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Biomedical subjects

D W Scheifele

Publications and source records attributed to D W Scheifele.

At least 37 records · Page 2Linked to original sources

Influenza immunization in children with chronic arthritis: a prospective study.

OBJECTIVE: Influenza immunization is recommended for children with chronic conditions and children receiving chronic acetylsalicylic acid therapy. Our study assessed the safety and immunogenicity of this vaccination in children with chronic arthritis. METHODS: The frequency of possible adverse reactions following influenza vaccination, and virus specific HI antibody levels prior to and 4 weeks after vaccination with an inactivated split virus vaccine prepared for the 1991/92 season, were assessed in a prospective open study of children with chronic arthritis. Thirty-four patients were assessed clinically at vaccination and one month later. Local symptoms at the injection site and systemic symptoms were assessed by diary in 26 patients and 13 immunized healthy control children. RESULTS: Tenderness and/or redness at the injection site, and fever occurred equally in patients and controls. Malaise/nausea occurred in 12 patients and 3 controls (p = 0.3), but patients had more symptomatic days than controls (p = 0.01). No child with inactive arthritis developed a swollen joint following immunization. There were no significant differences between the 2 visits for a.m. stiffness, pain (VAS), global assessment, joint count or erythrocyte sedimentation rate (ESR). More patients improved than deteriorated by each measure. Three patients deteriorated by global assessment, 7 patients had an increased joint count. At least 95% of patients developed presumably protective levels of antibodies (HI titers > or = 40) to each virus. Preimmunization titers, seroresponse rates (4 x rise or rise from < 20 to > or = 40) and final titers were the same between patients (whether or not they were taking prednisone or a second line antirheumatic drug) and controls. CONCLUSION: There was no convincing evidence that influenza vaccination is associated with significant adverse reactions or arthritis flares in children with chronic arthritis. Children with chronic arthritis appeared to respond adequately to influenza vaccination.

Adolescent↗

Adverse reactions to the preschool (fifth) dose of adsorbed diphtheria-pertussis-tetanus vaccine in Canadian children.

OBJECTIVE: To quantify accurately the rate of adverse reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine and to test the hypothesis that large local reactions are attributable to the diphtheria toxoid. DESIGN: Double-blind randomized controlled trial. SETTING: Suburban community public health unit. PARTICIPANTS: Healthy children 4 to 5 years of age with a history of having received four doses of adsorbed DPT vaccine. INTERVENTIONS: Subjects were given either the standard DPT vaccine (with 25 Lf units of diphtheria toxoid) or a modified DPT vaccine (with 10 Lf units of diphtheria toxoid). They were assessed 24 hours later by a nurse. Serum samples obtained before vaccination were tested for diphtheria and tetanus antitoxin levels by means of neutralization assay and enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of large local reactions (an area of redness or swelling or both of 5 cm or greater) 24 hours after vaccination in the two groups. Relation between serum antitoxin levels before vaccination and the rate of large local reactions in each group. RESULTS: Of the 250 subjects enrolled 124 received the standard vaccine and 126 the modified one. Large local reactions occurred in 71% of the subjects receiving the standard vaccine and 52% of those receiving the modified one (p less than 0.01). In the former group large erythematous reactions occurred significantly more often in those with an elevated prevaccination diphtheria antitoxin level than in those without an elevated level; no relation was found between such reactions and the prevaccination tetanus antitoxin level. Reduced arm movement was evident in 45% of the children in the two groups. Few had systemic adverse reactions. CONCLUSIONS: Large local reactions occur frequently after the preschool administration of the DPT vaccine. These reactions are uncomfortable but not serious. They result in part from the large amount of diphtheria toxoid in the standard DPT vaccine.

Child, Preschool↗

Comparison of adverse reactions to whole-virion and split-virion influenza vaccines in hospital personnel.

OBJECTIVE: To compare the adverse effects, particularly generalized aching, of a trivalent, inactivated whole-virion vaccine (WVV) and split-virion vaccine (SVV) for influenza in hospital personnel. DESIGN: Recipient-blinded study; first-time vaccinees were randomly assigned to receive either of the vaccines from one manufacturer in the 1989-90 influenza season. Subjects were asked to complete a symptom questionnaire during the 48 hours after immunization. SETTING: Annual influenza program for staff of a tertiary care children's hospital. PARTICIPANTS: Volunteers were sought among approximately 2200 members of the hospital staff. Of the 358 vaccinated for the first time, 333 (93%) returned the questionnaire. RESULTS: During the 48 hours after vaccination 13% of the SVV recipients reported generalized aching, as compared with 26% of the WVV recipients (p less than 0.01). Also, the SVV group reported fewer visible local reactions and more transient arm soreness, but the actual differences between the two groups were small. The occurrence of mild symptoms was equally common in the two groups (local reactions in at least 70% of cases, systemic reactions in at least 33%). In each group 1% of the subjects reported missing work because of the vaccination. CONCLUSIONS: The use of SVV reduces the rate of the most objectionable of the common adverse effects of influenza vaccination. Therefore, as with children, it might be more acceptable to health care workers than the current use of WVV.

Absenteeism↗

Evaluation of adverse events after influenza vaccination in hospital personnel.

Reactogenicity of trivalent influenza vaccine prepared for the 1988-89 season was assessed as part of a first-time voluntary influenza prevention program among hospital staff. Of approximately 500 full-time workers in areas with the highest concentrations of patients at high risk for influenza complications offered the vaccine 288 accepted. Of these, 266 (92%) returned a questionnaire regarding any symptoms experienced within 48 hours after vaccination; 238 (90%) of the respondents reported adverse effects. Soreness at the injection site was described by 229 subjects, 58 (25%) of whom had constant aching and 123 (54%) soreness with arm movement. Symptoms resolved in 1 to 2 days, and only 21 (9%) of those who reported symptoms said they took analgesic medication. Systemic adverse effects were described by 130 subjects (49%). Intercurrent illness accounted for some of these complaints, but 65 people (24%) described at least two of the following symptoms: generalized aching, tiredness, nausea, chills or onset of fever within 12 hours after vaccination (a symptom complex previously attributed to influenza vaccine). Systemic symptoms resolved within 0.5 to 2 days. Thirteen subjects (5%) reported missing work because of arm soreness (1 subject) or systemic symptoms (12). Adverse effects were encountered more often than expected, probably because most of the workers were young and lacked immunity to influenza. Acceptability of the program could likely be improved by using a split-virus vaccine.

Absenteeism↗

Neonatal necrotizing enterocolitis associated with delta toxin-producing methicillin-resistant Staphylococcus aureus.

Delta toxin-producing coagulase-negative staphylococci previously have been associated with necrotizing enterocolitis in neonates. We identified three preterm infants (body weight, 845 +/- 59 g) infected with methicillin-resistant Staphylococcus aureus (MRSA) who had a similar clinical syndrome, characterized by pustular dermatitis, bacteremia and necrotizing enterocolitis accompanied by gastric residua, abdominal distention, hematochezia and pneumatosis intestinalis. MRSA was recovered from all three infants at infected skin sites, blood or venous catheters and from two of three infants in stool specimens. Two infants also had Staphylococcus epidermidis isolated from stool. All MRSA isolates had identical microbiologic profiles: four plasmids with identical molecular weights; coproduction of enterotoxins A and B; and the same antibiotic susceptibilities. Of one skin isolate, two blood isolates and two stool isolates of MRSA that were tested, all had characteristic delta toxin hemolytic activity. All culture supernatants of these isolates evaluated for delta toxin were positive by Western blot analysis. The two strains of S. epidermidis isolated from stool were negative for delta-like toxin by a standardized enzyme-linked immunoassay. The clustering of these cases, the similarity of the clinical syndrome, and the prior association of necrotizing enterocolitis with delta-like toxins produced by S. epidermidis, suggest that delta toxin-producing MRSA (or other S. aureus isolates) also may be etiologic agents in some cases of necrotizing enterocolitis in newborns.

Bacterial Toxins↗

Amino acid sequence of a deltalike toxin from Staphylococcus epidermidis.

A deltalike toxin produced by a clinical isolate of Staphylococcus epidermidis was purified, and the amino acid sequence was determined. The toxin molecule consisted of 25 amino acid residues and shared a high degree of molecular homology with delta toxin purified from a Staphylococcus aureus human isolate.

Amino Acid Sequence↗

Gentamicin penetration into cerebrospinal fluid in experimental Haemophilus influenzae meningitis.

We studied the effect of meningitis and the method of parenteral gentamicin administration (intramuscular injection, a 30-min intravenous infusion, or intravenous bolus administration) on achievable concentrations of drug in cerebrospinal fluid (CSF). In normal animals, only intravenous bolus administration of 2 to 8 mg/kg produced a gentamicin concentration of greater than 0.1 microgram/ml in CSF in some animals. All CSF samples contained less than the limit of detection (0.1 microgram/ml) after the intramuscular administration of 6 mg/kg. In animals with meningitis, gentamicin penetration into cisternal CSF was increased significantly after a bolus administration of 6 mg/kg (mean, 0.197 +/- 0.063 microgram/ml in normal animals versus 1.68 +/- 0.38 micrograms/ml in animals with meningitis; P less than 0.01). In meningitic animals that received 6 mg/kg as an intravenous bolus, lumbar CSF had the highest maximum concentration (4.25 +/- 1.08 micrograms/ml), in comparison with ventricular CSF (3.10 +/- 0.66 micrograms/ml). The gentamicin concentration in cisternal CSF decreased more slowly than it did in serum (elimination half-life, 238.70 +/- 64.56 min in cisternal CSF versus 82.73 +/- 2.91 min in serum), yielding a relative increase in the percentage of penetration. We conclude that maximum penetration by gentamicin into CSF occurs after intravenous bolus administration and that the maximum concentration occurs in lumbar CSF.

Animals↗

Delta toxin activity in coagulase-negative staphylococci from the bowels of neonates.

Coagulase-negative staphylococci are prominent in stools of neonates in some intensive care units and have been associated with necrotizing enterocolitis. A plausible mediator of bowel damage is delta-like toxin, which is produced in vitro by most coagulase-negative staphylococci, but factors influencing the expression of toxin in the bowel are unknown. We examined 105 coagulase-negative staphylococcus isolates from stools of neonates by using an enzyme-linked immunosorbent assay and detected delta toxin production by 92 isolates (88%). The amount present in 18-h broth cultures varied over 100-fold, from 933 to 125,000 ng/ml. All broths positive by enzyme-linked immunosorbent assay except one caused hemolysis of human erythrocytes. The threshold concentration for consistent cytotoxicity to fibroblasts was greater than or equal to 24,000 ng/ml. Only 56% of Staphylococcus epidermidis isolates were capable of producing this much toxin, and these were more often obtained from premature infants in intensive care than from healthy full-term infants (P = 0.003) and were more often resistant to multiple antibiotics (P less than 0.001). Cultures grown anaerobically seldom caused hemolysis (4 positive of 29 tested; P less than 0.001) because potency of the toxin was decreased (at least ninefold for S. epidermidis isolates). We conclude that only a portion of the fecal coagulase-negative staphylococci tested produced enough delta toxin in vitro to be cytotoxic, that such isolates have accumulated in our intensive care nursery, and that development of toxin-mediated bowel injury may also require a favorable redox potential within the host bowel.

Aerobiosis↗

Vaccines for prevention of head and neck infections.

Many current vaccines are directed against pathogens that infect the upper airway on their way to causing greater damage elsewhere in the body. This article focuses on vaccines against pathogens that contribute importantly to infections of the head and neck per se. The discussion includes vaccines for diphteria, mumps, measles, HIB infections, and infections caused by Streptococcus pneumoniae.

Adolescent↗

Comparison of two antibiotic regimens for neonatal necrotizing enterocolitis.

Treatment of neonatal necrotizing enterocolitis (NEC) regularly includes broad-spectrum antibiotics but there has been no comparative study of alternative regimens. We have studied 90 infants with definite NEC; 46 cases in 1982-3 were treated with ampicillin and gentamicin, while 44 cases in 1984-5 received cefotaxime and vancomycin. Groups were well matched and managed uniformly. Infants greater than or equal to 2200 g birthweight did well with either regimen. Smaller infants given cefotaxime and vancomycin had a lower risk of culture-positive peritonitis (P = 0.01), and as a result, were less likely to die (P = 0.048) or develop thrombocytopenia (P = 0.004). The better outcome might be explained by the greater suppression by cefotaxime and vancomycin of the gut flora of treated patients (P less than 0.001). Both regimens were well-tolerated. Our data suggest that carefully chosen antibiotic regimens can improve the outcome of NEC.

Ampicillin↗

Delta-like toxin produced by coagulase-negative staphylococci is associated with neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a serious neonatal disorder of uncertain cause, although fecal bacteria have been implicated in some outbreaks. We examined coagulase-negative staphylococci (CONS) as possible etiologic agents. In our unit, CONS colonized the bowels of most infants studied, including 46% of 70 NEC cases (mean concentration, 10(9.1) CFU/g of stool). Over 90% of tested isolates produced a hemolysin resembling delta toxin of Staphylococcus aureus. Toxin purified from a NEC-associated isolate of Staphylococcus epidermidis resembled reference delta toxin from S. aureus in size, biologic properties, and antigenicity. This delta-like toxin was enteropathic, causing mucosal necrosis and hemorrhage in injected loops of the bowels of infant rats. Adjacent, nonexposed bowel remained normal, as did loops injected with lecithin-neutralized toxin. Using a new enzyme-linked immunosorbent assay (ELISA), we detected delta-like toxin in the stools of 11 of 35 infants colonized with CONS positive for delta-like toxin (Tox+). Positive tests were strongly associated with NEC. Of 18 cases with Tox+ CONS, 10 were positive (56%), whereas only 1 of 17 control infants so colonized was positive (6%, P = 0.002). In NEC patients, the mean fecal toxin concentration was 1,012 ng/g. Toxicity to fibroblasts was demonstrable in filtrates of each of six ELISA-positive samples tested but was absent in all five ELISA-negative samples tested. We conclude that delta-like toxin is elaborated in the bowels of some infants with Tox+ CONS, and its association with NEC suggests that such CONS are enteropathic. In our unit, this mechanism was apparent in 23% of 44 recent cases of endemic NEC.

Bacterial Toxins↗

Lack of nosocomial spread of Varicella in a pediatric hospital with negative pressure ventilated patient rooms.

All patients at the new British Columbia's Children's Hospital with chickenpox or Herpes zoster are nursed with appropriate precautions in single-bed rooms provided with negative pressure ventilation. Over a period of 1 year, no nosocomial infections were detected on follow-up of 110 susceptible patients who had been on wards at the same time as six cases of chickenpox and one immunocompromised patient with cutaneous dissemination of Varicella zoster. In a preceding study at the previous hospital, with similar staff, control measures, and patient population, in an isolation facility without negative pressure ventilation, nosocomial infections occurred in seven out of 41 susceptible patients who were on the same ward as two patients with chickenpox. These findings suggest that a simple negative pressure ventilation system without air locks is a useful adjunct in the control of cutaneous Varicella infections.

Air Microbiology↗

Endotoxinemia and thrombocytopenia during neonatal necrotizing enterocolitis.

Thrombocytopenia frequently complicates neonatal necrotizing enterocolitis (NEC) and has been postulated to result from absorption of bacterial endotoxins from the injured gut. The authors tested blood obtained during 47 episodes of NEC for endotoxin-like activity (ELA), using a Limulus amoebocyte lysate assay and found 23 patients (49%) had positive results. Concentrations of ELA in plasma ranged from 0.26 to 300 ng/mL of Escherichia coli equivalent activity, with a geometric mean of 1.1 ng/mL. Serial platelet measurements were available from 40 infants, 11 (28%) of whom had nadir counts below 100,000/mm3 following NEC onset. Nine of 19 infants (47%) with ELA in plasma and only 2 of 21 without (9.5%, P less than 0.05) developed thrombocytopenia, suggesting that endotoxinemia may indeed contribute to platelet depletion during NEC.

Ascitic Fluid↗

Spontaneous endotoxinemia in premature infants: correlations with oral feeding and bowel dysfunction.

Infants admitted to a tertiary care nursery were tested serially to determine the frequency and epidemiology of spontaneous endotoxinemia, a phenomenon suggested by previous studies. Plasma and stools were tested for endotoxin-like activity (ELA) using a Limulus amoebocyte lysate method and results were correlated with clinical data. We detected ELA in plasma of 28 of 47 infants (60%) tested throughout their hospital stay: only two of 58 separate episodes could be attributed to infection. Endotoxinemia was not consistently associated with classical signs of fever, shock, and jaundice. Prior to oral feeding, little or no ELA was detected in stools and endotoxinemia was ascertained in only six of 45 infants (13%). With feeding, fecal ELA concentrations rose sharply, and endotoxinemia was detected in 56% of remaining infants (p less than 0.001). Bowel disease predisposed to endotoxinemia: 16 of 20 infants (80%) with necrotizing entercolitis or difficult establishment on feeding were affected, compared to five of 17 infants (29%) without such problems (p less than 0.01). Fecal ELA concentrations were not abnormally elevated in those with bowel disease. We conclude that endotoxinemia occurs commonly in immature infants as their fecal flora develops with feeding but the amount of circulating endotoxin required for injury and the patterns this takes require further investigation.

Endotoxins↗