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Biomedical subjects

A H Cushing

Publications and source records attributed to A H Cushing.

At least 19 recordsLinked to original sources

Secretory IgA in cervical mucus.

PURPOSE: Sexually active adolescent girls are uniquely vulnerable to sexually transmitted disease, including cervical cancer and AIDS. Little is known about the development of genital immunity in adolescents. Secretory IgA (sIgA) in cervical mucus is an important component of genital immunity. We studied sIgA levels in cervical mucus samples for both adolescent and adult females. METHODS: Samples were collected in a university-based adolescent medicine clinic and a university student health center. Participants consisted of 13 sexually active adolescent girls and fourteen adult controls. Samples were collected in the course of routine pelvic exams. All subjects were at least two years post menarche. Mucus was aspirated directly from the cervical os. Diluted samples were liquefied with a proteolytic enzyme (bromelain). Secretory IgA levels were measured by radial immunodiffusion using IgA2 from pooled human plasma as a standard. RESULTS: Secretory IgA levels for the adolescent group (mean 0.157 g/L SD 0.080) were slightly lower than for the adult group mean (0.199 g/L SD 0.130) although not statistically significant. CONCLUSIONS: Cervical sIgA levels were comparable between sexually active adolescents and adults.

Adolescent

Nitrogen dioxide and respiratory illness in children. Part III: Quality assurance in an epidemiologic study.

This report describes the quality assurance and quality control program developed for the previously reported epidemiologic study of nitrogen dioxide (NO2) and respiratory illness in children (Health Effects Institute Research Report 58, Parts I and II). The specific aims of the program were to make certain that data were sufficiently accurate, complete, verifiable, and retrievable. The quality assurance and quality control program consisted of: a written protocol, standard operating procedures, written records, a project management system, appropriate data processing, data verification, and data analysis planning, and was staffed by qualified and appropriately trained personnel. Within the activities of the overall program, two focused quality assurance studies were conducted. During the first of these focused studies, parents maintained a calendar-diary of their child's daily respiratory symptoms. Telephone interviews were conducted at intervals of two weeks, and parents used the calendars to report on symptom occurrence since the previous call. To assess the comparability of illness events based on symptom reports from the parents with usual clinical diagnostic methods, nurse practitioners examined children during illness, and office and clinic records of outpatient visits were reviewed. Using the parent reports, respiratory illnesses were defined as symptom episodes of at least two consecutive days; lower respiratory illnesses included at least one day of either wet cough or wheeze. Runny or stuffy nose was reported for 93% of illnesses; and wet cough for 33% and wheeze for 6% of illnesses. In comparison with the diagnoses made by a nurse practitioner, parent reports of wet cough or wheeze were sensitive (93.4%) for detecting lower respiratory illnesses, but nonspecific (with specificity of only 24.2%). The majority of the false-positive lower respiratory illnesses had the symptom of wet cough. The comparison of parent reports with outpatient records provided similar findings. These findings indicate that standardized reporting of respiratory illnesses can be achieved with regular telephone interviews, but the classification of specific illnesses from the observations of parents' information may differ from diagnoses made by clinicians. The second focused quality assurance study evaluated the measurement error associated with the parents' use of passive diffusion samplers for NO2. Midway through the study, technicians conducted home visits to assess compliance with stated procedures, and to make independent measurements of NO2. Based on criteria for placement and use of the samplers, conditions of noncompliance were observed on about 40% of visits.(ABSTRACT TRUNCATED AT 400 WORDS)

Data Collection

Comparability of parent reports of respiratory illnesses with clinical diagnoses in infants.

In a cohort study of respiratory illnesses from birth through age 18 months, the investigators assessed the occurrence of illness by telephone reports of respiratory symptoms. To assess the comparability of illness events based on symptom reports with usual clinical modalities, a nurse practitioner examined children during illnesses, and office and clinic records of outpatient visits were reviewed. Respiratory illnesses were defined as symptom episodes of at least 2 days; lower respiratory illnesses included at least 1 day of either wet cough or wheeze. This report is based on 10,771 illnesses in the 1,315 subjects enrolled. Runny or stuffy nose was reported for most (93%) illnesses, wet cough in 33%, and wheeze in 6%. In comparison with the diagnoses made by a nurse practitioner, parent report of wet cough or wheeze was sensitive (93.4%) for detecting lower respiratory illnesses, but nonspecific with specificity of only 24.2%. The majority of the false-positive lower respiratory illnesses had the symptom of wet cough. The comparison of parent reports with outpatient records provided similar findings. Standardized reporting of respiratory illnesses can be achieved with a telephone surveillance system but classification of specific illnesses from the surveillance information may differ from diagnoses made by clinicians.

Cohort Studies

Nitrogen dioxide and respiratory illnesses in infants.

Nitrogen dioxide is an oxidant gas that contaminates outdoor air and indoor air in homes with unvented gas appliances. A prospective cohort study was carried out to test the hypothesis that residential exposure to NO2 increases incidence and severity of respiratory illnesses during the first 18 months of life. A cohort of 1,205 healthy infants from homes without smokers was enrolled. The daily occurrence of respiratory symptoms and illnesses was reported by the mothers every 2 wk. Illnesses with wheezing or wet cough were classified as lower respiratory tract. Indoor NO2 concentrations were serially measured with passive samplers place in the subjects' bedrooms. In stratified analyses, illness incidence rates did not consistently increase with exposure to NO2 or stove type. In multivariate analyses that adjusted for potential confounding factors, odds ratios were not significantly elevated for current or lagged NO2 exposures, or stove type. Illness duration, a measure of illness severity, was not associated with NO2 exposure. The findings can be extended to homes with gas stoves in regions of the United States where the outdoor air is not heavily polluted by NO2.

Air Pollutants

Nitrogen dioxide and respiratory illness in children. Part I: Health outcomes.

We have carried out a prospective cohort study to test the hypothesis that exposure to nitrogen dioxide increases the incidence and severity of respiratory infections during the first 18 months of life. Between January 1988 and June 1990, 1,315 infants were enrolled into the study at birth and followed with prospective surveillance for the occurrence of respiratory infections and monitoring of nitrogen dioxide concentrations in their homes. The subjects were healthy infants from homes without smokers; they were selected with stratification by type of cooking stove at a ratio of four to one for gas and electric stoves. Illness experience was monitored by a daily diary of symptoms completed by the mother and a telephone interview conducted every two weeks. Illnesses with wheezing or wet cough were classified as involving the lower respiratory tract; all other respiratory illnesses were designated as involving the upper respiratory tract. Exposure to nitrogen dioxide was estimated by two-week average concentrations measured in the subjects' bedrooms with passive samplers. This analysis is limited to the 1,205 subjects completing at least one month of observation; of these, 823 completed the full protocol, contributing 82.8% of the total number of days during which the subjects were under observation. Incidence rates for all respiratory illnesses, all upper respiratory illness, all lower respiratory illnesses, and lower respiratory illness further divided into those with any wheezing, or wet cough without wheezing, were examined within strata of nitrogen dioxide exposure at the time of the illness, nitrogen dioxide exposure during the prior month, and type of cooking stove. Consistent trends of increasing illness incidence rates with increasing exposure to nitrogen dioxide were not evident for either the lagged or unlagged exposure variables. The effect of nitrogen dioxide exposure on illness occurrence during at-risk intervals of two weeks' duration was examined using the generalized estimating equation approach. In these multivariate analyses, none of the odds ratios was significantly elevated for unlagged nitrogen dioxide exposures, lagged nitrogen dioxide exposures, or stove type. Duration of illness was assessed in relation to the same exposure variables; illness duration and nitrogen dioxide exposure were not associated. We have found that indoor exposure to nitrogen dioxide is associated with neither the incidence nor the duration of respiratory illnesses. The study was designed to have sufficient power to detect effects of nitrogen dioxide exposure of magnitudes previously reported and in a range relevant to public health concern; the lack of association cannot be attributed to potential bias from misclassification of outcome or exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Pollutants

Rapid noninvasive techniques for determining etiology of bronchitis and pneumonia in infants and children.

Table 2 lists the names, abbreviations, and principle underlying most of the rapid diagnostic techniques we have described. Table 3 lists the pathogens most likely to cause lower respiratory tract infections in pediatric patients, the specimens needed for each rapid diagnostic test now generally available, and the approximate time required for its actual performance. For maximal cost-effectiveness, it is recommended that laboratory diagnosis be pursued in a stepwise manner: 1) The usual patient with acute respiratory illness who is to be managed as an outpatient may need little if any laboratory evaluation. 2) For the child for whom hospital admission is being considered, serum C-reactive protein screen, urine bacterial antigen tests, and a cold agglutinin test (at the appropriate age) will help to classify the etiology of the infection as likely or unlikely to be bacterial. If antibiotic therapy is to be given, a blood culture should be obtained before starting. 3) For the child admitted to the hospital with a possible chlamydial or viral lower respiratory infection for whom specific therapy is considered, nasopharyngeal secretions should be examined for Chlamydia and for antigens of respiratory syncytial, parainfluenza, and influenza viruses to help select the appropriate antimicrobial. Serum for IgM level may be helpful. 4) For the child who has been intubated for respiratory support, a specimen of deep respiratory secretions should be sent for Gram stain, bacterial culture, for Chlamydia, and viral antigens and culture. 5) For patients presenting with atypical symptoms, signs, or clinical course additional diagnostic possibilities should be considered and appropriate tests done even if results may not be available within 48 hours.

Agglutinins

Evaluation of a skin test for chicken pox.

Results with a VZV skin test as a marker of past infection were compared with histories of chicken pox and specific antibody detected by ELISA in 100 individuals--25 of whom were pediatric patients with malignant diseases. A negative or uncertain history was not reliable, neither were the skin test results among the oncology patients. However, among the normal individuals, the skin test when compared with the ELISA had a sensitivity of 85%, a specificity of 100%, and a positive predictive value of 100%.

Adult

Gastrointestinal carriage of toxigenic bacteria: relation to diarrhea and to serum immune response.

We followed up a cohort of babies from birth to two years by examination of fecal samples for heat-labile enterotoxigenic (LT+) bacteria and administration of a questionnaire about any episodes of diarrhea each week. We sampled serum at birth, every six months, at the beginning of an episode of diarrhea, and two weeks later. We tested sera for antibody to cholera toxin. We identified LT+ bacteria in 16% of fecal samples, LT+ Escherichia coli in 11%. Thirty-four episodes of diarrhea occurred within a week of isolation of LT+ bacteria. Bacterial species and weeks of exposure to LT+ bacteria correlated with diarrhea. Fourfold rises in antibody titer followed 53% of diarrhea episodes caused by LT+ bacteria. Whether a baby had an immune response was not related to his age, duration of diarrhea, cord serum antibody, previous asymptomatic carriage of LT+ bacteria, or breast-feeding. Second episodes did not boost antibody levels. Rises in antibody titers followed diarrhea without the presence of toxin but did not follow asymptomatic carriage of LT+ bacteria.

Age Factors

Necrotizing enterocolitis with Escherichia coli heat-labile enterotoxin.

Twenty-one babies occupied a newborn intensive care unit during two separate clusters of necrotizing enterocolitis (NEC). Seven babies had suspected NEC, seven had proved NEC, two had diarrhea only, and five were unaffected. Of affected babies, 15 had toxigenic Escherichia coli or heat-labile E coli toxin in feces detected by enzyme-linked immunosorbent assay. One of five unaffected babies had fecal toxin (P = .01). Four of 12 affected babies had a fourfold immunoglobulin M (Igm) antitoxin titer rise within 3 weeks of the fecal studies. None of five unaffected infants had a serologic immune response. The clinical disease seen in the babies was not characteristic of previously described E coli heat-labile toxin-associated diarrhea.

Diarrhea

Serum immune response to carriage of toxigenic fecal bacteria with and without diarrhea.

The relationship between asymptomatic fecal carriage of enterotoxigenic bacteria (ETB), diarrhea and serum immune response in children has not been systematically explored. We studied 40 babies between birth and two years with weekly health histories, weekly fecal samples and serum samples every six months and with diarrhea. Toxigenic bacteria and fecal toxin were identified by ELISA (cholera toxin) and Y-1 cell assay. Serum antitoxin was identified by ELISA (IgG and IgM) and toxin neutralization (Y-1 assay). Thirty-eight babies had fecal ETB 457 weeks; 36 of them had toxigenic E. coli (ETEC) 220 weeks. Twenty babies had 36 episodes of diarrhea within one week of isolation of ETB or demonstration of fecal toxin. Nineteen (53%) episodes in 11 (55%) babies were followed by an antibody response within one to three weeks. Sixty-one sera were positive. Forty-three (69%) of the positives were preceded within one month by toxin and diarrhea. Ten (17%) were preceded by diarrhea but no toxin; five were preceded by toxin but no diarrhea; three were preceded by neither. Twenty-four (64%) of the babies who carried ETB had a serologic response to toxin at some time during the observation period. Antibody responses followed identification of toxigenic E. coli in 17 instances, Klebsiella in four, Citrobacter in two, colony pools in four, and fecal water in 21. Asymptomatic carriage of enterobacteria which elaborated toxin immunologically and functionally similar to cholera toxin was common among these babies but serum antibody responses were significantly more common following toxin-related diarrhea.

Antibodies, Bacterial

Pediatric plague.

The large reservoir of animal plague in the American West led to 121 cases of human plague from 1970 to 1980. The majority (55%) of recent cases have occurred in children 16 years of age and younger. In New Mexico 38 pediatric plague cases were reviewed to determine the epidemiologic, clinical, and laboratory feature of this disease. Thirty-one patients (82%) had bubonic plague and seven (18%) had primary septicemic disease. Primary septicemic plague had a significantly higher case-fatality ratio (71% vs 3%; P = .0002) and an increased risk of plague pneumonia (57% vs 6%; P = .01) compared with bubonic disease. Symptoms at onset, physical examination, and laboratory data at hospitalization (mean of three days after onset) were consistent with an acute, systemic febrile illness. Recovery from plague was slow, requiring an average of 5.9 days from initiation of effective antibiotics until fever lysis. Only a minority of plague patients were initially suspected to have plague, even by the time of hospitalization. Whereas clinical evidence, particularly in bubonic disease, should suggest plague, residing in or visiting a rural are of the West (especially from June through September) during the week prior to illness may be the only useful epidemiologic clue for the majority of patients who lack a history suggestive of exposure to animals or fleas. The importance of pediatric plague stems from the recent increase in cases, the significant increase in the proportion of all cases occurring in children, the public health implications of plague pneumonia (16% of cases), and the demonstrated potential for plague patients to travel to areas of the country unfamiliar with the disease and its sylvatic home in the American West.

Adolescent

Diarrhea in breast-fed and non-breast-fed infants.

During the first year of life a group of babies was prospectively observed for diarrhea and for fecal carriage of heat-labile toxigenic bacteria, with or without colonization factor, and rotavirus. Approximately half of the babies were breast-fed for the first six months of life. There was no difference between groups (breast-fed vs non-breast-fed) in number of babies who had diarrhea during any two-month period. Nor was there any difference between groups in the number of babies who had diarrhea while carrying toxigenic bacteria, with or without colonization factor. Secretory antibody to toxin was found in 37% of colostrum and milk samples. There was a small but insignificant difference in the number of babies who had diarrhea when they carried toxigenic bacteria depending on the presence of antibody in the breast milk they received.

Bacterial Toxins

Suppression of rabbit peritoneal macrophage migration by heat-labile E. coli toxin.

Migration of rabbit peritoneal macrophages toward casein-serum was inhibited by preincubation of the cells with heat-labile toxin of Escherichia coli in direct relationship to the concentration of toxin in the incubation mixture. Cells preincubated with heated toxin or with toxin-antiserum migrated the same as those which had been incubated in toxin-free media. Toxin-preincubated cells had levels of cyclic AMP which were increased in direct relationship to the concentration of toxin in the preincubation mixture. Heated toxin failed to induce increased levels of cAMP in the cells at the highest concentration tested.

Animals

Cellulitis and necrotizing fasciitis of the abdominal wall in pediatric patients.

Soft tissue infections of the abdominal wall in 14 children were classified as cellulitis (8), necrotizing fasciitis (5), or myositis/myonecrosis (1). These 3 categories were characterized by increasing anatomic depth of infection, clinical severity, and need for more radical surgical treatment. Ten of the 14 children were neonates. The most frequent associations were omphalitis (5), necrotizing enterocolitis (4), and urachal anomalies (3). The severest infections were usually polymicrobial and contained both aerobic and anaerobic bacteria. Important clinical findings in children with necrotizing fasciitis and myositis/myonecrosis were tachycardia, systemic toxicity, severe edema, and, in older children, pain out of proportion to the apparent degree of infection. None of the children had fever or crepitation of the wound. An ominous sign, indicative of the need for immediate, radical debridement was the appearance of a patch of dusky or gangrenous skin. There were two deaths associated with delayed diagnosis of necrotizing fasciitis. One child did not receive radical debridement, and the other received it too late to be of benefit. Although these infections are rare in children, their lethal potential and early diagnostic signs must be recognized.

Abdominal Muscles