[Revision of the "Smoker's Paradox": smoking is not a good prognostic factor immediately after myocardial infarction]. / Révision du "paradoxe du fumeur": le tabac n'est pas un facteur de bon pronostic au décours immédiat de l'infarctus du myocarde.

In order to determine the reasons for the low mortality after myocardial infarction in smokers compared with non-smokers (the smoker's paradox), the authors analysed the initial clinical data, the therapeutic interventions and hospital mortality in 790 consecutive patients (555 smokers, 235 non-smokers) admitted to hospital within 6 hours of the first symptoms of acute myocardial infarction and treated by intravenous thrombolytic agents and/or coronary angioplasty. Multivariate analysis with linear regression was used to identify the predictive factors of hospital mortality. The main differences between smokers and non-smokers were age (56 vs 67 years, p < 0.0001), gender (male, 90 vs 60%, p < 0.01), cardiogenic shock on admission (3 vs 8%, p < 0.01). TIMI 3 flow was obtained in the culprit artery in 84% of smokers and 79% of non-smokers (NS). Hospital mortality was 5% in the smoking population and 16% in non-smokers (p < 0.0001). In multivariate analysis, the variables of cardiogenic shock, age, gender and hypertension provided most of the prognostic information and tobacco consumption did not appear to have a protective effect. In patients admitted to hospital with acute myocardial infarction, identical incidences of early reperfusion are obtained in smokers and in non-smokers. However, mortality is higher in the non-smoking group due to more severe clinical characteristics on admission. Tobacco consumption is not a protective factor in the immediate period after acute myocardial infarction.

A new T-287C polymorphism in the 5' regulatory region of the tissue factor pathway inhibitor gene. Association study of the T-287C and C-399T polymorphisms with coronary artery disease and plasma TFPI levels.

Tissue factor pathway inhibitor (TFPI) is an important regulator of the extrinsic blood coagulation pathway. We screened the untranslated 5' region of the TFPI gene for polymorphisms and investigated their possible involvement in arterial thrombosis. The allele frequencies of a new polymorphism, located 287 base pairs upstream of the transcription start site (T-287C), and that of the previously described C-399T polymorphism, were similar in cases and controls. In controls, the -287C allele was associated with significantly higher levels of total TFPI antigen, arguing for an effect of this polymorphism on TFPI gene expression. In controls, the C-399T polymorphism did not alter TFPI levels. In the cases, however, decreased total and post-heparin free TFPI levels and increased F1+2 levels were significantly associated with the -399T allele. These findings suggest that the T-287C and C-399T polymorphisms are not associated with an increased risk of coronary heart disease, a result which should be confirmed by a larger study. However, their influence on outcome, or a link with subtypes of acute coronary syndromes, cannot be excluded.

["Early repolarization". The diagnostic pitfall of an atypical form of ST elevation]. / "Repolarisation précoce". Le piège diagnostique d'une forme atypique de sus-décalage du segment ST.

The authors report the case of a coloured man who was treated with intravenous thrombolysis for chest pain and "atypical" ST elevation related to early repolarisation. The interest of this case is to underline the electrocardiographic criteria of early repolarisation and to propose, in appropriate conditions of management, emergency coronary angiography in patients with an uncertain diagnosis of infarct-like chest pain associated with suspicious electrocardiographic changes.

Tolerance and nasal histopathologic effects of long-term, low-dose intranasal recombinant interferon alpha-2A (Roferon-A).

The dose-related tolerance and histopathologic effects of intranasal recombinant interferon alpha-2a (rIFN-alpha 2a) were determined in a blind study in which healthy subjects were randomized to receive sprays of interferon (IFN) (3 or 6 MU/day) or placebo for 28 days. Adverse nasal symptoms (bleeding, obstruction, irritation) tended to occur more often in the IFN 6 MU/day group. Blind analysis of biopsy samples collected before and after IFN treatment revealed that both IFN groups had significant histologic changes, most commonly an increased degree of lymphocytic infiltration in the subepithelium and underlying glandular zones. Changes developed in 61% of 18 recipients of IFN 6 MU/day, 37% of 19 recipients of IFN 3 MU/day, and 6% of 18 placebo recipients. Serum antibodies to rIFN-alpha 2a detectable by EIA were found in 4 recipients of IFN 3 MU/day and 2 recipients of IFN 6 MU/day, one-third of whom were positive by neutralization bioassay. The findings would predict that these rIFN-alpha 2a dosages would be associated with an excess of adverse side effects during long-term use in healthy adults.

Management of cancer patients receiving interferon alfa-2a.

This is a review of the data on the safety and tolerance of interferon alfa-2a in the treatment of cancer patients and is particularly aimed at patient care. Since 1981, interferon alfa-2a prepared from human sources has been administered to over 2500 cancer patients and 2500 patients with viral diseases. Adverse effects have been invariably produced following parenteral injections of greater than 3 X 10(6) IU. These were mainly flu-like symptoms (greater than 90%), fatigue (90%), gastrointestinal (85%), central nervous system (65%) and musculoskeletal (60%) disorders. Laboratory abnormalities, though common (greater than 75%) were rarely dose limiting. Their severity can be reduced by using dose schedules which promote tachyphylaxis, co-medication with paracetamol and evening administration. Fatigue is best controlled by careful dose attenuation and occasional therapy rest periods. At dosages of 3 X 10(6)-18 X 10(6) IU/injection, interferon alfa-2a therapy can be safely managed on an out-patient basis, requiring minimal or no hospitalization. The frequency and low titre of antibody development to interferon alfa-2a indicates that it is a weak antigen and is suitable for long-term therapeutic application.

A phase I clinical tolerance study of rDNA alpha 2 human interferon in patients with non-reticuloendothelial system malignancies.

Twenty-seven patients with non-reticuloendothelial malignancies were treated with a single intramuscular injection of recombinant leukocyte alpha 2 interferon (rIFN) to assess clinical tolerance and define a maximum tolerated dose. A single patient in each of six increasing dosage groups (0.3 X 10(6) IU, 1 X 10(6) IU, 3 X 10(6) IU, 10 X 10(6) IU, 30 X 10(6) IU, 100 X 10(6) IU) received a low dose (0.01 X 10(6) IU) and served as a control for subjective and objective toxicity measurements. Severe fatigue proved dose-limiting at 100 X 10(6) IU, and all dosages above 3.0 X 10(6) IU produced one or more signs or symptoms, which typically resembled a 'flu-like' syndrome. Objective toxicity was mild to moderate (leukopenia, thrombopenia) and no toxicities were found not already known from work with interferon obtained directly from leukocytes. Evidence of an antitumor effect was apparent in 3/19 evaluable patients.

Human T-lymphocyte colonies: generation of colonies in different lymphocyte subpopulations.

The generation of human T-lymphocyte colonies from different lymphocyte subpopulations in the presence of PHA alone, or PHA plus media conditioned by PHA-stimulated lymphocytes (PHA-LCM) has been investigated. The separation technique consisted of phagocytic cell depletion by carbonyl iron treatment and fractionation of non-phagocytic cells (NP cells) into B cells and T + null cells by affinity chromatography on an anti-F(ab')2 column. The T cells were separated from the null cells by E-rosette sedimentation. Under these conditions, we showed that: no T-lymphocyte colonies were obtained from the null-cell subset in the presence of PHA of PHA + PHA-LCM; T-lymphocyte-colony formation potential was retained in the T-cell subset. Some variability was observed in the production of T colonies using peripheral blood lymphocytes (PBL) from different donors. Low producers and high producers of T-lymphocyte colonies were encountered. The low production of T-lymphocyte colonies observed in some donors was due to a suppressive effect mediated by the phagocytic cells, probably monocytes. The anti-F(ab')2 immunoadsorbent retained a cell population necessary for T-lymphocyte colony growth.

Immune imbalance in cancer patients.

The immune status of the tumor-bearing patient remains poorly defined. In various solid-tumor-bearing patients, we demonstrated the absence of ADCC modifications in the patient in relapse or in evolution. These same patients presented a significant increase in immune complexes when compared with patients in remission. Furthermore, we noted a decreased NK activity, a decreased number of ARFC, corresponding to a helper T cell subpopulation, and a corollary increase in T-dependent suppressor activity. These results, on the whole, suggest an immune imbalance and that the helper cell-suppressor cell ratio should be investigated in greater depth within the context of the immune response in the cancer patient.

Correlation between macrophage intracellular electrical potentials and malignant melanoma growth in a murine model.

Peritoneal macrophages were collected from mice at varying periods after transplantation of an allogeneic malignant melanoma in the hind limb. The intracellular electrical potentials of these macrophages were measured and a correlation was found to exist between tumor growth measured by size and pathological examination, and the development of large negative intracellular potentials. We propose that this change in intracellular potential is correlated with changes in the immune system and may be triggered by membrane permeability changes possibly in response to calcium ions.

Lymphokine-induced changes in macrophage transmembrane electrical potentials.

Intracellular electrical potentials have been measured in nonactivated and immunologically-activated macrophages obtained from the peritoneal cavities of mice. Normal macrophage potentials were established and found to become significantly more electronegative after in vitro exposure for 10 minutes to a lymphokine-containing supernatant which induced macrophage activation. This approach may reflect very early concomitants of such activation and is also useful in the study of other immunologic systems.

The effect of local irradiation on the immune response in mice. II.--Alterations due to low dose scattering.

The effect of localized irradiation given as single dose on the immune response of tumour-bearing mice was evaluated using the CRT. The tumour system (MBL2 on C57BL/6 females) was regularly lethal, although presence of CTL was demonstrated 15 days after transplantation (50,000 cells in the left hind limb). This T-dependent, antigen-specific cytotoxic activity observed on day 15 in the non-irradiated tumour-bearing group was abolished in the irradiated group (but not in the sham-irradiated group) and their CTL were incapable to mount a secondary response in MLTC-CML. The scattering of the 1,600 rad-single dose was sufficient to provoke this inhibition.

[Effect on macrophages of acute stress induced in mice by local irradiation]. / Effet sur le macrophage du résultat de l'agression aiguë induite chez la souris par l'irradiation locale.

In examining the role of radiation in inducing immunosuppression in tumor-bearing Mice it has been shown that the experimental acute stress inadvertently generated by the procedure is profoundly immunosuppressive. It would appear that monocytes under the influence of glucocorticoïds are sequestered in the spleen. This monocyte immobilisation leads to rapid suppression of local inflammatory reactions including delayed hypersensitivity. The increased number of marcrophages in the spleen is co-incident with non-specific non T cell splenocyte anti-tumour activity. Stress induced suppression of inflammation is prevented by previous adrenalectomy and restored by hydrocortisone.

[Differences in the intracellular potentials of human peripheral lymphocytes]. / Différences entre les potentiels intracellulaires des lymphocytes humains périphériques.

The intra-cellular potentials of human blood mononuclear cells have been measured using a microelectrode and a modified classical neurophysiological system. The results obtained in vitro suggest that different lymphocyte sub-populations and monocytes have characteristics intra-cellular potentials. We have also shown that a change from negative to positive intra-cellular potential occurs in lymphocytes stimulated by Phytohemaglutinine and Concanavaline A.