The Subgingival Microbiome Relationship to Periodontal Disease in Older Women.

Understanding of the oral microbiome in relation to periodontal disease in older adults is limited. The composition and diversity of the subgingival microflora and their oligotypes in health and levels of periodontal disease were investigated in this study on older postmenopausal women. The 16S rRNA gene was sequenced using the Illumina MiSeq platform in 1,206 women aged 53 to 81 y. Presence and severity of periodontal disease were defined by Centers for Disease Control and Prevention/American Academy of Periodontology criteria. Composition of the microbiome was determined by 16S rRNA amplicon sequencing and the abundance of taxa described by the centered log2-ratio (CLR) transformed operational taxonomic unit (OTU) values. Differences according to periodontal disease status were determined by analysis of variance with Bonferroni correction. Bacteria oligotypes associated with periodontal disease and health were determined by minimum entropy decomposition and their functions estimated in silico using PICRUSt. Prevalence of none/mild, moderate, and severe periodontal disease was 25.1%, 58.3%, and 16.6%, respectively. Alpha diversity of the microbiome differed significantly across the 3 periodontal disease categories. ß-Diversity differed between no/mild and severe periodontal disease, although considerable overlap was noted. Of the 267 bacterial species identified at ≥0.02% abundance, 56 (20.9%) differed significantly in abundance according to periodontal disease status. Significant linear correlations for pocket depth and clinical attachment level with bacterial amounts were observed for several taxa. Of the taxa differing in abundance according to periodontal disease status, 53% had multiple oligotypes appearing to differ between none/mild and severe periodontal disease. Among older women, taxonomic differences in subgingival microbiome composition and diversity were observed in relation to clinical periodontal disease measures. Potential differences in bacterial subspecies (oligotypes) and their function were also identified in periodontal disease compared with health.

Vitamin D Status and Prevalent Early Age-Related Macular Degeneration in African Americans and Caucasians: The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVES: Vitamin D status has been hypothesized to protect against development of early age-related macular degeneration (AMD) via its anti-inflammatory properties and its possible beneficial influence on blood pressure control. We investigated the association between vitamin D status and prevalent early AMD in a community-based cohort. DESIGN: This was a cross-sectional study. SETTING: This was a secondary data analysis of already existing data from the Atherosclerosis Risk in Communities Study (ARIC) cohort collected from 1990 to 1995. PARTICIPANTS: There were 9,734 (7,779 Caucasians, 1,955 African American) ARIC participants (aged 46 to 70 at visit 2 [1990-1992]) with 25(OH)D data available at visit 2, AMD assessment at visit 3 (1993-1995), and complete covariate data. MEASUREMENTS: Vitamin D status was assessed with serum 25-hydroxyvitamin D (25(OH)D) concentrations from bloods drawn at visit 2. Prevalent, early AMD (n=511) was assessed at visit 3 (1993-95) with nonmydriatic retinal photographs of one randomly chosen eye. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD by categories of 25(OH)D in nmol/L (deficient <30, inadequate 30-<50, and two categories of adequate status: 50-<75 and ≥75). Linear trend was estimated using continuous 25(OH)D concentrations. ORs were adjusted for age, race, and smoking status. We further adjusted for hypertension status to examine if vitamin D status influenced early AMD via its effects on blood pressure. Exploratory analyses of effect modification by age, sex, race and high risk genotypes [Y402H complement factor H (CFH) rs1061170 and the A69S age-related maculopathy susceptibility 2 (ARMS2) rs10490924 polymorphisms] were conducted. RESULTS: The prevalence of early AMD was 5%, and 5% of participants were vitamin D deficient. The adjusted OR (95% CIs) for early AMD among those with adequate (≥75 nmol/L) compared to deficient (<30 nmol/L) vitamin D status was 0.94 (0.59-1.50), p-trend=0.86. Further adjustment for hypertension status did not influence results (OR [95% CI]=0.95 [0.59-1.52], p-trend=0.84). Results did not vary significantly by age, race, sex, early AMD subtype (soft drusen or retinal pigment epithelium depigmentation), or ARMS2 genotype. Results did not vary significantly by CFH genotype in African Americans. The p for multiplicative interaction between 25(OH)D and CFH genotype was 0.06 in Caucasians, but OR [95% CIs] for AMD by vitamin D status were similar in each CFH genotype and not statistically significant. CONCLUSIONS: Vitamin D status was not associated with early AMD in this cohort sample.

S-phase cyclin-dependent kinases promote sister chromatid cohesion in budding yeast.

Genome stability depends on faithful chromosome segregation, which relies on maintenance of chromatid cohesion during S phase. In eukaryotes, Pds1/securin is the only known inhibitor that can prevent loss of cohesion. However, pds1Δ yeast cells and securin-null mice are viable. We sought to identify redundant mechanisms that promote cohesion within S phase in the absence of Pds1 and found that cells lacking the S-phase cyclins Clb5 and Clb6 have a cohesion defect under conditions of replication stress. Similar to the phenotype of pds1Δ cells, loss of cohesion in cells lacking Clb5 and Clb6 is dependent on Esp1. However, Pds1 phosphorylation by Cdk-cyclin is not required for cohesion. Moreover, cells lacking Clb5, Clb6, and Pds1 are inviable and lose cohesion during an unperturbed S phase, indicating that Pds1 and specific B-type cyclins promote cohesion independently of one another. Consistent with this, we find that Mcd1/Scc1 is less abundant on chromosomes in cells lacking Clb5 and Clb6 during replication stress. However, clb5Δ clb6Δ cells do accumulate Mcd1/Scc1 at centromeres upon mitotic arrest, suggesting that the cyclin-dependent mechanism is S phase specific. These data indicate that Clb5 and Clb6 promote cohesion which is then protected by Pds1 and that both mechanisms are required during replication stress.

A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults.

Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2×10(9) (n=12), or 2×10(10) (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses.

p38 MAPK regulates group IIa phospholipase A2 expression in interleukin-1beta -stimulated rat neonatal cardiomyocytes.

Group IIa phospholipase A(2) (GIIa PLA(2)) is released by some cells in response to interleukin-1beta. The purpose of this study was to determine whether interleukin-1beta would stimulate the synthesis and release of GIIa PLA(2) from cardiomyocytes, and to define the role of p38 MAPK and cytosolic PLA(2) in the regulation of this process. Whereas GIIa PLA(2) mRNA was not identified in untreated cells, exposure to interleukin-1beta resulted in the sustained expression of GIIa PLA(2) mRNA. Interleukin-1beta also stimulated a progressive increase in cellular and extracellular GIIa PLA(2) protein levels and increased extracellular PLA(2) activity 70-fold. In addition, interleukin-1beta stimulated the p38 MAPK-dependent activation of the downstream MAPK-activated protein kinase, MAPKAP-K2. Treatment with the p38 MAPK inhibitor, SB202190, decreased interleukin-1beta stimulated MAPKAP-K2 activity, GIIa PLA(2) mRNA expression, GIIa PLA(2) protein synthesis, and the release of extracellular PLA(2) activity. Infection with an adenovirus encoding a constitutively active form of MKK6, MKK6(Glu), which selectively phosphorylates p38 MAPK, induced cellular GIIa PLA(2) protein synthesis and the release of GIIa PLA(2) and increased extracellular PLA(2) activity 3-fold. In contrast, infection with an adenovirus encoding a phosphorylation-resistant MKK6, MKK6(A), did not result in GIIa PLA(2) protein synthesis or release by unstimulated cardiomyocytes. In addition, infection with an adenovirus encoding MKK6(A) abrogated GIIa PLA(2) protein synthesis and release by interleukin-1beta-stimulated cells. These results provide direct evidence that p38 MAPK activation was necessary for interleukin-1beta-induced synthesis and release of GIIa PLA(2) by cardiomyocytes.

Enacting narrative pedagogy. The lived experiences of students and teachers.

Reforming nursing education to meet contemporary challenges in educational and clinical environments is needed through the development and implementation of new pedagogies. Nancy Diekelmann is advancing the science of nursing education by describing a new phenomenological pedagogy, Narrative Pedagogy, identified through interpretive research in nursing education. Narrative Pedagogy is an approach to reforming nursing education that is always site specific and not generalizable from school to school. However, the processes of Narrative Pedagogy are transferable and can be enacted in many contexts. This study describes the common experiences and shared meanings of teachers and students engaging in or enacting Narrative Pedagogy. Diekelmann gathered seven teachers and students in five schools of nursing in four midwestern states to share their experiences. Interpretive phenomenology was used to analyze the group interview. One of the findings identified during this analysis, Enacting Narrative Pedagogy, is explicated, and two themes, Decentering Skill Acquisition and Content and Attending to the Practices of Thinking, are described.

Program development and routine notification in a large, independent OPO: a 12-year review.

Since its inception 12 years ago, a large, independent OPO experienced a 631% growth in the number of organ donors. These increases in organ recovery were achieved initially through successful mergers, and later, following the mergers, through focused management, OPO organizational development, and hospital marketing and system development. The cumulative percentage increases beginning in 1987 resulted in the OPO achieving 27.2 donors per million population. In 1996 a system of routine notification of all hospital deaths was implemented and a 24-hour communications center was operated. After 3 full years of routine notification, 73% of all deaths were called to the OPO, resulting in the following increases: total referrals, 691%; organ referrals, 41%; organ donors, 16%; bone donors, 149%; skin donors, 123%; and heart valve donors, 78%. The 16% increase in organ donors was twice the national growth rate and significantly more than the 2% growth experienced by the OPO in the year preceding the implementation of routine notification. The OPO has demonstrated sustained growth over the past decade in a time when erosion of donor recovery levels is always a possibility and frequently a reality for many OPOs.

Selection strategy for site-directed mutagenesis based on altered beta-lactamase specificity.

Conventional approaches to oligonucleotide-directed mutagenesis rely upon the application of a selection strategy to maximize mutagenesis efficiencies. We have developed a mutagenesis procedure that incorporates a novel antibiotic resistance for selection. The selection involves altering the substrate specificity of TEM-1 beta-lactamase, the enzyme responsible for bacterial resistance to beta-lactam antibiotics such as ampicillin. The gene encoding beta-lactamase is commonly found on cloning and shuttle vectors used in molecular biology. Amino acid substitutions in several active site residues of beta-lactamase result in increased hydrolytic activity against extended-spectrum penicillins and cephalosporins. This increased activity confers a novel resistance specific to the mutant and thus provides the basis of the selection strategy. We describe a simple and efficient mutagenesis procedure and its application to creating a range of oligonucleotide-directed mutants.

Effect of varying atrial sensitivity, AV interval, and detection algorithm on automatic mode switching.

UNLABELLED: Automatic mode switching (AMS) is absolutely dependent on atrial tachyarrhythmia detection. The effects of programming several features that could influence tachyarrhythmia detection were assessed in 18 patients (six women; mean age 64 years) with pacemakers having AMS capability. The atrial electrogram amplitude in sinus rhythm at implant (SR-EGM), last measured atrial sensing threshold prior to tachycardia (A-SENS), and atrial sensing threshold for effective AMS during atrial tachyarrhythmia (AMS-SENS) were obtained. Additionally, ten patients had AV intervals increased from 60 to 200 ms, while seven patients had detection algorithms made more stringent from 5 beats at 150 beats/min to 11 beats at 200 beats/min to assess their effects on AMS efficacy. RESULTS: Sensitivities:Mean SR-EGM = 3.55 mV; mean A-SENS = 2.06 mV; and mean AMS-SENS = 1.46 mV. Fourteen patients developed atrial fibrillation and four atrial flutter. Thirteen of 14 patients who developed atrial fibrillation sensed adequately at > or = 1.0 mV in normal sinus rhythm (NSR), but only six patients had effective AMS at these settings in atrial fibrillation. Three of four patients who developed atrial flutter had effective AMS at > or = 2.0 mV. AV Interval:AMS was effective in eight of ten patients at AV intervals up to 200 ms. One patient lost AMS at an AV interval of 120 ms. Algorithm: In two of seven patients, AMS was not effective if the detection algorithm was more stringent than five beats at 150 beats/min. CONCLUSIONS: (1) In atrial fibrillation, effective AMS requires more sensitive atrial settings than in NSR; (2) AV intervals as short as 120 ms can interfere with AMS function; and (3) More stringent detection algorithms may be inappropriate for effective AMS function.

The immunopathology of HIV infection.

Fourteen years into the global epidemic of the acquired immunodeficiency syndrome, the exact mechanisms by which the human immunodeficiency virus (HIV) causes the destruction of the immune system remain unresolved. Infection with HIV is characterized by both continual virus replication and a vigorous immune response. The length of time from initial infection to the almost inevitable loss of CD4 positive T helper lymphocytes averages 10 years, indicating the dramatic and prolonged interplay of the virus and the host immune response. In this article we discuss many of the leading hypotheses for both direct and indirect mechanisms that have been proposed to explain the loss of CD4 cells. Current evidence suggests strongly that direct infection of CD4 cells is adequate to explain their loss, but that cofactors and indirect mechanisms may contribute to the overall process. This leads to the conclusion that the immunopathology of HIV infection can be most effectively countered by using antiretroviral chemotherapy.

Long-term follow-up of pacemaker lead systems: establishment of standards of quality.

The functional details of all 5,405 pacemaker leads implanted on Montefiore Medical Center were contemporaneously recorded between 1960 and May 31, 1993. Some models have been observed for as long as 24 years. Ventricular leads with more than 50 and atrial leads with more than 30 implanted units have been continually and repeatedly subjected to actuarial cumulative survival rate (CSR) analysis during which clinical decisions, such as continued lead implantation, cessation of use, or early withdrawal from service, were made. CSR evaluation for many lead models by the Mantel-Haenszel method allowed comparison of the performance of contemporaneous lead models with older and new technologies. No effect on lead longevity, durability, on mode of end of lead service, lead removal independent of function (e.g., for infection), materials, or physiological failure was found due to an operator or anatomical route of venous access. Multifilar silicone rubber insulated leads have longevity (CSR) superior to monofilar silicone rubber leads. The cumulative survival of silicone rubber insulated monofilar models 6901, 6907, continuous lead (CL), 4 mm, and 2 mm was 79%-91%, 20 years after implantation. Multifilar silicone rubber insulated models 6961 and 4116 had a cumulative survival of 99%-100%, 15 years after implantation. Among multifilar polyurethane insulated leads, distinct longevity differences exist between formulations and contemporaneous models that are normally similar, yielding a bimodal longevity distinction; model 6971 (ventricular) has 95% CSR and 6991U (atrial) has 94% CSR, 10 years after implantation. Both performed less well than other contemporaneous models, which approximate 100% CSR. The 10-year CSR for leads implanted between 1960-1975 (Era 1) is 98.7%, and the 10-year CSR of leads implanted between 1981-1985 (Era 3) is 99.4%. Comparison of individual lead models, and all leads of specific eras, allows development of survival expectations and standards of quality for comparison between contemporaneous lead models and different eras of manufacture. As the highest available lead CSR sets the standard, statistical deviation of a model from the best performance of a specific era should be considered as an indication of reduced quality.

A region of the third variable loop of HIV-1 gp120 is recognized by HLA-B7-restricted CTLs from two acute seroconversion patients.

HIV-1 envelope-specific CTL clones were isolated from the peripheral blood of two patients from within weeks of seroconversion. These clones were CD8+ and restricted by the HLA-B7 molecule. The minimum epitope recognized by the clones was determined to be the 30-amino acid (aa) sequence RPNNNTRKSI within the third variable (V3) loop of the envelope glycoprotein gp120. The aa sequence of this epitope is consistent with the motif found in naturally processed peptides eluted from HLA-B7 molecules. This region of the V3 loop is reasonably well conserved among clade B and some nonclade B isolates of HIV-1, especially at the anchor residues that determine binding to the HLA-B7 molecule. Using peptides based upon virus sequences present within each patient, we determined that autologous viruses were recognized by the clones, and we detected no escape variants from the initial clonal response during the acute phase of infection. Interestingly, a serine to arginine change at position 9 of the epitope abrogated clone recognition in one of the patients. This aa change is one factor that has been associated with a change from a nonsyncytium-inducing to a syncytium-inducing phenotype of HIV-1, raising the possibility that in HLA-B7-expressing patients, escape from this clonal CTL response and a change in viral phenotype may be linked. This study demonstrates that human CTL can be generated against sequences within the third variable loop of HIV-1 gp120. Because multiple vaccine strategies are based upon the V3 loop of HIV-1 gp120, this defined epitope can be exploited in determining the ability of certain vaccines to stimulate a CTL response in a select population of individuals.

Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.

Virologic and immunologic studies were performed on five patients presenting with primary human immunodeficiency virus type 1 (HIV-1) infection. CD8+ cytotoxic T lymphocyte (CTL) precursors specific for cells expressing antigens of HIV-1 Gag, Pol, and Env were detected at or within 3 weeks of presentation in four of the five patients and were detected in all five patients by 3 to 6 months after presentation. The one patient with an absent initial CTL response had prolonged symptoms, persistent viremia, and low CD4+ T-cell count. Neutralizing antibody activity was absent at the time of presentation in all five patients. These findings suggest that cellular immunity is involved in the initial control of virus replication in primary HIV-1 infection and indicate a role for CTL in protective immunity to HIV-1 in vivo.

Characterization of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte clones isolated during acute seroconversion: recognition of autologous virus sequences within a conserved immunodominant epitope.

Virus-specific cytotoxic T lymphocytes (CTL) are involved in protective immunity to many virus infections. It has recently been shown that CTL are detectable early during primary infection with the primate lentiviruses, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus. To better characterize the CTL response during acute HIV-1 infection, HIV-1-specific CTL clones were generated from two patients during symptomatic HIV-1 seroconversion. These CTL clones demonstrated specificity for env of HIV-1 and recognized sequences within gp41. Two human histocompatibility leukocyte antigen (HLA) A31-restricted clones from the same individual were found to have differing virus strain specificities. Both clones recognized the 11-amino acid peptide RLRDLLLIVTR from position 770-780 of gp41. A change from T to V at position 779 in this epitope abrogated lysis by one clone but not the other. A CTL clone from the other patient, restricted by a different class I HLA allele, recognized the nine-amino acid peptide HRLRDLLLI from position 769-777 of gp41. Of note, the peptide RLRDLLLIVTR has been shown by others to be presented to CTL by HLA-A3.1. Autologous virus sequences from seroconversion and up to 15 wk after presentation in these two patients were recognized by the CTL clones isolated during acute infection. None of the CTL clones recognized the MN strain of HIV-1, indicating the problems inherent in relying on a single virus strain in the development of a vaccine. These studies have identified an immunodominant and promiscuous area for the generation of CTL responses within gp41. This recognition of autologous virus sequences by the initial CTL response is consistent with the hypothesis that a single virus strain is transmitted to the seroconverter and that the CTL response is involved in the initial control of that virus. These studies indicate the importance of the CTL response to HIV-1 infection and have implications in the design of vaccines.

Surgical removal of infected transvenous pacemaker leads.

Infection, though uncommon, can be the most lethal of all potential complications following transvenous pacemaker implantation. Eradication of infection associated with pacemakers requires complete removal of all hardware, including inactive leads. Since 1972, 5,089 patients have had 8,508 pacemaker generators implanted at Montefiore Medical Center. There were 91 infections (1.06%); four of our patients required surgical removal. Nine additional patients were referred for surgical removal of infected transvenous pacemaker leads from other institutions. Surgical methods for removal included use of cardiopulmonary bypass or inflow occlusion. Surgery may be safely used in unstable or elderly patients and should not be reserved as a last resort. This article reviews our surgical experience removing infected pacemaker leads at Montefiore Medical Center.

hu-PBL-SCID mice can be protected from HIV-1 infection by passive transfer of monoclonal antibody to the principal neutralizing determinant of envelope gp120.

OBJECTIVE: To determine whether passive transfer of a monoclonal antibody specific for the principal neutralizing determinant in the V3 region of HIV-1IIIB gp120 can protect mice with severe combined immunodeficiency (SCID) transplanted with normal human peripheral blood leukocytes (hu-PBL), designated hu-PBL-SCID mice, from subsequent challenge with the homologous viral strain. DESIGN AND METHODS: hu-PBL-SCID mice were given intraperitoneal injections of an anti-HIV-1 neutralizing murine monoclonal antibody (BAT123), its mouse-human chimeric form (CGP 47 439), or a control murine antibody (PNTU), at a dose of 40 mg/kg. The mice were then challenged intraperitoneally with 10 mouse infectious doses of HIV-1IIIB. Three weeks later the mice were killed, and spleen cells and peritoneal lavage collected for determination of infection by coculture for viral isolation and by detection of HIV-1 DNA using polymerase chain reaction (PCR). RESULTS: All three antibodies had similar serum half-lives of 9-12 days. No toxicity was observed in the animals. HIV-1 was recovered by coculture from five out of the six mice given PNTU, and by PCR from two out of the six mice given PNTU, but was not recovered by either technique from any of the 12 mice given BAT123 or CGP 47 439. CONCLUSION: BAT123 and CGP 47 439, which are specific for the principal neutralizing determinant of HIV-1IIIB, protect hu-PBL-SCID mice from infection by this viral strain. Our findings support the use of the hu-PBL-SCID mouse as an in vivo model for studying protection against HIV-1 infection by passive immunization with anti-HIV-1 neutralizing antibodies.

Retrograde (ventriculoatrial) conduction in congenital complete heart block.

Retrograde ventriculoatrial (VA) conduction is documented at the time of dual chamber pacemaker implantation in a 36-year-old patient with congenital complete atrioventricular (AV) block. Programmed ventricular stimulation with stimuli of increasing prematurity demonstrated a lack of decremental conduction via a unidirectional retrograde pathway. Because retrograde VA conduction has been associated with pacemaker mediated endless loop tachycardia, the status of retrograde conduction should be assessed in all patients undergoing dual chamber pacemaker implantation, including those with congenital complete AV block who have previously been considered to have no conductive tissue between atria and ventricles.

Effect of desmopressin on vein graft patency in a microvascular model.

Desmopressin acetate decreases blood loss after cardiac surgery by activating platelets. We studied whether this effect was detrimental to small-caliber vein grafts in rats. Thirty minutes before femoral artery grafting with 0.75-mm-diameter reverse autogenous saphenous vein grafts, 20 rats received desmopressin acetate intravenously at 1.0 micrograms/kg over 10 minutes, and 20 control rats received normal saline intravenously over 10 minutes. In each group, 10 rats received a 6-mm-long graft and 10 an 18-mm-long graft. Graft patency was evaluated at 20 minutes, 24 hours, and 30 days. Intimal thickening was assessed by light and scanning electron microscopy. At 30 days, 9 short grafts and 8 long grafts in the desmopressin-treated group were patent, whereas only 8 short control grafts and only 6 long control grafts were patent. Intimal thickening and platelet deposition were the same in both groups. These data show no detrimental effects of desmopressin acetate on saphenous vein graft patency.

Pacemaker implantation in children: a 21-year experience.

Forty-one children, 20 boys and 21 girls, aged 11 days to 19 years (mean 9.9 years) at initial pacemaker implant, were followed 1 to 248 months (mean 90 months). Ten (mean age 8.2 years) were implanted between 1966 and 1972 (Group I), 14 (mean age 9.9 years) between 1973 and 1980 (Group II) and 17 (mean age 10.9 years) from 1981 through April 1988 (Group III). Arrhythmias were congenital complete heart block in 19, postoperative heart block in 15, acquired heart block in 3, sick sinus syndrome in 3, and bradycardia-induced ventricular fibrillation in 1. Twenty-eight of 41 children had a transvenous implant: 40% of Group I, 71% of Group II and 82% of Group III. Thirteen were cephalic, four subclavian and 11 jugular. Generator site was pectoral in 19, abdominal in 12, intrathoracic in one, and retromammary in nine of 12 girls aged 10 years or more at implant. In Groups I, II and III, 5, 14 and 6 had VOO or VVI units; 5, 0 and 8 dual chamber (VAT, VDD and DDD) pacemakers; 0, 0 and 1 AAI; and 0, 0 and 2 rate-modulated (VVIR) units at initial implant. The average interval between pacer-related hospitalizations in Groups I, II and III was 20, 42, and 39 months. Complications included infection in six, hemothorax in one, and impending pacemaker erosion in one. Six patients died, one of pacer infection, four from primary cardiac disease, and one suddenly without apparent reason. Follow-up continues in 31: 14 are employed full-time, three are homemakers, eight are full-time students, and six are active pre-schoolers.(ABSTRACT TRUNCATED AT 250 WORDS)