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Biomedical subjects

S Orloff

Publications and source records attributed to S Orloff.

At least 19 recordsLinked to original sources
PubMed1998

Impact of zidovudine use on risk and risk factors for perinatal transmission of HIV. Perinatal AIDS Collaborative Transmission Studies.

OBJECTIVES: To evaluate the impact of perinatal zidovudine use on the risk of perinatal transmission of HIV and to determine risk factors for transmission among women using perinatal zidovudine. DESIGN: Prospective cohort study of 1533 children born to HIV-infected women between 1985 and 1995 in four US cities. METHODS: The association of potential risk factors with perinatal HIV transmission was assessed with univariate and multivariate statistics. RESULTS: The overall transmission risk was 18% [95% confidence interval (CI), 16-21]. Factors associated with transmission included membrane rupture > 4 h before delivery [relative risk (RR), 2.1; 95% CI, 1.6-2.7], gestational age < 37 weeks (RR, 1.8; 95% CI, 1.4-2.2), maternal CD4+ lymphocyte count < 500 x 10(6) cells/l (RR, 1.7; 95% CI, 1.3-2.2), birthweight < 2500 g (RR, 1.7; 95% CI, 1.3-2.1), and antenatal and neonatal zidovudine use (RR, 0.6; 95% CI, 0.4-0.9). For infants exposed to zidovudine antenatally and neonatally, the transmission risk was 13% overall but was significantly lower following shorter duration of membrane rupture (7%) and term delivery (9%). The transmission risk declined from 22% before 1992 to 11% in 1995 (P < 0.001) in association with increasing zidovudine use and changes in other risk factors. CONCLUSIONS: Perinatal HIV transmission risk has declined with increasing perinatal zidovudine use and changes in other factors. Further reduction in transmission for women taking zidovudine may be possible by reducing the incidence of other potentially modifiable risk factors, such as long duration of membrane rupture and prematurity.

Adult↗
PubMed1997

The effect of maternal viral load on the risk of perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the effect of maternal viral load at delivery on the risk of perinatal transmission of HIV-1. DESIGN: A nested case-control study within a prospectively followed cohort of HIV-1-infected pregnant women and their infants. SETTING: The multicenter New York City Perinatal HIV Transmission Collaborative Study. PARTICIPANTS: Fifty-one women who gave birth to HIV-1 infected infants were frequency-matched within CD4+ cell count quintiles with 54 non-transmitting mothers. MAIN OUTCOME MEASURES: Maternal quantity of HIV-1 viral RNA was assayed in plasma obtained near delivery using the nucleic acid sequence-based amplification assay system. RESULTS: Viral RNA was detected in 73 (70%) out of 105 women and the median viral load was 16,000 RNA copies/ml in transmitters and 6,600 in non-transmitters (P < 0.01). When adjusted for maternal CD4+ count near delivery, women with measurable viral load were nearly sixfold more likely to transmit HIV-1 than women with viral load below detection [adjusted odds ratio (AOR), 5.8; 95% confidence interval (CI), 2.2 15.5]. The odds ratio for perinatal transmission of log10 viral load, adjusted for CD4 count was 2.7 (95% CI, 1.5-5.1). When stratified by the stage of HIV-1 disease, the only group with significant association between log10 viral load and transmission were AIDS-free women with CD4+ count > 500 x 10(6)/l (AOR, 9.1; 95% CI, 2.6-31.5). CONCLUSIONS: High maternal viral load increases the likelihood of perinatal transmission of HIV-1 in women without AIDS and advanced immunosuppression. HIV-1 infected pregnant women without advanced disease, shown by others to have the lowest risk of perinatal transmission, may benefit the most from efforts to identify and decrease viral load at delivery.

Adult↗
PubMed1997

Early detection of perinatal human immunodeficiency virus (HIV) type 1 infection using HIV RNA amplification and detection. New York City Perinatal HIV Transmission Collaborative Study.

Early diagnosis of perinatally transmitted human immunodeficiency virus type 1 (HIV) infection can guide early interventions. HIV coculture and DNA polymerase chain reaction (DNA-PCR) detect few HIV-infected infants at birth and 90%-100% by age 3 months. Because extracellular HIV RNA may appear soon after infection, a plasma HIV RNA assay was compared with DNA-PCR for early detection of perinatally infected infants. Blood-draw specimens (108) obtained at the same time from 49 HIV-infected infants and 10 specimens from 8 uninfected infants were tested. HIV RNA and DNA-PCR positivity rates were 56% and 33%, respectively, in 36 specimens from 36 infants <28 days of age (binomial test, P = .001). Among 81 specimens obtained after age 14 days, 79 (98%) were positive by HIV RNA testing. No HIV-infected infant specimens were DNA-PCR-positive and HIV RNA-negative. All specimens from 8 uninfected infants were HIV RNA-negative. These results suggest that plasma HIV RNA was detectable earlier and more reliably than HIV DNA in perinatal infection.

Female↗
PubMed1994

[Considerations for optimizing joint implants].

Despite the increasing use of orthopaedic implants, there is still a lack of adequate testing procedures and legal guidelines. Examples of the consequences of this neglect are given. Modern techniques for the calculation of stresses (finite element method [FEM]) and the prediction of life cycle duration are presented. Such methods, applied in the development and manufacturing phases of standard and special implants, may ensure an adequate prosthetic life cycle, with particular emphasis being placed on the biomedical optimization of the implant/bone interface and surrounding bone.

Biomechanical Phenomena↗
PubMed1991

Long-term sequelae of pelvis irradiation: histological and microradiographical study of a femoral head.

Despite the lack of radiological signs, a femoral head showed histological and microradiographical features of osteonecrosis, 54 years after massive irradiation of the right hip. Intertrabecular spaces were invaded by connectivo-vascular tissue with focal accumulation of mast cells, and several resorption foci were filled with mononucleated cells. Moreover, all the microradiographs showed peculiar hypercalcified lines, sometimes containing empty osteocytic lacunae, the origin of which is difficult to precise. This study suggests that massive irradiation of weight-bearing epiphyses may be responsible for particularly long-term hypovascularity, osteonecrosis and disturbed bone remodeling.

Female↗
PubMed1991

Analysis of synergism/antagonism between HIV-1 antibody-positive human sera and soluble CD4 in blocking HIV-1 binding and infectivity.

We tested human immunodeficiency virus type 1 (HIV-1) antibody-positive human sera and sCD4, alone and in combination, for synergistic, additive, or antagonistic effects on blocking of HIV binding and infectivity. Data were analyzed by an application of the median effect principle derived from the law of mass action. This allows the assessment of synergism/antagonism at any desired level of effect. Using three assays (whole virus binding to CD4 cells, neutralization of HIV infectivity, and binding of purified gp120 to solid-phase sCD4), we generally observed additive effects or slight synergism between antibody and sCD4 in inhibiting gp120-CD4 interaction. We used a fourth assay to measure the irreversible inactivation of HIV infectivity by sCD4, a property that can also be mediated by antibody but with considerably less potency than sCD4. The reduction in HIV infectivity mediated by mixtures of sCD4 and antibody was always equal to or greater than the arithmetic sum of the reductions by either agent alone. The relevant antiviral effects of sCD4 and anti-HIV sera may include reversible blockage of receptor binding, irreversible inactivation of HIV infectivity, and in the case of antibody, additional reactions that are independent of receptor binding. Although predictions concerning the in vivo situation are speculative, we find no evidence in vitro for antagonism between sCD4 and antibody with respect to the net effect of the two in blocking HIV binding and infectivity.

Binding, Competitive↗
PubMed1987

Bilateral non-traumatic aseptic osteonecrosis in the femoral head. An experimental study of incidence.

Thirty-five patients who were seen with non-traumatic aseptic osteonecrosis of the femoral head were included in a study of the contralateral hip to evaluate the incidence of bilateral disease. We used not only conventional radiography and scintigraphy but also measurement of intramedullary pressure and core biopsy. Pain was caused by 14.3 per cent of the contralateral hips, a lesion was demonstrated on plain radiographs in 51.4 per cent, and increased isotopic uptake was seen in 31.4 per cent. Histological study of specimens obtained by osteomedullary biopsy (after special procedure) showed bilateral necrosis in 88.5 per cent of the patients. After a mean follow-up of thirty-four months, only one of nine hips that were painless and had negative radiographic and isotopic findings, but had positive findings on biopsy, became painful and radiographically positive. The intramedullary pressure in the intertrochanteric area was recorded in each hip, and no correlation was found with the radiographic stage or with pain.

Adult↗
PubMed1983

Relationship of cell growth to collagen synthesis in glucocorticoid treated A/J and C57BL6/J neonatal mouse dermal fibroblasts.

Primary cultures of neonatal dermal fibroblasts from two strains of mice (A/J and C57BL6/J) were utilized as an in vitro system to investigate the effects of glucocorticoids on cell growth and collagen synthesis. Protein and DNA synthesis were lower in untreated (control) A/J fibroblasts than in C57BL6/J fibroblasts. Treatment with glucocorticoids for 4 days resulted in dose-dependent inhibition of [3H]thymidine incorporation into DNA and a reduction in collagen synthesis. Collagen synthesis was differentially more susceptible to glucocorticoids than was total protein synthesis. Neonatal dermal fibroblasts obtained from A/J mice were more sensitive to glucocorticoids than were cells from C57BL6/J mice. Reduction in collagen production by anti-inflammatory steroids in this system may be related to adverse effects observed in vivo following treatment with these steroids.

Animals↗
PubMed1982

Gonococcal arthritis-dermatitis syndrome. Study of serum and synovial fluid immune complex levels.

Immune complexes from serum and synovial fluid were detected by the C1q binding assay in 12 patients with disseminated gonococcal infection. Since immune complexes were regularly higher in synovial fluids than in paired sera and were not detected by the monoclonal rheumatoid factor radioimmunoassay, we suggest that IgM may be present in these complexes and that this represents a primary immune response. In contrast, only 2 of 10 patients with local gonococcal infection were slightly positive both with the C1q assay and the monoclonal rheumatoid factor assay. In patients with disseminated gonococcal infection, immune complexes closely paralleled the disease activity and negatively correlated with complement levels. Synovial fluid immune complexes seem to occur in the early and aseptic phase of polyarthritis and to aid the entrance of circulating gonococcal organisms. From the results of our study, it seems that immunologic processes initiate and/or sustain inflammation in disseminated gonococcal infections that appear, at least in part, as a form of reactive arthritis.

Adolescent↗
PubMed1981

Lipochromosome mediated gene transfer: identification and probable specificity of localization of human chromosomal material and stability of the transferents.

Using lipochromosomes (phospholipid-entrapped chromosomes) were have transferred the human HGPRT gene into HGPRT deficient mouse cells (A9) with a frequency of approximately 1 x 19(-5) (Mukherjee et al. Proc. Natl. Acad. Sci. USA 75: 1361-1365; 1978). Two other genes located on the long arm of the human X-chromosome were also expressed two independently derived populations of transferents (A9/GT3 and A9/GT4). We report here the chromosomal and enzymatic composition of human HGPRT-positive clones from each subpopulation analyzed in detail with alkaline Giemsa-11 staining. All the clones expressed human PGK and HGPRT, but one (A9/GT4C6) lacked human G6PD. In each of four clone examined microscopically, a small piece of presumptive human chromatin was visible in the karyotypes of most cells. The chromatin fragment was free or attached in each cell of an individual clone. When integrated, the human chromosomal fragment in each clone appeared associated with the centromere of the same telocentric A9 chromosome (No. 6 Q-banding). These data suggest that: (a)substantial human chromosomal fragments can be transferred into recipient cell using the lipochromosome technique; (b) clones from human HGPRT positive A9 transferent subpopulations may or may not possess other human X-linked markers: (c) the stability of lipochromosomally transferred genes varied from clone to clone and stability is generally poor in the absence of continuous selection pressure (e.g., HAT); (d) when multiple X-linked human genes were transferred to mouse cells a cytologically detectable human chromosomal fragment was identified free or attached to a host chromosome; and (e) integration of transferred human chromosomal material into mouse chromosomes may occur at preferential site(s) in the recipient genome.

Animals↗
PubMed1981

Bone mineral content of the radius: good correlations with physicochemical determinations in iliac crest trabecular bone of normal and osteoporotic subjects.

Specific gravity, porosity index (physical parameters), hydroxyproline, calcium, magnesium, and phosphorus (chemical parameters) were determined in iliac crest trabecular bone of normal and osteoporotic subjects. These physical and chemical parameters were compared to bone mineral contents (BMC) measurements by x-ray photodensitometry of the radius. BMC values correlated negatively with porosity index, specific gravity, and degree of mineralization of trabecular bone matrix, which all increase with osteoporosis. There was a negative correlation between calcium and magnesium contents per net bone volume. "Distal" scans of the radius reflected better the axial skeleton mass than "proximal" scans, and physicochemical data correlated better with bone mineral content values than with bone mineral mass (BMM) values.

Adult↗
PubMed1981

Pantetheinase activity and cysteamine content in cystinotic and normal fibroblasts and leukocytes.

Cysteamine is the most effective agent known for the reduction of the elevated cystine content of cells from patients with cystinosis. A defect in endogenous cysteamine generation could account for many of the metabolic features of this disorder. To test this hypothesis, we have developed improved methods for measuring pantetheinase (cysteamine-generating) activity and intracellular cysteamine levels and used these methods to measure such parameters in cystinotic and normal leukocytes and cultured skin fibroblasts. Pantetheinase activity as defined in the test was similar in extracts of cystinotic and normal cells [leucocytes, normal, 78 +/- 15 (S.E.), cystinotic, 56+/- 6.4; fibroblasts, normal, 9.4 +/- 1.5; cystinotic, 7.7 +/- 1.7]. Cysteamine levels were normal in leukocytes from cystinotics receiving no cysteamine or doses of oral cysteamine too low to reduce leukocyte cystine content. The results indicate that the cause of cystinosis is unlikely to be related to a failure to generate of sustain normal intracellular cysteamine levels.

Amidohydrolases↗
PubMed1981

Synovial fluid hydroxyproline fractions before and after osmic acid treatment in rheumatoid arthritis.

Synovial fluid total, dialysable and non-dialysable hydroxyproline were determined in patients with Rheumatoid Arthritis before intra-articular osmic acid injection and on days 2 and 4 after this local treatment. On day 2 the increase in dialysable hydroxyproline paralleled the increase in non-dialysable hydroxyproline. Patients with the highest pre-treatment dialysable hydroxyproline levels also had the highest levels of this fraction on day 2 suggesting that articular damage proceeds after osmic acid injection. However, on day 4 dialysable hydroxyproline levels were consistently lower than before the treatment; the same pattern was observed with non-dialysable hydroxyproline, except for all the joints but one, where effusion recurred 6-12 months after osmic acid treatment. This study suggests that the determination of synovial fluid non-dialysable levels 4 days after osmic acid injection may provide a clue to the prediction of recurrent joint effusion and possibly justify a complementary injection either with osmic acid or with a beta-emitting isotope.

Adult↗