Aplastic anemia following chloramphenicol therapy still happens!
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Biomedical subjects
Publications and source records attributed to M L Lepow.
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Sixty 9- to 15-month-old infants were randomly assigned to receive two doses, 1 month apart, of a Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) or PRP vaccine, each containing 20 micrograms PRP. There were no significant local or systemic reactions. After one dose of PRP-D, 93% of the subjects attained levels of greater than or equal to 0.15 microgram/ml and 59% achieved greater than or equal to 1 microgram/ml antibody protein. These percentages rose to 100% and 86%, respectively, after the second dose, at which time the geometric mean titer of anti-PRP antibody was 4.8 micrograms/ml. IgG anti-PRP levels were 4.3 times higher than IgM. The proportion of IgG to IgM antibody induced by PRP-D increased with age. After two doses, 33% of the PRP recipients responded with a level of greater than or equal to 0.15 microgram/ml and only 19% responded to a level of greater than or equal to 1.0 microgram/ml. One year later, all of the PRP-D recipients tested still had greater than or equal to 0.15 microgram/ml and more than half had greater than or equal to 1.0 microgram/ml antibody protein.
In contrast to the usual indirect enzyme-linked immunosorbent assay (ELISA) method for detection of antibody responses, a modified direct ELISA technique was used to measure immunoglobulin G (IgG) and IgM responses to pneumococcal capsular types 1, 3, 9N, and 23F in humans. Individual capsular polysaccharides were covalently bound to poly-L-lysine before adsorption to the solid phase. The coupling reaction was enhanced by maintenance of a constant pH of 8.2 after the addition of all reactants. The evaluation of four diluents (phosphate-buffered saline [PBS]-Tween; PBS-Tween plus 10% fetal calf serum; PBS-Tween plus 10% bovine serum albumin; and PBS-Tween plus 20% normal goat serum) showed that the sensitivity and specificity of the assay was increased with normal goat serum (10-fold). Serum samples from 10 subjects immunized with polyvalent pneumococcal vaccine were tested by direct ELISA and by radioimmunoassay. At 4 weeks postimmunization, the ELISA method showed that IgG was the predominant antibody and that IgM responses were lower or had diminished. Isotype shifts during this period would have been undetected by the radioimmunoassay method. The changes in antibody response measured by ELISA were comparable to the radioimmunoassay results. The direct ELISA method for the detection of antipneumococcal capsular antibody has been found to be a sensitive and reproducible assay for the detection of IgG and IgM antibodies.
Patients with Wiskott-Aldrich Syndrome have an increased incidence of serious infections, often with microorganisms that usually produce mild disease in immunologically normal subjects. Three patients with Wiskott-Aldrich syndrome complicated by progressive varicella are reported. There have been no previous reports of similar cases. Two of the patients were treated with adenine arabinoside and had rapid recovery.
In a multicenter study, responses to a combined vaccine containing standard diphtheria-tetanus-pertussis (DTP) and polyribosylribitol phosphate (PRP), the capsular polysaccharide of Haemophilus influenzae type b, were evaluated in 107 infants who received single doses at two, four, and six months of age and compared with those in 61 infants given single doses of DTP alone on the same schedule. Reaction rates were comparable in the two treatment groups. At seven months of age 61% of the subjects given the combined DTP-PRP vaccine and 8% and of those given DTP alone showed an antibody response to PRP, as defined as a twofold increase in titer over the lowest previous level. Among those given the DTP-PRP combined vaccine, 92% of the positive antibody responses occurred after the third dose. There was a variation in antibody response, possibly due to a difference in the vaccine lots administered.
Sixty-one adults received either Haemophilus influenzae type b capsular polyribosephosphate (PRP) vaccine or H. influenzae type b polysaccharide-diphtheria toxoid conjugate (PRP-D) vaccine in two doses, one month apart. Both vaccines were well tolerated with no fever or systemic reactions. There were no significant local reactions. Mild local tenderness was reported by about half of the subjects in both groups. There was no observed effect of the vaccines on hematologic parameters, including reticulocyte and platelet counts, evaluated before immunization, one month after the first dose, and seven to 10 days after the second dose. A single dose of PRP-D induced levels of IgG antibody to PRP three times that observed with PRP alone one month after the first inoculation.
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Among 50 Indo-Chinese children 18 years of age or younger who were screened at the Albany County (New York) Health Department, during 1979, 14 had a history of BCG vaccination. These patients were not intradermally tested with 5 TU of PPD because it was assumed that the reactions would not be interpretable. To test this hypothesis, nine patients were available for testing. Six patients had a negative reaction, two had a reaction greater than 10 mm of induration, and one had an equivocal reaction. Nine of the 36 patients without a history of BCG vaccination also had positive reactions to the same dose of PPD. All patients with positive reactions had normal chest x-ray films and received isoniazid prophylaxis, regardless of BCG history in accordance with Centers for Disease Control recommendations. A history of BCG vaccination should not preclude skin testing with PPD (given in tuberculin units), and a patient with a positive reaction should receive appropriate treatment.
Two 9-week-old, breast-fed premature infants developed acrodermatitis and hypozincemia because of low zinc content in their mothers' breast milk. All symptoms of zinc deficiency disappeared within seven days after the infants were treated orally with zinc and did not recur when zinc was discontinued after 11 months (infant 1) and three weeks (infant 3). After a subsequent term pregnancy, one of the mothers had lower breast milk zinc content (P less than .025) and greater exponential decline (P less than .025) of zinc content through 40 weeks of lactation compared with 34 control subjects. Her second infant (infant 2) had hypozincemia at 7 months of age but did not develop clinical zinc deficiency. When the mothers of the affected infants took oral zinc supplements, there was no increase in their breast milk zinc content. Zinc secretion into breast milk appears to be a controlled process that is independent of maternal zinc intake or serum zinc level. Breast milk may be low in zinc because of defective mammary secretion and this may lead to severe symptomatic zinc deficiency in premature infants.
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A cohort of infants, previously immunized once or twice between three and 12 months of age with vaccines containing polysaccharide of groups A and C Neisseria meningitidis, received boosters at two and five and one-half years of age with bivalent A/C vaccine. Antibody concentrations were measured by a radioactive antigen-binding assay. Concentrations of antibody to groups A and C N. meningitidis were 5.59 and 2.86 microgram/ml, respectively, by four years of age. After booster immunization at five and one-half years of age, concentrations of antibody to groups A and C N. meningitidis increased to 15.67 and 7.59 microgram/ml, respectively. Protective levels of antibody to group A meningococci may be achievable throughout early childhood by routine immunization with the A vaccine. Although the group C vaccine is effective in control of epidemics, the rapid decline in the concentration of antibody to group C meningococci following immunization of young children suggests that protection may not be long-lasting.
Neisseria meningitidis group Y has been considered to be an uncommon pathogen. Meningococcal group Y disease has recently been reported with increased frequency in military training camps coincident with the routine use of meningococcal group C vaccine. Pneumonia produced by the group Y organism may mimic disease caused by common respiratory tract pathogens, and isolation by routine methods may be difficult. A 16-year-old asthmatic female developed lobar pneumonia secondary to N meningitidis group Y while on alternate day steroids. We speculate that neither steroid therapy nor an isolated serum IgA deficiency in the presence of secretory IgA discovered after her recovery predisposed her to sinopulmonary disease. The true incidence of group Y disease is unknown. Awareness of its potential pathogenicity may have clinical significance with the availability of a group Y vaccine.
Asymptomatic carriage of Neisseria meningitidis and Neisseria lactamica was studied in a total of 2,969 healthy infants and children in Danbury, Conn., between October 1971 and June 1975. The prevalence of N. meningitidis averaged 0.71% during the first four years of life and increased to 5.4% by 14--17 years. Rates of carriage of N. lactamica increased from 3.8% in three-month-old infants to a peak of 21.0% at 18 months and then declined to 1.8% by 14--17 years of age. Of the children who acquired N. lactamica, 66% developed fourfold or greater rises in titers of IgG antibody to groups A, B, and/or C meningococci as determined by immunofluorescence compared with only 5% of control children. Of new carriers of N. lactamica, 40% developed increased titers of bactericidal antibody to groups A, B, and/or C meningococci as compared with 7% of noncarriers. Carriage of N. lactamica may assist in the development of natural immunity to N. meningitidis by induction of cross-reactive antibodies.
Infants were immunized with group A Neisseria meningitidis polysaccharide vaccine at two, four, and six months of age. Two lots of group A vaccine that differed in molecular weight were used; lot no. 1980A was of significantly larger molecular size than lot no. A-7. No significant adverse reactions occurred. The geometric mean concentration of serum antibody to group A N. meningitidis one month after the third dose of lot no. 1980A was 0.89 microgram/ml, nearly twice the concentration induced by lot no. A-7 (0.48 microgram/ml). When the infants were 12 months of age, concentrations of antibody in both groups had declined to similar levels, which were still greater than the mean concentration of antibody in unimmunized children. By 18 months of age, the antibody levels of immunized and unimmunized infants were the same. The three-dose schedule resulted in significantly lower concentrations of antibody than previously studied schedules of two doses given three to four months apart.
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Fifty-one Caucasian, middle-class children (aged three to 10 years) from the suburbs of Hartford, Connecticut, were immunized with two subcutaneous doses each of 200 chick cell-agglutinating units of influenza A/New Jersey/76 subunit virus vaccine/0.5 ml. The reactivity of the vaccine was negligible, and there was no increase in reactivity with a second dose. Administration of a single dose resulted in seroconversion in one-third of the subjects. Two weeks following the second dose, 84% of the children had reciprocal titers of hemagglutination-inhibiting antibody of greater than or equal to 10, and the geometric mean titer was 51. There was no significant difference in antibody response according to age. We concluded that inoculation of two doses of subunit virus vaccine is a safe and effective means of inducing a significant antibody response. The levels of antibody required for protection and for duration of antibody response are not known.