Risk factors of infantile spasms compared with other seizures in children under 2 years of age.

To analyze the magnitude of the risk factors for infantile spasms, we evaluated the records of 80 children with infantile spasms, 474 children with other types of epilepsy, 2,196 children with febrile seizures, and 262 children with CNS infections. There was a family history of seizures in 13.8% of children with infaNtile spasms, 28.5% of children with other forms of epilepsy, 25.5% of children with febrile seizures, and 5.3% of children with CNS infections. Children with a family history of seizures were 2.82 times more likely to have infantile spasms, 7.05 time more likely to have other epilepsy, and 6.08 time more likely to have febrile seizures than controls (children with CNS infections). However, a family history of seizures increased the risk for infantile spasms only in the cryptogenic group. Children with infantile spasms were significantly more likely to have cerebral palsy, microcephaly, hydrocephaly, CNS malformations, neonatal hypoxia, or neonatal seizures than children with other types of epilepsy, febrile seizures, or CNS infections. There was a modest genetic predisposition to seizures in children with infantile spasms. However, our data suggest a much stronger association with underlying neurologic abnormalities, mainly neonatal seizures, neonatal hypoxia, and CNS malformations.

Household contact study of Bordetella pertussis infections.

Household contacts of primary pertussis cases were evaluated. Infection was determined by culture, direct fluorescent antibody assay, and serological criteria. Agglutinin titers and values of ELISA IgG and IgA antibodies to lymphocytosis-promoting factor, filamentous hemagglutinin, and pertactin were determined. In 39 households 255 subjects were exposed; 114 remained well (group 1), 53 had mild illness (group 2), and 88 had pertussis (group 3). The infection rates were 46% (group 1), 43% (group 2), and 80% (group 3). In a subgroup of subjects seen within 14-28 days of exposure, it was found that none with clinical pertussis had a value of IgG antibody to pertactin in acute-phase sera of > or = 50 ELISA units (EU) per mL or an agglutinin titer of > 256. Of the primary cases, 53% were > or = 13 years of age. These data point out the importance of Bordetella pertussis infections in adolescents and adults as a source of infection in young children. Our subgroup data suggest that high values of antibody to pertactin and high agglutinin titers may be predictive of protection against clinical pertussis.

Frequency of unrecognized Bordetella pertussis infections in adults.

To investigate the frequency of unrecognized Bordetella pertussis infections in adults, we performed IgA and IgG ELISA antibody studies with four B. pertussis antigens--i.e., lymphocytosis-promoting factor, filamentous hemagglutinin, pertactin, and fimbriae-2--in 51 health care workers from whom six consecutive yearly serum samples (from 1984 to 1989) were available. Overall, 90% of the subjects had a significant increase in antibody (IgA or IgG) to one or more antigens between 2 consecutive years during the 5-year study period; 55% of subjects had evidence of two infections, 17% had three infections, and 4% had four infections. Infections occurred in all study years, with the following rates: 1984-1985, 32%; 1985-1986, 24%; 1986-1987, 40%; 1987-1988, 29%; and 1988-1989, 43% (P = .12). Some antibody rises may have been due to responses to cross-reacting antigens (Bordetella parapertussis, nontypable Haemophilus influenzae), but overall these data suggest that B. pertussis infections in adults are common, endemic, and usually unrecognized.

Comparison of values of antibody to Bordetella pertussis antigens in young German and American men.

Pertussis is well controlled in the United States by routine childhood immunization. In contrast, this disease is endemic and epidemic in Germany because routine immunization has not been implemented. To gain information relating to the epidemiology of Bordetella pertussis infections, we examined the prevalence and magnitude of B. pertussis agglutinins and of IgG and IgA antibodies (detected by enzyme-linked immunosorbent assay) to four B. pertussis antigens--lymphocytosis-promoting factor, filamentous hemagglutinin, pertactin, and fimbriae-2--in the sera of 119 American university students and 119 German military recruits of similar age. Geometric mean titers of agglutinins and geometric mean values for IgG antibodies to the four antigens were two- to threefold higher in sera from the American students than in sera from German recruits. In contrast, the geometric mean IgA values and the percentage of subjects with detectable IgA antibodies to the four antigens were similar in the two populations. Since IgA antibody results mainly from infection and not from immunization, our data suggest that B. pertussis infections are common among both American and German young adults despite the marked difference in rates of clinical pertussis in the two countries.

Clinical characteristics of illness caused by Bordetella parapertussis compared with illness caused by Bordetella pertussis.

In conjunction with a pertussis vaccine efficacy trial in Germany, nasopharyngeal specimens were collected from May, 1992, to March, 1993, from patients with cough illnesses. Clinical data were obtained by initial and follow-up questionnaires. Bordetella parapertussis was isolated from 38 patients (mean age, 3.5 years; 68% girls). Clinical characteristics in these cases were compared with those of 76 patients (matched by age and sex) with illness caused by Bordetella pertussis during the same period. Findings were: (B. pertussis/B. parapertussis): cough > 4 weeks 57%/37% (P = 0.06); whoop 80%/59% (P = 0.07); whoop > 2 weeks 26%/18% (P = 0.05); paroxysms 90%/83% (P = 0.5); body temperature > or = 38 degrees C 9%/0% (P = 0.17); vomiting 47%/42% (P = 0.69); and mean leukocyte and lymphocyte counts 12,500/mm3 and 7600/mm3 (P < 0.0001) and 7800/mm3 and 3500/mm3 (P < 0.0001), respectively. Illness caused by B. parapertussis was typical of pertussis but less severe than that caused by B. pertussis. In contrast with B. pertussis infection, lymphocytosis is not a characteristic of B. parapertussis infection. This is most likely a result of the lack of production of lymphocytosis-promoting factor toxin by B. parapertussis.

Comparative study of Lederle/Takeda acellular and Lederle whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines in infants in Germany.

In preparation for a large efficacy trial in Germany, a pilot study was initiated in December 1990. In this study 149 infants were enrolled; with double-blind randomization 75 received Lederle/Takeda acellular pertussis component diphtheria-tetanus-pertussis vaccine (APDT) and 74 received Lederle whole-cell pertussis component diphtheria-tetanus-pertussis vaccine (DTP). The mean age at first dose was 3.5 months, and the second and third doses followed at 6-week intervals. Reactions were relatively mild with both vaccines; in general they were less frequent following APDT. The IgG antibody responses to lymphocytosis promoting factor (LPF) and fimbriae-2 were similar in both groups whereas the responses to pertactin and filamentous haemagglutinin (FHA) were greater in APDT recipients. DTP recipients had greater responses to tetanus and diphtheria toxoids. When age of first dose was examined (8-12 weeks versus 16-20 weeks), it was found that young age had a suppressive effect on antibody responses in DTP but not APDT recipients to LPF toxoid, pertactin, fimbriae-2, and tetanus and diphtheria toxoids. High values of transplacentally acquired antibody lessened the response to LPF toxoid and tetanus toxoid in DTP recipients and to tetanus toxoid in APDT vaccinees. The IgG immune response to LPF toxoid, FHA and fimbriae-2 was found to be more uniform in APDT recipients than in DTP vaccinees. An IgA antibody response to fimbriae-2 was noted in 13% of DTP recipients but in no APDT vaccinees. The broad immunogenicity and mild reactogenicity of this APDT vaccine justifies its use in the German efficacy trial.

Growth of the human optic disk and nerve during gestation, childhood, and early adulthood.

We measured vertical and horizontal diameters of the optic disk and retrobulbar optic nerve in eyes from 95 patients on whom autopsies were performed at the UCLA Medical Center over a 20-year period. Ages at death ranged from 4.8 months' gestation to 21.9 years. Optic disk surface area and nerve cross-sectional area were calculated for each subject by using the formula for an ellipse. Approximately 50% of the growth of the optic disk and nerve occurs by 20 weeks' gestation, and 75% by birth; 95% of the growth occurs before the age of 1 year. All optic disk and nerve measurements correlate strongly (correlations > .67; P < .0001) with subject height and globe anteroposterior diameter. We applied our results to the current understanding of optic disk and nerve development, and compared them to previous clinical and pathologic studies of optic nerve dimensions in adults and older children.

Pertussis immunization and characteristics related to first seizures in infants and children.

In a previous study in which we examined the relationship of pertussis immunization to the onset of neurologic disorders during 1967 and 1968 and during 1972 and 1973 in Denmark, there were 554 children with initial onset of epilepsy and 2158 children with first febrile convulsions. In the study population there were 112 children with epilepsy and 229 children with febrile convulsions for whom the exact date of pertussis immunization and the exact date of the onset of illness were known. We analyzed selected clinical variables by specific time intervals between pertussis immunization and the first seizure. In the children with epilepsy, no relationship was found between time of pertussis immunization and the specific variables that were examined. In contrast, the following characteristics in children with febrile seizures were significantly more common when pertussis immunization had occurred within 3 days, compared with more than 7 days of the event: first seizure more than 10 minutes in duration, the occurrence of more than one seizure, the longest seizure (when there was more than one) more than 10 minutes in duration, and the occurrence of a seizure described as focal. The lack of specific characteristics in epilepsy that had its onset in a temporal relationship to pertussis immunization is further evidence that pertussis vaccine does not cause this disorder. The cause of increased severity of febrile seizures apparently associated with pertussis immunization is unknown.

Severe reactions associated with diphtheria-tetanus-pertussis vaccine: detailed study of children with seizures, hypotonic-hyporesponsive episodes, high fevers, and persistent crying.

OBJECTIVE: The pathophysiology of severe reactions to diphtheria-tetanus-pertussis (DTP)vaccine is not well understood. Active pertussis toxin in DTP vaccine has been proposed to cause severe DTP vaccine reactions. Large doses of pertussis toxin cause hyperinsulinemia and hypoglycemia as well as leukocytosis with a predominant lymphocytosis in animal models. To learn more about the causes of and risk factors for severe DTP vaccine reactions, children experiencing severe DTP vaccine reactions were studied. DESIGN: Prospective, referral-based surveillance. SETTING: Los Angeles, CA. SUBJECTS: Children experiencing severe reactions within 48 hours of DTP immunization and evaluated within 24 hours of the reaction. Severe reactions included encephalopathy, persistent crying > or = 3 hours, hypotonic-hyporesponsive episodes (collapse episodes), fever > or = 40.5 degrees C, or seizures. Some comparisons were made between children with DTP vaccine-associated seizures and a comparison group of children experiencing febrile seizures unrelated to immunization. OUTCOME MEASURES: A history and physical examination were performed. Follow-up examinations were performed 1 month later. Blood was collected for complete blood cell count with leukocyte differential count, serum chemistry measurements, and insulin and glucose values. Serum was assayed for active pertussis toxin, both in free and immune-complex masked states. RESULTS: Sixty children experienced severe reactions within 48 hours of DTP immunization: 32 children had seizures only, 14 subjects had hypotonic-hyporesponsive episodes, 2 subjects had fever > or = 40.5 degrees C only, 4 subjects had persistent crying > or = 3 hours, 6 children had seizures and fever > or = 40.5 degrees C, and 2 children had persistent crying and seizures. The children with seizures had a high rate of personal and family histories of seizures, and 90% had documented fevers (> or = 38 degrees C). Persistent crying was associated with painful local reactions. Effects that may have been due to vaccine pertussis toxin were not found. Lymphocytosis did not occur, nor did hypoglycemia. Some relatively elevated insulin values were noted; however, this finding was also noted in the comparison group of children experiencing febrile seizures unrelated to immunization. No biologically active pertussis toxin was found in the acute sera of children experiencing severe DTP vaccine reactions. CONCLUSIONS: Seizures associated with DTP vaccine have similar clinical characteristics as febrile seizures, and persistent crying is initiated by painful local reactions. Vaccine endotoxin is a cause of febrile DTP vaccine reactions. We found no evidence that DTP vaccine pertussis toxin plays a role in severe DTP vaccine reactions.

Reliability of filter-strip sampling of gingival crevicular fluid for volume determination using the Periotron.

This study explored gingival cervicular fluid (GCF) volumes as measured by the Periotron in an attempt to find a more objective measure of gingival inflammation that could be used in dental compliance studies. The first step in this process was to assess the reliability of the method of collecting and determining GCF volumes as described by the manufacturer. Collections of GCF from both the buccal and lingual surfaces of 6 teeth from 18 subjects with good to moderate plaque accumulation was accomplished. At a later time these same surfaces were retested for a comparison with the initial value for reliability determination. We found that only 23% of the tooth surface pairs varied by less than 20% and 57% of these pairs differed by at least 50%. These values were similar for both good and moderate plaque accumulation subjects. In these subjects, reliability measurements at individual tooth surfaces did not approach acceptable levels of reliability. However, when the GCF values from the 12 tooth surfaces were averaged for each subject, differences between the two measurements improved markedly. Sixty-one percent of these subject pairs differed by less than 20%. Therefore, the average GCF value from subjects with good to moderate plaque accumulations may be compared with reasonable accuracy.

Immunogenicity and reactogenicity of Takeda acellular pertussis-component diphtheria-tetanus-pertussis vaccine in 2- and 3-month-old children in Japan.

OBJECTIVE: To compare the reactogenicity and immune response to the Takeda acellular pertussis-component diphtheria-tetanus-pertussis (APDT) vaccine in children when immunization commenced at 2 months (group A) vs 3 months (group B) of age. DESIGN: Longitudinal, nonblinded, comparative study. SETTING: Pediatric well-child clinics. PARTICIPANTS: Healthy 50- to 98-day-old infants. RESULTS: Good antibody responses to lymphocytosis-promoting factor, filamentous hemagglutinin, agglutinogens, and pertactin occurred in both age groups after both the third and fourth vaccine doses. Both young age and transplacentally acquired maternal antibody independently and together have a suppressive effect on the response to the four antigens in this APDT vaccine. However, these effects appear to be minor. Vaccine reactions were mild; group A children had slightly but not significantly higher rates than group B children. CONCLUSION: The present US diphtheria and tetanus toxoids and pertussis vaccine immunization schedule should also be satisfactory with this acellular pertussis component vaccine.

Pathophysiology of reactions associated with pertussis vaccine.

Many adverse clinical events occur after pertussis immunization in children, but the pathophysiology is not well understood. It has been suggested that some of these adverse events may be due to biologically-active LPF and endotoxin present in DTP vaccines. Fifty-six children were studied who experienced severe reactions (fever greater than or equal to 40.5 degrees C, seizures, persistent crying greater than or equal to 3 hours or hypotonic-hyporesponsive episodes) within 48 hr of DTP immunization. Leukocytosis with neutrophilia was noted acutely (after vaccination) compared to follow-up (approximately one month later). No changes in insulin or glucose values were noted. Utilizing the CHO cell assay, no biologically-active LPF was found in the acute sera of children who had DTP-associated seizures. We found no evidence that biologically-active LPF or altered insulin/glucose metabolism were related to severe DTP-associated reactions.

Papanicolaou smear cell recovery techniques used by primary care physicians.

Nine hundred Tennessee-based internists, family physicians, and obstetrician-gynecologists were randomly selected and surveyed to identify Papanicolaou smear cell recovery methods used in their practices. This 16-item survey also requested typical laboratory reporting procedures on Papanicolaous smears. The most frequently reported cell sampling technique was the combination cotton-tipped applicator and spatula, which was used by 47 percent of all physicians. Use of the cervical cytobrush for Papanicolaou smears, which has been shown to improve the detection of cervical dysplasia, was used alone or in combination by 19 percent of those surveyed, of whom 72 percent were gynecologists. Cervical sampling should contain cells from the transformation zone as evidenced by an adequate number of endocervical cells on the smear. Laboratories reporting the presence of endocervical cells were significantly different (P less than 0.05) among the specialties, with 26 percent of the internists', 18 percent of the family physicians', and 15 percent of the obstetricians' laboratories not providing this information in their reports. Reporting inadequate smears is a necessary first step toward improved sampling technique. Without this information, physicians risk missing pathology through reports of false-negative Papanicolaou smears.

Quantifying interictal metabolic activity in human temporal lobe epilepsy.

The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on [18F]fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a single investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism.

Metabolic and hematologic effects and immune complex formation related to pertussis immunization.

Selected metabolic, hematologic, and immunologic functions were evaluated in 3- to 6-mo-old Finnish infants who received whole-cell pertussis-component diphtheria and tetanus toxoids and pertussis vaccine, adsorbed (DTP) vaccine, and in 4- to 6-y-old Los Angeles children who received either a licensed DTP vaccine or an acellular pertussis component DTP vaccine. One d after immunization, there was an increase in total leukocytes and neutrophils and a decrease in lymphocytes in all vaccinees. In 4- to 6-y-old children the leukocytosis and neutrophilia were greater in recipients who received the standard DTP vaccine than in vaccinees who received an acellular pertussis component DTP vaccine. In infants there was an increase in the mean plasma insulin concentration but no change in the glucose concentration 24 h after immunization; no increase in the mean plasma insulin was noted in the 4- to 6-y-old children. Three 4- to 6-y-old vaccinees had higher circulating immune complex concentrations after immunization and two of these children had high clinical reaction scores. The etiology of adverse reactions after DTP immunization is multifactorial. In contrast with findings in animals, our findings do not demonstrate a clinically significant effect due to lymphocytosis-promoting factor on glucose metabolism in vaccinated children. Neutrophilia in vaccinees is probably due to endotoxin, and some reactions may be due to circulating immune complexes.

Comparison of acellular and whole-cell pertussis-component DTP vaccines. A multicenter double-blind study in 4- to 6-year-old children.

An acellular pertussis-component combined diphtheria and tetanus toxoids, and pertussis (APDT) vaccine adsorbed was compared with a licensed whole-cell pertussis-component combined diphtheria and tetanus toxoids, and pertussis (DTP) vaccine adsorbed for reactogenicity and immunogenicity when given as the fifth DTP immunization to eighty-two 4- to 6-year-old children. The reaction rates with both vaccines were low; APDT vaccine recipients had significantly less pain and warmth at the injection site than did DTP vaccine recipients. Antibody responses to pertussis antigens (lymphocytosis-promoting factor, filamentous hemagglutinin, and agglutinogens) and to diphtheria and tetanus toxoids were all brisk. The APDT vaccine recipients had a more marked response in antibodies to filamentous hemagglutinin and a less marked response in agglutinins than whole-cell vaccine recipients. On the day after immunization, both APDT and DTP vaccine recipients had an increase in mean leukocyte and neutrophil counts. This APDT vaccine is immunogenic and less reactogenic than a DTP vaccine with a whole-cell pertussis component when administered as a booster to 4- to 6-year-old children.

Variability of indexes for myocardial ischemia: a comparison of exercise treadmill test, ambulatory electrocardiographic monitoring and symptoms of myocardial ischemia.

Fifty-four patients with chronic stable angina were studied to determine and compare weekly variability of indexes for the detection of myocardial ischemia. All patients underwent three single-blind placebo periods, each lasting 1 week. An exercise treadmill test, 24 h ambulatory electrocardiographic (Holter) monitoring (analyzed blindly) and an accurate diary of anginal attacks and nitroglycerin use were obtained at the end of each placebo period. An unbalanced, completely random component of variance analysis was used to calculate a component for within subject variability and a component for among subject variability. The coefficient of variation and percent variation (within subjects) of onset of chest pain during exercise were 19% and 30%, respectively; the corresponding values were 28% and 33% for onset of 1 mm ST depression, 15% and 15% for exercise duration, 44% and 27% for number of ischemic episodes/24 h, 56% and 43% for anginal frequency and 55% and 27% for nitroglycerin consumption, respectively. With use of this statistical method and variation within subjects, the change in the value of each variable necessary to exceed those attributable to spontaneous variation was determined. The trade-off between repeated measurements and number of subjects, the sample size estimated for planning studies and the minimal sample size for using various designs were also determined. Although the data indicate that all indexes for myocardial ischemia, both during exercise and during daily activity, vary considerably, but the exercise variables have less variability and are more reproducible.(ABSTRACT TRUNCATED AT 250 WORDS)