Biomedical subjects
Publications and source records attributed to J Rodriguez.
Wolff-Parkinson-White syndrome is important for the anesthesiologist because the sudden development of tachyarrhythmias may result in deleterious hemodynamic changes. We describe an episode of reciprocating tachycardia triggered by the insertion of the guide wire during central venous cannulation in a patient with this syndrome.
This study evaluated the efficacy of allogeneic bone marrow transplantation (AlloBMT) in eight patients who had chronic lymphocytic leukaemia (CLL) in Richter's transformation. Five patients were in resistant relapse and three others were in sensitive or untreated relapse. Three out of eight patients (38%) were alive and in remission at 14 months, 47 months and 67 months respectively. Two of these three patients, including one with an unrelated-donor transplant and a prior, unsuccessful autologous transplantation, received a non-myeloablative preparative regimen. These data suggest that, compared with conventional chemotherapy, AlloBMT improves the prognosis for patients with Richter's syndrome. Further study of a larger number of patients is needed to confirm these results.
2D gel electrophoresis followed by microsequencing has been used to purify and identify a protein (catalogued in the database as SSP5111) from Drosophila wing imaginal discs of third instar larvae that showed significant differences in their level of expression when compared with other imaginal discs of the same age. The microsequence data showed identity with amino acids encoded by the human proliferation association gene, pag, which is a thiol-specific antioxidant. By virtue of this homology we have cloned and sequenced two cDNAs that appear to define the peroxiredoxin family of Drosophila. One of them, Jafrac1, encodes the SSP5111 protein searched, had 194 amino acids and mapped in the region 11E in the X chromosome. The other, Jafrac2, encodes a protein of 242 amino acids and mapped in the region 62F in the 3 L chromosome. Both new peroxidases contain two conserved cysteines and share homology with other peroxidases that extends over the entire sequence and ranges between 47% and 76%. An antiserum raised against the SSP5111 protein showed significant changes in the amount of protein in different stages of Drosophila development, being a major product in early embryos. In 2D gels the antibody not only recognizes the SSP5111 polypeptide but also a related one (catalogued in the database as SSP6107) that exhibits identical amino-acid sequence over at least 85% of its sequence. The data also suggest that the SSP5111 polypeptide could be a maternal-effect product.
BACKGROUND: Foods from the Rosaceae botanical family have been increasingly reported as causes of allergic reaction. Patients frequently have positive skin tests or radioallergosorbent test results for multiple members of this botanical family. OBJECTIVE: Our purpose was to investigate the clinical cross-reactivity assessed by double-blind, placebo-controlled food challenge (DBPCFC) of Rosaceae foods (apricot, almond, plum, strawberry, apple, peach, and pear). METHODS: Thirty-four consecutive adult patients complaining of adverse reactions to Rosaceae were included in the study. Skin prick tests and CAP System (FEIA) were performed with Rosaceae foods in all patients. Clinical reactivity to Rosaceae was systematically evaluated by open food challenges (OFCs), unless there was a convincing history of a recent severe anaphylaxis. Positive reactions on OFCs were subsequently evaluated by DBPCFCs. RESULTS: Twenty-six and 24 patients had positive skin prick tests and CAP FEIA with Rosaceae, respectively; from these 88% and 100% had positive tests with >/=2. No evidence of clinical reactivity was found in 66% percent of positive skin prick tests and 63% of positive specific IgE determinations to fruits. A total of 226 food challenges (including OFC and DBPCFC) were performed in the 28 patients with positive skin prick tests or CAP System FEIA. Of 182 initial OFCs carried out, 26 (14%) reactions were confirmed by DBPCFCs. Overall, 40 reactions were considered positive in 22 patients with positive skin tests or CAP FEIA. Thirty-eight reactions had been previously reported, the remaining two were detected by systematic challenges. Most reactions were caused by peach (22 patients), apple (6), and apricot (5). Ten patients (46%) were clinically allergic to peach and other Rosaceae. CONCLUSION: Positive skin test and CAP System FEIA should not be taken as the only guide for multi-species dietary restrictions. Nevertheless, the potential clinical allergy to other Rosaceae should not be neglected. If the reported reaction is confirmed, current tolerance to other Rosaceae should be precisely established unless there has been ingestion without symptoms after the reaction.
BACKGROUND: Few studies have evaluated IgE-mediated hypersensitivity to melon with details of clinical reactions confirmed by double-blind, placebo-controlled, food challenges (DBPCFCs). OBJECTIVE: We sought to investigate clinical features (type and severity of reactions, age at onset, results of skin prick and in vitro tests, and incidence of other allergic diseases and associated food allergies) of acute allergic reactions to melon confirmed by DBPCFCs. METHODS: Fifty-three consecutive adult patients complaining of adverse reactions to melon were included in the study. Skin prick tests and detection of specific IgE were performed in all patients with melon, avocado, kiwi, banana, chestnut, latex, pollen, and other offending foods. Patients first underwent an open food challenge, unless they had a convincing history of severe anaphylaxis. Positive open food challenge reactions were subsequently evaluated by DBPCFCs. RESULTS: Actual clinical reactivity was confirmed in 19 (36%) of 53 patients. The most frequent symptom was oral allergy syndrome (n = 14), but two patients experienced life-threatening reactions, including respiratory symptoms and hypotension. The positive predictive value for a skin prick test was 42%, and that for specific IgE measurement was 44%. Forty-five reactions to 15 other foods were confirmed in 18 patients. The most common foods associated with melon allergy were avocado (n = 7), banana (n = 7), kiwi (n = 6), watermelon (n = 6), and peach (n = 5). Onset of melon-induced allergic symptoms occurred from 6 to 45 years (median, 20 years), preceded by seasonal rhinitis, asthma, or both in 88% (15/17). CONCLUSION: About one third of reported reactions to melon are confirmed by means of DBPCFC, which has been proven to be the most reliable procedure in the diagnosis of clinical fruit allergy. Isolated melon allergy is rare, with most patients either having allergic rhinitis, asthma, or both and associated food allergies.
BACKGROUND: Atherosclerosis associated with hyperlipidaemia is a major cause of morbidity and mortality after renal transplantation. Atorvastatin is a new HMG-CoA reductase inhibitor that has shown a favourable profile of lipid reduction when compared with other statins. The aim of the study was to assess the efficacy and safety of atorvastatin in hypercholesterolaemic renal transplant patients who had previously been on statins with little or no effect. METHODS: Atorvastatin, 10 mg/day, was administered to 10 renal transplant recipients with persistent hypercholesterolaemia (total cholesterol >240 mg/dl) for a period of 3 months. All of them had already been on statins for at least 3 months. RESULTS: Atorvastatin exerted a satisfactory lipid-lowering effect in seven of 10 patients. On average, serum total cholesterol (311+/-36.2 vs 253+/-48.8 mg/dl; P:<0.05) and serum LDL cholesterol (184+/-30.9 vs 136+/-22.9 mg/dl; P:<0.05) significantly decreased after atorvastatin therapy, whereas serum HDL cholesterol (86+/-14.6 vs 84+/-22.1 mg/dl) remained unchanged. In five subjects with a baseline serum triglyceride level above 150 mg/dl, a marked reduction in triglycerides was also observed (261+/-80.3 vs 193+/-53.3 mg/dl; P:<0.05). Lp(a) did not significantly change (13+/-16.3 vs 15+/-23.9 mg/dl, P:=NS). Serum creatinine, transaminases, creatinine phosphokinase (55+/-21.3 vs 56+/-29.4 IU/l) and fasting cyclosporin A levels were unaffected. The drug was generally well tolerated and neither myositis nor rhabdomyolysis was reported. CONCLUSION: Short-term therapy with the new HMG-CoA reductase inhibitor, atorvastatin, appears to be effective in lowering atherogenic lipids in renal transplant patients who had had little or no response to other statins.
Penaeidins are members of a new family of antimicrobial peptides isolated from a crustacean, which present both Gram-positive antibacterial and antifungal activities. We have studied the localization of synthesis and storage of penaeidins in the shrimp Penaeus vannamei. The distribution of penaeidin transcripts and peptides in various tissues reveals that penaeidins are constitutively synthesized and stored in the shrimp haemocytes. It was shown by immunocytochemistry, at both optical and ultrastructural levels, that the peptides are localized in granulocyte cytoplasmic granules. The expression and localization of penaeidins were further analysed in shrimp subjected to microbial challenge. We found that (1) penaeidin mRNA levels decrease in circulating haemocytes in the first 3 hours following stimulation and (2) an increase in plasma penaeidin concentration occurs after microbial challenge, together with (3) a penaeidin immunoreactivity in cuticular tissue, which can be related to the chitin-binding activity we demonstrate here for penaeidins.
Aggressive mantle cell lymphoma has a poor prognosis with current therapy and occurs frequently in an elderly population which cannot receive stem cell transplantation. Newer aggressive therapies are needed. In this study, 25 consecutive previously untreated patients 65 years or older with MCL were enrolled in two sequential phase II trials. The program included fractionated cyclophosphamide 1,800 mg/m2 administered with doxorubicin, vincristine and dexamethasone (hyper-CVAD), alternating every 3 weeks with high doses of methotrexate and cytarabine (M-A) for up to 8 cycles. Cytarabine was given as 1 gram/m2/dose. Six of 14 patients tested (50%) presented with gastrointestinal (GI) involvement, but only one had GI symptoms. The overall response rate was 92% (95% C.I. 73-99) and the complete remission (CR) rate was 68% (95% C.I. 46-85). With a median follow-up of 17 months, the median FFS for the entire group is 15 months. Hematologic toxicity was significant but only 5% of the cycles were associated with grade 3 infection. Treatment-related death occurred in 2 patients. In conclusion, GI involvement by MCL is common in this age group. Hyper-CVAD alternating with M-A with adjustment of the cytarabine is an active regimen in this elderly group of patients with untreated MCL and the toxicity is manageable. Strategies for eradicating minimal residual disease are still needed.
Natural Killer (NK) cell lymphomas, which include the nasal and the "nasal type" varieties, are defined as angiocentric lymphomas in the revised European American Lymphoma (R.E.A.L.) classification. This group of diseases is rare in the United States and Europe but is more common in Asia and Central America. It is associated with the Epstein-Barr virus (EBV) and its response to treatment and prognosis are usually very poor. The aim of this study was to describe our experience with 13 patients with angiocentric lymphomas seen at The University of Texas M. D. Anderson Cancer Center (UTMDACC) over the last 14 years. Thirteen patients with a diagnosis of nasal NK cell lymphoma were treated at UTMDACC from 1987 to 1999. Eleven patients were treated initially with doxorubicin based chemotherapy with or without radiotherapy. One patient received interferon (IFN)-alpha and vitamin A and another methotrexate, vincristine, L-Asparaginase, and radiotherapy. The median age was 44 years (range 15-76); there were four women and nine men. All patients presented with local disease involving the sinonasal region. Typical immunophenotypes expressing CD2+, CD3- and CD56+ surface markers as well as non rearrangement of T-receptors were present in all patients. Eight patients (62%) responded to therapy; six (46%) with complete response (CR) and two (16%) with partial response (PR). Five patients (38%) were alive, four with no evidence of disease (NED) at 1, 2, 3, and 9 years after treatment, and one patient was alive with disease (AWD) at the time of publication. One patient died while in CR from complications from allogeneic bone marrow transplant. Six patients had disease progression to extranodal sites including: testis (2), central nervous system (2), lung (1), bone marrow (2), liver (2), peripheral blood (2), and skin (2). In conclusion, the response to doxorubicin-containing regimens is inferior to that of patients with other non-Hodgkin's lymphomas and similar prognostic factors. Because the disease is associated with EBV virus in 90%-100% of the cases and the prognosis is poor, innovative therapies should be tried including immunotherapy that targets the expression of EBV by the tumor with or without myeloablative procedures.
Our objective was to investigate the prognostic significance of serum beta-2 microglobulin (B2M) levels among patients with chronic myelogenous leukemia (CML). All patients with Philadelphia chromosome-positive early chronic phase CML (i.e., within 1 year of diagnosis) treated with IFN alpha-based therapy at the M. D. Anderson Cancer Center between 1980 and 1997, in whom pretreatment B2M levels were available, were investigated. Two hundred one patients were evaluable. Their median B2M was 2.2 mg/dl (range, 1.1-20 mg/dl). Serum B2M levels were associated with other variables of prognostic significance, including age, spleen size, WBC count, percentage of peripheral and marrow blasts, and percentage of marrow basophils. Patients with B2M levels >2.9 mg/dl (ie., the upper quartile of the distribution) had a significantly lower rate of major cytogenetic response compared to those in the lower three quartiles (20 versus 52%; P < 0.01). They also had a shorter survival, with a 5-year survival rate of 48%, compared with 75% for those in the lower quartiles (P = 0.01). High B2M levels (>2.9 mg/dl) could identify a group of patients with an adverse outcome within patients in stage I disease (P = 0.02). Results for patients in stages 2-4 were inconclusive because of the small number of patients in these groups. We conclude that serum B2M levels are an important, and probably independent, prognostic factor for patients with CML in early chronic phase treated with IFN-based therapy.
This study evaluates 706 patients with 835 primary total hip replacements documented in a prospective fashion in a multicenter study with respect to correlation between heterotopic ossification (HO) and clinical outcome. Only patients without prophylaxis against HO entered the study. The mean clinical and radiological follow-up was 3.1 years (+/- 0.7). Heterotopic ossification was noted in 47% of all total hips replaced. It was graded as mild (Brooker I) in 29.1%, moderate (Brooker II) in 12.7%, and severe (Brooker III and IV) in 5.2%. All clinical parameters investigated were significantly affected with the increasing amount of heterotopic ossification. The strongest correlation was found in flexion range and spreading distance. Both factors were significantly decreased with higher degrees of ossification. The other clinical parameters investigated, walking capacity, limp, and use of analgesics, were altered to a lesser extent and only with higher degrees of heterotopic bone formation. Finally, patient satisfaction was significantly influenced by the degree of heterotopic ossification and dropped from almost 90% good or excellent patient satisfaction in the non-ossification group to less than 30% in the group with severe ossification.
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Autocatalytic activation of initiator caspases is the link between pro-apoptotic signals and the destruction machinery of apoptosis. Activation of caspase-9, which mediates oncogene and drug-induced apoptosis, requires binding to the protein APAF-1. We found that the proteolytic activity of caspase-9 in a complex with APAF-1 is several orders of magnitude higher than that of the free enzyme. Thus, this complex functions as a holoenzyme in which caspase-9 is the catalytic subunit and APAF-1 its allosteric regulator. We argue that caspase-9 is activated by allosteric regulation and suggest that this mechanism is common for other initiator caspases.
The caspase recruitment domain (CARD) of Apaf-1 binds to the CARD of caspase-9 to trigger a proteolytic cascade that leads to apoptotic cell death. We report the crystal structure of the Apaf-1 CARD at 1. 3 A resolution, solved in a two-element multiwavelength anomalous dispersion (MAD) X-ray diffraction experiment. This CARD adopts a six-helix bundle fold with Greek key topology surrounding an extensive hydrophobic core. This fold, which we call the "death fold", is found in other domains that mediate interactions in apoptotic signaling despite very low sequence identity. From a structure-based alignment, we identify conserved patterns that characterize the death fold and its subclasses. Like the Ig-fold, it provides a rigid structural scaffold upon which diverse recognition surfaces are assembled.
Formulations of a polymeric delivery system containing a 75/25 poly(DL-lactide-co-caprolactone dissolved in either N-methyl-2-pyrrolidone or dimethyl sulfoxide were injected both subcutaneously (SC) and intramuscularly (IM) into rhesus monkeys. Each monkey received an SC and IM injection of each of the two formulations, for a total injection volume of 4 mL. The monkeys were observed daily for overt signs of toxicity, and after 4 weeks biopsies of each implant site were fixed, stained, and evaluated histologically for tissue reaction to the polymer system. Tissue response was graded upon the presence and level of fibrous connective tissue and inflammatory cell infiltrate. The polymer formulations appeared to be safe, as the animals remained healthy and active throughout the study with no changes in food or water consumption, weight loss, or abnormal behavior observed. Tissue response to both formulations was considered mild and similar to that for other biodegradable polymers, in that the reaction was limited to tissue immediately adjacent to the residual polymer fragments and consisted of a mild fibroplasia with the presence of a few lymphocytes and macrophages. There were no differences between the two formulations in tissue response, and both formulations were considered acceptable for use as injectable implant systems.
Patients with Hodgkin's disease, which is either refractory or recurs after frontline chemotherapy with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or both regimens, generally have a poor prognosis. High-dose chemotherapy with autologous marrow or stem cell rescue (ABMT) is now a widely used salvage strategy in these patients. In this study, our objective was to determine the response rate to ASHAP (Adriamycin = doxorubicin, Solumedrol = methylprednisolone, High-dose Ara-C = cytosine arabinoside, and Platinum = cisplatinum), in a group of patients with Hodgkin's disease with such poor risk characteristics. The treatment was intended as a brief tumor reducing program before ABMT. Fifty-six patients with diagnosed relapsed or primary refractory Hodgkin's disease underwent this treatment. The program consisted of the administration of two cycles of ASHAP chemotherapy (doxorubicin 10 mg/m2/d intravenous (IV) continuous infusion (CI) over 24 hours, days 1 to 4; methylprednisolone 500 mg/d IV over 15 minutes daily for 5 days; cisplatinum 25 mg/m2/d IV CI over 24 hours, days 1 to 4; cytosine arabinoside 1.5 g/m2/d IV over 2 hours on day 5). After two courses of ASHAP the patients were evaluated for response, including a gallium scan test. Patients with progressive disease were taken off the study. Those with responding or stable disease received a third course of ASHAP, followed by consolidative treatment with ABMT. There were 19 complete responses (34% CR), 20 partial responses (36% PR), and 17 treatment failures, including 8 with minor responses and 9 with disease progression. Thus, in total there were 39 responses out of 56 patients (CR + PR = 70%). Myelosuppression was the main toxicity. There were no deaths due to toxicity. At this time, 23 patients are alive. There were 31 deaths due to disease progression and 2 due to other causes. The initial response to ASHAP before subsequent ABMT consolidation treatment correlated with survival. All 17 patients in whom ASHAP failed to achieve a response have died. The presence of B symptoms at relapse, and a duration of response to the last regimen of </=6 months, predicted a poor response to ASHAP. A short program of treatment with ASHAP is an effective tumor debulking approach in patients previously treated with both or either ABVD and MOPP, before ABMT.
We have previously demonstrated that mild traumatic brain injury (TBI) of the right parietal cortex results in a relatively selective deficit in conditioned fear responding. However, this behavioural deficit is very consistent and unrelated to the extent of the cortical necrotic lesion. We were therefore interested in determining if other brain regions might show a consistent response to mild TBI, and therefore, more reliably relate to the behavioural change. Increased expression of inducible transcription factors (ITFs) has been used to study which brain regions respond to a variety of events. In the present study, we examined the expression patterns of immunoreactivity (IR) for four ITFs (c-Fos, c-Jun, JunB, and Krox-24) at 3 h after mild fluid percussion TBI. Changes in ITF expression were only observed ipsilateral to the side of TBI. The clearest changes were observed in brain regions known to be involved in conditioned fear responding, such as the amygdala complex and hippocampal formation and several cortical regions. In contrast, no changes in IR for any of the ITFs were observed in the striatum, nucleus accumbens, nucleus basalis magnocellularis, septum or periacqueductal grey. Unlike the extent of visible damage to the cortex at the site of impact, the overexpression of ITFs showed a notable consistency between animals subjected to TBI. This consistency in regions known to be involved in conditioned fear responding (i.e., amygdala complex and hippocampal formation) lead us to suggest that it is these changes, rather than the more variable cortical necrotic lesion, that is responsible for the behavioural deficits we observe following mild TBI. Importantly, our results demonstrate that like the hippocampus, the amygdala is a sub-cortical structure particularly sensitive to the effects of mild brain trauma and underline the fact that cerebral regions distant from the location of the fluid impact can be affected.
It is debated whether follicular large cell lymphoma (FLCL) has a clinical behavior that is distinct from indolent follicular lymphomas, and whether there is a subset of patients who can be potentially cured. We report here our experience with 100 FLCL patients treated at our institution since 1984 with three successive programs. We evaluated the predictive value of pretreatment clinical features, including two risk models, the Tumor Score System and the International Prognostic Index (IPI). With a median follow-up of 67 months, the 5-year survival is 72% and the failure-free survival (FFS) is 67%, with a possible plateau in the FFS curve, particularly for patients with stage I-III disease. Features associated with shorter survival included age >/=60, elevated lactic dehydrogenase (LDH) or beta-2-microglobulin (beta2M), advanced stage, and bone marrow involvement. Stage III patients had significantly better survival than stage IV patients (P <.05). By the IPI and Tumor Score System, 80% of the patients were in the lower risk groups; both systems stratified patients into prognostic groups. Patients with FLCL have clinical features and response to treatment similar to that reported for diffuse large cell lymphoma. Prognostic risk systems for aggressive lymphomas are useful for FLCL. A meaningful fraction of patients may possibly be cured when treated as aggressive lymphomas.