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Biomedical subjects

C Pastor

Publications and source records attributed to C Pastor.

At least 19 recordsLinked to original sources

[Pancreatic transplant].

Diabetes mellitus is a health concern of the first order, given the high level of associated morbidity and mortality. The objective, in order to slow down the advance of its complications before they become irreversible, is based on correct metabolic control. The high rate of morbidity associated with the surgery of the vascularized pancreas transplant and the high index of rejection have for three decades formed an obstacle to this being considered a valid alternative in the treatment of these patients. Nowadays the pancreas transplant has come to occupy a key position, thanks to the new regimes of immunosuppression and to the perfection of surgical techniques. In this article we review the evolution of the pancreas transplant from its beginnings to its present state.

Adolescent↗

Attenuated response to purified protein derivative in patients with rheumatoid arthritis: study in a population with a high prevalence of tuberculosis.

BACKGROUND: The purified protein derivative (PPD) skin test is the only widely used method which detects latent tuberculosis infection (LTBI) and is dependent on a normal T cell function. In rheumatoid arthritis (RA) the T cell function is altered, which may result in an inability to develop an adequate PPD reaction. OBJECTIVES: To evaluate the response to PPD in patients with RA and to compare it with that of control subjects. METHODS: 112 patients with RA and 96 healthy controls were studied. PPD 5 U was applied using the Mantoux method, and skin reaction was measured at 72 hours. The reaction was considered negative for PPD <5 mm. RESULTS: There were no significant differences in age, sex, history of bacille Calmette-Guerin vaccination, or tuberculosis contact between the two groups. The median size of the PPD induration in the patients with RA was significantly less than that in the control group (4.5 v 11.5 mm, p<0.01). 79 (70.6%) patients with RA compared with 25 (26%) of the control group had a negative reaction to PPD (p<0.01), a response not influenced by disease activity or duration of disease in the patients with RA. CONCLUSION: A PPD skin test is not an appropriate test for recognising LTBI in patients with RA in our population.

Adult↗

[Laparoscopic bariatric surgery: proximal gastric bypass].

The spectacular increase in the prevalence of obesity in our society and the significant complications and comorbidities that it gives rise to have stimulated the interest of scientists and public in this pathology. Surgical treatment is at present the only efficient and lasting treatment for morbid obesity and in many cases it appreciably improves, and even definitively cures, associated complications such as the case of diabetes or hypertension. Amongst the different techniques of bariatric surgery, the gastric bypass (GBP) seems to be definitively establishing itself, since it offers an excellent balance between loss of weight (>70% of the excess), surgical risk and subsequent quality of life. The possibility of carrying out this technique employing a laparoscopic approach has improved its acceptance by doctors and patients while it has made it possible to reduce morbidity and mortality, length of hospital stay and costs. Proximal GBP is carried on those patients with an BMI <60 Kg/m2; for BMI >60 Kg/m2 the GBP employed is denominated distal. Between October 2003 and November 2005, our centre performed 55 laparoscopic proximal Roux-en-Y gastric bypasses via laparoscopy. These involved 42 women and 13 males with an average age of 44 years. The average BMI was 43.5 (35-55.8). The average basal weight was 116.15 Kg. There was no peroperative mortality, nor reinterventions. The BMI after 12 months was 28.4. The average basal weight was 74.2 Kg. Laparoscopic Roux-en-Y proximal gastric bypass is a safe and efficient technique for the treatment of morbid obesity.

Adult↗

[Minimally invasive surgery of the inguinal hernia].

The minimally invasive approach to the inguinal hernia shows advantages with respect to previous conventional approaches in bilateral and recurrent inguinal hernias; while the initial results were bad, new problems were added deriving from the laparoscopic approach. The aim of this article is to describe the surgical technique and analyse the preliminary results of our series of 600 totally extra-peritoneal hernioplasties, performed at the University Clinic of Navarra. The most frequent complication (25.7%) was the accidental rupture of the peritonea. There were no associated intra-abdominal complications. In the follow-up there were 9 relapses (1.5%) and 13 reinterventions. Eleven (1.8%) of the patients developed transitory neuropathic pain in the femoral cutaneous area. In our experience the totally extra-peritoneal approach is a technique that is especially indicated in relapsed and bilateral hernias. The advantages present, in terms of pain and postoperative discomfort, recovery of physical and labour activity, and the good results with respect to relapses and neuropathic pains, encourage us to indicate it not only in relapsed or bilateral inguinal hernias but also in primary ones.

Adolescent↗

[Hepatic and pancreatic laparoscopic surgery].

The development of laparoscopic surgery also includes the more complex procedures of abdominal surgery such as those that affect the liver and the pancreas. From diagnostic laparoscopy, accompanied by laparoscopic echography, to major hepatic or pancreatic resections, the laparoscopic approach has spread and today encompasses practically all of the surgical procedures in hepatopancreatic pathology. Without forgetting that the aim of minimally invasive surgery is not a better aesthetic result but the reduction of postoperative complications, it is undeniable that the laparoscopic approach has brought great benefits for the patient in every type of surgery except, for the time being, in the case of big resections such as left or right hepatectomy or resections of segments VII and VIII. Pancreatic surgery has undergone a great development with laparoscopy, especially in the field of distal pancreatectomy due to cystic and neuroendocrine tumours where the approach of choice is laparoscopic. Laparoscopy similarly plays an important role, together with echolaparoscopy, in staging pancreatic tumours, prior to open surgery or for indicating suitable treatment. In coming years, it is to be hoped that it will continue to undergo an exponential development and, together with the advances in robotics, it will be possible to witness a greater impact of the laparoscopic approach on the field of hepatic and pancreatic surgery.

Adenoma↗

[Laparoscopic biliary surgery].

The following article briefly sets out the possible new protocols that can be applied in biliary pathology, arising from the changes brought about by the appearance of new techniques of laparoscopic biliary surgery. It offers a synthesis of the latest and most novel articles on surgical technique and management in different biliary pathologies such as choledocholithiasis and cholecystitis. It can be concluded that management will differ greatly, depending on the technical capacities of the centre that is called upon to deal with one of these pathologies. A standard protocol for everybody cannot thus be established at present. The differences between endoscopic retrograde cholangiopancreatography and intraoperative laparoscopic cholangiography have still to be demonstrated, it is not possible to make generalisations about whether one technique is more useful than the other. The same could be said about whether access to the main biliary path should be achieved through the cystic conduct or whether, on the contrary, a choledochotomy should be performed.

Biliary Tract Surgical Procedures↗

Identification of Cucumisin (Cuc m 1), a subtilisin-like endopeptidase, as the major allergen of melon fruit.

BACKGROUND: Allergenic components in melon extracts have not been described in spite of the fact that melon (Cucumis melo) is a frequent allergy-eliciting fruit. The aim of this study was to evaluate allergenic components in melon extract and to report the identification of cucumisin as a major melon allergen. MATERIALS AND METHODS: Sera from 35 patients allergic to melon were selected on the basis of clinical symptoms, skin prick tests and oral challenge test. Allergenic components were detected by sodium dodecyl sulphate polyacrylamide gel electrophoresis and immunoblotting. Molecular characterization of IgE-binding bands was performed by N-terminal amino acid sequencing. RESULTS: More than 10 IgE-binding bands, between 10 and 80 kDa, were identified in melon extract. Out of them, four IgE-binding bands were major allergens: 14 kDa, 36 kDa, 54 kDa and 67 kDa. These major allergens, except 14 kDa band, showed the same N-terminal sequence: T-T-R-S-W-D-F-L. Research conducted with protein databases identified this N-terminal sequence as cucumisin, an alkaline serine protease, which shares structural homology with microbial subtilisin. The molecular mass of the identified bands corresponds with different molecular forms of cucumisin produced during the processing or degradation of the enzyme: 67 kDa native cucumisin, 54 kDa mature cucumisin and 36 kDa NH2-terminal cucumisin fragment. CONCLUSION: Cucumisin (Cuc m 1) and several N-terminal cucumisin fragments are the major allergens of melon. The ubiquitous distribution of this protein family (cucumisin-like proteases) in many plant species and its high structural similarity suggest its potential role as a new panallergen in plant foods.

Adolescent↗

Apoptosis and CD8 and CD54 cell expression in rat small bowel transplantation.

The importance of activated CD8 cells expressing IL-2R in small bowel and other organ rejection has been reported. Some authors even consider that a positive correlation might be demonstrated between the number of apoptotic enterocytes and the degree of graft rejection. In addition, moderate to intense activation of endothelial molecules in small bowel allograft in rats has been reported in chronic rejection. The aim of the present paper is to ascertain, in a heterotopic small bowel transplantation (HSBT) in rats, whether CD3, CD4, CD8, and CD54 cell expression in the allograft infiltrates shows some relationship with allograft enterocyte apoptosis when rejection is present. Wistar Furth male rats were allotted to two groups: group A was the control group without transplantation; group B received a heterotopic small bowel allograft from Fisher rats and an im dose of FK506 (0.25 mg/kg/day). A significant increase of CD8, CD54 cell receptor expression, and apoptosis in the group undergoing HSBT showed rejection. No significant differences have been observed in the variables under study between the control and HSBT without rejection groups or in CD3 and CD4 among the three groups. We observed a significant correlation between apoptosis and rejection, between CD8 and CD54 with apoptosis and with rejection, and between CD8 and CD54. This indicates that the activation of endothelial molecules and cells may play an important role in established HSBT chronic rejection. We consider that this study may contribute to the knowledge of small bowel allograft chronic rejection and its immunomodulation.

Animals↗

Serine 132 is the C3 covalent attachment point on the CH1 domain of human IgG1.

The covalent binding of C3 (complement component C3) to antigen-antibody complexes (Ag.Ab; immune complexes (ICs)) is a key event in the uptake, transport, presentation, and elimination of Ag in the form of Ag.Ab.C3b (IC.C3b). Upon interaction of C3 with IgG.IC, C3b.C3b.IgG covalent complexes are formed that are detected on SDS-polyacrylamide gel electrophoresis by two bands corresponding to C3b.C3b (band A) and C3b.IgG (band B) covalent complexes. This allows one to evaluate the covalent binding of C3b to IgG antibodies. It has been described that C3b can attach to both the Fab (on the CH1 domain) and the Fc regions of IgG. Here the covalent interaction of C3b to the CH1 domain, a region previously described spanning residues 125-147, has been studied. This region of the CH1 domain is exposed to solvent and contains a cluster of six potential acceptor sites for ester bond formation with C3b (four Ser and two Thr). A set of 10 mutant Abs were generated with the putative acceptor residues substituted by Ala, and we studied their covalent interaction with C3b. Single (Ser-131, Ser-132, Ser-134, Thr-135, Ser-136, and Thr-139), double (positions 131-132), and multiple (positions 134-135-136, 131-132-134-135-136, and 131-132-134-135-136-139) mutants were produced. None of the mutants (single, double, or multiple) abolished completely the ability of IgG to bind C3b, indicating the presence of C3b binding regions other than in the CH1 domain. However, all mutant Abs, in which serine at position 132 was replaced by Ala, showed a significant decrease in the ability to form C3b.IgG covalent complexes, whereas the remaining mutants had normal activity. In addition we examined ICs using the F(ab')2 fragment of the mutant Abs, and only those containing Ala at position 132 (instead of Ser) failed to bind C3b. Thus Ser-132 is the binding site for C3b on the CH1 domain of the heavy chain, in the Fab region of human IgG.

Amino Acid Sequence↗

Determination of the immunoglobulin E postoperative variation as a measure of surgical injury.

The aim of this study was to ascertain postoperative changes in immunoglobulin E (IgE) in patients undergoing different types of surgery and the possible correlation with the duration and type of surgery. Evidence suggests that surgery induces a predominant activation pattern through the T-helper-2 (Th2) cell pathway, increasing interleukins (IL-4, IL-5, IL-10, IL-13), inhibiting Th1 cell activation, and promoting B and Th2 cell activation. IgE production may indicate predominant Th2 pathway activation and may be a more persistent and easily measurable postoperative marker than IL-6 for measuring surgical trauma. Altogether, 180 patients undergoing different types of surgery for nonneoplastic and nonparasitic diseases were studied. All patients received the same type of anesthesia. Before surgery and on the first (1PO) and 7th (7PO) postoperative days we determined in peripheral blood the CD3, CD4, CD8, CD16, and CD19 cell percentages; IL-1, IL-2, IL-4, IL-6, and tumor necrosis factor (TNF) levels; and the IgA, IgG, IgM, total IgE, C3, C4, and CIC levels. On 1PO, all variables decreased except IgE, IL-1, IL-2, IL-4, IL-6, CIC, and CD19. Only IgE, IL-6, and CD19 increases showed a significantly statistical (ss) difference regarding preoperative values (0.01, 0.05, 0.001, respectively). Relations between the IL-4 and IgE increases (p < 0.01) and between the IgG decrease and IgE increase (p < 0.001) were found. On 7PO, only IgE was increased (p < 0.001). The IgE increase correlated with surgical trauma intensity (p < 0.05). We concluded that IgE increases during the early postoperative period, correlating with surgical injury intensity. The increase in the IgE level may be detected 24 hours after surgery and during the first 7 postoperative days depending on the type of surgery.

Adult↗

Molecular cloning and characterization of an IgE-reactive protein from Anisakis simplex: Ani s 1.

Ingestion of the parasitic nematode Anisakis simplex in undercooked fish can cause severe allergic reactions in some individuals. Using pooled human sera from sensitized patients we have probed an expression library for A. simplex antigens. One positive clone was found to encode a full length 21 kDa protein with strong homology to nematode troponins. The recombinant protein was expressed as a GST-fusion protein and found by immunoblot analysis to react with sera from 20% of allergic patients. The presence of functional EF-hand Ca(2+) binding motifs was demonstrated by gel-shift analysis.

Allergens↗

Administration of IgG Fc fragments prevents glomerular injury in experimental immune complex nephritis.

Most human nephritis is due to glomerular deposition and/or formation of immune complexes (IC). In cultured mesangial cells, Fc receptor stimulation induces proliferation, matrix synthesis, and release of several mediators implicated in the initiation and progression of glomerular injury. Since Ig Fc fragments in vitro modified these phenomena, we studied the effects of systemic administration of IgG Fc fragments on the evolution of experimental IC nephritis. Fc fragment injection (1 mg/day i.p.) to rats with ongoing nephritis (proteinuria 20-50 mg/24 h vs 9 +/- 0.2 mg/24 h in controls) markedly ameliorates proteinuria, renal function, and morphological renal lesions. This was accompanied by a reduction in the renal synthesis of chemokines (monocyte chemoattractant protein-1, IFN-inducible protein-10, and cytokine-induced neutrophil chemoattractant-1), matrix proteins, and growth factors (platelet-derived growth factor, and TGF-beta), and in the activity of transcription factors. The treatment did not affect the glomerular deposition of IgG IC and complement C1q. In contrast, a decrease in the renal expression and production of C3 was observed without changes in serum complement levels. In vitro, very low complement consumption and no C3b covalent interaction were observed with Fc fragments, confirming that they did not modify systemic complement activity. These results indicate that the administration of Fc fragments prevents the development of glomerular damage in an aggressive model of proliferative glomerulonephritis through mechanisms involving a reduced local generation of complement, chemokines and growth factors. Modulation of IC-mesangial cell interaction by Fc fragment administration could represent a new approach to the treatment of severe immune nephritis.

Animals↗

Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E(2) synthesis.

BACKGROUND: Animal model studies have shown that the colon tumour promoting effect of dietary fat depends not only on the amount but on its fatty acid composition. With respect to this, the effect of n9 fatty acids, present in olive oil, on colon carcinogenesis has been scarcely investigated. AIMS: To assess the effect of an n9 fat diet on precancer events, carcinoma development, and changes in mucosal fatty acid composition and prostaglandin (PG)E(2) formation in male Sprague-Dawley rats with azoxymethane induced colon cancer. METHODS: Rats were divided into three groups to receive isocaloric diets (5% of the energy as fat) rich in n9, n3, or n6 fat, and were administered azoxymethane subcutaneously once a week for 11 weeks at a dose rate of 7.4 mg/kg body weight. Vehicle treated groups received an equal volume of normal saline. Groups of animals were colectomised at weeks 12 and 19 after the first dose of azoxymethane or saline. Mucosal fatty acids were assessed at 12 and 19 weeks. Aberrant crypt foci and the in vivo intracolonic release of PGE(2) were assessed at week 12, and tumour formation at week 19. RESULTS: Rats on the n6 diet were found to have colonic aberrant crypt foci and adenocarcinomas more often than those consuming either the n9 or n3 diet. There were no differences between the rats on the n9 and n3 diets. On the other hand, administration of both n9 and n3 diets was associated with a decrease in mucosal arachidonate concentrations as compared with the n6 diet. Carcinogen treatment induced an appreciable increase in PGE(2) formation in rats fed the n6 diet, but not in those fed the n3 and n9 diets. CONCLUSIONS: Dietary olive oil prevented the development of aberrant crypt foci and colon carcinomas in rats, suggesting that olive oil may have chemopreventive activity against colon carcinogenesis. These effects may be partly due to modulation of arachidonic acid metabolism and local PGE(2) synthesis.

Adenocarcinoma↗

Homeostatic joint amplification of pulsatile and 24-hour rhythmic cortisol secretion by fasting stress in midluteal phase women: concurrent disruption of cortisol-growth hormone, cortisol-luteinizing hormone, and cortisol-leptin synchrony.

Short-term fasting as a metabolic stress evokes prominent homeostatic reactions of the reproductive, corticotropic, thyrotropic, somatotropic, and leptinergic axes in men and women. Although reproductive adaptations to fasting are incompletely studied in the female, nutrient deprivation can have major neuroendocrine consequences in the follicular phase. Unexpectedly, a recent clinical study revealed relatively preserved sex steroid and gonadotropin secretion during short-term caloric restriction in the midluteal phase of the menstrual cycle. This observation suggested that female stress-adaptive responses might be muted in this sex steroid-replete milieu. To test this hypothesis, we investigated the impact of fasting on daily cortisol secretion in healthy young women during the midluteal phase of the normal menstrual cycle. Eight volunteers were each studied twice in separate and randomly ordered short-term (2.5-day) fasting and fed sessions. Pulsatile cortisol secretion, 24-h rhythmic cortisol release, and the orderliness of cortisol secretory patterns were quantified. Within-subject statistical comparisons revealed that fasting increased the mean serum cortisol concentration significantly from a baseline value of 8.0+/-0.61 to 12.8+/-0.85 microg/dL (P = 0.0003). (For Systeme International conversion to nanomoles per L, multiply micrograms per dL value by 28.) Pulsatile cortisol secretion rose commensurately, viz. from 101+/-11 to 173+/-16 microg/dL/day (P = 0.0025). Augmented 24-h cortisol production was due to amplification of cortisol secretory burst mass from 8.2+/-1.5 to 12.9+/-2.0 microg/dL (P = 0.017). In contrast, the estimated half-life of endogenous cortisol (104+/-9 min), the calculated duration of underlying cortisol secretory bursts (16+/-7 min) and their mean frequency (14+/-2/day) were not altered by short-term fasting. The quantifiable orderliness of cortisol secretory patterns was also not influenced by caloric restriction. Nutrient deprivation elevated the mean of the 24-h serum cortisol concentration rhythm from 12.4+/-1.3 to 18.4+/-1.9 microg/dL (P = 0.0005), without affecting its diurnal amplitude or timing. Correlation analysis disclosed that fasting reversed the positive relationship between cortisol and LH release evident in the fed state, and abolished the negative association between cortisol and GH as well as between cortisol and leptin observed during nutrient repletion (P < 0.001). Pattern synchrony between cortisol and GH as well as that between cortisol and LH release was also significantly disrupted by fasting stress. In summary, short-term caloric deprivation enhances daily cortisol secretion by 1.7-fold in healthy midluteal phase young women by selectively amplifying cortisol secretory burst mass and elevating the 24-h rhythmic cortisol mean. Augmentation of daily cortisol production occurs without any concomitant changes in cortisol pulse frequency or half-life or any disruption of the timing of the 24-h rhythmicity or orderliness of cortisol release. Fasting degrades the physiological coupling between cortisol and LH, cortisol and GH, and cortisol and leptin secretion otherwise evident in calorie-sufficient women. We conclude that the corticotropic axis in the young adult female is not resistant to the stress-activating effects of short-term nutrient deprivation, but, rather, evinces strong adaptive homeostasis both monohormonally (cortisol) and bihormonally (cortisol paired with GH, LH, and leptin).

Activity Cycles↗

Abnormal fatty acid pattern in rheumatoid arthritis. A rationale for treatment with marine and botanical lipids.

OBJECTIVE: To assess the fatty acid pattern in plasma and synovial fluid (SF) in rheumatoid arthritis (RA) and to determine clinical factors related to possible abnormalities. METHODS: Thirty-nine patients with RA were included. SF samples were obtained from 9 patients. Disease activity was assessed using the Ritchie Articular Index and erythrocyte sedimentation rate. Fatty acids were assayed with gas liquid chromatography. RESULT: Decreased levels of eicosapentaenoic acid (p < 0.0001) and total n3 polyunsaturated fatty acids (p < 0.05) were observed in plasma and in joint fluid, respectively. An increase of the substrates of delta-5-desaturase (C20:3n6 and C20:2n6) and decrease of their products (C20:4n6 and C22:4n6) was observed in plasma total lipids and phospholipids. The long chain mono-unsaturated fatty acids (C20: 1n9, C22: 1n9, C24: ln9) were increased in the joint fluid and in plasma phospholipids. Patients with active disease showed a mild decrease of several saturated fatty acids, n3, and n6 polyunsaturated fatty acids. Minor abnormalities or no changes in fatty acid profile were found related to use of steroids, nonsteroidal antiinflammatory drugs, and gold salts, or malnutrition. CONCLUSION: The fatty acid pattern found in RA (decreased levels of n3 polyunsaturated fatty acids) may explain the beneficial effect of fish oil. Changes in n6 polyunsaturated fatty acids suggest that delta-5 desaturation is decreased and this might facilitate the antiinflammatory effect of botanical lipids in RA.

Aged↗