Biomedical subjects
T Townsend
Publications and source records attributed to T Townsend.
An unusual presentation of complete androgen insensitivity syndrome in general practice.
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Suboptimal response following intradermal hepatitis B vaccine in infants.
Two hundred and twenty-five infants were randomly assigned to receive 2 micrograms of plasma-derived hepatitis B vaccine (Heptavax) intradermally (ID-2), 10 micrograms intramuscularly (IM-10), or 2 micrograms intramuscularly (IM-2) in the deltoid region at birth, 2 and 4 months. At 6 months, ID-2 infants were less likely to have developed > or = 10 mIU ml-1 of antibody to hepatitis B surface antigen (anti-HBs) than IM-10 infants (91 versus 100%; p = 0.02) and had a lower geometric mean concentration of anti-HBs (312 mIU ml-1 versus 2248 mIU ml-1; p < 0.01). At 6 months IM-10 infants had significantly lower mean weights and lengths than infants receiving 2 micrograms doses of vaccine. Intramuscular administration of 2 micrograms and 10 micrograms doses of Heptavax in the deltoid of young infants was well tolerated and effective; however, intradermal administration of Heptavax provided no immunological benefit over intramuscular administration and resulted in significantly higher rates of induration and persistent hyperpigmentation. Intramuscular immunization at birth, 2 and 4 months is an acceptable, effective alternative schedule for immunizing infants.
Investigation of potential HIV transmission to the patients of an HIV-infected surgeon.
OBJECTIVE: To ascertain if a surgeon infected with the human immunodeficiency virus (HIV) transmitted HIV to patients during invasive surgical procedures. DESIGN: Survey of patients and acquired immunodeficiency syndrome (AIDS) case registries, and laboratory analysis of nucleotide sequence data. SETTING: One surgeon's private and institutional practices within one academic referral hospital. PATIENTS: A total of 1131 persons identified in hospital databases who underwent invasive surgical procedures from 1984 through 1990 and for whom the surgeon was listed as the admitting or operating surgeon. MEASUREMENT: Patients presumed to be living were surveyed by mailed questionnaire. The AIDS case registries were reviewed for all patients having undergone invasive procedures and death certificates were obtained. Person-hours of surgery during which exposure might have occurred were calculated for surgical procedures. RESULTS: Of 1131 patients, 101 were dead, 119 had no address, 413 had test results known, and 498 did not respond to the questionnaire. No study patient name was found in reported AIDS case registries. One newly detected, HIV-seropositive patient was determined (through nucleotide sequencing) to have been most probably infected in 1985 during a transfusion. There was no HIV transmission in 369 person-hours of surgical exposure, indicating that HIV transmission to patients is unlikely to occur more frequently than once per 1000 person-hours of surgical exposure. CONCLUSIONS: If study validity and resources permit, investigation of publicly disclosed, HIV-infected health care workers whose practices involve invasive procedures should be pursued. The risk of HIV transmission during surgery may be so small that it will be quantified only by pooling data from multiple, methodologically similar investigations.
Doesn't everyone grieve in the abortion choice?
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Efficacy and pharmacokinetics of intravenous immune globulin administration to high-risk neonates.
UNLABELLED: OBJECTIVE--To determine whether intravenous immune globulin (IVIG) administration modifies the incidence of infections in high-risk neonates. DESIGN--Randomized, double-blind study. SETTING--Neonatal intensive care unit at a tertiary care center. PARTICIPANTS: A total of 170 infants were enrolled, 82 of whom received IVIG and 88 of whom received the placebo preparation. Infants were stratified by birth weight into one of three groups (category 1, those weighing less than 1000 g; category 2, those weighing between 1000 and 1500 g; and category 3, those weighing more than 1500 g). INTERVENTIONS--Intravenous immune globulin (750 mg/kg of body weight), or albumin placebo was administered within 72 hours of admission to the tertiary care center and every 14 days thereafter until discharge from the neonatal intensive care unit or age 3 months. Serum IgG levels were measured and data collected relating to the incidence of systemic and localized infections and to the course of hospitalization. MEASUREMENTS AND MAIN RESULTS--The administration of IVIG had no major side effects and resulted in higher serum IgG levels in infants in all birth weight categories compared with infants receiving the placebo. Systemic infections developed in five IVIG-treated infants and five placebo-treated infants. Administration of immunoglobulin had no significant effect on the rate of localized infections or necrotizing enterocolitis. It also did not affect hospital course of the infants as measured by length of hospitalization or the number of days on assisted ventilation, supplemental oxygen, or antibiotics was required. CONCLUSIONS--The general administration of IVIG using this dosage regimen has limited effects on the clinical course of infants in a neonatal intensive care unit.
Differences in antibody response to whole-cell pertussis vaccines.
It has been assumed that whole-cell pertussis vaccines (WCVs) commercially distributed in the United States are of comparable immunogenicity, as all must comply with established standards for licensure. However, we have recently noted significant differences in antibody responses between groups of infants receiving the two WCVs commercially available in the United States. In separate studies performed concurrently under similar protocols at Vanderbilt and Johns Hopkins universities, infants were randomized to receive either an acellular pertussis vaccine or WCV. The acellular pertussis vaccine used at the two sites was identical, but the WCVs were from different manufacturers. Antibody responses to acellular pertussis vaccine did not differ between the two studies; responses to WCV differed dramatically, with infants receiving the Lederle WCV producing a 46-fold increase in antibody to pertussis toxin, compared with a 2.4-fold increase for infants receiving the Connaught WCV (P = .00003). Evaluation of other comparative data sets that were available provided further support for the conclusion that the two commercially available WCVs consistently differed in their ability to induce antibody to pertussis toxin. These findings have important implications for the design and interpretation of clinical trials comparing acellular and WCV products.
Primary cutaneous aspergillosis associated with Hickman intravenous catheters.
We describe nine patients with underlying hematologic cancer in whom primary cutaneous aspergillosis developed at the sites of Hickman intravenous catheters. Our patients, 17 to 74 years of age, were all immunocompromised either from their primary disease or from chemotherapy, and the Hickman catheters had been placed to provide venous access for chemotherapy or hyperalimentation or both. Clinical signs of infection included erythema, induration, and cutaneous or subcutaneous necrosis at the point of entry into the subclavian vein, in the subcutaneous tunnel, or at the exit site from the skin. Diagnosis was confirmed by positive wound culture for Aspergillus flavus in all but one patient. Treatment consisted of intravenous amphotericin B, oral flucytosine, and local wound care. Three patients recovered completely without operative débridement; three others recovered after operative débridement and delayed grafting. Two patients died of disseminated aspergillosis, and one died of unrelated causes while recovering from primary cutaneous aspergillosis. Successful treatment required resolution of aplasia or leukopenia, catheter removal, systemic treatment with amphotericin B, and local wound care. We conclude that primary cutaneous aspergillosis, a rare infection, may occur at the sites of Hickman catheters in immunocompromised patients, and that it is a serious complication requiring prompt diagnosis and treatment.
Safety and immunogenicity of bovine rotavirus vaccine RIT 4237 in 3-month-old infants.
To assess the safety and immunogenicity of bovine rotavirus vaccine, we administered attenuated strain RIT 4237 to 54 inner-city infants randomized to one of three groups in a double-blind fashion to receive a dose at 3 and 5 months of age of either placebo, vaccine virus at 10(7) TCID50/ml, or vaccine virus at 10(8) TCID50/ml. Vaccination began in early fall 1984, and continued through spring 1985. Forty-nine infants received one dose of vaccine or placebo; 43 received both doses of vaccine or placebo. At 2 and 3 months after vaccination, homologous geometric mean neutralizing antibody titers were significantly higher in children who received either dose of vaccine compared with placebo recipients. Cumulative seroconversion to bovine rotavirus after either dose of vaccine virus was 87% at 6 months of age. Seroconversion was significantly higher (P less than 0.01) in both vaccine groups compared with the placebo group. No ill effects were associated with vaccine administration. RIT 4237 vaccine appears to be safe and immunogenic when administered to young infants living in the United States.
Interactions between core histones and chromatin at physiological ionic strength.
Addition of core histones to chromatin or chromatin core particles at physiological ionic strength results in soluble nucleohistone complexes when polyglutamic acid is included in the sample. The interaction between nucleosomes and added core histones is strong enough to inhibit nucleosome formation on a closed circular DNA in the same solution. Complexes consisting of core particles and core histones run as discrete nucleoprotein particles on polyacrylamide gels. Consistent with the electrophoretic properties of these particles, protein cross-linking with dimethyl suberimidate indicates that added core histones are bound as excess octamers. Histones in the excess octamers do not exchange with nucleosomal core histones at an ionic strength of 0.1 M and can be selectively removed from core particles by incubating the complexes in a solution containing sufficient DNA. Under conditions where added histones are confined to the surface of chromatin, the excess histones are mobile and can migrate onto a contiguous extension of naked DNA and form nucleosomes.
HMG 14/17 binding affinities and DNAase I sensitivities of nucleoprotein particles.
We show that ordinary (bulk) chicken erythrocyte nucleosomes are digested more rapidly by DNAase I when they are associated with high mobility group (HMG) proteins 14/17. Digestion of HMG 14/17-nucleosome complexes, under conditions where the DNA in control nucleosomes is digested to 10 to 20% acid solubility, results in a particular depletion of single-strand DNA fragments greater than 80 nucleotides in length, relative to the DNA fragments produced from control nucleosomes. Additionally, we show that staphylococcal nuclease digests of H1/H5-depleted chromatin contain an abundant subclass of nucleosomes that are not present in appreciable amounts in digests of native chromatin. These nucleosomes contain longer lengths of DNA and have lower electrophoretic mobilities than core particles. HMG 14/17 associates highly preferentially with these nucleosomes and renders them sensitive to DNAase I, similar to what has been found for active nucleosomes.