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Biomedical subjects

F Pardo

Publications and source records attributed to F Pardo.

At least 19 recordsLinked to original sources

Conversion of liver transplant recipients on cyclosporine with renal impairment to mycophenolate mofetil.

The management of liver transplant recipients with renal function impairment remains controversial because cyclosporine withdrawal from triple immunosuppression regimens may be followed by graft rejection. A nonnephrotoxic and powerful immunosuppressant such as mycophenolate mofetil (MMF) could allow a reduction of cyclosporine dosage or its withdrawal and an improvement in renal function in these patients. Eleven patients with serum creatinine levels greater than 1.5 mg/dL, normal graft function, and a rejection-free period of at least 1 year started MMF at a dose of 2000 mg/d (reduced in case of adverse events) while cyclosporine dosage was slowly reduced. At last follow-up (63 +/- 5 weeks), 7 patients remained free of cyclosporine (6 of those patients are also free of steroids), 2 patients reduced their cyclosporine dose, and 2 patients developed mild acute rejection that responded to a switch to tacrolimus therapy. Serum creatinine and urea levels in the 7 patients free of cyclosporine decreased from 2.22 +/- 0.13 to 1.90 +/- 0.19 mg/dL (P =.05) and 0.95 +/- 0.10 to 0.60 +/- 0.10 g/L (P <.001), respectively. Creatinine clearance increased from 38.16 +/- 5.60 to 47.01 +/- 6. 76 mL/min (P =.005). Control of arterial hypertension also improved. Tolerance to MMF was good, but 6 patients required dose reductions, mainly because of asymptomatic anemia. In conclusion, in liver transplant recipients with stable graft function, MMF may allow cyclosporine dose reduction or discontinuation, thus improving renal function and the control of arterial hypertension. This change of treatment must be carefully monitored because of the frequent need for MMF dose reduction and the risk for rejection.

Aged

Human immunoglobulin isotype profiles produced in response to antigens recognized by monoclonal antibodies specific to Anisakis simplex.

BACKGROUND: Anisakis simplex is a medically important pathogen which not only causes anisakiasis but may provoke allergy reactions, ranging from mild urticaria to anaphylactic shock. OBJECTIVE: To investigate anti-Anisakis isotype profiles in anisakiasis and Anisakis allergy patients. METHODS: Capture ELISA techniques were used to investigate the isotype profiles of antibodies specific for two defined Anisakis simplex antigens, in serum from Japanese patients with confirmed anisakiasis and from Spanish patients with allergy to Anisakis. The antigens were 'UA2R antigens' (two proteins with MW of 48 and 67 kDa, recognized by our monoclonal antibody UA2) and 'UA3R antigens' (two proteins with MW of 139 and 154 kDa, recognized by our monoclonal antibody UA3). RESULTS: Considering IgG, the two most frequent isotypes in the response to the UA2R antigens were IgG1 and IgG2, with IgG4 detected in only one case; in response to the UA3R antigens, by contrast, the two most frequent isotypes were IgG1 and IgG4 (though IgG2 remained reasonably frequent). As regards potential utility for serodiagnosis, 95% of the Japanese anisakiasis patients and 84% of the allergy patients showed detectable IgG1 antibodies to the UA3R antigens. Furthermore, all allergy patients showed IgE antibodies to these antigens. CONCLUSION: Anisakis simplex contains antigens that induce responses which are differentially regulated. Because of their immunogenicity, immunodominance and allergenic nature, we consider that the 139/154-kDa antigens recognized by our MoAb UA3 are good candidates for use in tests for the diagnosis of anisakiasis and of the allergy caused by this parasite.

Anaphylaxis

Splanchnic and leg substrate exchange after ingestion of a natural mixed meal in humans.

The disposal of a mixed meal was examined in 11 male subjects by multiple (splanchnic and femoral) catheterization combined with double-isotope technique (intravenous [2-3H]glucose plus oral U-[14C]starch). Glucose kinetics and organ substrate balance were measured basally and for 5 h after eating pizza (600 kcal) containing carbohydrates 75 g as starch, proteins 37 g, and lipids 17 g. The portal appearance of ingested carbohydrate was maximal (1.0 mmol/min) between 30 and 60 min after the meal and gradually declined thereafter, but was still incomplete at 300 min (0.46+/-0.08 mmol/min). The total amount of glucose absorbed by the gut over the 5 h of the study was 247+/-26 mmol (45+/-6 g), corresponding to 60+/-6% of the ingested starch. Net splanchnic glucose balance (-6.7+/-0.5 micromol x kg(-1) x min(-1), basal) rose by 250-300% between 30 and 60 min and then returned to baseline. Hepatic glucose production (HGP) was suppressed slightly and only tardily in response to meal ingestion (approximately 30% between 120 and 300 min). Splanchnic glucose uptake (3.7+/-0.6 micromol x kg(-1) x min(-1), basal) peaked to 9.8+/-2.0 micromol x kg(-1) x min(-1) (P<0.001) at 120 min and then returned slowly to baseline. Leg glucose uptake (34+/-5 micromol x leg(-1) x min(-1), basal) rose to 151+/-29 micromol x leg(-1) x min(-1) at 30 min (P<0.001) and remained above baseline until the end of the study, despite no increase in leg blood flow. The total amount of glucose taken up by the splanchnic area and total muscle mass was 161+/-16 mmol (29+/-3 g) and 128 mmol (23 g), respectively, which represent 39 and 30% of the ingested starch. Arterial blood lactate increased by 30% after meal ingestion. Net splanchnic lactate balance switched from a basal net uptake (3.2+/-0.6 micromol kg(-1) x min(-1) to a net output between 60 and 120 min and tended to zero thereafter. Leg lactate release (25+/-11 micromol x leg(-1) x min(-1), basal) drastically decreased postprandially. Arterial concentration of both branched-chain amino acids (BCAA) and non-branched-chain amino acids (N-BCAA) increased significantly after meal ingestion (P<0.001). The splanchnic area switched from a basal net amino acid uptake (31+/-16 and 92+/-48 micromol/min for BCAA and N-BCAA, respectively) to a net amino acid release postprandially. The net splanchnic amino acid release over 5 h was 11.3+/-4.2 mmol for BCAA and 37.8+/-9.7 mmol for N-BCAA. Basally, the net leg balance of BCAA was neutral (-3+/-5 micromol x leg(-1) x min(-1)), whereas that of N-BCAA indicated a net release (54+/-14 micromol x leg(-1) x min(-1)). After meal ingestion, there was a net leg uptake of BCAA (20+/-6 micromol x leg(-1) x min(-1)), whereas leg release of N-BCAA decreased by 50%. It is concluded that in human subjects, 1) the absorption of a natural mixed meal is still incomplete at 5 h after ingestion; 2) HGP is only marginally and tardily inhibited; 3) splanchnic and peripheral tissues contribute to the disposal of meal carbohydrate to approximately the same extent; 4) the splanchnic area transfers >30% of the ingested proteins to the systemic circulation; and 5) after meal ingestion, skeletal muscle takes up BCAA to replenish muscle protein stores.

Adult

[Usefulness of polymerase chain reaction (PCR) in the diagnosis of meningococcal meningitis].

BACKGROUND: The aim of this work was to evaluate the applicability of polymerase chain reaction (PCR) in the microbiological diagnostic of meningococcal meningitis as compared with the conventional methods (Gram stain and culture). METHODS: One hundred and fifteen cerebrospinalis fluid samples from 115 patients with suspicious symptoms of meningitis were studied. 47 of them belonged to patients suspicious for meningococcal disease; 28 to patients with bacterial meningitis of other infectious etiologies; 10 to patients with meningitis showing lymphocytic pleocytosis and 30 to patients with an unconfirmed meningitis. The cerebrospinalis fluid samples were processed for culture by standard procedures and by PCR according to the method described by Newcombe et al for peripheral blood samples. RESULTS: Thirty five out of 39 patients suspicious of meningococcal meningitis were microbiologically confirmed, being 22 culture and PCR positive, 3 microscopically and PCR positive, 1 only microscopically positive, and 9 positive only by PCR. By using PCR methodology, the number of confirmed diagnostics of meningococcal meningitis increased in a 23% as compared to those obtained by microscopic observation and culture. Sensitivity, specificity, predictive positive value and predictive negative value were 87.1, 98.7, 97.1 and 94.1 respectively for the PCR method. CONCLUSIONS: Our results indicate that PCR can be used on routine basis as a complementary technique to the standard laboratory procedures for diagnosis of meningococcal meningitis.

Humans

[Evaluation of an automatic system (MB/BacT) for the isolation of Mycobacterium spp].

BACKGROUND: The study purpose was to evaluate the MB/BacT automated system against Löwenstein-Jensen solid media for the isolation of Mycobacterium species. METHODS: 1,511 specimens were processed from 15/10/96 to 28/4/97. For digestion and decontamination NALC-NaOH was used. Auramine smear was performed and both culture media were inoculated after digestion-decontamination. Inoculation on MB/BacT bottles was performed according to the manufacturer's instructions, apart from a modification in MAS antibiotic supplement with the addition of vancomycin at 1 microgram/ml as final concentraction. Both media were incubated for 40 days at 37 degrees C. RESULTS: In total 101 (6.6%) mycobacteria species were isolated. 78 M. tuberculosis, 14 M. avium, 6 M. gordonae, 2 M. chelonae and 1 M. fortuitum. 98 (6.4%) Mycobacterium spp. were isolated in MB/BacT and 79 (5.2%) were isolated in Löwenstein-Jensen. 22 (1.4%) out of 101 grew only in MB/BacT and 3 (0.2%) out of 101 grew only in Löwenstein-Jensen. Sensitivity in MB/BacT was 97% compared to 78% in Löwenstein-Jensen, this difference was estatically significant (p < 0.001). Contamination rate was 1.8% in MB/BacT and 13.3% in Löwentein-Jensen. The average time to detection of Mycobacterium spp. was 15.9 days in MB/BacT and 22.4 in Löwenstein-Jensen. CONCLUSIONS: We believe that MB/BacT is a good system for rapid and reliable detection of Mycobacterium spp.

Automation

Repair of ventral hernias with expanded polytetrafluoroethylene patch.

BACKGROUND: Operations for large and recurrent abdominal hernias have a high associated recurrence rate, although it is lower when prosthetic material is used. Expanded polytetrafluoroethylene (ePTFE) seems to be the best tolerated prosthetic material in surgery. METHODS: A series of 45 ventral hernias repaired using ePTFE for closure or reinforcement of the herniorrhaphy has been evaluated prospectively. Thirty-six were midline incisional hernias and nine were transverse or pararectal ventral hernias. There were 13 recurrent ventral hernias and three defects were operated as an emergency procedure. The patch was sutured to the anterior aponeurosis with a running non-absorbable suture. Some other kind of intra-abdominal procedure was undertaken in 12 cases. RESULTS: ePTFE was well tolerated. Complications occurred in five patients. Major complications were found in three patients: cutaneous necrosis requiring a myocutaneous flap; and infection of the prosthesis (primary, and secondary to enterocutaneous fistula due to diverticulitis, both requiring removal of the patch). Mean follow-up was 39 months and hernia recurrence occurred in only one patient. CONCLUSION: This clinical experience shows that ePTFE is a very reliable prosthetic material for the repair of abdominal wall hernias.

Adult

Liver transplantation in cirrhotic patients over 60 years of age.

Although life expectancy in Spain is above seventy years, age over sixty is considered a relative contraindication for liver transplantation (LT) in most centers. The aim of this study was to assess the outcome of LT in patients over sixty years of age comparing them to patients under that age. From January 1992 to August 1995, 61 cirrhotic patients underwent LT at our institution; of them, 43 (group I) were younger than 60 years (mean +/- SEM: 51.9 +/- 0.9 years, range: 37-59) and 18 patients (group II) were 60 years or older (64.1 +/- 0.7, range: 60-71). Main pre-transplant variables (sex, etiology of liver disease, presence of hepatocarcinoma, Child-Pugh's score and renal function) were similar in both groups. The follow-up (median and range) for group I was 28 and 3-47 months, and for group II 16.5 and 3-48 months. Actuarial survival rates at one and four years post-LT were respectively 88.3% and 85.6% for group I, and 87.8% and 87.8% for the group II (p = n.s.). There were no differences between both groups regarding the incidence of rejection, major infections, neurologic complications, renal failure, pathological bone fractures, diabetes mellitus or hypertension. Nevertheless, cardiovascular complications were significantly more frequent in group II (p = 0.002) although they were not the cause of death. In conclusion, our results show that the outcome of LT in patients over sixty years old is comparable to that observed in patients under that age. LT should not be contraindicated on the only basis of an age greater than 60 years.

Adult

Preoperative chemotherapy followed by esophagectomy compared with surgery alone in the treatment of squamous cell carcinoma of the esophagus.

The aim of this study is to assess the effect of concomitant preoperative radio-chemotherapy in the treatment of epidermoid esophageal cancer. We studied a total of 45 patients, divided into two groups. Group I consisted of 20 patients diagnosed with epidermoid esophageal cancer who had been treated initially with esophagectomy. Group II consisted of 25 patients treated with preoperative radiotherapy and two cycles of chemotherapy (cisplatin and 5-fluorouracil), one at the beginning and the other at the end of the radiation treatment, on whom an esophagectomy was subsequently performed. The clinical characteristics were similar in both groups. In group II, there were 12 cases (48%) with absence of tumor in the esophageal wall, three of which had node involvement. The operative mortality was similar in both groups (10% and 8% respectively). The only significant difference found in the postoperative complications was the incidence of anastomotic leak; but this was related to the different esophagectomy techniques used rather than the type of therapy. A decrease in the number of patients with tumor recurrence was observed in Group II, especially where the local component was concerned. The best actuarial survival rate at five years was in patients with no presence of tumor after neoadjuvant treatment (44.4%). However, the radio-chemotherapy seems not to have had any benefit in cases with node involvement.

Antineoplastic Combined Chemotherapy Protocols

Patterns of failure and long-term results in high-risk resected gastric cancer treated with postoperative radiotherapy with or without intraoperative electron boost.

BACKGROUND: To evaluate the possible role of adjuvant radiotherapy in the management of high-risk resected gastric carcinoma. METHODS: From 1982 to 1993, 62 patients surgically resected of a primary gastric cancer with adverse pathological features (serosal and/or regional lymph node involvement) were treated with postoperative radiotherapy with (Group I) or without (Group II) intraoperative electron boost to the surgical bed and coeliac axis (IORT). RESULTS: After a median follow-up of 75.6 months (range 4-120+) for IORT patients and 91.2 months (range 6-149+) for non-IORT patients, overall relapse rates for Group I and Group II patients were 44.5% and 48.6% and local-regional relapse rates were 11.1% and 20%, respectively. Actuarial survival rates projected at the maximum follow-up were 41% and 38% in Groups I and II, respectively. CONCLUSIONS: This retrospective analysis suggests a beneficial effect of adjuvant external radiotherapy in promoting local-regional control in high-risk resected gastric cancer.

Adult

Hemostatic markers in surgery: a different fibrinolytic activity may be of pathophysiological significance in orthopedic versus abdominal surgery.

Without prophylaxis, patients subjected to major abdominal surgery have a risk of deep vein thrombosis of approximately 30%, while the rate varies between 40% and 60% in orthopedic surgery. The reasons for this discrepancy are not completely understood. The present study was designed to compare the pre- and postoperative behavior of different coagulation and fibrinolysis parameters in patients undergoing both types of surgery, receiving low molecular weight heparin prophylaxis. Samples were taken before operation and on postoperative days 1, 3, and 7. The following parameters were assessed: prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, fibrinopeptide A, tissue plasminogen activator, plasminogen activator inhibitor, plasmin-alpha 2-antiplasmin complexes, and fibrin degradation products. We found a significant increase in the clotting markers postoperatively compared with preoperative values (P < 0.05), both in abdominal and orthopedic surgery, indicating a marked hemostatic activation which remained until postoperative day 7. A significant increase in plasminogen activator inhibitor (P < 0.01) and a decrease in tissue plasminogen activator and plasmin-alpha 2-antiplasmin complexes was also observed early after operation. The plasminogen activator inhibitor activity decreased, while tissue plasminogen activator and plasmin-alpha 2-antiplasmin levels increased significantly on days 3 and 7 (P < 0.05). Fibrin degradation products significantly increased throughout the postoperative period (P < 0.01). Preoperatively, we found higher plasminogen activator inhibitor activity and lower tissue plasminogen activator and plasmin-alpha 2-antiplasmin complexes (P < 0.05) in patients undergoing hip replacement compared with abdominal surgery. Fibrin degradation products were also significantly lower on postoperative day 3 in patients undergoing hip replacement (P < 0.01). We suggest that the lower preoperative fibrinolytic activation observed in patients undergoing orthopedic surgery compared with abdominal surgery might have pathophysiological consequences. Our results also indicate that the hemostatic activation persists beyond the 7th postoperative day despite prophylaxis.

Abdomen

Genetic history of cystic fibrosis mutations in Italy. I. Regional distribution.

Earlier analysis of the Italian population showed patterns of genetic differentiation that were interpreted as being the result of population settlements going back to pre-Roman times. DNA disease mutations may be a powerful tool in further testing this hypothesis since the analysis of diseased individuals can detect variants too rare to be resolved in normal individuals. We present data on the relative frequencies of 60 cystic fibrosis (CF) mutations in Italy and the geographical distribution of the 12 most frequent CF mutations screened in 3492 CF chromosomes originating in 13 Italian regions. The 12 most frequent mutations characterize about 73% of the Italian CF chromosomes. The most common mutation, delta F508, has an average frequency of 51%, followed by N1303K and G542X, both with average frequencies around 5%. Multivariate analyses show that the relative frequencies of CF mutations are heterogeneous among Italian regions, and that this heterogeneity is weakly correlated with the geographical pattern of non-DNA 'classical' genetic markers. The northern regions are well differentiated from the central-southern regions and within the former group the western and eastern regions are remarkably distinct. Moreover, Sardinia shows the presence of mutation T338I, which seems absent in any other European CF chromosome. The north-western regions of Italy, characterized by the mutation 1717-1G-->A, were under Celtic influence, while the north-east regions, characterized by the mutations R1162X, 2183AA-->G and 711 + 5G-->A, were under the influence of the Venetic culture.

Cystic Fibrosis