T-cell-mediated cytotoxicity against HIV in seropositive patients: a physiopathological approach.
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Biomedical subjects
Publications and source records attributed to P Joly.
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The presence of a left bundle branch block (LBBB) may hamper the electrocardiographic diagnosis of diseases that involve the QRS complexes. That it may conceal, or even completely erase, major abnormalities of ventricular repolarization induced by certain drugs is not so well known. In this paper, two highly demonstrative examples of such abnormalities observed with bepridil (case 1) or with the amiodarone-aprindine combination (case 2) are reported. In both cases, the intermittent character of the LBBB revealed the phenomenon which deserves to be known as it is not without practical consequences: in patients under treatments likely to modify repolarization and induce severe dysrhythmias (notably torsades de pointes) the presence of a LBBB indicates that the QT and/or QU intervals must be very carefully measured. In case of phase 3 LBBB compression of the carotid sinus or intravenous ATP injection helps the diagnosis since in the presence of even moderately prolonged ventricular cycles such manoeuvres create a refinement of QRS complexes which then demonstrate the major alteration of the underlying repolarization.
Both diltiazem (D) and nifedipine (N) have been shown to be effective in the treatment of spastic angina, but they sometimes prove inadequate, even in high doses. These two drugs have been given in combination on the grounds of a possible synergistic action, but the results obtained were limited by side-effects. We decided to administer the combined treatment in half doses to patients with spastic angina and normal coronary vessels in order to assess its effectiveness and acceptance. The trial was conducted on 13 patients: 11 men and 2 women aged from 37 to 71 years (mean 53 years) with normal or subnormal coronary arteriography. In the absence of any treatment, these patients responded to the ergonovine test by a coronary spasm which we were subsequently unable to prevent with either D or N. Each patient underwent, at the same hours, 4 ergonovine tests, the product being injected intravenously every 3 minutes in incremental doses of 1, 2, 3 and 6 micrograms/kg. These tests were performed without treatment, after 3 days of treatments with D alone (360 mg/kg), after 3 days of treatment with N alone (60 mg/kg) and after 3 days of treatment with D (180 mg/kg) plus N (30 mg/kg). Without treatment, ergonovine triggered the coronary spasm in all 13 patients at a mean threshold dose of 2.7 micrograms/kg. Under treatment with D or N given separately, no test became negative, but the threshold doses of ergonovine rose to 4.5 and 4.6 micrograms/kg respectively (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
To assess the immediate and medium term efficacy of percutaneous transluminal coronary angioplasty (PTCA) for restenosis, we retrospectively studied 102 patients undergoing a second PTCA between August 1983 and October 1987. The patients were 89 males and 13 females, mean age 61 +/- 7 years. Before the second PTCA, 13 patients were asymptomatic, 31 had effort angina and 58 resting angina. Exercise stress test performed in 50 patients was positive in 40 cases, negative in 9 and uninterpretable in 1. The coronary lesions were: 59 one vessel disease (58 p. 100) and 43 multivessel disease in which PTCA was performed on 1 lesion in 40 and on 2 lesions in 3. Primary success of PTCA was obtained in 100 patients (98 p. 100); 2 patients underwent coronary artery bypass graft (CABG), 1 as an emergency. At 6 months 45 patients had recurrent chest pain (46 p. 100) and 52 were asymptomatic. Control coronary angiogram performed in 70 patients (72 p. 100) after a mean delay of 7.4 +/- 6 months showed a second restenosis in 34, symptomatic in 31. Medium term follow-up was obtained for 96 patients (96 p. 100) with a mean follow-up period of 22.3 +/- 13.2 months. There were 5 cardiac deaths (5.2 p. 100) and 4 non fatal myocardial infarctions (4.2 p. 100). A new revascularization procedure after the second PTCA was performed in 33 patients (34.4 p. 100). Twenty-five patients underwent a third PTCA (26 p. 100), 5 patients a fourth PTCA (5.2 p. 100) and 11 patients underwent a CABG (11.4 p. 100).(ABSTRACT TRUNCATED AT 250 WORDS)
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We tested the usefulness of aspirin (325 mg twice daily), heparin (1000 units per hour by intravenous infusion), and a combination of the two in the early management of acute unstable angina pectoris in a double-blind, randomized, placebo-controlled trial involving 479 patients. The patients entered the study as soon as possible after hospital admission (at a mean [+/- SD] of 7.9 +/- 8.0 hours after the last episode of pain), and the study was ended after 6 +/- 3 days, when definitive therapy had been selected. Major end points--refractory angina, myocardial infarction, and death--occurred in 23, 12, and 1.7 percent of the 118 patients receiving placebo, respectively. Heparin was associated with a decrease in the occurrence of refractory angina (P = 0.002). The incidence of myocardial infarction was significantly reduced in the groups receiving aspirin (3 percent; P = 0.01), heparin (0.8 percent; P less than 0.001), and aspirin plus heparin (1.6 percent, P = 0.003), and no deaths occurred in these groups. There were too few deaths overall to permit evaluation of the effect of treatment on this end point. The combination of aspirin and heparin had no greater protective effect than heparin alone but was associated with slightly more serious bleeding (3.3 vs. 1.7 percent). We conclude that in the acute phase of unstable angina, either aspirin or heparin treatment is associated with a reduced incidence of myocardial infarction, and there is a trend favoring heparin over aspirin. Heparin treatment is also associated with a reduced incidence of refractory angina.
Adriamycin (ADM) can increase sialic acid content in K 562 cells and reduce their susceptibility to NK-mediated lysis. In this report, hypothetical relationship between this resistance and augmentation in sialylation has been investigated. Variations in the time of exposure to ADM showed that 12 hours were sufficient to cause maximal recruitment of benzidine-positive cells, growth inhibition and resistance to NK-mediated lysis. On the contrary, the membrane sialic acid density seemed stable and 24 hours of drug exposure were necessary to observe a clear rise in sialic acid. Neuraminidase treatment of control and ADM-treated K 562 cells was associated with an obvious enhancement in their susceptibility to NK-mediated lysis which can be explained by an increase in the target-effector binding ability as assessed by a direct conjugate-forming cell assay. However, the neuraminidase treatment did not modify the sensitivity difference to lysis between untreated and ADM-treated cells. As compared to control the reactivity of ADM-treated cells was higher with an antiglycophorin A (GPA) MAb and lower with an antitransferrin receptor (TFR) MAb. Kinetic studies suggested that GPA expression is a better index of ADM-induced resistance to NK-mediated lysis than TFR expression. In addition, neuraminidase treatment showed that TFR and GPA modulations induced by ADM can be correlated with sialylation alterations.
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To evaluate the incidence of spasm in patients with angiographically normal coronary arteries or with stenosis less than or equal to 50%, methergin testing was done consecutively in 1,200 patients (742 men and 458 women). The methergin test was performed 850 times during coronary angiography and 350 times after it. The test was globally positive in 11% (127 of 1,200 patients), positive in 7% among 921 patients presenting with atypical chest pain, 13% of 31 patients with effort angina, 54% of 54 with angina at rest, 57% of 53 with Prinzmetal's angina, 3% of 59 with acute myocardial infarction and 1% of 82 miscellaneous patients without chest pain. Another test was done in 291 patients after blockade of the cardiac autonomous nervous system with 0.04 mg/kg of atropine and 2 mg/kg of labetolol. The frequency of positive results in the methergin test increased after blockade from 8 to 19% (p less than 0.01). The increase of positive results was especially obvious among patients with atypical chest pain (from 6 to 14%). Thus, frequency of spasm in these patients with normal coronary arteries or without significative lesions was 11%. This incidence was influenced by the composition of the patient population and increased with blockade of the cardiac autonomous nervous system.
The relation between restenosis and progression of atherosclerosis in other coronary segments after angioplasty was studied in 98 consecutive patients with 110 coronary stenoses successfully treated with angioplasty. At early angiographic restudy (5 +/- 2 months after angioplasty) 37 patients (38%) had restenosis (defined as a stenosis greater than or equal to 50% of the luminal diameter or loss of greater than or equal to 50% of the gain achieved by angioplasty); progression of atherosclerosis was observed in 4 patients with and 7 without restenosis (13 versus 11%, p = NS). Ninety of the 98 patients underwent a late angiographic restudy a mean of 34 +/- 11 months after angioplasty. Late restenosis was found in one patient. Progression of coronary artery disease (defined as a greater than or equal to 20% decrease in the diameter of a vessel initially narrowed by greater than or equal to 50% or a greater than or equal to 30% decrease when the initial stenosis was less than 50%) was examined in relation to restenosis in 85 of the 90 patients. It occurred in 9 of 27 patients with and 22 of 58 patients without restenosis (33 versus 38%, p = NS). Restenosis developed more rapidly than did progression of disease. Diameter stenosis increased from 35 +/- 8 to 73 +/- 11% at the early restudy in lesions with restenosis; in lesions with disease progression it increased from 9 +/- 18 to 20 +/- 28% (p less than 0.001) at the early restudy to 53 +/- 21% (p less than 0.001) at the late restudy.(ABSTRACT TRUNCATED AT 250 WORDS)
The treatment of polymyalgia rheumatica (PMR) and temporal arteritis (TA) is still controversial. To assess the influence on the course of these diseases of the clinical symptoms at initial presentation and of the starting dosage of corticosteroid (CS) treatment the data for 210 patients, who were diagnosed as having PMR or TA from 1976 to 1986 and were followed up closely, were reviewed. One hundred and thirty two patients were diagnosed as having 'clinically pure' PMR; prednisone starting doses of over 15 mg daily provided more CS related adverse effects without any advantage. The mean duration of treatment was 25.7 months. Nine patients later developed symptoms of TA, and there were no predictive features for this. None experienced visual or neurological complications. Seventy eight patients were diagnosed as having clinical TA. Twenty five patients treated with low starting doses of prednisone, ranging from 10 to 20 mg/d (mean 16.2 mg/d), developed less CS related adverse effects and did not have more visual or neurological complications than 53 patients treated with higher doses. The mean duration of treatment was 30.9 months. Fifteen patients experienced visual or neurological complications and men (10/30) developed these complications more frequently than women (5/48) (p less than 0.02). These results suggest that (a) clinically pure PMR is a benign disease requiring low doses of CS treatment; (b) low doses of CS seem an adequate treatment for most cases of TA; (c) a worse prognosis seems attached to the male sex in TA.
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The bactericidal interactions in vitro of two antibiotics active at the cell wall (teicoplanin and vancomycin) or two inhibitors of DNA gyrase (coumermycin and ciprofloxacin) combined with two inhibitors of protein synthesis (rifampicin and LM 427) were assessed against five Staphylococcus aureus strains. The S. aureus isolates included two oxacillin-sensitive and three oxacillin-resistant strains. The concentrations tested covered the range usually obtained in the serum with recommended doses. Coumermycin + rifampicin or LM 427, and ciprofloxacin + rifampicin or LM 427 were antagonistic when the concentration of either drug was higher than the MIC, and additive when sub-MIC concentrations were tested. Teicoplanin or vancomycin + rifampicin or LM 427 produced variable results. Of the synergic combinations, 14 of 15 included teicoplanin. Of the antagonistic combinations, 20 of 33 included LM 427. Antagonism with LM 427 was due to the higher intrinsic activity of LM 427 alone than teicoplanin, vancomycin or rifampicin. Teicoplanin (20 mg/l) + rifampicin or LM 427 (1 mg/l) was synergic (9/10).
A case of dermatitis herpetiformis in a 60-year-old woman with polycystic kidney disease on hemodialysis is reported. Bullous dermatoses associated with hemodialysis are analyzed.
An ergonovine test (ET) was performed in 1,200 patients-742 men, 458 women aged from 34 to 73 years (mean: 49.5 years)-either during (850 cases) or after (350 cases) coronary arteriography. Another ET made more sensitive by blocking the cardiac autonomous nervous system (CANS) with labetalol 0.04 and 2 mg/kg was performed in 291 of these patients. The ET test was positive in 10.7 p. 100 (127) of all patients and in 11.2 p. 100 (127/1125) of patients presenting with retrosternal pain. In the group where spontaneous angina could be confirmed by ECG recordings during the attack, the percentage of positive responses rose significantly to 53.7 p. 100 patients with ST depression and 56.6 p. 100 of patients with ST elevation. When the anginal nature of the retrosternal pain was not confirmed before the test, the proportion of positive responses was 6.6 p. 100. In patients who had the sensitized test the positive response rate increased in all groups and globally rose significantly from 7.9 p. 100 to 18.6 p. 100 (p less than 0.01). Thus, the usually low frequency of positive ergonovine tests differs according to the population selected and increases after CANS blockade.
In this retrospective study changes in the prognosis of recent myocardial infarction were evaluated by comparing 731 patients hospitalized in the 1970-1974 period (group I) with 755 patients hospitalized in the 1984-1986 period (group II). The possible factors responsible for the changes observed were investigated. A 34 percent decrease in hospital mortality was recorded (19.2% in group I versus 12.6% in group II; P less than 0.001). The decrease was present irrespective of the patients' sexes and ages; it was more pronounced in patients under 65 (-42%) and in elderly women (-43%). Compared with group I patients, group II patients showed a significant decrease in cardiogenic shock (P less than 0.02), atrial fibrillation (P less than 0.05) and, chiefly, atrioventricular block (P less than 0.001). The improvement in prognosis cannot be ascribed to a change of population since both groups were matched in male to female ratio, age distribution and presence of the main risk factors. Three factors may have contributed to a better prognosis: (1) more rapid admission to hospital; the proportion of patients admitted within 6 hours of the initial symptoms rose from 37.5% in group I to 49.8% in group II (P less than 0.001); (2) modification of the conventional treatment, with a reduced prescription of digitalis and a less frequent recourse to temporary electrical pacing; (3) introduction of new treatments aimed at limiting the size of the necrotic area; these include thrombolytic agents which were administered in 19.2% of patients under 65 and may well have played the principal role in the improvement of outcome.
The popliteal venous aneurysm is a rare cause of recurrent phlebitis and pulmonary embolus. In reference to 3 personal cases, their etiology, their role in the occurrence of phlebitis, the place of phlebography and vascular sonotomography respectively, are discussed. The treatment is essentially surgical.