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Biomedical subjects

L L Lewis

Publications and source records attributed to L L Lewis.

At least 37 records · Page 2Linked to original sources

CD4 status and P24 antigenemia. Are they useful predictors of survival in HIV-infected children receiving antiretroviral therapy?

OBJECTIVE: To determine the relationship between CD4 status and the P24 antigen level and survival in children infected with the human immunodeficiency virus. DESIGN: Cohort, case-control. SETTING: Clinical Center at the National Institutes of Health, Bethesda, Md. PARTICIPANTS: One hundred forty-seven children infected with the human immunodeficiency virus enrolled in antiretroviral therapy protocols at the National Cancer Institute were reviewed and the relationships between CD4 counts, P24 antigenemia, and death were analyzed. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: The presence of a very low CD count, less than 21% of the lower limit of normal values for age (equivalent to 0.05 x 10(9)/L in an adult), was associated with a significantly increased risk of death within 2 years. Although the risk of death was highest for children with CD4 counts below this level and who had detectable P24 antigen levels, P24 antigenemia by itself contributed little to the prognostic value of the CD4 count alone. However, it was also notable that a group of children with low CD4 counts also experienced prolonged survival. CONCLUSIONS: The association between low CD4 counts and death suggests that the age-adjusted CD4 count should be used as a marker to guide therapeutic intervention. At the same time, the presence of a very low CD4 count alone should not be considered a reason for therapeutic nihilism.

Age Factors↗

Cerebral artery aneurysms in children infected with human immunodeficiency virus.

More than 250 children treated at our institution on antiretroviral treatment protocols have been monitored with brain imaging studies. We documented the occurrence and progression of aneurysms of major cerebral arteries in two children with advanced human immunodeficiency virus infection. In both cases these lesions remained clinically silent initially, despite progression to marked dilation.

Brain↗

Defining the population of human immunodeficiency virus-infected children at risk for Mycobacterium avium-intracellulare infection.

We reviewed the 22 cases of Mycobacterium avium-intracellulare (MAI) infection that occurred among 196 human immunodeficiency virus-infected children seen at the National Cancer Institute Pediatric Branch from December 1986 through April 1991, and an additional 65 charts from children with cultures negative for MAI. All patients with proven MAI were receiving antiretroviral therapy with zidovudine, dideoxyinosine, or a combination of zidovudine and dideoxycytidine. All patients had disseminated MAI infection, except one adolescent who had only evidence of localized lymphadenitis. All cases of MAI but one were diagnosed before death. The overall incidence of MAI was 11% in our patients but increased to 24% in patients whose absolute CD4 cell counts were < 100 cells/mm3. Symptoms most commonly associated with MAI infection included recurrent fever (86% of patients), weight loss or failure to thrive (64%), neutropenia (55%), night sweats (32%), and abdominal pain (27%). Children infected with MAI had a mean CD4 percentage of 2% (range, 0% to 7%) and a mean absolute CD4 count of 12 cells/mm3 (range, 0 to 48 cells/mm3), significantly lower than in the remainder of the clinic population or the group of children with cultures negative for MAI. Of 20 patients with MAI infection who were tested, 10 had measurable p24 antigen with a mean value 939 pg/ml (range, 77 to 3270 pg/ml) compared with 19 of 59 patients without MAI infection in whom the mean positive value was 413 pg/ml. There was no difference in survival time between those children with documented MAI infection (median survival time, 45.5 weeks) and those with similarly low CD4 counts and cultures negative for MAI (median survival time, 50.4 weeks). Future improvements in therapeutic options may make screening of pediatric human immunodeficiency virus-infected patients with low CD4 counts a reasonable plan.

AIDS-Related Opportunistic Infections↗

Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human immunodeficiency virus infection.

Bone marrow suppression is the major dose-limiting toxic effect of zidovudine (azidothymidine; AZT) in children with human immunodeficiency virus infection. We evaluated the effect of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in pediatric patients whose absolute neutrophil count was less than 0.8 x 10(9)/L during AZT therapy despite dosage reductions to 120 mg/m2 every 6 hours. Nineteen patients between 6 months and 20 years of age were treated with AZT and G-CSF and monitored for 2 to 12 months. All had previously shown improvement while receiving AZT but had required dosage reduction or discontinuation. By using a sliding dosing schedule of G-CSF, we attempted to maintain the absolute neutrophil count between 1.5 and 5.0 x 10(9)/L. Administration of G-CSF resulted in a significant increase in the median leukocyte count (2.0 x 10(9)/L to 4.14 x 10(9)/L; p = 0.004), and the median absolute neutrophil count (1.02 x 10(9)/L to 2.96 x 10(9)/L; p = 0.0006). G-CSF was well tolerated, but mild thrombocytopenia developed in nine children. Administration of G-CSF and AZT was discontinued in two patients because of continuing neutropenia. With doses of G-CSF ranging from 1 to 20 micrograms/kg per day, 17 of 19 patients were able to tolerate AZT at a dose of 120 to 180 mg/m2 every 6 hours. We conclude that G-CSF therapy enables patients who have had AZT-related neutropenia to receive therapeutic doses of AZT.

Adolescent↗

Pseudomonas infections in children with human immunodeficiency virus infection.

Thirteen bacteremias and 25 nonbacteremic infections caused by Pseudomonas spp. occurred in 22 of 236 children with human immunodeficiency virus infection with a rate of infection of 0.098 (bacteremia, 0.030) per patient year. Four patients were neutropenic (less than 500/microliters). Central venous catheter (CVC)-related infections were most frequent (n = 20) followed by otitis externa (n = 6) and pneumonia (n = 5). Pseudomonas aeruginosa was the most common isolate and caused both CVC-related and CVC-unrelated infections, whereas other Pseudomonas spp. and Xanthomonas maltophilia were almost exclusively associated with CVC-related infections. The children who received appropriate therapy had a favorable outcome. In 7 CVC-related infections (35%) the catheter was removed. Pseudomonas spp. are of increasing importance in human immunodeficiency virus-infected children causing significant morbidity and increased hospitalization. These infections may be life-threatening if appropriate therapy is not vigorously initiated.

Adolescent↗

Congenital syphilis. Serologic diagnosis in the young infant.

The diagnosis of congenital syphilis in the newborn or young infant must incorporate epidemiologic, clinical, and serologic evidence of infection. Anti-treponemal IgM assays such as the 19S-IgM-FTA-ABS, which can be performed at the CDC at the request of state health departments, and the IgM ELISA being developed by Ortho Diagnostics represent the most available of the new assays. Discrimination of CNS involvement by T. pallidum by new methods continues to be difficult in the absence of a "gold standard" for comparison; thus, the current recommendation is to treat all infected infants with a regimen adequate to eradicate neurosyphilis. Although tremendous progress has been made in recent years in new serologic techniques applicable to congenital syphilis, none have proved reliable enough yet to be widely used by physicians evaluating infants at risk. In conclusion, there is still no single serologic assay that will reliably diagnose congenital syphilis in the young infant and the weight of therapeutic decisions still rests on the physician's ability to synthesize epidemiological, clinical, and laboratory data.

Humans↗

The incidence of Encephalitozoon cuniculi in a commercial barrier-maintained rabbit breeding colony.

Between 1982 and 1987 sera from 4952 New Zealand White rabbits (Oryctolagus cuniculus) obtained from a single commercial supplier were tested for the presence of antibodies to Encephalitozoon cuniculi. A commercially available carbon immunoassay test kit was used. Initially 32.9% of the rabbits were seropositive with the number progressively decreasing to 2.3% by 1987. The reason for the significant decline in the incidence of infection was most likely due to a selection process for breeding stock instituted by the supplier based upon productivity, posture and weight of each animal.

Animals↗

Evaluation of immunoglobulin M western blot analysis in the diagnosis of congenital syphilis.

Western immunoblots of solubilized Treponema pallidum antigens were reacted with sera and cerebrospinal fluid (CSF) and developed with enzyme-conjugated antibodies to immunoglobulin M (IgM). A blot was considered positive if reactions included bands at the 47-, 17-, and 15.5-kilodalton positions along with a variable pattern at other low-molecular-weight positions. Sera from 23 of 25 symptomatic infants diagnosed with congenital syphilis yielded positive reactions. Of 80 asymptomatic infants considered at risk for developing symptomatic infection, 16 exhibited IgM patterns consistent with those seen in congenital syphilis, although 5 of these 16 gave reactions that were equivocal. To exclude false-positive reactions due to IgM rheumatoid factor, sera were fractionated and the IgM fractions were retested. Only the five initially equivocal sera gave nonreactive blots with the IgM fractions, whereas all others gave more prominent reactions that were qualitatively similar to those seen in serum samples. Sera from 18 normal infants failed to show any IgM reactivity to T. pallidum antigens on Western blots. The IgM Western blot was both more sensitive and more specific than the fluorescent treponemal antibody-absorbed (IgM) test using fractionated serum. Of the 17 CSF samples from infants with symptomatic congenital syphilis, 14 showed IgM reactivity in Western blots, whereas only 12 had a reactive CSF in the Venereal Disease Research Laboratory test. Our results indicate that this technique can be used to identify both symptomatic and asymptomatic infection in infants with T. pallidum, in some cases before standard serologic studies can confirm the diagnosis.

Antibodies, Bacterial↗

Utilization of femoral head for estimating the skeletal burden of U and Pu in humans.

Uranium and Pu were determined in vertebrae, ribs and femoral head samples obtained from the same population. Vertebrae and rib samples were obtained at autopsy and femoral head samples were obtained from persons undergoing hip surgery. The results indicate that there was no statistically (p less than or equal to 0.05) significant difference between the mean concentration of 239,240Pu in vertebrae and ribs. Also, there was no significant difference between the mean concentration of 239,240 Pu in ribs and femoral head. Also, statistical tests were performed to see whether the mean concentrations of 238U and 234U in three different bones differ from each other. The results suggest that there was no statistically significant difference between vertebrae and ribs, vertebrae and head of the femur nor between ribs and femoral head. These results indicate that femoral head may be an appropriate substitute for vertebrae or ribs, the most commonly used bone for inferring the skeletal burden of U and Pu in human. Femoral head samples can be obtained from living persons undergoing hip surgery, while vertebrae and ribs are obtained only at autopsy.

Body Burden↗

Adaptation of bone and tendon to prolonged hindlimb suspension in rats.

The rat hindlimb suspension model was used to ascertain the importance of ground reaction forces in maintaining bone and tendon homeostasis. Young female Sprague-Dawley rats were randomly assigned to either a suspended or a nonsuspended group. After 28 days, femur bones and patellar tendons were obtained for morphological and biochemical analyses. Prolonged suspension induced a significant change in the geometric configuration of the femur middiaphysis by increasing the minimum diameter (12%) without any significant alterations in cortical area, density, mineral, and collagen concentrations. Femur wet weight, length, DNA, and uronic acid concentrations of suspended animals were not significantly different from bones of nonsuspended rats. However, the collagen and proteoglycan concentrations in patellar tendons of suspended rats were 28% lower than the concentrations of matrix proteins in tissues obtained from nonsuspended animals. These data suggest that elimination of ground reaction forces induces alterations in tendon composition and femur diaphyseal shape by changing regional rates in bone remodeling and localized tendon strain. Therefore it appears that ground reaction forces are an important factor in the maintenance of cortical bone and patellar tendon homeostasis during weight-bearing conditions.

Adaptation, Physiological↗

Relationship of anxiety level and recall of information to the interval between orientation and first patient care day.

Sophomore students' responses to two different intervals between orientation and first clinical day in medical/surgical nursing were examined. Variables studied were anxiety state and ability to recall information which had been presented. Prior to orientation all students were given the Spielberger STAI-S and STAI-T anxiety scales. At the beginning of the first laboratory session the students completed the STAI-S scale and a teacher-made quiz on information presented in orientation. Students in Group I (n = 51) had their first laboratory one week after orientation. Group II (n = 39) had their first laboratory the day following orientation. There was no significant difference between the two groups on cumulative grade point average, beginning STAI-T or STAI-S. Likewise, there was no significant difference between the scores made on the quiz. (The validity and reliability of the quiz were not determined.) There was a significant difference between the two groups on changes in state anxiety from orientation to the first laboratory. Group I (laboratory one week after orientation) was more anxious than Group II (laboratory one day after orientation) (p = 0.024). Both groups were significantly more anxious in the Spring than Fall quarter (p = 0.034). It was concluded that anxiety related to a new clinical experience might be lessened if the first clinical day closely followed orientation. It was also noted that students may be more anxious in the Spring than in the Fall of the year.

Anxiety↗

Economic and technical considerations in the procurement of laboratory rodents.

Research cost effectiveness is an increasing fact of life in this climate of spiraling inflation, restricted budgets, advancing technology and increased regulatory complexities. Because rodent procurement is an easily identifiable cost center, it may become a target for budgetary restriction without judicious consideration of its impact on the total research effort. If such reductions compromise sound biologic, genetic or health principles, the result may be research delays or repetition, inefficient or ineffective use of scientific personnel and increased project costs. Procurement decisions should be based on the development of specific biologic, genetic and health parameters required by the project design. Potential sources of supply should be assessed to determine compliance with these criteria. Further analysis must include an evaluation of institutional resources to determine compatibility with procurement standards over the term of the project. Only then can procurement costs be placed in proper perspective.

Animal Husbandry↗

Conversion of l- and d-Phenylalanine to Phenylacetate via Phenylpyruvate in Sorghum Leaf Extracts.

The incorporation of dl-[(14)C]phenylalanine into phenylacetate reported previously in leaf enzyme preparations has been found to be catalyzed by two separate enzyme activities leading to phenylpyruvate, one using the l-, the other the d-isomer. Since both reactions occur anaerobically and are increased by the addition of pyridoxal phosphate and alpha-ketoglutarate, two transaminase (aminotransferase) activities appear to be involved. The activities of the l- and d-dependent forms are approximately equal in a crude particulate fraction, but range from 1:1 to 3:1 in a soluble supernatant fraction. Nonisotopic as well as isotopic assays to separate d- and l-activities are described.

Journal Article↗

Interference by a phenylacetate pathway in isotopic assays for phenylalanine ammonia-lyase in leaf extracts.

Particulate and soluble fractions from leaves of Sorghum, Spinacia (spinach), and Coleus, capable of metabolizing l-phenylalanine to cinnamate or to caffeate, are also able to convert l-and d-phenylalanine to phenylacetate. Since cinnamate and phenylacetate are not effectively separated in commonly used chromatographic solvents, some of the isotropic assays used for phenylalanine ammonia-lyase are rendered ambiguous by the interference of this second pathway. Therefore, a "double decker," two-dimensional paper chromatographic method was designed to separate cinnamate and phenylacetate. This was combined with the use of phenylalanine labeled randomly or just in either the carbon 1 or 2 position of the side chain.

Journal Article↗

Isolation and characterization of a dog serum lipoprotein having apolipoprotein A-I as its predominant protein constituent.

The serum high density lipoproteins (HDL) of normolipemic dogs (beagles) were isolated in the density range of p 1.063 to 1.21 g/ml, and characterized in terms of composition and physical properties (flotation and diffusion coefficients, partial specific volume, molecular weight, electrophoretic mobility, ultraviolet absorption, and circular dichroism). The results indicated that canine HDL is a relatively homogeneous class with a molecular weight of about 230 000 and general properties similar to those reported for human HDL. After delipidation, the resulting apolipoprotein, apo-HDL, was fractionated by Sephadex G-200 column chromatography in urea or guanidine hydrochloride solutions. About 90% of the apo-HDL consisted of a protein with a molecular weight of about 28 000, similar in amino acid composition to human apolipoprotein A-I and having the same NH2 terminus (aspartic acid) and COOH terminus (glutamine) and no carbohydrates. Two other proteins were isolated, one having an apparent mol wt of 55 000 and representing, at least in part, an aggregate of apolipoprotein A-I and the other component with a mol wt of 8000, not yet characterized. The results indicate that canine HDL, as an intact complex, has general physical properties that lie between those reported for human HDL2 and HDL3, and that it differs compositionally from the human products mainly in its predominant content of apo-A-I. These findings together with evidence for the relatively homogeneous nature of the canine HDL provide new prospects for unraveling the relationship between polypeptide composition and HDL structure.

Amino Acids↗