"Crochetage" (notch) on R wave in inferior limb leads: a new independent electrocardiographic sign of atrial septal defect.

OBJECTIVES: This study sought to determine the clinical significance of a "crochetage" pattern--a notch near the apex of the R wave in electrocardiographic (ECG) inferior limb leads--in secundum atrial septal defect. BACKGROUND: Atrial septal defect is often overdiagnosed on the basis of classical clinical features. Thus, more specific signs on the ECG for screening are needed. Methods. We searched for a crochetage pattern in 1,560 older children and adults: 532 with secundum atrial septal defect, 266 with ventricular septal defect, 146 with pulmonary stenosis, 110 with mitral stenosis, 47 with cor pulmonale and 459 normal subjects. RESULTS: This pattern was observed respectively in 73.1%, 35.7%, 23.3%, 6.4%, 10.6% and 7.4% of these groups (p<0.001). In atrial septal defect, its incidence increased with larger anatomic defect (p<0.0001) or greater left-to-right shunt (p<0.0001), even in the presence of pulmonary hypertension. By multiple regression analysis, only shunt size (p<0.0006) and defect location (p<0.0001) were the determinants of its presence. In all groups, the specificity of this sign for the diagnosis was remarkably high when present in all three inferior limb leads (> or = to 92%), even when comparison was limited to patients with an incomplete right bundle branch block (> or = 95.2%). Early disappearance of this pattern was observed in 35.1% of the operated-on patients although the right bundle branch block pattern persisted. CONCLUSIONS: A crochetage pattern of the R wave in inferior limb leads is frequent in patients with atrial septal defect, correlates with shunt severity and is independent of the right bundle branch block pattern. Sensitivity and specificity of this sign are remarkably high when it is associated with an incomplete right bundle branch block or present in all inferior limb leads.

The French Randomized Optimal Stenting Trial: a prospective evaluation of provisional stenting guided by coronary velocity reserve and quantitative coronary angiography. F.R.O.S.T. Study Group.

OBJECTIVES: We sought to make a prospective comparison of systematic stenting with provisional stenting guided by Doppler measurements of coronary velocity reserve and quantitative coronary angiography. BACKGROUND: Despite the increasing use of stents during percutaneous transluminal coronary angioplasty, it is unclear whether systematic stenting is superior to a strategy of provisional stenting in which stents are placed only in patients with unsatisfactory results or as a bail-out procedure. METHODS: Two hundred fifty-one patients undergoing elective coronary angioplasty were randomly assigned either to provisional stenting (group 1, in which stenting was performed if postangioplasty coronary velocity reserve was <2.2 and/or residual stenosis > or =35% or as bail-out) or to systematic stenting (group 2). The primary end point was the six-month angiographic minimal lumen diameter (MLD). Major adverse cardiac events were secondary end points (death, acute myocardial infarction and target lesion revascularization). RESULTS: Stenting was performed in 48.4% of patients in group 1 and 100% of patients in group 2 (p<0.01). Six months after angioplasty, the MLD did not differ between groups (1.90+/-0.79 mm vs. 1.99+/-0.70 mm, p = 0.39), as was the rate of binary restenosis (27.1% vs. 21.4%, p = 0.37). Among patients with restenosis, 13/32 (40.6%) in group 1 but 100% (25/25) in group 2 had in-stent restenosis (p<0.01). Target lesion revascularization (15.1% vs. 14.4% in groups 1 and 2 respectively, p = 0.89) and major adverse cardiac events (15.1% vs. 16.0%, p = 0.85) were not significantly different. CONCLUSIONS: Systematic stenting does not provide superior angiographic results at six months as compared with provisional stenting.

High-titer HIV-1 neutralizing antibody response of rhesus macaques to gp160 and env peptides.

Three groups of four rhesus macaques were immunized twice, one month apart with purified recombinant HIV-1LAI gp160 in the presence of either alum, incomplete Freund's adjuvant (IFA), or SAF-1. Two months later, the animals were injected twice again with a synthetic peptide with the sequence of the principal neutralization determinant (PND) of the HIV-1LAI isolate mixed with the same adjuvants. All animals received a booster injection of gp160 and PND peptide at 6 months. This regimen of immunization induced in the SAF-1 and IFA groups a high-titer neutralizing antibody response that declined progressively over the course of the following 6 months. In contrast, only a weak response was observed in the alum group. Neutralizing antibody titers varied as anti-PND titers, suggesting that they were principally targeted to the PND. A shortened immunization protocol comprising two injections of gp160 at 0 and 1 month followed by one injection of PND peptide at 3 months is suggested as optimal for the induction of high titers of HIV-1 neutralizing antibodies in primates.

[Response of bone metastases to medical treatment: definition of evaluation criteria and classification trials]. / Réponse des métastases osseuses aux thérapeutiques médicales: définition des critères d'évaluation et essai de classification.

Bone metastases are very frequent. Some are sensitive to the action of anticancer drugs. However, there is as yet an unsolved methodological problem in the evaluation of response to these drugs. The uniquely radiological UICC criteria are quite insufficient, in as much as they appear with a long delay and sometimes give erroneous results. In this work we give a brief review of biological and clinical knowledge about bone metastases, and we attempt to give an array of the possible evaluation criteria and their respective value. We propose as a working hypothesis a classification of responses taking into account the criteria: the urinary hydroxyproline to urinary creatinine ratio, the serum dosage of bone isoenzyme of alkaline phosphatase and propeptide of type III procollagen (P III NP), and as an essential element, an analysis of all available imaging techniques. A visual study of bone scintillation scans must precede that of radiographs and, when possible, it must be associated to computerized scintillation scanning. When metastasis are located to the pelvis, the vertebral column, or the sternum, a CT scan or better, a nuclear magnetic resonance study (IRM), is indispensable in order to have a direct measure of the tumor extension to soft tissues. Furthermore, in the case of isolated metastases, one of these imaging techniques allows a diagnostic biopsy. Finally an analysis of response at the bone level will always be associated with a measure of their duration and an evaluation of metastases to other sites.

[Recombinant vaccine and extracting vaccine against hepatitis B in patients with kidney insufficiency: comparative immunogenicity]. / Vaccin recombinant et vaccin d'extraction contre l'hépatite B chez l'insuffisant rénal: immunogénicité comparée.

OBJECTIVES: Patients with chronic renal failure respond rather poorly to hepatitis B vaccines. A better response could be expected from recombinant vaccines including both the S and the pre-S2 antigens. We therefore prospectively compared the immunogenicity of plasma-derived Hevac B vaccine (H) with that of recombinant GenHevac B vaccine (G). METHODS: Vaccinations were performed in 120 non-dialyzed patients with chronic renal failure. The patients were randomly divided into two groups. Group G included 60 patients (24 males, mean age 58 +/- 16 years, mean creatinine clearance 25.3 +/- 12.6 ml/min) who were given the Hevac B vaccine at the dose of 5 micrograms. Group H included 60 patients (31 males, mean age 60 +/- 15 years, mean creatinine clearance 24.4 +/- 11.1 ml/min) who were given GenHevac B vaccine at the dose of 20 micrograms. All vaccinations were repeated at 0, 1, 2, 4 and 12 months. RESULTS: Following the fourth injection, seroconversion (anti-Hbs > or = 2 mlU/ml) was observed in 50/59 (85%) of the patients in group G versus 38/58 (67%) in group H (p < 0.02). Seroprotection (> or = 10 mlU/ml) was obtained in 42/59 (71%) vs 34/58 (59%), (NS) in the two groups respectively with a geometric mean titer of 112 versus 229 mlU/ml (NS) in responders. Following the booster injection at the 12th month, seroconversion was achieved in 48/51 (94%) vs 40/53 (76%) (p < 0.01) and seroprotection in 84% vs 70% (p = 0.053) respectively. The mean geometric titers were 879 and 1001 mlU/ml. CONCLUSIONS: Recombinant GenHevac B vaccine elicits seroconversion and seroprotection in a higher proportion of patients with chronic renal failure than the plasma-derived Hevac B vaccine, with comparably high antibody titers in responders. Therefore, GenHevac B vaccine should be recommended for vaccinating patients with chronic renal failure against hepatitis B.

[IPAD-DTCP: study of the tolerability and serum antipoliomyelitic efficacy in a maternal-child health center at Pikine (Dakar)]. / IPAD DTCP: étude de tolérance et d'éfficacité serologique antipoliomyélitique dans un centre de P.M.I. de Pikine (Dakar).

A study of the tolerance and potency of a quadruple vaccine adsorbed on calcium phosphate was carried out in Senegal. After a follow up of four months the local tolerance was better when the vaccine was inoculated by intramuscular injection. A high level of passively acquired antibodies was found for the three subtypes of polioviruses and seemed to delay the immunological reaction. 90%, 96% and 92% of the total group of children involved in this study had a positive reaction.

[Presence of immunoglobulins and complement in the walls of the coronary arteries in atherosclerosis]. / Présence des immunoglobulines et du complément dans la paroi des artères coronaires au cours de l'athérosclérose.

A histopathological and histoimmunological comparison was performed on 143 fragments on coronary arteries taken from 43 patients who died of ischemic heart disease and from 20 patients who died of other diseases. The immunological study research of Ig (A, G, M) and C3 fraction of complement in the 3 coronary layers was done by the immuno-peroxidase technique. The fixation was essentially observed in fibromyocytes. A good correlation existed between atherosclerosis lesions and fixation of Ig and C3 fraction of complement in both the media and the intima. On the other hand, this correlation was not observed in the adventitia. Accumulation of immunoglobulins and of the C3 fraction of complement in atherosclerosis seemed specific and proportional to the degree of arterial well lesion. The significance and the role of this accumulation remains to be studied. It may be hypothesized that Ig and complement fixation on fibromyocyte cell receptors or on the fibrous tissue fundamental substance is followed by the formation of antigen-antibody complexes, which act as foreign bodies which are either responsible for (or a reflection) of the onset of lesions or, at least, of their increasing severity or their persistence.

Calcium-phosphate-adjuvanted allergens: total and specific IgE levels before and after immunotherapy with house dust and Dermatophagoides pteronyssinus extracts.

Results of total and specific IgE levels before and after immunotherapy carried out with calcium-phosphate-adjuvanted house dust and mite allergens for 36 patients are reported here. Total and specific IgE levels were evaluated by radioimmunological methods based on the IgE/anti-IgE interaction. Total IgE levels were not significantly different before and after immunotherapy; most of the specific IgE levels remained on the same order. IgE levels after immunotherapy varied only slightly in most patients and were not correlated with therapeutic results. Advantages of calcium phosphate compared to aluminium compounds are reported.

Randomized dose range study of a recombinant hepatitis B vaccine produced in mammalian cells and containing the S and PreS2 sequences.

The safety and immunogenicity of different doses (2, 5, 10, and 20 micrograms of a recombinant hepatitis B virus (rHBV) vaccine containing the S and PreS2 sequences and produced in mammalian cells were compared to those of a plasma-derived hepatitis B virus vaccine (Hevac B Pasteur) in 482 volunteers. Local and general side effects were mild and transient. No transaminase level elevation and autoantibody production were observed. The antibody to hepatitis B surface antigen (HBsAg) seroconversion rates did not differ in the groups receiving the rHBV vaccine and the subjects receiving the plasma-derived vaccine. Both vaccines elicited levels of antibodies to HBsAg in greater than 90% of the participants. Geometric mean titers of antibodies to HBsAg induced by the 10- and 20-micrograms doses of the rHBV vaccine did not differ from that induced by the plasma-derived vaccine and were higher than those induced by the 2- and 5-micrograms rHBV vaccine doses. The striking feature of the rHBV vaccine compared to the plasma-derived vaccine was an early and high production of antibodies to PreS2, which may constitute an advantage in prevention of hepatitis B virus infection.

Three-week hepatitis B vaccination provides protective immunity.

To determine whether a 3-week hepatitis B (HB) vaccination could achieve protective immunity, 89 healthy non-immunized young adults received three doses of 20 micrograms each of HBs antigen (GenHevac B, Pasteur) and were randomly assigned to schedule A (n = 44): two doses at day 0, one dose at day 21; or schedule B (n = 45): one dose at days 0, 10 and 21. Seroprotection rates (anti-HBs > or = 10 mIU ml-1) for groups A and B respectively were: 23 and 40% at day 21; and 77 and 91% at day 82 (not significant). Anti-HBs geometric mean titres were higher in group B than in group A (p < 0.05) at days 21 (6.4 versus 3.8) and 82 (77.6 versus 33.5). One year after primary vaccination, the seroprotection rate remained as high as 90% in the vaccinees of group B; after boosting all vaccinees had protective levels of anti-HBs antibodies. Thus 3-week HB vaccination with GenHevac B allowed early and durable protective immunity.

Study of combined vaccination against yellow fever and measles in infants from six to nine months.

A study has been carried out in the Ivory Coast to assess the efficacy of a combined vaccine against yellow fever and measles relative to that of each vaccine administered separately. Healthy children aged six to nine months were recruited and divided into two age groups: less than seven months (group I) and more than eight months (group II). In each group, they were randomly assigned to receive either yellow fever vaccine only (A), measles vaccine only (B), or the combined vaccine (C). The serological responses to measles and yellow fever were assessed in 219 initially seronegative children 45 days after immunization. More than 90% of the children developed yellow fever haemagglutination inhibiting antibodies. Neither age nor combination with measles vaccine influenced the responses to yellow fever vaccine. Measles haemagglutinational inhibiting antibodies were found in 97% of the children and the seroconversion rate was influenced neither by age nor by combination with yellow fever vaccine. Younger infants had lower titres of measles antibody. No particular adverse reactions were notified during the follow up. This study shows that combined yellow fever and measles vaccines are immunogenic in infants from the age of six months. Controlling yellow fever in endemic areas and the prevention of measles in young infants may greatly benefit by this combination.

Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma.

BACKGROUND: Verapamil (VER), a potent calcium channel blocker, has been found to overcome P-gp-mediated multi-drug resistance (MDR) and to increase sensitivity to cytotoxic anticancer drugs in refractory myeloma and non-Hodgkin lymphoma. The value of VER for treating solid tumors is still a matter for debate. PATIENTS AND METHODS: We performed a prospective study in 99 patients with anthracycline-resistant metastatic breast carcinoma (MBC), to assess the clinical effect of oral VER given in association with chemotherapy. Instead of retreating patients with anthracycline, we used a partially noncross-resistant regimen (VF), combining vindesine (VDS) and 5-fluorouracil given as a continuous infusion (5-FU CI). Patients were randomly assigned to two cohorts. One cohort (47 patients) was treated in 28-day cycles, each involving the administration of VDS (3 mg/m2 i.v. bolus on days 1 and 10) and 5-FU CI, (400 mg/m2/day i.v. from day 1 to day 10). The other cohort (52 patients) received the same VDS and 5-FU treatment and an additional oral VER treatment (240 mg/day divided in 2 doses), from day 1 to day 28 of each cycle. Patients were treated until progression. RESULTS: The treatment was well tolerated and no side effects that could be attributed to VER were detected. Patients treated with VER had longer overall survival (OS) (median OS: 323 vs. 209 days, P = 0.036) and a higher response rate (27% vs. 11%, P = 0.04) than those not given VER. Progression-free survival (PFS) was also longer but the difference was not statistically significant (median PFS: 4.6 and 2.7 months for the VER and non-VER groups respectively, P = 0.6). CONCLUSIONS: This clinical trial demonstrates that a chemosensitizer, such as VER, can increase the survival of MBC patients with acquired anthracycline resistance.