Biomedical subjects

Leslie Berry

Publications and source records attributed to Leslie Berry.

6 recordsLinked to original sources

PubMed2006

Tracking the prevalence of transmitted antiretroviral drug-resistant HIV-1: a decade of experience.

Transmitted resistance to antiretroviral drugs in acute and early HIV-1 infection has been well documented, although overall trends vary depending on geography and cohort characteristics. To describe the changing pattern of transmitted drug-resistant HIV-1 in a well-defined cohort in New York City, a total of 361 patients with acute or recent HIV-1 infection were prospectively studied over a decade (1995-2004) with respect to HIV-1 genotypes and longitudinal T-cell subsets and HIV-1 RNA levels. The prevalence of overall transmitted resistance changed from 13.2% to 24.1% (P = 0.11) during the periods 1995 to 1998 and 2003 to 2004. Nonnucleoside reverse transcriptase inhibitor resistance prevalence increased significantly from 2.6% to 13.4% (P = 0.007) during the same periods, whereas prevalence of multidrug-resistant virus shifted from 2.6% to 9.8% (P = 0.07) but did not achieve statistical significance. A comparable immunologic and virologic response of appropriately treated individuals was observed regardless of viral drug susceptibility status, suggesting that initial combination therapy guided by baseline resistance testing in the case of acute and early infection may result in a favorable treatment response even in the case of a drug-resistant virus. These data have important implications for selection of empiric first-line regimens for treatment of acutely infected antiretroviral-naive individuals and reinforce the need for baseline resistance testing in acute and early HIV-1 infection.

Adult↗

PubMed2005

Age-related differences in heparin response.

INTRODUCTION: Major physiological differences in the coagulation system throughout childhood, compared to adults, are well documented. However, the impact of this on anticoagulant drugs is unknown. This study aimed to determine whether heparin therapeutic range determination is affected by the age of plasma donors and whether age-specific therapeutic ranges for heparin therapy may need to be considered in the clinical setting. MATERIALS AND METHODS: Plasma samples were obtained from healthy children and adults, and pooled into age-specific pools. These were spiked with different concentrations of heparin and APTT; Anti-Factor Xa and Anti-Factor IIa were measured using standard techniques. The experiments were repeated using three separate plasma pools, and results expressed as means with standard deviations. RESULTS AND CONCLUSIONS: The results show clear age-related differences in APTT for the same Anti-Factor Xa heparin concentration. The differences were more pronounced in younger children, with higher APTT for same Anti-Factor Xa. The Anti-Factor IIa activity of heparin for a given Anti-Factor Xa activity also differed between age-specific plasma pools. This study suggests that when using heparin in children, basic assumptions about the drug mechanism of action and implications for therapeutic ranges need to be considered.

Adolescent↗

PubMed2005

Volutrauma activates the clotting cascade in the newborn but not adult rat.

Coagulopathy and alveolar fibrin deposition are common in sick neonates and attributed to the primary disease, as opposed to their ventilatory support. Hypothesizing that high tidal volume ventilation activates the extrinsic coagulation pathway, we air ventilated newborn and adult rats at low (10 ml/kg) or high (30 ml/kg) tidal volume and compared them with age-matched nonventilated controls. Blood was collected at the end of the experiment for measurement of clot time, tissue factor, and other coagulation factor content. Similar measurements were obtained from lung lavage material. The newborn clot time (44+/-1) was lower and plasma tissue factor content higher (103.4+/-0.4) than adults (88+/-4 s and 26.6+/-1.4 units; P<0.01). High, but not low, tidal volume ventilation of newborns for as little as 15 min significantly reduced clot time and increased plasma tissue factor content (P<0.01). High volume ventilation increased plasma factor Xa (0.1+/-0.1 to 1.6+/-0.4 nM; P<0.01) and thrombin (1.3+/-0.2 to 2.2+/-0.4 nM; P<0.05) and decreased antithrombin (0.12+/-0.01 to 0.05+/-0.01; P<0.01) in the newborn. Lung lavage material of high volume-ventilated newborns showed increased (P<0.01) factor Xa and thrombin. No changes in these parameters were observed in adult rats that were high volume ventilated for up to 90 min. Compared with adults, newborn rats have a greater propensity for volutrauma-activated intravascular coagulation. These data suggest that mechanical ventilation promotes neonatal thrombosis via lung tissue factor release.

Aging↗

PubMed2002

Antithrombin-heparin covalent complex: a possible alternative to heparin for arterial thrombosis prevention.

BACKGROUND: The anticoagulant effect of heparinoids is attributed to their cofactor activity for antithrombin (AT) and heparin cofactor II. In patients with thrombosis, however, thrombin is often protected from AT-dependent, heparin-mediated inactivation. The purpose of this study was to compare the properties of unfractionated/standard heparin (UFH/SH) and those of a novel covalent AT-heparin complex (ATH) in a rabbit arterial thrombosis prevention and bleeding model. METHODS AND RESULTS: Thrombosis in the distal aorta was triggered by vessel wall injury and critical stenosis. Blood flow in the damaged arterial segment was monitored with a flow probe placed distal to the constrictor. Rabbits were given doses of SH (62.5 to 187.5 IU x kg(-1) x 90 min(-1)) or ATH (16 to 65 IU x kg(-1) x 90 min(-1)). Cumulative blood loss from skin incisions was used to assess drug safety. The antithrombotic effects of ATH were greater than those of SH as measured by clot weight, blood flow, and vessel patency; eg, complete thrombus resolution was achieved with ATH (33 to 65 IU/kg), but not SH (125.0 to 187.5 IU/kg). At doses that produced equivalent vessel patency (50% to 60%), blood loss induced by ATH (60.2 microL) was 2.6-fold lower (P<0.05) than that induced by SH (154.6 microL). CONCLUSIONS: In our experimental system, ATH was able to control arterial thrombosis more effectively than its SH precursor, without pronounced bleeding.

Animals↗

PubMed2002

Adsorption of proteins from infant and adult plasma to biomaterial surfaces.

The hemostatic mechanism of the newborn is immature. In general, the clotting times in screening tests are prolonged, the coagulation factors are low, and the coagulation inhibitors (with the exception of alpha-2-macroglobulin) are low. Recognizing that many of the proteins present in infant plasma are at low levels, it is of interest to determine if, following exposure to artificial surfaces, the profile of adsorbed proteins is different for infant versus adult plasma. The question of whether differences in protein profiles could lead to differences in thromboembolic episodes associated with the use of central venous catheters (or other blood-contacting devices) in infant versus adult subjects also is relevant. To address these issues, the adsorption of proteins from pooled infant plasma and pooled normal adult plasma to three different polymer surfaces (polyvinyl chloride, PVC; polymethyl methacrylate, PMMA; and polyethylene oxide-modified polyurethane, PEO-PU) was studied using SDS-PAGE and immunoblotting techniques. The total amount of protein adsorbed to each surface also was determined. It was found that the PMMA and PVC surfaces adsorbed considerably more protein than the PEO-PU surface. Furthermore, the amount of protein adsorbed to the PMMA and PVC surfaces from infant plasma was significantly less than that adsorbed from adult plasma. No such difference was seen for the protein-repellent PEO-PU surface. The immunoblot responses of proteins bound to the PMMA and PVC surfaces from infant plasma were, in general, weaker than those bound from adult plasma. It is likely that these differences were due to decreased protein levels in infant plasma.

Adsorption↗

PubMedDate not supplied

Infection with multidrug resistant, dual-tropic HIV-1 and rapid progression to AIDS: a case report.

BACKGROUND: Rapid progression to AIDS after acute HIV-1 infection, though uncommon, has been noted, as has the transmission of multidrug resistant viruses. Here, we describe a patient in whom these two factors arose concomitantly and assess the effects. METHODS: We did a case study of a patient with HIV-1 seroconversion. We genotyped the virus and host genetic markers by PCR and nucleotide sequencing. To ascertain the drug susceptibility of our patient's HIV-1 we did phenotypic studies with the PhenoSense assay. We assessed viral coreceptor use via syncytium formation in vitro and with a modified PhenoSense assay. FINDINGS: Our patient seems to have been recently infected by a viral variant of HIV-1 resistant to multiple classes of antiretroviral drugs. Furthermore, his virus population is dual tropic for cells that express CCR5 or CXCR4 coreceptor. The infection has resulted in progression to symptomatic AIDS in 4-20 months. INTERPRETATION: The intersection of multidrug resistance and rapid development of AIDS in this patient is of concern, especially in view of his case history, which includes high-risk sexual contacts and use of metamfetamine. The public health ramifications of such a case are great.

Acquired Immunodeficiency Syndrome↗