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Biomedical subjects

L Feldman

Publications and source records attributed to L Feldman.

At least 37 records · Page 2Linked to original sources
PubMed1999

Reactivation of chronic Chagas' disease following allogeneic bone marrow transplantation and successful pre-emptive therapy with benznidazole.

This report shows the early detection of reactivation of chronic Chagas' disease (CCd) in a 27-year-old man with chronic myelogenous leukemia undergoing allogeneic bone marrow transplantation (ABMT). Pre-emptive therapy with benznidazole during a period of 7 weeks led to a rapid recovery of the patient, who remains free of parasitemia 2 years after the bone marrow transplantation.

Adult↗
PubMed1999

Escherichia coli O157:H7 outbreak associated with an improperly chlorinated swimming pool.

A cluster of gastrointestinal illnesses, including one case of hemolytic-uremic syndrome and one culture-confirmed Escherichia coli O157:H7 infection, followed a trailer park pool party. We interviewed a cohort of party attendees and park residents. A primary case was defined as the first gastrointestinal illness within a household between 5 July and 20 July in which the titer of IgG antibody to E. coli O157 (if determined) was elevated. Of 51 party attendees and trailer park residents, 18 developed a gastrointestinal illness, including 10 who met the definition of a primary case. Swimming in the pool significantly increased the risk of primary illness (relative risk = 6.3; 95% confidence interval = 1.8-18.9). No other exposure was significantly associated with primary illness, after pool exposure was controlled for. The implicated pool had little to no chlorine added during the period of 4-10 July. This outbreak provides new evidence of the importance of proper pool maintenance in controlling the spread of E. coli O157:H7.

Chlorides↗
PubMed1998

Expansion of clonotypic T-cell populations in the peripheral blood of asymptomatic Gran Chaco Amerindians infected with HTLV-IIB.

Peripheral blood mononuclear cells from asymptomatic HTLV-II-infected and uninfected Gran Chaco Amerindians were analyzed using polymerase chain reaction (PCR) for expansions of T-cell receptor (TCR) V-beta gene clonotypes. Analyses were performed using primer pairs designed to identify expanded T-cell familial clonotypes based on their unique TCR beta gene rearrangements. Of the 30 HTLV-IIB-positive samples tested, five showed evidence of V-beta clonotypic T-cell expansion. Of the five expansions, two were monoclonotypic and the remaining three were oligoclonotypic. In comparison, 30 HTLV-II-negative Amerindians showed no evidence of clonotypic T-cell expansion. Amplified DNA from one of the monoclonotypic samples was subsequently cloned and sequenced and was found to have uniform variable/ diversity/joining sequences confirming its unique monoclonal T-cell expansion. This method of detecting clonal TCR beta gene rearrangements has the advantage over traditional Southern blot techniques of being more sensitive and specific even with suboptimal specimens. The prognostic significance of clonotypic T-cell expansion in a group such as the HTLV-II-infected Gran Chaco Amerindians remains to be determined.

Argentina↗
PubMed1998

Human erythropoietin dimers with markedly enhanced in vivo activity.

Human erythropoietin, a widely used and important therapeutic glycoprotein, has a relatively short plasma half-life due to clearance by glomerular filtration as well as by other mechanisms. We hypothesized that an erythropoietin species with a larger molecular size would exhibit an increased plasma half-life and, potentially, an enhanced biological activity. We now report the production of biologically active erythropoietin dimers and trimers by chemical crosslinking of the conventional monomeric form. We imparted free sulfhydryl residues to a pool of erythropoietin monomer by chemical modification. A second pool was reacted with another modifying reagent to yield monomer with maleimido groups. Upon mixing these two pools, covalently linked dimers and trimers were formed that were biologically active in vitro. The plasma half-life of erythropoietin dimers in rabbits was >24 h compared with 4 h for the monomers. Importantly, erythropoietin dimers were biologically active in vivo as shown by their ability to increase the hematocrits of mice when injected subcutaneously. In addition, the dimers exhibited >26-fold higher activity in vivo than did the monomers and were very effective after only one dose. Dimeric and other oligomeric forms of Epo may have an important role in therapy.

Animals↗
PubMed1998

Frontal dysfunction in neurologically normal chronic alcoholic subjects: metabolic and neuropsychological findings.

BACKGROUND: Neuropsychological and imaging studies suggest that frontal dysfunction may occur in apparently normal chronic alcoholic subjects. METHODS: To investigate this issue further, we performed neuropsychological and fluorodeoxy-glucose-PET studies in 17 chronic alcoholics without patent neurological and psychiatric complications. RESULTS: Metabolic abnormalities were found in the mediofrontal and in the left dorsolateral prefrontal cortex, but not in the orbitofrontal cortex. Neuropsychological testing revealed significantly reduced verbal fluency and impaired performance on the Stroop test. The mediofrontal hypometabolism correlated with the reduction in verbal fluency and the time necessary to perform the interference condition of the Stroop test. The left dorsolateral prefrontal hypometabolism correlated with the number of errors on the Stroop test. CONCLUSION: These data indicate that circumscribed frontal dysfunctions may occur in chronic alcoholic subjects before clinically obvious neurological complications, and may account for some of the alcohol-related neuropsychological and behavioural impairments.

Adult↗
PubMed1998

Arterial response to mild balloon injury in the normal rabbit: evidence for low proliferation rate in the adventitia.

BACKGROUND: The role of constrictive remodeling, spasm and proliferation (particularly in the adventitia) in the genesis of chronic lumen narrowing after balloon injury remains under debate. This study analyzed the time course of these components following mild injury in normal arteries. METHODS: Iliac injury was induced by balloon overstretch in 32 rabbits, sacrificed at timed intervals from day 3 to 28. Angiographic response to nitrates, morphometric, immunohistochemical and biochemical analysis were performed at each time point. RESULTS: Quantitative angiography showed a decrease in lumen diameter and no change in response to nitrates over time. On morphometric analysis, remodeling was usually constrictive, appeared as early as day 3 and was responsible for 69+/-14% of the histologic lumen area stenosis at day 28. Constrictive remodeling was correlated negatively to intimal hyperplasia (r= 0.51, P< 0.002) and positively to the lumen area stenosis (r= 0.92, P< 0.0001). Macrophages (labeled by anti-RAM 11 antibodies) were very rare at all time points. Immunohistochemistry identified a high rate of proliferating smooth muscle cells in the media (13+/-7%) and intima (49+/-8%) at day 7, which decreased rapidly. Proliferating cells in the adventitia were rare (3+/-2% at day 7). The number of proliferating cells was time-dependent (r= 0.82, P< 0.0001) and related to cyclin A mRNA measured by reverse transcription-polymerase chain reaction (r= 0.84, P< 0.0001). CONCLUSIONS: In this model, luminal loss was mainly caused by constrictive remodeling rather than intimal hyperplasia. Constrictive remodeling appeared early and was not time-dependent. Macrophages, spasm and adventitial proliferation did not contribute to this constrictive remodeling.

Angioplasty, Balloon↗
PubMed1998

[Gene therapy of restenosis].

Although angioplasty has undergone considerable development, restenosis remains an unsolved problem. No drugs have been proved effective in the prevention of restenosis. Prophylactic stenting is the only treatment with some efficacy. The pathophysiology of restenosis involves both intimal hyperplasia with a major proliferative component at the dilated site and geometric constrictive remodeling of the artery. Stenting seems to prevent the remodeling but does not prevent and may even worsen the intimal hyperplasia. Gene therapy may be effective in preventing the proliferative component of the intimal hyperplasia: therapeutic genes can be delivered locally to the arterial wall cells at the dilated site during or immediately after angioplasty, using viral (e.g., adenoviruses) or nonviral vectors. The main candidate genes stimulate a variety of endogenous mechanisms whose effects consist in inhibition of smooth muscle cell proliferation (Rb gene); sensitization of proliferating cells to the effects of cytotoxic substances, thus allowing selective chemotherapy (HSV-tk gene); or stimulation of reendothelization (VEGF gene). Other genes have also yielded promising results (ecNOs, p21, Coxl, etc.). Clinical application of these techniques cannot be envisioned until studies are available proving that the delivery methods (transfer vectors or local delivery systems) are completely safe, and that the candidate genes are effective in "realistic" models. If these hurdles are cleared successfully, preventive gene therapy for gene restenosis may well become a clinical reality.

Angioplasty, Balloon, Coronary↗
PubMed1997

Reduction of restenosis after angioplasty in an atheromatous rabbit model by suicide gene therapy.

BACKGROUND: Gene delivery of the thymidine kinase (tk) gene combined with ganciclovir (GCV) limits intimal hyperplasia after abrasion of normal arteries. However, the low efficiency of adenoviral-mediated gene transfer to atherosclerotic arteries has raised concerns about the applicability of this strategy to the prevention of restenosis. METHODS AND RESULTS: A replication-defective adenoviral vector expressing tk (Ad-RSVtk) demonstrated selective toxicity toward GCV-treated arterial smooth muscle cells, with oligonucleolytic cleavage suggesting apoptosis. In vivo, after demonstration of tk expression after Ad-RSVtk delivery, the combination of Ad-RSVtk followed by GCV was tested in a rabbit model of angioplasty of atheromatous iliac arteries. Angioplasty (8 atm, 20 minutes) was performed by use of a hydrogel balloon coated with Ad-RSVtk (4x10(9) plaque forming units). GCV was infused (25 mg.kg(-1) I.V. BID) from days 2 through 7 after angioplasty in 8 of 12 rabbits. Four weeks later, morphometric analysis demonstrated a reduced intima-to-media ratio in the group receiving combination therapy compared with Ad-RSVtk alone (3.0+/-1.2 versus 5.2+/-0.5, P<.018). GCV per se had no effect on intimal hyperplasia after arterial injury. CONCLUSIONS: In vitro, Ad-RSVtk demonstrates selective toxicity toward GCV-treated arterial smooth muscle cells involving apoptosis. In vivo, GCV conditions reduction of neointimal formation after percutaneous delivery of Ad-RSVtk during angioplasty of atheromatous arteries.

Angioplasty, Balloon↗
PubMed1997

Measuring postoperative complications in general surgery patients using an outcomes-based strategy: comparison with complications presented at morbidity and mortality rounds.

BACKGROUND: This study was undertaken to compare the incidence of adverse postoperative outcomes recorded in a prospective general surgery database with that identified through weekly morbidity and mortality (M&M) rounds and to measure the impact of feedback of information to the providers of care. METHODS: Data were collected on patients admitted to one general surgery service between October 1, 1995, and May 15, 1996, and recorded in a computer database. Postoperative complications were graded in severity from I (minor) to IV (mortality). RESULTS: Of 479 admissions entered into the database during the study period, 325 (311 patients) led to operations and were further analyzed. Admissions resulting in complications were associated with longer hospital stays, regardless of complication grade, compared to uncomplicated admissions (p < 0.01). A total of 29 of 106 patients with postoperative complications were presented at M&Ms (27.4%). Whereas 15.4% of database patients with grade I complications were presented at M&Ms, this proportion increased to 22.2% for grade IIa, 34.8% for grade IIb, 33.3% for grade III, and 87.5% for grade IV. (p < 0.05 for grade I, IIa, and IIb compared to grade IV). A total of 58 of 142 patients in the first part of the study period developed complications (40.8%), compared to 53 of 183 patients in the second part of the study (29%, p = 0.034). CONCLUSIONS: Although most severe complications are recorded at M&M rounds, a large proportion of complications remain unreported. Monitoring of outcomes may contribute to improvements in quality of care.

Databases as Topic↗
PubMed1997

Arterial gene therapy: a molecular biological perspective for the treatment of arterial ischemia.

Since most cells do not naturally incorporate foreign DNA, strategies for arterial gene transfer have generally relied on agents designed to augment cellular DNA uptake such as liposomes, viral vectors, and protein conjugates. However, even when DNA has been successfully introduced into a cell, the likelihood of gene expression remains uncertain because the transgene has to escape lysosomal degradation, be transferred to the nucleus for transcription of mRNA, and be exported to the cytoplasm for translation and/or post-translation modification of the protein product. Transfection efficiency represents the final index of this regulatory sequence. The extent to which this compromises human gene therapy for cardiovascular disease depends in part on the presence or absence of a signal sequence permitting active secretion of the gene product. The implication of these issues is discussed with regard to restenosis and angiogenesis.

Animals↗
PubMed1997

Pancreatic schwannoma: report of two cases and review of the literature.

Solitary intrapancreatic schwannoma is a rare tumor. We present two patients with this tumor and review 13 previously reported cases from the English-language literature. While the final diagnosis was made based on pathological examination of the tumors, both computed tomography scan and magnetic resonance imaging helped establish the benign nature of the lesion, narrow the differential diagnosis, and define the anatomical locations of the small tumors. Both tumors were treated by enucleation from the surrounding pancreatic parenchyma, and both patients, after 2 years of follow-up, are alive and well. It is concluded that multimodality radiologic investigations are useful in the workup of unusual pancreatic masses. In addition, based on the known biologic behavior of schwannomas occurring elsewhere in the body, simple enucleation, rather than more radical resection, is likely to be adequate therapy for these tumors.

Anatomy, Cross-Sectional↗
PubMed1996

Multivariate analyses of prognostic factors associated with hematopoietic recovery in autograft patients with different sources of progenitor cells. A GATMO experience. Argintine Group of Bone Marrow Transplant.

OBJECTIVE: To evaluate in a multivariate analysis the prognostic factors associated with hematopoietic recovery and the supportive care requirements after autotransplant of progenitor cells (PC) from various sources: bone marrow (BMPC), BMPC & peripheral blood (PBPC), and PBPC alone. PATIENTS AND METHODS: A total of 570 patients with hematological malignancies and solid tumors underwent high-dose therapy followed by autotransplant. PBPC were obtained after mobilization with chemotherapy and/or cytokines. One-hundred five patients received BMPC, 217 received BMPC & PBPC and 248 PBPC alone; all of the patients received G-CSF or GM-CSF after infusion. RESULTS: In a multivariate analysis the recovery of neutrophils was adversely associated with low numbers of nucleated cells infused (P < 0.13), bone marrow progenitor cell source, and diagnosis of multiple myeloma and acute leukemia (P < 0.001). The factors that adversely affected platelet recovery were low number of nucleated cells and diagnosis of multiple myeloma and acute leukemia (P < 0.001). CONCLUSIONS: We conclude that BMPC adversely affect neutrophil recovery while low numbers of nucleated cells and diagnosis of multiple myeloma and acute leukemia adversely affect both neutrophil and platelet recovery.

Adolescent↗
PubMed1996

[Do arrhythmias after infarction deter patients from smoking?].

Although the short-term outcome of patients treated by thrombolysis during the acute phase of myocardial infarction is now well known, data concerning the repercussions of the coronary accident on smoking are less clearly established. This aspect is particularly important, as cessation of smoking is one of the most effective measures in the context of secondary prevention, with an excellent cost-benefit ratio. Between 1985 and 1991, 218 consecutive patients underwent thrombolysis for myocardial infarction. With a follow-up of 35 +/- 20 months, 11.5% of patients have died, including 6% while in hospital. A questionnaire was sent to 193 surviving patients with a response rate of 97.4%, 27.3% of patients continued to smoke after the myocardial infarction. Smoking patients were younger (p = 0.001) and had generally returned to work (p = 0.05). Continuation of smoking was not influenced by either the patency of the artery or the type of revascularization, and was not correlated with residual symptoms. The frequency of arrhythmias during the acute phase was not related to previous smoking. On the other hand, smoking patients who survived after an infarction appear to quit smoking twice as frequently when they had experienced a cardiac arrhythmia during the acute phase of the infarction (p = 0.005), as confirmed by multivariate analysis. Can the "stress" induced by the arrhythmia, possibly combined with the doctor's reactive anxiety explain cessation of smoking in these patients? If so, it would open new horizons in terms of secondary prevention of myocardial infarction.

Adult↗
PubMed1996

Chagas' disease after bone marrow transplantation.

Chagas' disease is caused by Trypanosoma cruzi. It is endemic in Latin America where 16 to 18 million people are infected. Immunocompromised patients such as BMT recipients are at risk of Chagas' disease either due to reactivation or transfusion. We report a case of acute Chagas' disease in the setting of BMT.

Bone Marrow Transplantation↗
PubMed1996

Vascular applications of human gene therapy.

Complexing recombinant DNA with cationic liposomes is a convenient means of introducing foreign genes into cells (lipofection) and could potentially form the basis for genetically modifying diseased blood vessels in patients. The mechanism of lipofection is incompletely understood but it is recognized that the degree of successful gene transfer is highly dependent on cell type. We have transfected primary cultures of human vascular smooth muscle cells with a plasmid expressing either firefly luciferase (Luc) or nuclear-localized beta-galactosidase (NL-beta-gal). Cells were derived from either normal human internal mammary arteries, fragments of primary atherosclerotic plaque, or fragments of restenotic lesion. Concurrent lipofection of rabbit vascular smooth muscle cells and NIH 3T3 cells was performed as well. Compared to NIH 3T3 cells, expression in human vascular smooth muscle cells was markedly reduced: in cells derived from internal mammary artery, Luc expression, normalized for protein content, was 123-fold lower than in NIH 3T3 cells, while the proportion of cells expressing NL-beta-gal was 30-fold lower. Luc expression in cells derived from restenotic tissue was significantly greater than from cells derived from primary plaque. Within a given population of cells, the mitotic index of cells expressing the recombinant gene was significantly higher than the mitotic index for the total population of cells (p < 0.05). Finally, cotransfection experiments, in which lipofection of smooth muscle cells was performed using genes for NL-beta-gal and for human growth hormone, showed that among positive transfectants, a high proportion of cells (23-36%) co-expressed both genes. Thus, the efficiency of successful lipofection in human vascular smooth muscle cells in vitro is low. Transfection appears to be preferentially facilitated in cells derived from restenotic tissue and specific properties of smooth muscle cells, including growth rates, appear to be critical for successful transfection. Further elucidation of cell properties that promote transfection is required to augment the efficiency of liposome-mediated gene transfer in human vascular cells.

Adenoviridae↗