HIV and smooth muscle tumors.
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Biomedical subjects
Publications and source records attributed to E G Chadwick.
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We report the occurrence of multiple leiomyomata and leiomyosarcomata in three children with the acquired immunodeficiency syndrome. The children were infected with human immunodeficiency virus as infants (one perinatally and two through transfusions) and each was profoundly immunosuppressed (absolute CD4 cell count, less than 75/mm3). They experienced multiple infections prior to the diagnosis of neoplasms at ages 4, 5, and 8 years, respectively. The tumors in each case were mainly involving the lungs and gastrointestinal tract. The smooth-muscle origin of the tumors was proved by light and electron microscopy and immunohistochemical staining for muscle-specific actin and desmin. Leiomyomata and leiomyosarcomata are rare tumors in childhood, suggesting a nonrandom association of tumors of smooth-muscle origin and the acquired immunodeficiency syndrome. We postulate that human immunodeficiency virus infection may play a direct or indirect role in tumor formation.
We describe two children with human immunodeficiency virus infection in whom pyoderma gangrenosum developed. Although pyoderma gangrenosum most commonly occurs in children with inflammatory bowel disease, it has also been described in patients with a variety of immunodeficiencies. In such patients a vigorous search to exclude a treatable infection should be made before the lesions are treated as pyoderma gangrenosum.
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A case of Haemophilus influenzae type b (Hib) meningitis in which the diagnosis and treatment were delayed because of normal cerebrospinal fluid analysis is presented. A retrospective review was conducted at two children's hospitals to determine the frequency and clinical characteristics of patients with Hib meningitis whose spinal fluid had a normal total white blood cell count, normal chemistries, and negative Gram stain, but subsequent growth of Hib in culture. Of 379 cases of Hib meningitis, two had completely normal CSF, and two had CSF containing small numbers of polymorphonuclear cells as the sole abnormality. In three of the four cases, the duration of symptoms was less than 24 hours, and appropriate therapy was significantly delayed because of benign-appearing CSF. Normal CSF cell counts, chemistries, and Gram stain do not exclude the possibility of bacterial meningitis, and one should remain suspicious when a child has clinical findings suggesting meningitis.
The Haemophilus influenzae vaccine consisting of purified type b capsular polysaccharide (polyribosylribitol-phosphate [PRP]) was shown in Finland to be protective, with 90% efficacy in children older than 18 to 23 months of age. However, a wide range of estimates of vaccine efficacy has been reported in the United States after its licensure in 1985. These estimates range from -55% to +89%. In addition, the PRP vaccine was not effective in children younger than 18 months of age, in whom 70% to 80% of meningitis cases occur. A further development was the introduction of H influenzae type b polysaccharide-protein conjugate vaccines such as the PRP-D. These conjugate vaccines were found to be more immunogenic than PRP vaccine in children of all ages. Two doses of PRP-D in infants 7 months of age and older induced antibody levels equal to or greater than levels in infants 24 months of age who received the PRP vaccine alone. Recently, Eskola et al reported that repeat vaccinations with PRP-D at 3, 4, 6, and 14 months of age was 83% protective (95% confidence interval, 26% to 96%). Yet PRP-D vaccine elicits only low serum antibody levels in infants younger than 7 months of age. Because of the discrepancy in efficacy results for the PRP vaccine in the United States and Finland and the lack of data about the protective efficacy of PRP-D vaccine in infants in the United States, the PRP-D vaccine is currently recommended only for children 18 months of age or older.(ABSTRACT TRUNCATED AT 250 WORDS)
The presence of the human immunodeficiency virus type 1 (HIV) provirus was assessed in peripheral blood mononuclear cells (PBMCs) from 27 offspring of HIV-infected mothers, 12 of these mothers, and 4 HIV-uninfected mother-infant control pairs. Enzymatic amplification of specific conserved regions of the gag and env genes was performed directly in PBMC lysates using the polymerase chain reaction (PCR) technique. The enzymatically amplified gene products were evaluated using the oligomer hybridization detection procedure. PBMCs from infected infants (as determined by Centers for Disease Control clinical criteria) and from HIV-infected mothers manifested a characteristic HIV oligomer hybridization product. Clinically uninfected seropositive infants with declining HIV antibody titers and infants who became seronegative lacked an enzymatically amplified HIV gene product. These preliminary data indicate that PCR is a valuable diagnostic technique to detect or exclude HIV infection in young infants and children.
Primary varicella-zoster (VZ) infection in eight children with perinatally acquired human immunodeficiency virus infection tended to be severe, prolonged, complicated by bacterial infections and in one case fatal. Depletion of CD4-lymphocytes was associated with chronic and recurrent VZ infection. In some patients convalescent VZ antibody titers were low and did not correlate with recurrence of VZ lesions. Administration of acyclovir appeared to be beneficial in suppressing VZ in human immunodeficiency virus-infected children with primary or recurrent VZ infection.
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Combinations of beta-lactam and aminoglycoside antibiotics are frequently used in the treatment of pediatric infections. At our institution, amikacin has been the sole aminoglycoside utilized for the past five years. Such regimens are used empirically in specific patient populations to treat the pathogens most likely to be responsible for a symptom complex, e.g., sepsis in the immunocompromised host, pneumonitis in patients with cystic fibrosis, neonatal infections such as sepsis or meningitis, and infections in patients with intestinal perforations. Beta-lactam and aminoglycoside combinations are employed as definitive therapy when synergistic interactions can be predicted, such as in systemic Pseudomonas infections, viridans streptococcal endocarditis, or enterococcal infections. In all of these circumstances, we have utilized amikacin extensively as the sole aminoglycoside, with highly satisfactory results. In vitro antibiotic synergy studies, including those employing aminoglycosides such as amikacin, may be used to predict in vivo antibiotic interactions. However, definitions of in vitro synergy vary with the laboratory method used to evaluate synergy. Furthermore, recent data from our laboratory suggest that the absence of demonstrated in vitro synergy between amikacin and imipenem may not correlate with improved survival of neutropenic rats with gram-negative sepsis that are treated with both agents. Thus, in vitro studies of synergy may underestimate the frequency of improved outcomes with combination antibiotics, especially with amikacin and imipenem. There are potential risks associated with the use of multiple, broad-spectrum antibiotics, including fungal or bacterial superinfection and increased drug toxicity. Although the former is common in pediatric patients, aminoglycoside (amikacin) toxicity has rarely been a problem. Combination antibiotic regimens that include an aminoglycoside such as amikacin continue to have an important role in pediatrics and should be used empirically or definitively for the specific indications discussed.
The predictive value of in vitro studies of antibiotic interaction for clinical drug interactions is unclear. Five clinical isolates (two Klebsiella, two Pseudomonas aeruginosa, and one Serratia marcescens) were evaluated by the time-kill curve method for in vitro synergy between amikacin and imipenem. When we used the stringent definition of synergy of Hallander et al., no synergy was present for any study strain; however, when we used a more-conventional definition of synergy, these drugs interacted synergistically against all study strains. The results of these in vitro studies were correlated with in vivo interactions by using neutropenic infant rats injected ip with study organisms and given various treatment regimens. For 80% of the study strains, treatment of rats with amikacin and imipenem resulted in significantly greater survival than did therapy with either drug alone or than could be predicted by addition of survival rates achieved with either agent alone (P less than .005). In vitro studies predicted this in vivo synergy in 80% of the cases when the more-conventional definition of synergy was used, whereas they were not predictive when the more-stringent definition of synergy was used. This rat model of neutropenia and gram-negative sepsis may provide more insight into in vivo drug interactions than do current methods.
Acyclovir [9-(2-hydroxyethoxymethyl)guanine] is a newly licensed acyclic nucleoside analog that is active in vitro and in vivo against herpes simplex virus (HSV) and varicella zoster virus (VZV). This agent is available in the United States in topical and intravenous forms, and the oral preparation is currently being evaluated in clinical trials. The precise therapeutic role for acyclovir in patients with herpesvirus infections is still evolving. This article reviews the current status of this exciting new antiviral agent.
Ceftriaxone has greater in vitro and in vivo efficacy against many common bacteria than other third-generation cephalosporins. Single-dose ceftriaxone pharmacokinetics were studied in 17 patients, aged 0.6 to 52 months, with infections of the central nervous system. Patients received a randomized dose of 50 or 75 mg/kg ceftriaxone intravenously over 5 minutes on the second to fifth day of illness. Serial blood samples were collected over 24 hours in all patients, and cerebrospinal fluid (CSF) was obtained 1 to 4.5 hours after injection. Ceftriaxone mean peak plasma concentrations, determined by high-power liquid chromatography, were 267 and 184 microgram/ml for the 75 and 50 mg/kg dosage groups, respectively. The harmonic mean elimination half-life was 4.2 hours, and the mean percent drug penetrance into CSF was 4.8 +/- 3.5%. Of CSF studies evaluated, the glucose concentration was correlated most closely (inversely) with CSF penetration of ceftriaxone. Individual CSF concentrations of ceftriaxone exceeded the minimal inhibitory concentrations of the respective bacteria causing infection by 480 to 5,600 times. Ceftriaxone may be useful in the treatment of serious pediatric infections, including meningitis.
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