Efficacy and Safety of Appropriate Shocks and Antitachycardia Pacing in Transvenous and Subcutaneous Implantable Defibrillators: Analysis of All Appropriate Therapy in the PRAETORIAN Trial.

BACKGROUND: The PRAETORIAN trial (A Prospective, Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy) showed noninferiority of subcutaneous implantable cardioverter defibrillator (S-ICD) compared with transvenous implantable cardioverter defibrillator (TV-ICD) with regard to inappropriate shocks and complications. In contrast to TV-ICD, S-ICD cannot provide antitachycardia pacing for monomorphic ventricular tachycardia. This prespecified secondary analysis evaluates appropriate therapy and whether antitachycardia pacing reduces the number of appropriate shocks. METHODS: The PRAETORIAN trial was an international, investigator-initiated randomized trial that included patients with an indication for implantable cardioverter defibrillator (ICD) therapy. Patients with previous ventricular tachycardia <170 bpm or refractory recurrent monomorphic ventricular tachycardia were excluded. In 39 centers, 849 patients were randomized to receive an S-ICD (n=426) or TV-ICD (n=423) and were followed for a median of 49.1 months. ICD programming was mandated by protocol. Appropriate ICD therapy was defined as therapy for ventricular arrhythmias. Arrhythmias were classified as discrete episodes and storm episodes (≥3 episodes within 24 hours). Analyses were performed in the modified intention-to-treat population. RESULTS: In the S-ICD group, 86 of 426 patients received appropriate therapy, versus 78 of 423 patients in the TV-ICD group, during a median follow-up of 52 months (48-month Kaplan-Meier estimates 19.4% and 17.5%; P=0.45). In the S-ICD group, 83 patients received at least 1 shock, versus 57 patients in the TV-ICD group (48-month Kaplan-Meier estimates 19.2% and 11.5%; P=0.02). Patients in the S-ICD group had a total of 254 shocks, compared with 228 shocks in the TV-ICD group (P=0.68). First shock efficacy was 93.8% in the S-ICD group and 91.6% in the TV-ICD group (P=0.40). The first antitachycardia pacing attempt successfully terminated 46% of all monomorphic ventricular tachycardias, but accelerated the arrhythmia in 9.4%. Ten patients with S-ICD experienced 13 electrical storms, versus 18 patients with TV-ICD with 19 electrical storms. Patients with appropriate therapy had an almost 2-fold increased relative risk of electrical storms in the TV-ICD group compared with the S-ICD group (P=0.05). CONCLUSIONS: In this trial, no difference was observed in shock efficacy of S-ICD compared with TV-ICD. Although patients in the S-ICD group were more likely to receive an ICD shock, the total number of appropriate shocks was not different between the 2 groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022.

Subcutaneous or Transvenous Defibrillator Therapy.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) was designed to avoid complications related to the transvenous ICD lead by using an entirely extrathoracic placement. Evidence comparing these systems has been based primarily on observational studies. METHODS: We conducted a noninferiority trial in which patients with an indication for an ICD but no indication for pacing were assigned to receive a subcutaneous ICD or transvenous ICD. The primary end point was the composite of device-related complications and inappropriate shocks; the noninferiority margin for the upper boundary of the 95% confidence interval for the hazard ratio (subcutaneous ICD vs. transvenous ICD) was 1.45. A superiority analysis was prespecified if noninferiority was established. Secondary end points included death and appropriate shocks. RESULTS: A total of 849 patients (426 in the subcutaneous ICD group and 423 in the transvenous ICD group) were included in the analyses. At a median follow-up of 49.1 months, a primary end-point event occurred in 68 patients in the subcutaneous ICD group and in 68 patients in the transvenous ICD group (48-month Kaplan-Meier estimated cumulative incidence, 15.1% and 15.7%, respectively; hazard ratio, 0.99; 95% confidence interval [CI], 0.71 to 1.39; P = 0.01 for noninferiority; P = 0.95 for superiority). Device-related complications occurred in 31 patients in the subcutaneous ICD group and in 44 in the transvenous ICD group (hazard ratio, 0.69; 95% CI, 0.44 to 1.09); inappropriate shocks occurred in 41 and 29 patients, respectively (hazard ratio, 1.43; 95% CI, 0.89 to 2.30). Death occurred in 83 patients in the subcutaneous ICD group and in 68 in the transvenous ICD group (hazard ratio, 1.23; 95% CI, 0.89 to 1.70); appropriate shocks occurred in 83 and 57 patients, respectively (hazard ratio, 1.52; 95% CI, 1.08 to 2.12). CONCLUSIONS: In patients with an indication for an ICD but no indication for pacing, the subcutaneous ICD was noninferior to the transvenous ICD with respect to device-related complications and inappropriate shocks. (Funded by Boston Scientific; PRAETORIAN ClinicalTrials.gov number, NCT01296022.).

Device-related complications in subcutaneous versus transvenous ICD: a secondary analysis of the PRAETORIAN trial.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is developed to overcome lead-related complications and systemic infections, inherent to transvenous ICD (TV-ICD) therapy. The PRAETORIAN trial demonstrated that the S-ICD is non-inferior to the TV-ICD with regard to the combined primary endpoint of inappropriate shocks and complications. This prespecified secondary analysis evaluates all complications in the PRAETORIAN trial. METHODS AND RESULTS: The PRAETORIAN trial is an international, multicentre, randomized trial in which 849 patients with an indication for ICD therapy were randomized to receive an S- ICD (N = 426) or TV-ICD (N = 423) and followed for a median of 49 months. Endpoints were device-related complications, lead-related complications, systemic infections, and the need for invasive interventions. Thirty-six device-related complications occurred in 31 patients in the S-ICD group of which bleedings were the most frequent. In the TV-ICD group, 49 complications occurred in 44 patients of which lead dysfunction was most frequent (HR: 0.69; P = 0.11). In both groups, half of all complications were within 30 days after implantation. Lead-related complications and systemic infections occurred significantly less in the S-ICD group compared with the TV-ICD group (P < 0.001, P = 0.03, respectively). Significantly more complications required invasive interventions in the TV-ICD group compared with the S-ICD group (8.3% vs. 4.3%, HR: 0.59; P = 0.047). CONCLUSION: This secondary analysis shows that lead-related complications and systemic infections are more prevalent in the TV-ICD group compared with the S-ICD group. In addition, complications in the TV-ICD group were more severe as they required significantly more invasive interventions. This data contributes to shared decision-making in clinical practice.

Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death.

AIMS: This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation. METHODS AND RESULTS: We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality. CONCLUSION: Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.

Analysis of mesothelioma cases and National Cancer Registry data to assess asbestos exposure in India.

SETTING: Asbestos exposure can cause mesothelioma, a form of cancer which should be recorded by cancer registries. However, such registries currently cover only a small fraction (16%) of the population in India. Because India still uses asbestos, it is important to understand its health impact, especially the number of mesothelioma cases. OBJECTIVE: To assess the number of mesothelioma cases in India and compare these to the number reported to the National Cancer Registry. DESIGN: We used the Right to Information Act 2005 to gather data for 83 hospitals across India from 2012 to 2022-2023. RESULTS: From a total of 83 hospitals, there were 2,213 cases of mesothelioma from 2012 onwards. During the 2012-2016 period, the number of reported cases in the Cancer Registry was 54, whereas 1,126 cases were reported by these hospitals for this period. Only 21 (25%) of the hospitals assessed in this study were part of the population-based national cancer registry programme. Overall, cases of mesothelioma occur far more frequently than are reported in cancer registries. CONCLUSION: National record-keeping is inadequate and the system needs to be expanded and improved across all of India. This will provide more effective reporting and help to highlight the risk of exposure to asbestos.

CONTEXTE: L'exposition à l'amiante peut provoquer un mésothéliome, une forme de cancer qui devrait être répertoriée dans les registres du cancer. Cependant, ces registres ne couvrent actuellement qu'une petite fraction (16%) de la population indienne. L'Inde utilisant encore l'amiante, il est important de comprendre son impact sur la santé, en particulier le nombre de cas de mésothéliome. OBJECTIF: Évaluer le nombre de cas de mésothéliome en Inde et le comparer au nombre de cas déclarés au Registre National du Cancer. CONCEPTION: Nous avons utilisé la loi de 2005 sur le Droit à l'information pour recueillir les données de 83 hôpitaux indiens entre 2012 et 2022­2023. RÉSULTATS: Sur un total de 83 hôpitaux, 2 213 cas de mésothéliome ont été recensés à partir de 2012. Au cours de la période 2012­2016, le nombre de cas signalés dans le Registre du Cancer était de 54, alors que 1 126 cas ont été signalés par ces hôpitaux pour cette période. Seuls 21 (25%) des hôpitaux évalués dans cette étude faisaient partie du programme national de registre du cancer basé sur la population. Dans l'ensemble, les cas de mésothéliome sont beaucoup plus fréquents que ceux signalés dans les registres du cancer. CONCLUSION: La tenue des registres nationaux est inadéquate et le système doit être étendu et amélioré dans toute l'Inde. Cela permettra d'améliorer l'efficacité des rapports et de mettre en évidence le risque d'exposition à l'amiante.

Predictive value of the PRAETORIAN score for defibrillation test success in patients with subcutaneous ICD: A subanalysis of the PRAETORIAN-DFT trial.

BACKGROUND: The PRAETORIAN score estimates the risk of failure of subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy by using generator and lead positioning on bidirectional chest radiographs. The PRospective randomized compArative trial of subcutanEous implanTable cardiOverter-defibrillatoR ImplANtation with and without DeFibrillation Testing (PRAETORIAN-DFT) investigates whether PRAETORIAN score calculation is noninferior to defibrillation testing (DFT) with regard to first shock efficacy in spontaneous events. OBJECTIVE: This prespecified subanalysis assessed the predictive value of the PRAETORIAN score for defibrillation success in induced ventricular arrhythmias. METHODS: This multicenter investigator-initiated trial randomized 965 patients between DFT and PRAETORIAN score calculation after de novo S-ICD implantation. Successful DFT was defined as conversion of induced ventricular arrhythmia in <5 seconds from shock delivery within 2 attempts. Bidirectional chest radiographs were obtained after implantation. The predictive value of the PRAETORIAN score for DFT success was calculated for patients in the DFT arm. RESULTS: In total, 482 patients were randomized to undergo DFT. Of these patients, 457 (95%) underwent DFT according to protocol, of whom 445 (97%) had successful DFT and 12 (3%) had failed DFT. A PRAETORIAN score of ≥90 had a positive predictive value of 25% for failed DFT, and a PRAETORIAN score of <90 had a negative predictive value of 99% for successful DFT. A PRAETORIAN score of ≥90 was the strongest independent predictor for failed DFT (odds ratio 33.77; confidence interval 6.13-279.95; P < .001). CONCLUSION: A PRAETORIAN score of <90 serves as a reliable indicator for DFT success in patients with S-ICD, and a PRAETORIAN score of ≥90 is a strong predictor for DFT failure.

Analysis of the Indian Government's position on the use of asbestos and its health effects.

Based on WHO guidance, all forms of asbestos are a health risk. In India, the mining of asbestos has been stopped, but chrysotile (a type of asbestos) is still imported and processed in large quantities. Chrysotile is mainly used for asbestos-cement roofing, and the manufacturers claim its use to be safe. We sought to understand the Indian Government's position on the use of asbestos. To do so, we have analysed the replies of the executive wing of the Indian Government to questions on asbestos in the Indian Parliament. This revealed that, despite a mining ban, the government has defended the import, processing and continued use of asbestos.

Selon les directives de l'OMS, toutes les formes d'amiante présentent un risque pour la santé. En Inde, l'extraction de l'amiante a été arrêtée, mais le chrysotile (un type d'amiante) est encore importé et transformé en grandes quantités. Le chrysotile est principalement utilisé pour les toitures en ciment-amiante, et les fabricants prétendent que son utilisation est sûre. Nous avons cherché à comprendre la position du gouvernement indien sur l'utilisation de l'amiante. Pour ce faire, nous avons analysé les réponses de l'aile exécutive du gouvernement indien aux questions sur l'amiante posées au Parlement indien. Cela a révélé que, malgré l'interdiction de l'extraction minière, le gouvernement a défendu l'importation, la transformation et l'utilisation continue de l'amiante.

Atrioventricular and interventricular delay optimization in cardiac resynchronization therapy: physiological principles and overview of available methods.

In this review, the physiological rationale for atrioventricular and interventricular delay optimization of cardiac resynchronization therapy is discussed including the influence of exercise and long-term cardiac resynchronization therapy. The broad spectrum of both invasive and non-invasive optimization methods is reviewed with critical appraisal of the literature. Although the spectrum of both invasive and non-invasive optimization methods is broad, no single method can be recommend for standard practice as large-scale studies using hard endpoints are lacking. Current efforts mainly investigate optimization during resting conditions; however, there is a need to develop automated algorithms to implement dynamic optimization in order to adapt to physiological alterations during exercise and after anatomical remodeling.

Localization of Acid phosphatase in lipofuscin granules and possible autophagic vacuoles in interstitial cells of the Guinea pig testis.

The intracellular localization of acid phosphatase in guinea pig testicular interstitial cells was investigated by incubating nonfrozen thick sections of glutaraldehyde-perfused testis in a modified Gomori medium and preparing the tissue for electron microscopy. Lipofuscin pigment granules in these cells contain dense pigment, granular matrix, and often a lipid droplet. Reaction product is seen in the matrix of the pigment granules, and they may therefore be called residual bodies. At least some of the dense pigment appears to be derived from myelin figures and membrane whorls, since suitable intermediates can be seen. Lipid droplets found free in the cytoplasm are another possible source of pigment. In both cases the chemical mechanism is presumed to be autoxidation of unsaturated lipid. Acid phosphatase is present in the inner cisterna of Golgi elements. Enzyme activity also appears in possible autophagic vacuoles bounded by double membranes; the reaction product lies between the membranes. Consideration of the enzyme as a tracer suggests that the autophagic vacuoles are derived from the Golgi complex. Possible stages in the formation of these vacuoles by the inner Golgi cisternae are observed.

Long-term organ culture of human bronchial epithelium.

Human bronchial epithelium has been maintained in organ culture in serum-supplemented medium for 4 months. After 4 to 6 weeks in culture, various changes in morphology were apparent. There was an increase in autophagic vacuoles in mucous, ciliated, and basal cells, a reduction in the height of the columnar cells, a decrease in the number of goblet mucous cells, and an increase in cells with small mucous granules. After 3 months in culture, the basal lamina was frequently covered by 2 or 3 layers of epithelial cells consisting of nonkeratinizing squamous cells with short microvilli and small mucous granules. Less frequently, keratinizing squamous cells were seen. Differentiated epithelium incorporated precursors into macromolecules in serum-free medium, supplemented with vitamin A, at 1 week of culture. These explants exhibited changed epithelium by 2 weeks, similar to that described for epithelium in serum-supplemented medium after 4 to 6 weeks.

Binding of (3H)benzo(a)pyrene to DNA in cultured human bronchus.

The studies reported here demonstrate some of the factors affecting the binding of benzo(a)pyrene (BP) to macromolecules in cultured human bronchial mucosa. Bronchial specimens were obtained at either surgy or "immediate" autopsy from patients with and without lung cancer. Grossly normal-appearing pieces of bronchus were cultured in a chemically defined medium, i.e., CMRL 1066 medium containing 1 mug insulin per ml, 0.1 mug beta-retinyl acetate per ml,, 0.1 mug hydrocortisone hemisuccinate per ml, 2 mM L-glutamine, 100 units penicillin G per ml, and 100 mug streptomycin per ml. After 7 days, explant cultures were exposed to [3H]BP, usually for 24 hr, and then binding to total cellular macromolecules was studied by autoradiography, and binding to DNA was measured following isolation of DNA from bronchial mucosal cells. The extent of binding of [3H]BP was dependent on dose of BP, length of exposure to [3H]BP, and temperature. By autoradiography, bronchial epithelial cells bound more [3H]BP than stromal fibroblasts. Both 7,8-benzoflavone and butylated hydroxytoluene appeared to reduce the level of [3H]BP bound to DNA, while nicotine apparently did not alter the level of binding. These studies demonstrate that the bronchial mucosa, an important human cancer target tissue, has the capability to form metabolites of BP which bind to macromolecules including DNA. In addition, 7,8-benzoflavone and butylated hydroxytoluene, both known to alter the microsomal metabolism of BP, reduce the level of [3H]BP bound to DNA.

Does flecainide regain its antiarrhythmic activity after electrical cardioversion of persistent atrial fibrillation?

OBJECTIVES: The purpose of this study was to evaluate the hypothesis that presumed reversion of electrical remodeling after cardioversion of atrial fibrillation (AF) restores the efficacy of flecainide. BACKGROUND: Flecainide loses its efficacy to cardiovert when AF has been present for more than 24 hours. Most probably, the loss is caused by atrial electrical remodeling. Studies suggest electrical remodeling is completely reversible within 4 days after restoration of sinus rhythm (SR). METHODS: One hundred eighty-one patients with persistent AF (median duration 3 months) were included in this prospective study. After failure of pharmacologic cardioversion by flecainide 2 mg/kg IV (maximum 150 mg in 10 minutes) and subsequent successful electrical cardioversion, we performed intense transtelephonic rhythm monitoring three times daily for 1 month. In case of AF recurrence, a second cardioversion by flecainide was attempted as soon as possible. RESULTS: AF recurred in 123 patients (68%). Successful cardioversion by flecainide occurred only when SR had been maintained for more than 4 days (7/51 patients [14%]). Failure to cardiovert was associated with a prolonged duration of the recurrent AF episode and concurrent digoxin use. Multivariate logistic regression confirmed that successful cardioversion was determined by digoxin use (odds ratio [OR] 0.093, P = .047) and by the interaction between the duration of SR and the (inverse) duration of recurrent AF (OR 6.499, P < .001). When flecainide was administered within 10 hours after AF onset and the duration of SR was greater than 4 days, the success rate was 58%. CONCLUSIONS: Flecainide recovers its antiarrhythmic action after cardioversion of AF. However, successful pharmacologic cardioversion occurs only after SR has lasted at least 4 days and is expected only for recurrences having duration of a few hours. Immediate pharmacologic cardioversion of AF recurrence may be a worthwhile strategy for management of persistent AF.

Synthesis and Characterization of a Brønsted Pair Functionalized Shape-Persistent Macrocycle.

The first shape-persistent macrocycle 1 offering a Brønsted pair functionalized interior is described. Via postcyclization transformation, this heterosequenced compound can be obtained from its corresponding ester 2. The macrocycles differ dramatically in their characteristics such as solubility and appearance. Theoretical investigations suggest that those contrasts might originate from conformational changes due to the formation of a strong O-H-N hydrogen bond in 1.

Influenza vaccination of children during acute asthma exacerbation and concurrent prednisone therapy.

OBJECTIVES: The influenza vaccination rate is very low among children with moderate to severe asthma. This may be partly because of poor patient motivation and failure to visit clinics for vaccination. Another important factor may be health care providers' deferral of vaccination because of concern about the efficacy and safety of influenza vaccination during asthma exacerbations and concurrent prednisone therapy. We therefore examined the safety and immunogenicity of influenza vaccination during acute asthma exacerbation with concomitant prednisone therapy. SETTING: A pediatric allergy and pulmonology clinic and a pediatric emergency department. DESIGN: Children (n = 109) with a known diagnosis of asthma 6 months to 18 years of age were recruited. All participating patients, 59 without asthma symptoms (no prednisone, control group) and 50 with acute asthma exacerbation requiring prednisone burst therapy (prednisone group) received trivalent subvirion influenza vaccine. Fifteen children in the control group and 12 in the prednisone group received a booster dose according to American Academy of Pediatrics guidelines. Serum antibody titers to influenza A/Beijing/32/92 (H3N2), influenza A/Texas/36/91 (H1N1), and influenza B/Panama/45/90 were measured before and 2 weeks after vaccination. Adverse effects noted within 48 hours after vaccine dose were ascertained during the follow-up visit. RESULTS: The antibody response was analyzed by comparing mean postvaccine titers, the percentage of patients achieving protective antibody levels (> or = 5log2), and the percentage of patients achieving rises in titers of 2log2 or greater. Antibody responses to influenza A/Beijing/32/92 (H3N2) and influenza A/Texas/36/91 (H1N1) in the prednisone-treated and control groups were not different. A significantly better response to the influenza B/Panama/45/90 antigen was seen in the prednisone group for all three parameters. Children who received a booster dose and the subgroup of children with low prevaccination titers (< or = 3log2) showed similar patterns. Adverse effects, including asthma exacerbation, local swelling at the injection site, fever, rash, and headache, were not different in the two groups. CONCLUSIONS: Influenza vaccination can be given safely and effectively to asthmatic children regardless of asthma symptoms or concurrent prednisone therapy when necessary. Vaccination of all moderate to severe asthmatic patients visiting clinics or emergency departments would improve the overall vaccination rate significantly.

Haemophilus influenzae type b immunization of children with sickle cell diseases.

Haemophilus influenzae type B vaccine is recommended for children 1.5 to 6 years of age with sickle cell anemia, but the adequacy of their response is unknown. A total of 69 children with sickle cell syndromes, 1.5 to 5.6 years of age, were immunized with two vaccines alternatively, single blind. PRP vaccine was given to 36 children and a diphtheria toxoid conjugated vaccine, PRP-D, was given to 36. Coded pre- and postvaccine sera were tested by radioimmunoassay for anti-PRP antibody. The groups did not differ in age distribution or type of sickle hemoglobinopathy. Preexisting antibody levels were low in both vaccine groups; 65% were less than 0.15 microgram/mL. The vaccines were safe but associated with frequent minor reactions. PRP-D gave higher geometric mean titers and mean fold titer increase than PRP in all children (15.58 micrograms/mL [234-fold] v 2.63 micrograms/mL [29-fold]) and in the subgroups 1.5 to 2.5 years of age or with pretiter values less than 0.15 microgram/mL. Titers for 64% of children receiving PRP and 94% receiving PRP-D were greater than or equal to 1.0 microgram/mL. Thus, both vaccines were useful in this population, but PRP-D was more immunogenic. Duration of antibody levels postvaccination, booster responses, and PRP-D immunogenicity in younger children with sickle cell syndromes all require further study.

Breast-feeding and respiratory virus infection.

Thirty-nine breast-fed and 42 bottle-fed infants were followed up from birth over a four-year period. Virus infection was documented by culture and serologic testing, and history and physical examination were recorded for all episodes of respiratory illness. There were no statistically significant differences in rates or distributions of infection with individual viruses or with all viruses over the first three or six months or during the second six months of life in the two groups, nor were there statistically significant differences in rates or distributions of disease of the upper and lower respiratory tract or total respiratory disease, except for decreased disease of the lower respiratory tract in bottle-fed infants in the second six months. There were trends to decreased morbidity in breast-fed infants in the first three and six months and more episodes of pneumonia and bronchiolitis in bottle-fed infants in the first six months (P less than .05) but similar use of medical care by both groups. High cord blood titers to two viruses were not associated with evidence of breast-feeding protection from infection with those two agents. Breast-fed babies do not have fewer respiratory virus infections or illnesses but may experience less severe illness.

Human monoclonal antibodies to influenza virus: IgG subclass and light chain distribution.

Three adults and three children were immunized with inactivated or live attenuated influenza vaccines and 98 IgG monoclonal antibodies derived from EBV immortalization of their blood lymphocytes were studied. All antibodies reacted specifically with influenza A H3N2 or H1N1 whole virus and 73 of 74 tested reacted with the purified HA glycoproteins. The majority (76%) of 77 monoclonal antibodies adequately tested by ELISA or solid phase RIA contained lambda light chains. ELISA analysis of the IgG subclass of the six persons' postimmunization anti-influenza serum activity and of monoclonal antibodies derived from them showed a similar predominance of IgG1.

Relation of serum antibody to glycoproteins of respiratory syncytial virus with immunity to infection in children.

Immunity in relation to passively transferred maternal and naturally-induced serum antibody to the viral proteins was determined in 34 children who were followed from birth through three years of age for respiratory syncytial virus infection (RSV). Sera were tested by immunoglobulin class-specific enzyme-linked immunosorbent assay using the attachment and fusion proteins of the Long strain. The basis for immunity for maternal antibody in primary infection was assessed by a comparison of the distribution of antibody titers in a) 7 children who had an upper respiratory illness to 12 whose illness was accompanied by lower respiratory disease and of b) 13 children with an RSV-associated illness in the first 6 months of life who were age-matched as to month and approximate day of birth with 11 not infected in the same period. Infection induced immunity was evaluated by a comparison of antibody titers in 19 children who were reinfected with RSV in the year following their primary infection to 15 in whom reinfection was not documented. A statistical analysis of titers revealed that antibody to the fusion protein is an important correlate of immunity. In all three comparisons, the children with less RSV disease had significantly higher IgG anti-F titers prior to infection. No differences were observed between IgA anti-F or IgG and IgA anti-G titers.

Clinical observations following asbestos exposure.

There is a spectrum of clinical entities following occupational exposure to asbestos. Methods of evaluation for these problems are reviewed. Nonmalignant clinical conditions include asbestos warts, asbestos bodies, parenchymal fibrosis (asbestosis), pleural fibrosis and calcification, and benign asbestotic pleural effusion. Asbestosis, though a benign process, is a significant cause of death. Malignant conditions associated with asbestos exposure include lung cancer, accounting for about 20% of all deaths among insulation workers and significantly related to cigarette smoking. The lung cancers tend to occur more frequently in the lower lobes and are more peripheral. Pleural and peritoneal mesothelioma and some excesses in gastrointestinal cancers are found with asbestos exposure, although these are not related to cigarette smoking. Increased rates of malignancy first become significant after 20 years from onset of exposure and are also related to duration of exposure. Difficulties with the use of death certificate data are reviewed.