Biomedical subjects
C Zamora
Publications and source records attributed to C Zamora.
Retreatment with interferon and ribavirin vs interferon alone according to viraemia in interferon responder-relapser hepatitis C patients: a prospective multicentre randomized controlled study.
Low pretreatment viral load has consistently been shown to be an independent predictor of sustained response (SR) in patients with chronic hepatitis C infection. We assessed the efficacy of interferon (IFN) plus ribavirin vs IFN alone in low viraemic patients (<2 millions copies/mL) who had relapsed to a previous course of IFN and the efficacy of 24 vs 48 week combination therapy in high viraemic patients. Two hundred and ninety-seven patients were randomly assigned to one of the four regimens after stratification on pretreatment viral load. All patients received IFN-alpha2b (6 million units thrice weekly for 24 weeks and 3 million units thrice weekly for 24 weeks). Patients with low viraemia received either IFN-alpha2b alone for 48 weeks (R1: 42 patients) or IFN-alpha2b plus ribavirin (600 mg/day) for 24 weeks and IFN-alpha2b alone for the next 24 weeks (R2: 48 patients). Patients with high viral load received either IFN-alpha2b plus ribavirin for 24 weeks and then IFN-alpha2b alone for the next 24 weeks (R3: 104 patients) or IFN-alpha2b plus ribavirin for 48 weeks (R4: 103 patients). In low viraemic patients the rate of SR was 37.7% in group R1 and 59.6% in group R2 (P < 0.05). In high viraemic patients, the rate of SR was 44.7% in group R3 and 51.4% in group R4 (P: NS). Thirty-one patients discontinued treatment (10.4%) without difference regarding treatment regimen. In the regimen using ribavirin we found no difference in terms of SR between patients receiving a dose of ribavirin below 10.6 mg/kg/day (55%) or over 10.6 mg/kg/day (58%). Histological improvement occurred in 70.2% of patients regardless of the regimen. Logistic regression showed that genotype 2 and 3, Knodell score <6 and alanine aminotransferase pretreatment level >3 x upper limit of normal were significantly and independently correlated with SR. In low viraemic patients who relapsed to a previous IFN treatment, combination therapy using high-dose IFN and low-dose ribavirin is better than high-dose IFN alone. In high viraemic patients there was no benefit in increasing the duration of combination therapy from 24 to 48 weeks. In this study, it was found that low dose of ribavirin can be used safely and there is no effect of ribavirin dose on SR.
Donor age-related differences in PBPC mobilization with rHuG-CSF.
BACKGROUND: Data on the administration of rHuG-CSF to normal donors <18 years old are very limited. STUDY DESIGN AND METHODS: The results of rHuG-CSF administration to 61 donors <18 years old (Group A) were retrospectively evaluated and compared with results from 353 donors > or = 18 years old (Group B) who are included in the Spanish National Donor Registry. The mean age (range) in Group A and B was 14 (1-17) and 38 (18-71) years, respectively (p<0.001). The mean dose of rHuG-CSF was 10 microg per kg per day (range, 9-16) during a mean of 5 days (range, 4-6). Central venous access was placed more frequently in younger donors (25% vs. 6%; p<0.001). RESULTS: The mean number of CD34+ cells collected was 7.6 and 6.9 x 10(6) per kg of donor's body weight in Group A and B, respectively. Fifty-six percent of Group A donors needed only one apheresis to achieve > or = 4 x 10(6) CD34+ cells per kg versus 39 percent of Group B donors (p = 0.01). Side effects were more common in Group B (71% vs. 41%; p<0.001). CONCLUSION: The administration of rHuG-CSF to donors <18 years old leads to CD34+ cell mobilization in a pattern similar to that observed in adults. Greater age was associated with a more frequent requirement for more than one apheresis to achieve a similar number of CD34+ cells.
Intraductal papillary or mucinous tumors (IPMT) of the pancreas: report of a case series and review of the literature.
OBJECTIVE: Despite a better understanding of these conditions, intraductal papillary or mucinous tumors (IPMT) of the pancreas still present difficulty relating to the predictive factors of malignancy and the risk of relapse after surgical resection. The aim of this study was to report on our experience and to compare it to previously published cases. METHODS: We studied retrospectively 26 patients (mean age 60.3 yr) presenting with IPMT. Of the 26 patients, 19 had surgical resection and seven did not. The main clinical feature was acute pancreatitis occurring in 38% of the patients. Segmental pancreatectomy was performed in all the cases. At pathological assessment of resection margins, tumor resection was considered as complete in 17 cases. Margins exhibited benign mucinous involvement, and resection was considered to be incomplete in one multifocal case and in one case with diffuse spread of the tumor. RESULTS: A total of 11 tumors were benign and five were malignant. Carcinomas were invasive in four cases (two invading the pancreatic parenchyma, one the duodenum, and one the peripancreatic nodes) and in situ in one case. Malignancy was not diagnosed preoperatively except when invasion was evident (duodenal spread). Although main pancreatic duct type and obstructive jaundice appeared as suggestive features for the risk of malignancy, no reliable preoperative predictive factors for malignancy could be identified as regarding to clinical parameters, biological examinations, carcinoembryonic antigen or CA19-9 levels in serum or in pure pancreatic juice, imaging, and cytological methods. Within 40.8 months mean follow-up after surgery (range 2-96 months), three patients (16%), two with malignant and one with benign tumor, had tumor relapse after respectively 7, 27, and 14 months. Margins were positive without malignant features in the two malignant cases and negative in the other case. Tumor relapse was malignant with diffuse spreading in the three cases, and the patients died within 34 months after surgical resection. CONCLUSIONS: Our series and the review of the literature indicate that preoperative indicators of malignancy in IPMT are still lacking. Concerning resection margins, complete tumor resection is usually possible by segmental pancreatectomy. Malignant relapses are not exceptional. Incomplete resection and diffuse or multifocal tumor represent poor prognostic factors. Total pancreatectomy should be considered in such cases.
[Pancreatic intubation ifn pancreas divisum].
AIM: Long-term results of endoscopic pancreatic stenting in pancreas divisum is still debated. The aim of this retrospective study was to evaluate the efficacy of dorsal duct stenting in patients presenting with acute recurrent pancreatitis. PATIENTS AND METHODS: Between 1980 and 1998, among 34 patients presenting with recurrent acute pancreatitis associated with pancreas divisum, 21 were treated by pancreatic stenting during a mean time of 11 months. There were 13 men and eight women (mean age: 50 years). RESULTS: The median follow-up was 50 (range 11-105) months. The number of patients presenting with acute pancreatitis before pancreatic stenting, at the end of stenting and at the end of the follow-up was respectively 21/21 (100%), 2/19 (10%) and 2/18 (11%) (P < 0.01). The number of patients presenting with chronic pain before stenting, at the end of stenting and at the end of the follow-up was respectively 17/21 (80%), 6/19 (31%) and 5/18 (27%) (P = 0.07). The overall morbidity rate was 8/21 patients (38%) including mainly acute pancreatitis (three cases); all but one complication were managed conservatively. CONCLUSION: In patients with pancreas divisum, dorsal duct stenting decreases the rate of recurrent acute pancreatitis but the improvement of chronic pain appears less obvious.
Autologous peripheral blood progenitor cell transplantation with <2 x 10(6) CD34(+)/kg: an analysis of variables concerning mobilisation and engraftment.
INTRODUCTION: This study analyses the factors affecting mobilisation and engraftment in autologous peripheral blood progenitor cell transplantation according to the number of CD34(+) re-infused. MATERIALS AND METHODS: A total of 190 patients underwent mobilisation with G-CSF alone (n=113) or in combination with chemotherapy (n=77). A total of 116 patients (61%) were autografted with <2 x 10(6) CD34(+) cells/kg and 74 patients were transplanted with >2 x 10(6) CD34(+) cells/kg. Rates of granulocyte and platelet recovery were estimated using the product-limit method of Kaplan-Meier and compared using a log-rank test. The Cox regression model was used for the multivariate analysis of factors influencing engraftment. Differences between cohorts were evaluated by one-way ANOVA or Mann-Whitney tests, and multivariate analysis was performed using a stepwise lineal regression. RESULTS: Neutrophil and platelet engraftment was significantly longer with <2 x 10(6)/CD34(+)/kg (12 vs 10 days, P=0.014 and 16 vs 13 days, P=0.0001 respectively). Platelet recovery was affected by exposure to alkylating agents (P=0.04), refractory disease (P=0.02) and AML (P=0.0001), but only the last two variables remained significant in Cox regression (P<0.01). Granulocyte engraftment was longer in CML (univariate, P=0.04) and in refractory disease (multivariate, P=0.02). In patients re-infused with >2 x 10(6)/CD34(+)/kg, the Cox model did not identify prognostic factors for haematopoietic recovery. CONCLUSION: Although mobilisation schedules and disease status influenced not only the yield of progenitor cells, but also the engraftment kinetics, the number of CD34(+) re-infused was the main predictor of haematopoietic recovery. While engraftment succeeded in most of the cases, the re-infusion of >2 x 10(6)/CD34(+)/kg resulted in significantly shorter recovery times.
The detection of alloantibodies against red cells in patients with warm-type autoimmune haemolytic anaemia.
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[Small bowel perforation and occlusion after migration of biliary and cystogastric prosthesis].
We report on two cases of intestinal complications associated with the migration of biliary and cystogastrostomy stents. In the first case, intestinal perforation occurred after migration of an Amsterdam type biliary stent. In the second case, a double pig tail endoprosthesis induced intestinal occlusion which was successfully managed without surgery. Complications after intestinal migration of biliopancreatic stents are very rare and usually involve the colon. Our observations point out the potential gravity of intestinal migration of biliopancreatic stents and, as in the second case, the possible resolution of stent related intestinal occlusion after medical management.
Taenia solium cysticercosis: immunity in pigs induced by primary infection.
The present study demonstrates that pigs experimentally infected with Taenia solium eggs develop resistance to reinfection that lasts at least five months. Thirteen 2-month-old piglets were infected with eggs of Taenia solium. After 5 months, two pigs were euthanized and five were challenged with eggs from a second tapeworm. Nine months after the first infection, six pigs were challenged with a third tapeworm. All 11 challenged pigs were euthanized 2 months after reinfection. In order to confirm the infectivity of the eggs, several piglets were inoculated with each taenia. Two of the five pigs reinfected after 5 months did not develop metacestodes, two showed few caseous non-infective forms and in the fifth pig, 14% of the metacestodes were vesicular and 86% colloidal and caseous. In the six animals challenged 9 months after the first infection, three were heavily infected with vesicular metacestodes and the other three showed only colloid and caseous forms in muscles. All parasites found in brains were vesicular. We conclude that immunity due to primary infection lasts at least 5 months. At 2 months of infection antigens of 24 and 39-42 kDa were the most frequently recognised. In those pigs with only a few caseous cysts in muscles and/or vesicular ones in brains no antibodies were detected.
Hair cell formation in cultures of dissociated cells from the vestibular sensory epithelium of the bullfrog.
HYPOTHESIS: Bullfrog vestibular hair cells are capable of regenerating in vitro. BACKGROUND: Recent studies have established that sensory organs in the inner ear of vertebrates continue to produce hair cells after birth. However, the mechanisms responsible for the regulation of this process are not well understood. The current study reports the development of a novel method for the culture of dispersed cells from the bullfrog inner ear. METHODS: New hair cell formation in this in vitro preparation was shown by sequential photomicroscopy. Studies with the selective marker for mitotic activity 5-bromo-2-deoxyuridine (BrdU) were done to estimate the level of cell proliferation and to quantify postmitotic hair cell formation. Finally, confirmation of cell type was obtained by scanning electron microscopy and by the use of specific markers for hair cells. RESULTS: Once the optimal culture conditions were established in the initial experiments, the formation of new hair cells was directly visualized in all unstained live cultures and fixed preparations without exception. Asymmetric division of progenitor cells, with subsequent differentiation of one of the daughter cells into new hair cells, also was documented by photomicroscopy. Approximately 12% of the cells were labeled with BrdU, of which 6% were hair cells, showing that new hair cell formation was subsequent to mitotic division in vitro. The identity of newly formed hair cells was verified as follows: 1) morphologically by scanning electron microscopy; 2) by positive labeling with phalloidin-rhodamine, a marker for actin; and 3) by positive calmodulin immunocytochemistry. CONCLUSIONS: This study reports the development of an in vitro culture preparation in which undifferentiated epithelial cells proliferate to become new hair cells. Evidence is provided of division of hair cell progenitors and subsequent differentiation of the daughter cells as one of the mechanisms involved in new hair cell formation in the culture preparation. This newly developed cell culture technique provides a powerful tool for further study of the process of hair cell formation in the vestibular end organ.
[Determination of the cytokine level during storage of partially leukocyte-depleted (<0.5 x 10(9)) or totally leukocyte-depleted (<0.5 x 10(6)) platelets].
PURPOSE: To evaluate the levels of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) during the storage of pools of PCs obtained after removing the buffy-coat, in comparison with the amount of leukocytes present in these components. MATERIAL AND METHODS: Blood was collected in quadruple-bag-system containing 63 mL of CPD as anticoagulant and 100 mL of SAG-M solution as additive for the red cells. Approximately twelve hours after collection, blood separation was made automatically by Compomat (NPBI) and platelet concentrates were prepared from the buffy-coat fraction. Five or six PCs were mixed to obtain a pool (n = 28). Eight pools were WBC reduced by filtration (PXL-8, Pall España). Before storage a sample of each pool was obtained in order to count platelets and WBC as basal values. All kind of pools were stored at room temperature with continuous agitation during a period of 10 days. Volumes were measured by weight and specific gravity. Platelets and leukocytes were counted in the Coulter-counter (STKR Counter. Izasa) or in Nageotte chamber for the filtered products. On days 1, 4 and 7 interleukins were measured by ELISA (EASIA Kits, Medgenix Diagnostics, Brussels), Lecture was done at 450 nm using a spectophotometer (ANTHOS 2001). Lower limits of sensitivity were 2 pg/mL for IL-1 beta and 3 pg/mL for IL-6 and TNF-alpha according to the manufacturer. Wilcoxon test was used for statistical analysis. RESULTS: The average volume of the pools was 460 mL and 374 for the filtered ones. The total platelet amount was 3.63 x 10(11) and 2.8 x 10(11) respectively, with a WBC contamination of 380 x 10(6) and 0.54 x 10(6) for the filtered. The yield of platelets after filtration was 84% with a loss of 99.90% of WBC (3-log). The measures of interleukins were not homogeneous, but a great variability was found shown among the different pools, not always in relationship with the amount of leukocytes. The levels of IL-1 beta were 3.58 pg/mL on day 1, 6.36 pg/mL on day 4 and 8.76 pg/mL on day 7 (p < 0.005). For the IL-6 we found 13.08 pg/mL on day 1, 15.43 pg/mL on day 4 and 19.77 on day 7 (p < 0.05). For the TNF-alpha, 13.65 pg/mL an day 1,24.33 pg/mL on day 4 and 30.10 pg/mL on day 7 (p < 0.05). In the filtered pools the detections of IL-1 beta and IL-6 were always under the sensibility threshold, but there was an increment of TNF-alpha on day 7 (16.91 pg/mL). Microbiologic cultures were always negative. CONCLUSION: The accumulation of IL-1 beta, IL-6 and TNF-alpha is not prevented by the fact of removing the buffy-coat layer when preparing PCs, although these levels are considerably lower in comparison with those obtained by the PRP technic. Filtration of pooled PCs avoids the presence of these cytokines except TNF-alpha, where a low amount can be detected.
[Fatal sub-fulminant hepatitis caused by cyproterone acetate. A new case].
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Posttransfusion hepatitis after induction chemotherapy in acute nonlymphoblastic leukemia: implications for long-term management and outcome.
BACKGROUND: The purpose of this study was to evaluate 1) the incidence of hepatitis and its influence on the clinical management of and outcome in acute nonlymphoblastic leukemia (ANLL) patients in first complete remission and 2) the impact of routine hepatitis C virus screening on the incidence of hepatitis in these patients. STUDY DESIGN AND METHODS: Clinical and blood bank charts were reviewed for 65 consecutive ANLL patients between 1985 and 1993 who achieved complete remission after a course of daunomycin and cytarabine (cytarabine: 200 mg/m2/day x 7 days in continuous infusion; daunomycin: 60 mg/m2/day for the first 3 days of the 7, as a bolus). RESULTS: Only 43 percent of patients who developed hepatitis completed the scheduled therapy. Hepatitis did not decrease the probability of relapse (66 +/- 9% vs. 66 +/- 11%), but patients with changes in planned treatment, due to hepatitis or other causes, tended to have a higher relapse rate than patients without changes in consolidation therapy (56.5% vs. 40.4%; p = 0.10). This did not result in a decrease in disease-free survival, however, because of the higher number of treatment-related deaths in the patients without hepatitis (who completed the therapy). Over the period from 1985 through 1989, the 6-month actuarial probability of developing hepatitis was 42 percent. However, since 1989, when hepatitis C screening of blood donors was implemented, the incidence was reduced to 12.5 percent (p < 0.05), in spite of greater transfusion support (172 +/- 46 vs. 89 +/- 53, p < 0.01). No new cases of hepatitis were observed after the introduction of second-generation hepatitis C virus assays. CONCLUSION: Hepatitis precludes the use of consolidation therapy in about half of ANLL patients, resulting, in the experience described here, in a trend toward a higher rate of relapse. Hepatitis C virus screening of blood components reduces the incidence of hepatitis in ANLL patients.
Filgrastim post-chemotherapy mobilizes more CD34+ cells compared to its use during steady-state haemopoiesis.
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Circulating stem cell collection in lymphoma and myeloma after mobilization with cyclophosphamide and granulocyte colony-stimulating factor for autologous transplantation.
We report the results of 72 leukapheresis procedures performed for autologous peripheral blood stem cell collection in 18 patients with lymphoma and myeloma, after combined mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF). The numbers of mononuclear cells (MNCs), CD34+ cells and granulocyte-macrophage colony-forming units (CFU-GM) either in the peripheral circulation (preleukapheresis sample) or in the product obtained from leukapheresis (leukapheresis sample) were evaluated. A highly superior proportion of CD34+ cells (14-fold) and CFU-GM (5-fold) resulted from the mobilization therapy. CFU-GM and CD34+ cells were highly enriched with respect to all MNCs (relative recoveries: 2.13, range 0.3-41, and 1.08, range 0.2-8.5, respectively) due to an additional mobilization effect by the leukapheresis procedure. Also, a relatively strong linear correlation between the three different parameters was found in the leukapheresis product (CD34+:CFU-GM, r = 0.81; MNCs:CD34, r = 0.69; MNCs:CFU-GM, r = 0.75; CFU-GM:CD34+, and MNCs, r = 0.85). Our data suggest that the number of MNCs and CD34+ cells obtained after combined mobilization with cyclophosphamide and G-CSF can be used as predictor of the number of granulomonocytic progenitors.
Response diversity of pontine and deep cerebellar nuclear neurons to air puff stimulation of the eye in the alert cat.
The discharge of antidromically identified brainstem and cerebellar nuclear neurons involved in the corneal reflex was recorded in the alert cat during corneal air puffs. Eye movements were measured with the search coil technique. Recorded sensory, motor, reticular formation and cerebellar nuclear neurons showed a wide diversity in latencies and patterns of response to air puff stimulation. This diversity suggests that each part of the circuit may contribute different properties to information processing for the corneal reflex, for sustained eyelid closure and, possibly, for the classical conditioning of the nictitating membrane response.
Serum alanine aminotransferase (ALT) assay and incidence of posttransfusion non-A,non-B hepatitis.
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[Prevalence of high ALAT and serologic markers of hepatitis B virus in blood donors incriminated in non-A, non-B posttransfusion hepatitis].
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