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Biomedical subjects

L Feldman

Publications and source records attributed to L Feldman.

At least 55 records · Page 3Linked to original sources

[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↗

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↗

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↗

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 with 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%) coexpressed 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.

Journal Article↗

The health belief model and adherence with a community center-based, supervised coronary heart disease exercise program.

Some investigators have concluded that health beliefs do not influence the maintenance of coronary heart disease (CHD) exercise adherence. However, the beliefs tested have not been specific to CHD nor exercise. In addition, much of the research has been atheoretical. We conducted a retrospective study to explore the possible utility of the Health Belief Model (HBM) for explaining attendance at a supervised CHD exercise program, based in a community center. Two dimensions of the model, general health motivation and perceived severity of CHD, were associated with attendance in the theoretically predicted direction, while a third dimension, perceived benefits of exercise, was associated in a direction opposite that predicted by the model. The model as a whole accounted for 29% (adjusted R2) of the variance. This study provides some initial evidence that health beliefs are associated with CHD exercise adherence.

Attitude to Health↗

[Comparative study of four commercialized serologic methods for the diagnosis of gastric Helicobacter pylori infection].

OBJECTIVE: Four commercially available enzyme-linked immunosorbent assays (ELISA) were evaluated for serological diagnosis of Helicobacter pylori (H. pylori) infection in 79 untreated patients. METHODS: Infection has been diagnosed in 40 patients, in whom culture and/or urease test and histopathology from antral biopsies, were positive for H. pylori. RESULTS: Sensitivity (Se) and specificity (Sp) of these tests, calculated with indeterminate serological results (9 patients) classified as positive (ind +) or negative (ind -), were not statistically different: GAP-test (Bio-Rad), Se = 95% (ind +), 90% (ind -), Sp = 84.6% (ind +), 89.7% (ind -); Pylori-Stat (Biowhittaker), Se = 97.5% (ind + or -), Sp = 71.8% (ind +), 71.9% (ind -); Premier H. pylori (Biomedical Diagnostics), Se = 92.5% (ind +), 90% (ind -), Sp = 84.6% (ind +), 81.2% (ind -); Cobas-Core (Roche), Se = 92.5% (ind + or -), Sp = 76.9% (ind +), 79.5% (ind -). There was a strong correlation between mucosal inflammation and H. pylori status. Discrepancies between infectious status and at least one serology result were observed in 16 patients (11 H. pylori negative and 5 H. pylori positive patients). CONCLUSION: These 4 tests are of equivalent diagnostic value. Thus, the selection of one of them should take into account cost and practicability.

Adolescent↗

[Results of a controlled trial comparing 3 suture threads at slow resorption for the closure of supra-umbilical midline laparotomies].

A randomized prospective trial was carried out between September 1987 and February 1989 to compare 3 different absorbable sutures (polyglactine 910, polydioxanone I, polydioxanone II) for closure of the abdominal wall after upper midline laparotomy for elective operations. The technique used to close the fascia was always a continuous suture. The criteria used to assess the results were the development of wound infection and wound dehiscence in the early postoperative period, and the development of suture sinuses and incisional hernia 1 year after operation. The early postoperative results in 235 patients revealed no wound infection and no -wound dehiscence. Suture sinuses developed in 4 patients (2%) 2 months after operation, but resolved spontaneously. We reviewed 203 patients after one year. The total number of incisional hernias detected 1 year postoperatively was 22 cases (11%), (polyglactine 910, 14.2%; polydioxanone I, 11.2%; polydioxanone II, 8.4%). The difference between the 3 groups was not statistically significant. The results of the trial indicate that absorbable sutures have a very low incidence of suture sinuses, and that polydioxanone II seems to be a good choice for closing laparotomies.

Adult↗

[Anaphylactoid reactions to colloid plasma substitutes: incidence, risk factors, mechanisms. A French multicenter prospective study].

Changes in transfusion behaviour induce a widespread use of colloid plasma substitutes, the range of which has recently been enlarged by the marketing of starch derivatives. The product chosen depends, at least in part, on its adverse effects, anaphylactoid reactions being a part of these. This study aimed to discover the frequency and severity of these reactions according to the type of substitute available in France, to look for possible risk factors, and determine the mechanisms involved. A prospective inquiry was carried out in 49 public and private hospitals spread throughout France. It lasted for 15 months, between June 1991 and October 1992. A data sheet was filled in for each patient who was given a plasma substitute, whether or not there was an incident. When a reaction did occur, an assessment was carried out in two stages: straightaway, with the measurement of the concentrations of serum tryptase, antigelatin antibodies, urinary methylhistamine; and four to six weeks later, with skin tests. A series of 19.593 patients was thus collected: 48.1% were given gelatins, 26.7% starches, 15.7% albumin, and 9.5% dextrans. 43 anaphylactoid reactions were recorded, giving an overall frequency of 0.219%, or 1 reaction for 456 patients. The frequency differed according to the substitute considered: 0.345% for gelatins, 0.273% for dextrans, 0.099% for albumin, and 0.058% for starches. These reactions (grades III and IV) were serious in 20% of cases. Multivariate analysis revealed four independent risk factors: giving gelatins (odds ratio: 4.81), giving dextrans (odds ratio: 3.83), a history of drug allergy (odds ratio: 3.16), and being male (odds ratio: 1.98). The relative risks of anaphylactoid reactions due to one type of substitute with respect to another were estimated to be 6 times less for starches with respect to gelatins, and 4.7 times less than with dextrans. The relative risk of albumin is 3.4 times less than that of gelatins, and almost identical to that of the starches. An immuno-allergological assessment was only carried out in 15 patients who had been given a gelatin (Plasmion). IgE-dependent anaphylaxis was proven in 7 of these. To conclude, it was shown that gelatins and dextrans should be avoided in patients with a known history of drug allergy. When a reaction does occur, an allergological assessment must be carried out, as this may be due to specific antibodies. Should this prove to be the case, that particular substitute would be contraindicated for the rest of the patient's life.

Anaphylaxis↗

[Analgesia after thoracotomy by extrapleural administration of continuous bupivacaine].

This study was aimed to assess the efficiency and the side effects of a continuous administration of bupivacaine into the paravertebral space. Twenty patients, ranked ASA 2 or 3, with a mean age of 57.9 years, and having had a posterolateral thoracotomy for resection of lung tissue, were randomly assigned to one of two groups, B or C. At the end of the surgical procedure, a 22 gauge catheter was inserted into the paravertebral extrapleural space, at T4 levels As soon as pain occurred during recovery (T0), the patients were given two-hourly intravenous boluses of buprenorphine. The patients in group B were also given, through the paravertebral catheter, a 20 ml bolus of 0.25% bupivacaine, followed by a continuous steady rate infusion (10 ml.h-1). Group C patients were given normal saline in the same way. All patients could improve their analgesia with 0.05 ml boluses of buprenorphine given by an auto-analgesia pump (Pharmacia). The following parameters were assessed during the 72 h which followed the first injection: pain with a visual analogic scale, quality of sedation (5 grades), heart and breathing rate, systolic and diastolic blood pressure, arterial blood gases. In group B, plasma bupivacaine concentrations were measured throughout the infusion, and for an 8-hour period after its end. The statistical analysis included 15 patients only, as the catheter had moved into the chest cavity in the other 5. Analgesia was qualified to be adequate by all patients, but there was no statistically significant difference in the amounts of self-administered buprenorphine between groups B and C.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗

Abnormalities in histamine pharmacodynamics in chronic urticaria.

Histamine plays a key role in the pathogenesis of chronic urticaria (CU). The authors of this paper have studied the effects of ingested histamine in 25 patients with CU. A 120 mg dose of histamine, well-tolerated in the healthy subject, was instillated into the duodenum. Concomitantly, plasma histamine (H) levels and plasma and urinary methylhistamine (MH) levels were measured. Intraduodenal administration of histamine was responsible for the development of an attack of urticaria in 64% of patients, while control subjects were asymptomatic. Plasma histamine levels were significantly higher after digestive histamine challenge (DHC) in patients with CU compared with controls. An abnormal increase in plasma histamine was observed in 72% of them. Plasma MH exhibited the same kinetic behaviour with a usually delayed time-pattern. Urinary MH concentration was higher in patients presenting with early-onset urticaria during the first hour than in those with the late-onset type between 1 and 12 hr after DHC. The coefficient of methylation (plasma MH/MH+H) was not significantly different in patients presenting with an attack of urticaria following DHC and in other subjects. Urinary excretion of MH and urinary flow increased significantly in patients presenting with an attack of urticaria following DHC which corresponds to increased absorption of histamine during the 5-hr period following DHC and its role on excretion by the kidney via vasodilation which it induces. This study demonstrates the abnormal frequency of disturbances in the metabolism of exogenous histamine in patients with CU. Increased plasma H accounts for the abnormal passage of H across the intestinal barrier which can result either from intestinal hyperpermeability and/or a deficit in the enzymatic catabolism of histamine. The systems of methylation and urinary clearance of MH appear to be effective. It is thus postulated that there is a deficit in diamine oxidase (DAO) in the enterocyte. The lack of correlation between the kinetic behaviour of plasma H and the onset of urticaria draws attention to the extent of individual variability in skin reactivity to histamine.

Administration, Oral↗

Antipeptide antibodies as probes of the recombinant and endogenous murine erythropoietin receptors.

The binding of erythropoietin (Epo) to its plasma membrane receptor activates signal pathways that result in erythroid cell proliferation and differentiation. To elucidate the structural features of the receptor that are important for hormone binding and signaling, we have developed a series of site-specific antibody probes. These antibodies were raised against synthetic peptides homologous to six exoplasmic domains and one cytoplasmic domain of the murine receptor and were affinity-purified by binding to their respective peptide antigen, immobilized on agarose. Western blot analyses demonstrated that the recombinant receptor expressed transiently in COS-7 cells is synthesized as three protein species of 62, 64, and 66 kd, consistent with previous observations. Importantly, probing the endogenous receptor in both virally transformed erythroleukemia cells and normal erythroid cells demonstrated similar 62- to 66-kd receptor species. The affinity-purified antibodies also recognized several antigenically related proteins. An examination of the capacity of the antireceptor antibodies to block receptor activation by Epo revealed that antibodies to five of the six exoplasmic domains blocked the receptor. This was reversed with excess Epo. Inhibition of receptor activation by antibody probes to five discrete hydrophilic domains suggests that receptor function may be critically dependent on the structural integrity (conformation) of the entire exoplasmic portion.

Amino Acid Sequence↗

A sensitive new bioassay for erythroid colony-stimulating factor.

Erythroid colony-stimulating factor (E-CSF) is a B cell-derived membrane protein that specifically affects the growth and development of human and murine committed erythroid progenitors. We report the development of a sensitive new bioassay for E-CSF, based on the ability of the growth factor to stimulate 3H-thymidine incorporation into cloned Rauscher murine erythroleukemia cells. The assay has among its advantages the ability to measure growth factor activity on a purified target cell population in the absence of endogenous growth factor-producing accessory cells. In addition, this assay measures E-CSF's proliferative effect on erythroid progenitors in the absence of erythropoietin (Epo) after 72 to 96 hours. In contrast, the standard bone marrow fibrin clot assay traditionally used to measure E-CSF requires the addition of Epo to promote the development of hemoglobinized erythroid colonies that are quantified after 7 days (for murine cells) to 12 days (for human cells). With the use of this new Rauscher cell bioassay, we have identified an E-CSF-producing human cell line and, further, have measured E-CSF activity derived from nonhuman splenic B lymphocytes.

Animals↗

[Diffuse cholesterol embolism after fibrinolysis for myocardial infarction].

The authors report the case of a 57 year old man admitted to hospital 3 hours after the onset of an infero-latero-basal infarct who underwent thrombolytic therapy with intravenous streptokinase, in whom the immediate outcome was complicated by multiple cholesterol embolisation which cause renal failure, mesenteric ischemia, medullary ischemia and livedo reticulosis of the lower half of the body complicated by gangrene of the toes, despite the fact that cardiac catheterisation had not been performed. This case (fifth reported case) of multiple cholesterol embolisation from the abdominal aorta caused by thrombolysis is the earliest presentation of this complication in the literature.

Cholesterol↗

Spectrin beta Tandil, a novel shortened beta-chain variant associated with hereditary elliptocytosis is due to a deletional frameshift mutation in the beta-spectrin gene.

An Argentinian family with hereditary elliptocytosis (HE) associated with a shortened beta-spectrin (Sp) chain was studied. As with most of the other shortened Sp beta-chains that have been described, this variant, called SpTandil, has impaired ability to participate in Sp dimer self-association, has lost its ability to become phosphorylated, and is associated with the presence of increased amounts of the alpha I 74-Kd fragment after partial tryptic digestion of Sp. The 3' ends of the beta-Sp gene of affected patients were analyzed. cDNA was prepared by reverse transcription of peripheral blood mRNA and amplified by the polymerase chain reaction (PCR) using primers corresponding to sequences 400 bp apart on the cDNA, spanning the last three exons (X, Y, Z) of the beta-Sp gene. Agarose gel electrophoresis of the cDNA amplification showed the presence of one band, the size of which was apparently the same as the band amplified from mRNA of a normal control. cDNA from one HE patient was subcloned and sequenced. Several clones showed the presence of a 7-bp deletion at codon 2041 in exon X. Genomic DNA of all the affected members of the family were amplified by PCR using primers flanking the deletion and corresponding to sequences 128 bp apart on exon X. Analysis of the PCR products using electrophoresis on polyacrylamide gel showed the presence of 121- and 128-bp bands in all HE subjects, and an additional doublet migrating more slowly than the two bands, which corresponded to the presence of heteroduplexes. The mutation results in a shift of the normal reading frame and leads to a new amino acid sequence at the C-terminus of the mutant beta-Sp chain. A new in-frame stop codon is encountered downstream, leading to premature chain termination. The identification of the molecular defect in Sp beta Tandil provides information regarding the region of the beta-Sp chain that is important for both Sp dimer self-association and an indication of potential sites of phosphorylation of the chain.

Amino Acid Sequence↗