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Biomedical subjects

M P Glode

Publications and source records attributed to M P Glode.

At least 19 recordsLinked to original sources

Periodic fever and pharyngitis in young children: a new disease for the otolaryngologist?

OBJECTIVE: A clinical entity consisting of periodic fever associated with aphthous stomatitis, pharyngitis and cervical adenitis termed "PFAPA syndrome" in young children (<5 years old) may be unfamiliar to otolaryngologists. We present our 5-year experience of PFAPA syndrome. DESIGN: Case series. SETTING: Tertiary academic. PATIENTS: A 5-year retrospective chart review for children (<5 years old) who have undergone tonsillectomies with and without adenoidectomies was conducted. Medical records from subjects who underwent the procedures for recurrent pharyngitis were reviewed with reference to a history of periodic fever and stomatitis associated with pharyngitis. INTERVENTIONS: Tonsillectomy with and without adenoidectomy. MAIN OUTCOME MEASURE: The objective measure was a comparison of the number of visits to the primary care physician for pharyngitis associated with fever in a 3-month period before and after the surgical intervention. The subjective measure was a telephone interview evaluating preoperative and postoperative symptoms. RESULTS: Of the 117 patients identified, 22 (19%) underwent surgery for recurrent pharyngitis. Five subjects (average age, 2.5 years) were identified as having PFAPA syndrome. The average number of preoperative PFAPA-related complaints was 11.6 compared with 0.2 for the number of postoperative PFAPA-related complaints (P=.03). CONCLUSIONS: Our experience suggests that PFAPA syndrome is an uncommon disease. Most of these children have undergone workup(s) for sepsis performed by their pediatricians because of the associated high fever. The clinical history of this cohort was quite distinctive. This small sample suggests a significant decrease if not cessation of pharyngitis following surgical intervention.

Adenoidectomy↗

Cerebrospinal fluid profile in patients with acute Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute vasculitis of infancy and early childhood for which there is currently no diagnostic test. The clinical presentation of KD may initially resemble other infectious diseases, including bacterial or viral meningitis. For this reason lumbar puncture (LP) is sometimes performed during the evaluation of these patients. To understand the range of cerebrospinal fluid (CSF) changes that may be associated with acute KD, a retrospective review of unselected KD patients from three pediatric centers was performed. METHODS: Retrospective chart review was performed on KD patients evaluated during the first 10 days of illness who had an LP performed before the administration of intravenous gamma-globulin. RESULTS: During the 6.5-year study period, 46 KD patients underwent LP as part of their clinical evaluation. Of these patients 18 (39.1%) had CSF pleocytosis, 1 (2.2%) had a CSF glucose <45 mg/dl and 8 (17.4%) had an elevated CSF protein. Of the patients with CSF pleocytosis, the median white blood cell count was 22.5 cells (range, 7 to 320 cells), with a median of 6.0% neutrophils (range, 0 to 79%) and 91.5% mononuclear cells (range, 11 to 100%). CONCLUSIONS: In the present series approximately one-third of KD patients who underwent an LP had CSF pleocytosis with a mononuclear cell predominance. No patient had significant hypoglycorrhachia, and elevation of the CSF protein was uncommon. CSF abnormalities were similar between US and Japanese KD patients. The basis for the CSF pleocytosis in acute KD patients remains unknown.

Acute Disease↗

Intravenous gamma-globulin treatment and retreatment in Kawasaki disease. US/Canadian Kawasaki Syndrome Study Group.

OBJECTIVE: To determine the prevalence and outcome of intravenous gamma-globulin (IVIG) retreatment in patients with Kawasaki disease (KD). METHOD: Multicenter, retrospective survey of all children with KD evaluated at nine clinical centers across North America during a 15-month period. RESULTS: Data were available for 378 patients. At 48 h after completion of the initial IVIG infusion, 50 patients (13.2%) remained febrile, 29 (58.0%) of whom were retreated with IVIG, including 4 (13.8%) with coronary artery abnormalities before their first IVIG infusion. Among 25 retreated patients with a normal baseline echocardiogram, 5 (20.0%) developed coronary abnormalities and were termed "treatment failures." Among the 323 patients with a normal baseline echocardiogram, only 9 (2.8%) were treatment failures; treatment failure occurred in 4 of 282 (1.4%) patients who became afebrile post-IVIG and in 5 of 41 (12.2%) patients with persistent or recrudescent fever after their first course of IVIG therapy (P=0.002). CONCLUSIONS: The overall prevalence of new coronary abnormalities in KD patients treated with IVIG and aspirin remains low. Persistent or recrudescent fever after the first course of IVIG was associated with an increased risk of treatment failure (P=0.002). IVIG retreatment in patients who remain febrile after the first course of IVIG is now common (58.0%), although the efficacy of this practice requires assessment with a randomized trial.

Chi-Square Distribution↗

Simultaneous administration of a diphtheria and tetanus toxoids and acellular pertussis vaccine with measles-mumps-rubella and oral poliovirus vaccines.

OBJECTIVE: To compare the safety and immunogenicity of Lederle Laboratories' (Pearl River, NY) diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine with diphtheria and tetanus toxoids and whole-cell pertussis (DTwP) vaccine when administered simultaneously with measles-mumps-rubella (MMR) vaccine and trivalent oral poliovirus (OPV) vaccine at 15 to 16 months of age. DESIGN: Randomized and double-blind. SETTING: Two general pediatric practices. PARTICIPANTS: Ninety-seven infants, aged 15 to 16 months, who had received three previous DTwP immunizations. SELECTION PROCEDURES AND INTERVENTIONS: Healthy children received the DTaP or DTwP vaccine. Infants received the MMR vaccine at a separate site and the OPV vaccine concurrently. Blood was obtained on day 0 and at 6 weeks. Adverse events were recorded by parents at specified times after immunization. MEASUREMENTS/RESULTS: Within 3 days of immunization, DTaP vaccine recipients had less fever, drowsiness, and irritability (P = .01, .04, .01, respectively). They also experienced less tenderness, erythema, and induration (.001, .001, and .002, respectively). There was no difference in the frequency of adverse reactions 6 to 14 days after immunization. Enzyme-linked immunosorbent assays were used to determine all antibody values. Antibody responses to filamentous hemagglutinin and pertussis toxoid were significantly greater in the DTaP group (P = .0001 and .02, respectively). Immune responses to the other measured antigens were similar. CONCLUSIONS: Simultaneous administration of the Lederle DTaP with MMR and OPV vaccines did not interfere with antibody response to pertussis antigens measured or measles, mumps, or rubella viruses and was associated with fewer local and systemic adverse events during the first 3 days following immunization when compared with the simultaneous administration of the DTwP, OPV, and MMR vaccines. We conclude that the DTaP vaccine can be administered at 15 months of age concurrently with the MMR and OPV vaccines.

Anorexia↗

Selective expansion of T cells expressing T-cell receptor variable regions V beta 2 and V beta 8 in Kawasaki disease.

Kawasaki disease (KD) is an acute vasculitis complicated by the development of coronary artery abnormalities. The etiology of KD is unknown. Based on the observation that KD is associated with marked activation of T cells and monocyte/macrophages, we hypothesized that KD may be caused by a superantigen [e.g., a bacterial toxin that stimulates T cells expressing particular T-cell receptor beta chain variable (V beta) gene segments]. Peripheral blood T cells from patients in the acute and convalescent phases of KD and from various control groups were analyzed for T-cell receptor V beta gene expression by using a quantitative PCR technique and cytofluorographic analysis with available anti-V beta monoclonal antibodies. Patients with acute KD demonstrated significantly elevated levels of circulating V beta 2+ and V beta 8.1+ T cells compared to the other control groups. none of the other 20 V beta populations analyzed by quantitative PCR were found to be significantly elevated. Using flow cytometry, we confirmed a significant elevation of T cells reactive with anti-V beta 8.1 and the lack of change in several other V beta subsets--i.e. V beta 5.1, -5.2, -6.7, and -12. During the convalescence phase of KD, there was a reduction in the abnormal levels of V beta 2+ and V beta 8.1+ T cells. These observations suggest that KD may be caused by a superantigen and may provide insight into the nature of the etiologic agent.

Gene Expression↗

Maximal voluntary work and cardiorespiratory fitness in patients who have had Kawasaki syndrome.

To assess the natural history of Kawasaki syndrome and its effect on maximal voluntary work and cardiorespiratory fitness, we performed cycle ergometry testing in 47 patients who had had the syndrome. Forty-one patients performed maximal effort as judged by achievement of 95% predicted heart rate response. Oxygen consumption, carbon dioxide production, and minute ventilation were performed in 23 patients. There was no difference in maximal voluntary work (total work, mean power) or maximal oxygen consumption between case subjects and control subjects. There were no differences between patients with and those without aneurysms. Serial exercise studies were performed in 10 patients; of these, two with initially normal exercise study findings had decreased maximal voluntary work and oxygen consumption with ischemic changes, and both were at high risk for the development of stenotic or occlusive coronary arteries. The other eight patients had normal cardiorespiratory reserve and no ischemic changes with serial studies. These results suggest that patients have normal cardiorespiratory fitness after Kawasaki syndrome. With the development of ischemic heart disease, they may have decreased cardiorespiratory reserve. Serial evaluation of cardiorespiratory fitness may demonstrate ischemic heart disease.

Adolescent↗

Diphtheria-tetanus toxoids-pertussis vaccination does not increase the risk of hospitalization with an infectious illness.

The purpose of this study was to determine whether children hospitalized with a primary diagnosis of infection were more likely than matched controls to have had a diphtheria-tetanus toxoids-pertussis immunization in the 30 days before hospitalization of the case. Cases were less likely than controls to have received an immunization (P = 0.003). They were also less likely to have been breast-fed (P < 0.001) and to have had a well-child care clinic visit (P = 0.01). Cases were significantly more likely to be preterm (< 38 weeks gestation), low birth weight (< 2500 g) and attending day care than their matched nonhospitalized controls (P = 0.003, 0.03 and 0.002, respectively). This study demonstrates no association between receipt of diphtheria-tetanus toxoids-pertussis immunization and subsequent hospitalization for an infectious illness.

Case-Control Studies↗

A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome.

BACKGROUND: Treatment of acute Kawasaki syndrome with a four-day course of intravenous gamma globulin, together with aspirin, has been demonstrated to be safe and effective in preventing coronary-artery lesions and reducing systemic inflammation. We hypothesized that therapy with a single, very high dose of gamma globulin would be at least as effective as the standard regimen. METHODS: We conducted a multicenter, randomized, controlled trial involving 549 children with acute Kawasaki syndrome. The children were assigned to receive gamma globulin either as a single infusion of 2 g per kilogram of body weight over 10 hours or as daily infusions of 400 mg per kilogram for four consecutive days. Both treatment groups received aspirin (100 mg per kilogram per day through the 14th day of illness, then 3 to 5 mg per kilogram per day). RESULTS: The relative prevalence of coronary abnormalities, adjusted for age and sex, among patients treated with the four-day regimen, as compared with those treated with the single-infusion regimen, was 1.94 (95 percent confidence limits, 1.01 and 3.71) two weeks after enrollment and 1.84 (95 percent confidence limits, 0.89 and 3.82) seven weeks after enrollment. Children treated with the single-infusion regimen had lower mean temperatures while hospitalized (day 2, P less than 0.001; day 3, P = 0.004), as well as a shorter mean duration of fever (P = 0.028). Furthermore, in the single-infusion group the laboratory indexes of acute inflammation moved more rapidly toward normal, including the adjusted serum albumin level (P = 0.004), alpha 1-antitrypsin level (P = 0.007), and C-reactive protein level (P = 0.017). Lower IgG levels on day 4 were associated with a higher prevalence of coronary lesions (P = 0.005) and with a greater degree of systemic inflammation. The two groups had a similar incidence of adverse effects (including new or worsening congestive heart failure in nine children), which occurred in 2.7 percent of the children overall. All the adverse effects were transient. CONCLUSIONS: In children with acute Kawasaki disease, a single large dose of intravenous gamma globulin is more effective than the conventional regimen of four smaller daily doses and is equally safe.

Acute Disease↗

Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki disease. United States Multicenter Kawasaki Disease Study Group.

STUDY OBJECTIVES: (1) To determine those diseases that most often mimic Kawasaki disease (KD) in the United States. (2) To examine the physical findings and laboratory studies that influenced experienced clinicians to exclude the diagnosis of KD. (3) To compare epidemiologic features of patients with KD and patients referred for evaluation of possible KD in whom alternative diagnoses were established. DESIGN: Case comparison study. SETTING: Seven pediatric tertiary care centers. PATIENTS: Consecutive sample of 280 patients with KD and 42 comparison patients examined within the first 14 days after onset of fever. MEASUREMENTS AND MAIN RESULTS: (1) Infectious diseases, particularly measles and group A beta-hemolytic streptococcal infection, most closely mimicked KD and accounted for 35 (83%) of 42 patients in the comparison group. (2) The standard diagnostic clinical criteria for KD were fulfilled in 18 (46%) of 39 patients in whom other diagnoses were established. (3) Patients with KD were significantly less likely to have exudative conjunctivitis or pharyngitis, generalized adenopathy, and discrete intraoral lesions, and more likely to have a perineal distribution of their rash. The patients with KD were also more likely to have anemia and elevated erythrocyte sedimentation rate; leukocyte count less than 10 X 10(3)/mm3 and platelet count less than 200 X 10(3)/mm3 were significantly less prevalent in patients with KD. (4) Residence within 200 yards of a body of water was more common among KD patients. CONCLUSIONS: (1) Measles and streptococcal infection should be excluded in patients examined for possible KD. (2) Laboratory studies that may be useful in discriminating patients with KD from those with alternative diagnoses include hemoglobin concentration, erythrocyte sedimentation rate, and serum alanine aminotransferase activity. (3) Residence near a body of water may be a risk factor for the development of KD.

Age Factors↗

Absence of interferon in sera of patients with Kawasaki syndrome.

We measured serum interferon concentrations in 42 patients with Kawasaki syndrome. The children ranged in age from 7 months to 6 years. All acute sera were obtained within 12 days of the onset of fever. Convalescent sera (illness day 19 to 56) were available from 25 of 42 patients. Sera were also obtained from 40 controls ranging in age from 2 months to 12 years. Control sera included healthy children (n = 14), children with bacterial infection (n = 10) and children with viral infection (n = 16). Sera were coded and interferon concentrations were measured blindly using human diploid fibroblast cell monolayers challenged with 10(4) plaque-forming units of vesicular stomatitis virus. Specimens from 10 of 16 patients with viral infection were positive for interferon. Three of 10 patients with bacterial infection had detectable serum interferon. No interferon was detected in specimens from the 14 healthy control children or the 42 children with Kawasaki syndrome. Despite the use of a sensitive assay we were unable to detect interferon in the sera of patients with Kawasaki syndrome.

Bacterial Infections↗

Outbreak of Kawasaki syndrome in Denver, Colorado: association with rug and carpet cleaning.

Between October 1984 and January 1985, the largest outbreak of Kawasaki syndrome reported to date in the continental United States (62 cases) occurred in the Front Range of the Rocky Mountains, extending from Colorado Springs, Colorado, to Cheyenne, Wyoming. Fifty-two (84%) of these Kawasaki syndrome patients lived in the Denver metropolitan area. A case-control study revealed that 16 (62%) of 26 Kawasaki syndrome patients compared with 10 (20%) of 49 matched control subjects had a history of exposure to shampooed (19%) or spot-cleaned (81%) rugs or carpets within 30 days of the Kawasaki syndrome onset date (odds ratio = 5, P less than .01). The time of exposure to shampooed or spot-cleaned rugs or carpets for 9 of 10 Kawasaki syndrome patients who had a single exposure and for all 6 Kawasaki syndrome patients who had multiple exposures were clustered within an interval 13 to 30 days before the onset of illness. Although the reason for this unusually large outbreak remains obscure, it is the third in which a statistically significant association between Kawasaki syndrome and rug or carpet cleaning has been found.

Case-Control Studies↗

Antigenic recognition by intravenous gamma-globulin of selected bacteria isolated from throats of patients with Kawasaki syndrome.

Kawasaki syndrome (KS) or mucocutaneous lymph node syndrome is an acute febrile exanthematous illness of unknown etiology. Therapy with intravenous gamma-globulin (IVGG) results in rapid defervescence, disappearance of signs and symptoms of inflammation and prevention of coronary artery aneurysms. We hypothesized that IVGG might neutralize a bacterial toxin produced by a staphylococcus or streptococcus present in the nasopharynx. We further speculated that this toxin might be detectable in serum or urine of patients. The goal of this work was to identify microbial antigens in different materials taken from patients with a clinical diagnosis of KS. We tested 23 aerobic bacterial isolates from throat cultures from 15 patients with KS, acute serum from 121 patients and 38 acute urine specimens from patients with KS. The patients ranged in age from 1 to 6 years. Specimens were tested in a standard system of counterimmunoelectrophoresis and reacted against IVGG prepared in a 25% solution. Ten of 23 aerobic bacteria (43.5%) isolated from throat cultures demonstrated a precipitation reaction with IVGG. Counterimmunoelectrophoresis testing of IVGG against acute serum and acute urine specimens was uniformly negative. IVGG contains precipitating antibody against a limited number of aerobic throat organisms. It is possible that antigenic products of one of these bacteria may be involved in the pathogenesis of KS.

Antigens, Bacterial↗

Serum antibodies to Giardia lamblia by age in populations in Colorado and Thailand.

We measured levels of antibodies to Giardia lamblia by age in serum specimens from persons in Denver, Colorado, and Soongnern, Thailand. Serum levels of immunoglobulin (Ig) G, IgM, and IgA G lamblia-specific antibodies measured by enzyme-linked immunosorbent assay increased substantially during childhood in both geographic areas, although children in Soongnern showed significantly higher mean levels of each antibody class (P less than .05). After adolescence, levels of G lamblia-specific IgM fell steadily with age in both populations. In contrast, specific IgA levels remained elevated throughout life among the Thai but decreased to low levels among adults in Denver. Similarly, rates of carriage of G lamblia were high among children aged 1 to 4 years in Denver and Soongnern (14.3% versus 26.5%, respectively) but were much lower among adults in Denver (0% versus 14%; P less than .01). These data suggest that levels of G lamblia-specific IgM may reflect exposure to the parasite early in life in both areas. Levels of parasite-specific IgA may reflect recurrent exposure to G lamblia in Soongnern, where G lamblia is endemic, but less frequent exposure to the parasite in Denver, where exposure is often episodic.

Adolescent↗

Effect of intravenous immune globulin on the coagulopathy of Kawasaki syndrome.

We studied the effects of immune globulin and aspirin versus aspirin alone on platelet count, platelet activation, and factor-mediated coagulation in patients with Kawasaki syndrome. Coagulation tests were performed on the day of admission to the study and 4 to 6 days later. Twenty-three patients were enrolled; 12 received immune globulin intravenously plus aspirin, and 11 received aspirin alone. At initiation of the study the groups were comparable with regard to age, sex, race, and time from onset of illness to study entry. Coagulation values were similar at entry with the exception that the aspirin group had a geometric mean platelet count that was higher than the platelet count in the aspirin-immune globulin group (p = 0.02). Four days after entry there were no significant differences between the two groups in any coagulation studies. Although the immune globulin preparation used has been effective in reducing the prevalence of coronary artery aneurysms, it appears to have no early effect on reduction of platelet activation or other measures of coagulopathy. The mechanism of action of immune globulin in patients with Kawasaki syndrome remains to be elucidated.

Adolescent↗

Neonatal rotavirus-associated necrotizing enterocolitis: case control study and prospective surveillance during an outbreak.

After the death of a premature infant from rotavirus-associated necrotizing enterocolitis, we instituted prospective surveillance for this disease in our neonatal intensive care unit. During the 4-month study period an additional six cases of necrotizing enterocolitis and eight cases of hemorrhagic gastroenteritis occurred. Rotavirus infection was documented in 11 of these 15 symptomatic infants, in comparison with only eight rotavirus infections in 147 asymptomatic or minimally symptomatic babies (P less than 0.0001). Stools from 110 nursery personnel tested during the outbreak did not contain rotavirus. However, 12 of 59 staff members had serum IgM antibody against rotavirus, suggesting recent infection. In a case-control study we compared babies with severe gastrointestinal illness with a control group randomly selected from asymptomatic babies in the nursery during the time of the outbreak. Univariate analysis found six categorical variables and nine continuous variables that were significantly associated with disease. Multivariate logistic regression analysis, however, found only birth weight (P less than 0.0001), rotavirus infection (P less than 0.0001), and age at time of first nonwater feeding (P less than 0.02) to be associated with gastrointestinal illness. This study provides further evidence for the role of infection in some cases of neonatal necrotizing enterocolitis and hemorrhagic gastroenteritis.

Colorado↗