undiagnosed by endomysial antibodies.

BACKGROUND: The screening and diagnosis of coeliac disease have been simplified by the advent of new serological tools. AIM: To assess the clinical utility of a newly developed kit for antibodies to human recombinant tissue transglutaminase (hu-anti-tTG) in a large population of patients undergoing intestinal biopsy for suspected intestinal disorders. METHODS: We evaluated 426 serum samples from consecutive adult patients (250 from untreated coeliac disease patients and 176 from individuals in whom a diagnosis of coeliac disease had been excluded), obtained at the time of intestinal biopsy. Samples were tested for immunoglobulin A (IgA) hu-anti-tTG by enzyme-linked immunoabsorbent assay, IgA endomysial antibodies (EmA) by indirect immunofluorescence and IgA and IgG antigliadin antibodies by enzyme-linked immunoabsorbent assay. A sub-group of samples was also assessed for a guinea-pig-based anti-tissue transglutaminase. RESULTS: According to the cut-off for hu-anti-tTG, the sensitivity, specificity and positive and negative predictive values were 91%, 96%, 97% and 87%, respectively. Simultaneous determination of EmA showed values of 86%, 100%, 100% and 83% for the same parameters. Although 19 coeliac disease patients (7.6%) were negative for EmA and hu-anti-tTG, both tests rendered superior statistical values to antigliadin antibody tests. At diagnosis, IgA deficiency was detected in 11 patients, but both assays were able to detect samples with mild to moderate deficiency. The comparison of hu-anti-tTG with EmA showed excellent concordance between the tests (kappa statistic, 0.85). Discordance was observed in 20 samples from coeliac disease patients (8%) and in nine samples from controls (5%). Fifteen samples had an EmA-negative but hu-anti-tTG-positive serology, and five showed the converse pattern. Comparison of human recombinant and guinea-pig tests showed concordant results in 96% of cases. CONCLUSIONS: The quantitative determination of hu-anti-tTG type IgA using a commercial enzyme-linked immunoabsorbent assay kit was highly sensitive and specific for the detection of coeliac disease. Our results in a large population of patients with a clinical condition suggestive of the disorder demonstrated that the test can be used to detect a substantial number of patients otherwise unrecognized by IgA EmA.

Adolescent↗

Pre- and post-treatment serum levels of cytokines IL-1beta, IL-6, and IL-1 receptor antagonist in celiac disease. Are they related to the associated osteopenia?

OBJECTIVE: Decreased bone mineral density is a common finding in untreated celiac disease patients. However, the precise pathophysiology of osteopenia remains incompletely understood. Pathological features of gluten sensitivity are associated with local release of proinflammatory and antiinflammatory cytokines. We investigated the serum levels of IL-1beta, IL-6, and IL-1 receptor antagonist in celiac patients and correlated them with bone density measurements. METHODS: We assessed serum samples of 16 female patients at the time of diagnosis (on an unrestricted diet) and after a mean time of 37 months on a gluten-free diet. At the same time, bone mineral density in the lumbar spine and total skeleton was determined by DEXA. RESULTS: Untreated patients had high serum levels of IL-1beta and IL-6 and normal IL-1-RA. Treatment produced a decrease in median IL-1beta levels (p = NS) and a significant diminution of IL-6 (p < 0.05). On the contrary, IL-1-RA increased significantly after treatment (p < 0.05). Baseline lumbar spine Z-score and IL-6 levels exhibited a significant inverse correlation (r = -0.61; p < 0.01). Patients with more severe baseline osteopenia (< -2 Z-scores) had a significantly lower IL-1-RA than those with less bone compromise (> -2 Z-scores). CONCLUSIONS: Our data demonstrate that the inflammatory process observed in active celiac disease is associated with high serum levels of IL-1beta and IL-6 and normal levels of IL-1-RA. Treatment significantly reduces both proinflammatory cytokines and significantly increases the antiinflammatory one. We also suggest that these cytokines might have a role in the osteopenia associated with celiac disease.

Absorptiometry, Photon↗

The histopathology of closed and open comedones of Favre-Racouchot disease.

OBJECTIVE: To determine the distinction between a comedo and an infundibular cyst of Favre-Racouchot disease. SETTING: A university hospital. PATIENTS: From the 8 patients included in the study, 19 cysts and comedones were evaluated. MAIN OUTCOME MEASURE: The distinguishing features between the cysts and comedones of Favre-Racouchot disease. RESULTS: All lesions were histologically indistinguishable from the primary comedones of acne vulgaris, except for the presence of a marked actinic elastosis in the surrounding dermis. The presence of a variable number of hair shafts and an abundant amount of bacteria, which was positive in the results of Gram staining and periodic acid-Schiff reaction and intermingled with sebum and eosinophilic laminated horny material within the dilated infundibulum, characterizes a comedo and differentiates it from an infundibular cyst. CONCLUSIONS: The cysts and comedones of Favre-Racouchot disease are closed and open comedones. They can be easily differentiated from an infundibular cyst by the histopathologic features rather than by the connection to the surface.

Aged↗

Effect of treatment on bone mass, mineral metabolism, and body composition in untreated celiac disease patients.

BACKGROUND/AIMS: Osteopenia is a common complication of celiac disease. The aims of this study were to evaluate whether treatment produces bone remineralization and whether calcium and vitamin D supplementation are necessary to reduce osteopenia. METHODS: Bone mineral density and biochemical parameters of bone and mineral metabolism were measured in 14 newly diagnosed adult celiac disease patients. All patients were treated with a gluten-free diet and were randomized to receive diet only (n = 7) or diet plus calcium (1.0 g/day) and vitamin D (32,000 IU/wk) supplementation (n = 7). Bone density was measured at baseline and at 6 and 12 months of follow-up. Tests for biochemical determinations were repeated every 3 months. RESULTS: At diagnosis, 11 patients had evidence of osteopenia (> 1 SD below normality) in the spine and total skeleton. After 12 months of gluten restriction, overall bone mass had increased 5.0% (p < 0.01) in the lumbar spine and 5.0% (p < 0.002) in the total skeleton. When one only considers those 11 patients who strictly followed gluten restriction, bone density increased 8.4% in the lumbar spine and 7.7% in the total skeleton. Remineralization occurred throughout the skeleton but was more pronounced in the axial than in the peripheral skeleton. The increase in bone mass was independent of age or menopause. Remineralization in patients treated with diet only was similar to that of patients treated with diet and supplements. Basal biochemical parameters showed a high bone turnover with secondary hyperparathyroidism. Treatment induced a decrease in bone turnover activity. However, a complete restoration of biochemical parameters was not achieved. CONCLUSIONS: Strict gluten avoidance promoted a significant increase in bone mineral density. However, values still remain markedly low after 1 yr in several patients. Although calcium and vitamin D supplementation did not provide additional benefit to that obtained by diet alone in the doses administered, our results do not preclude a possible effect of vitamin D at higher dose.

Adult↗

Abnormal colonic transit time in untreated celiac sprue.

Motility disorders of the digestive tract have long been implicated in the pathophysiology of diarrhea in patients with celiac sprue. However, the contribution of the colon to the intestinal transit of celiac sprue has not been reported. Our aim was to determine whether sprue alters gut transit and whether differences in the clinical status of the disease influences colonic transit. We prospectively studied 25 patients with untreated celiac sprue, 15 treated patients and 15 healthy controls. Oro-cecal transit time, measured by the lactulose breath H2 test, was significantly delayed in untreated patients compared with treated patients and controls (p < 0.001 and p < 0.01 respectively). The delayed transit through the stomach and small bowel was not related to the presence of the steatorrhea. Transit of radiopaque makers, a measure of total colonic transit, was significantly faster in untreated patients (p < 0.05). The major finding was that this abnormal colonic behavior was principally due to a subpopulation of untreated patients with very fast transit times (< 18 hours). A weakly significant inverse correlation between transit and fecal weight (r: -0.55, p < 0.01), and between transit and steatorrhea (r: -0.38, p < 0.05), was observed. We confirm previous descriptions of delayed oro-cecal transit time in untreated patients, and also provide the first evidence that disordered colonic transit contributes to the pathophysiology of the diarrhea in sprue.

Adolescent↗

Sperm-surface chymotrypsin-like protease activity required for fertilization in ascidians.

During fertilization, species-specific gamete binding must be followed by sperm penetration of egg vestments before gamete fusion can occur. Sperm proteases, called lysins, aid this process. Sperm from Ascidia ceratodes, Ascidia callosa, and Ascidia paratropa were found to have a surface-mounted chymotrypsin-like protease when studied by enzymology, biotinylated, immunolabeling, and histochemistry. Chymotrypsin substrates and inhibitors blocked fertilization in a concentration-dependent manner in A. ceratodes and decreased the number of sperm heads which penetrated the egg's vitelline coat, but had no effect on sperm binding to follicle cells. Sperm bound to agarose beads coated with the chymotrypsin inhibitor alpha 2-macroglobulin. Chymotrypsin-like enzyme activity, assayed fluorimetrically using N-succinyl-leucinyl-leucinyl-valinyl-tyrosinyl-7 -amido-4-methyl-coumarin as the substrate, was associated with head fractions prepared by differential centrifugation. Biotinylation of live sperm followed by detergent extraction showed that chymotrypsin-like activity could be removed from the detergent extract using avidin-agarose beads. Indirect immunofluorescence of unreacted and reacted sperm heavily labeled membrane domains overlying the mitochondrion and at the base of the head with occasional labeling of the sperm tip. Histochemical studies, which used N-succinyl-alanyl-alanyl-prolyl-phenylalanyl-beta-naphthylamide as the substrate, colocalized enzyme activity in head regions of unreacted and near the mitochondrion of reacted sperm. Thus, we conclude that in ascidian sperm a chymotrypsin-like protease is exposed on the external surface of the plasma membrane of the head, is required for fertilization, and plays a role in sperm penetration but not binding.

Animals↗

Fecal alpha 1-antitrypsin clearance in the differential diagnosis of steatorrhea.

We reviewed the fecal fat excretion and alpha 1-antitrypsin clearance results of 160 patients with steatorrhea in whom a final diagnosis was obtained, based on history, physical examination, and radiological, functional and morphological tests. Twenty-two patients had pancreatic diseases and 138 had steatorrhea due to gastrointestinal diseases. alpha 1-antitrypsin clearance was invariably normal in chronic pancreatitis, but there was only a 23 to 50% of correct etiological classification when the combination of steatorrhea and normal alpha 1-antitrypsin clearance was present. However, none of our patients diagnosed of chronic pancreatitis had abnormal alpha 1-antitrypsin clearance. The combination of steatorrhea and normal clearance of alpha 1-antitrypsin was a modest clue for diagnosis of pancreatic malabsorption.

Celiac Disease↗

[Hyposplenism in celiac disease. Role of a gluten-free diet].

Hyposplenism is a common complication of adult celiac disease. A study of splenic function in 17 adult patients with celiac disease was performed both before and during treatment with a gluten-free diet. Splenic hypofunction was assessed evaluating morphological changes in red cells (Howell-Jolly bodies, spherocytosis, achantocytosis). The hyposplenic changes were compared with: age of patients, duration of symptoms previous to diagnosis, severity of the clinical picture and histological response to treatment. We concluded that 82.4% of patients had hyposplenic changes and that there was a non significant tendency to improve such changes by a strict adherence to gluten-free diet.

Adolescent↗

[Evaluation of the complications of different types of right ventricular bypass by contrast echocardiography].

We evaluated 54 patients with different right heart by-pass by means of contrast echocardiography with rapid venous injection of shaken saline (3 cc, < 20 k; 6cc, > 20 k), in order to detect venous collateral circulation in partial by-pass, pulmonary arteriovenous fistulae in partial and total by-pass, and right-to-left shunt in total by-pass. Forty three patients had partial by-pass: 29 had a bidirectional cavopulmonary anastomosis with additional pulmonary flow (systemic-pulmonary anastomosis and/or restrictive anterograde ventricular flow); 10 had a partial ventricular correction (bidirectional cavopulmonary anastomosis and non restrictive anterograde ventricular flow; two had classical Glenn procedures; two had Kawashima operations (bidirectional cavopulmonary anastomosis and non restrictive anterograde ventricular flow; two had classical Glenn procedures; two had kawashima operations (bidirectional cavopulmonary anastomosis with inferior vena cava interruption), and 11 with total by-pass (10 atriopulmonary anastomosis and 1 with total cavopulmonary anastomosis). The age ranged from 2.5 to 33 years (x = 12.2 years), and the mean postoperative period was 4.3 years. Venous collateral circulation: 32/43 patients (74%) with partial by-pass, specially in those without partial biventricular correction: 29/33 patients (88%) compared to those with partial biventricular correction: 3/10 (30%) p < 0.01. Pulmonary arteriovenous fistulae: 6/43 patients (14%) with partial by-pass; 6/33 (18%) with partial biventricular correction, 0/10 patients with partial biventricular correction, and 0/11 with total by-pass. Right-to-left shunt: 2/11 patients (18%) with total by-pass, all of them with atriopulmonary anastomosis. Contrast echocardiography is an excellent noninvasive method for the initial evaluation of specific dysfunctions of different right heart by-pass. We emphasize the higher frequency of collateral venous circulation in cavopulmonary anastomosis, that would explain the dysfunction with progressive hypoxia in the evolution of these patients. Pulmonary arteriovenous fistulae were detected only in partial by-pass, without partial biventricular correction (p < 0.01). The minor frequency of these fistulae in bidirectional cavopulmonary anastomosis would be due to additional pulmonary flow.

Adolescent↗