PubMed Health⌕ Search

Biomedical subjects

David Margolis

Publications and source records attributed to David Margolis.

At least 19 recordsLinked to original sources
PubMed2006

A placebo-controlled pilot study of intensification of antiretroviral therapy with mycophenolate mofetil.

PURPOSE: We studied the safety, tolerability, virologic, and immunologic effects of mycophenolate mofetil (MMF) added to a stable antiretroviral therapy (ART) in the setting of low-level viremia. METHODS: MMF 500 mg BID or placebo was given to patients thought to be adherent on stable ART with plasma viremia between 200 and 4000 copies/mL. At week 4 unblinding was performed and patients on placebo were offered open-label MMF. RESULTS: Six patients were enrolled. At entry mean plasma HIV-1 RNA (VL) was 2.98 log10 copies/mL; mean CD4 count was 523. All subjects randomized to placebo elected to cross over to open label MMF. No significant adverse events were observed during MMF therapy. Three patients on MMF achieved VL < 50 copies/mL by week 4; a fourth had VL decline of > 0.5 log. Two patients on placebo had declines of VL. One of these had further decline on open label MMF. Cell surface markers of apoptosis, activation, and proliferation on CD4+ and CD8+ cells declined modestly or remained low. CD4 counts were stable at week 24. All but one subject had rebound of viremia by week 24, universally associated with missed doses of medication by pill count. CONCLUSION: MMF appears to be safe, and its administration lead to decreased T cell activation. During periods of adherence to therapy, the use of MMF was correlated with declines in viremia, but this small pilot study could not prove this association. Further study of MMF in patients with viremia should be considered for whom additional or alternative antiretrovirals are impractical.

Journal Article↗
PubMed2006

The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology.

Skin disease is one of the top 15 groups of medical conditions for which prevalence and health care spending increased the most between 1987 and 2000, with approximately 1 of 3 people in the United States with a skin disease at any given time. Even so, a national data profile on skin disease has not been conducted since the late 1970s. This study closes the gap by estimating the prevalence, economic burden, and impact on quality of life for 22 leading categories of skin disease. The estimated annual cost of skin disease in 2004 was 39.3 billion dollars, including 29.1 billion dollars in direct medical costs (costs of health services and products) and 10.2 billion dollars in lost productivity costs (defined as costs related to consumption of medical care, costs associated with impaired ability to work, and lost future earning potential because of premature death). Based on a methodology of willingness to pay for symptom relief, the additional economic burden of skin disease on quality of life amounted to an estimated 56.2 billion dollars. Including the economic burden on quality of life, the total economic burden of skin disease to the US public in 2004 was approximately 96 billion dollars.

Cost of Illness↗
PubMed2006

Clinical and experimental applications of NIR-LED photobiomodulation.

This review presents current research on the use of far-red to near-infrared (NIR) light treatment in various in vitro and in vivo models. Low-intensity light therapy, commonly referred to as "photobiomodulation," uses light in the far-red to near-infrared region of the spectrum (630-1000 nm) and modulates numerous cellular functions. Positive effects of NIR-light-emitting diode (LED) light treatment include acceleration of wound healing, improved recovery from ischemic injury of the heart, and attenuated degeneration of injured optic nerves by improving mitochondrial energy metabolism and production. Various in vitro and in vivo models of mitochondrial dysfunction were treated with a variety of wavelengths of NIR-LED light. These studies were performed to determine the effect of NIR-LED light treatment on physiologic and pathologic processes. NIRLED light treatment stimulates the photoacceptor cytochrome c oxidase, resulting in increased energy metabolism and production. NIR-LED light treatment accelerates wound healing in ischemic rat and murine diabetic wound healing models, attenuates the retinotoxic effects of methanol-derived formic acid in rat models, and attenuates the developmental toxicity of dioxin in chicken embryos. Furthermore, NIR-LED light treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. The experimental results demonstrate that NIR-LED light treatment stimulates mitochondrial oxidative metabolism in vitro, and accelerates cell and tissue repair in vivo. NIR-LED light represents a novel, noninvasive, therapeutic intervention for the treatment of numerous diseases linked to mitochondrial dysfunction.

Animals↗
PubMed2006

Hexamethylbisacetamide remodels the human immunodeficiency virus type 1 (HIV-1) promoter and induces Tat-independent HIV-1 expression but blunts cell activation.

Hexamethylbisacetamide (HMBA) induces human immunodeficiency virus type 1 (HIV-1) gene expression in latently infected T-cell and monocytoid cell lines. We find that HMBA activation of viral expression is Tat independent but, like Tat, increases the efficiency of elongation of the HIV-1 promoter (long terminal repeat [LTR]) transcripts. Further, exposure to HMBA induces chromatin remodeling at nucleosome 1 (Nuc-1) near the start site of LTR transcription but does so without increasing histone acetylation or altering histone methylation near Nuc-1. Of note, despite enhanced proviral expression, HMBA suppressed HIV infection ex vivo in primary blood mononuclear cell (PBMC) cultures. Treatment with HMBA did not alter expression of the HIV coreceptors, CCR5 and CXCR4, in PBMCs but down-regulated CD4. Finally, HMBA interferes with cell proliferation and activation; it suppressed expression of Ki67 and CD25 and in PBMCs exposed to mitogen. As HMBA has been tested in oncology trials, its unusual properties make it a useful reagent for future studies of HIV promoter regulation and a novel prototype molecule for therapeutics that abort the latent proviral state of chronic HIV infection.

Acetamides↗
PubMed2006

The prevalence of diagnosed cutaneous manifestations during ambulatory diabetes visits in the United States, 1998-2002.

BACKGROUND: The prevalence of diabetes has been rapidly increasing. Previous reports indicated that diabetics are prone to certain cutaneous diseases. OBJECTIVE: To determine the frequencies of diagnosed skin conditions during ambulatory diabetes visits in the USA. METHODS: We evaluated two national ambulatory medical care surveys between 1998 and 2002 and compared the diagnoses of 7 categories of skin conditions in diabetics (n = 9,626) to patients with hypertension (n = 15,997) or gastroesophageal reflux disease (GERD; n = 2,362) using chi2 tests and multivariate logistic regressions. RESULTS: Diabetics were prone to chronic skin ulcers (odds ratio = 62.5, 95% confidence interval = 3.95-989 compared to GERD; 9.97, 6.34-15.7 compared to hypertension), bacterial skin infections (5.95, 2.86-12.4 compared to GERD; 5.15, 3.74-7.08 compared to hypertension) and fungal skin infections (2.66, 1.15-6.16 compared to GERD; 1.99, 1.32-3.01 compared to hypertension) but not to other skin conditions. These findings remained true during primary care physician visits. CONCLUSION: Chronic skin ulcers, bacterial and fungal skin infections are more frequently diagnosed in diabetics. We could not verify that other skin conditions are associated with diabetes, in part due to potential underdiagnosis and underreporting.

Ambulatory Care↗
PubMed2005

Ex vivo modeling of the effects of mycophenolic acid on HIV infection: considerations for antiviral therapy.

Mycophenolate mofetil (MMF), the bioavailable form of mycophenolic acid (MPA), has been proposed as adjuvant therapy for human immunodeficiency virus type 1 (HIV-1) infection. MPA can inhibit viral replication and might blunt virus-induced immunopathology. However, other effects of this inhibitor might be detrimental in an HIV-infected patient. We therefore studied the effect of MPA on selected cellular processes of relevance to HIV infection. We found that MPA did not alter the expression of the primary HIV coreceptor CCR5 on primary resting lymphocytes, but modestly increased CCR5 expression after activation. Conversely, MPA modestly decreased the secretion of the CCR5 ligand RANTES in resting lymphocytes, but had no effect after activation. It has been suggested that the use of inhibitors of host nucleoside metabolism may enhance clinical toxicities induced by HIV-1 nucleoside reverse transcriptase inhibitors (NRTIs). We found no evidence that MPA induced mitochondrial dysfunction or enhanced dysfunction induced by NRTIs in an HepG2 cell line model of mitochondrial toxicity. Further, MPA did not selectively enhance apoptosis in HIV-1-infected lymphocytes. Our findings support the testing of MMF to augment suppression of viral replication. However, careful study will be required to demonstrate that MMF is beneficial when used without antiretroviral therapy, to inhibit residual replication, or to deplete the pool of latently infected nonactivated cells.

Apoptosis↗
PubMed2005

The psychometric properties of the psoriasis disability index in United States patients.

Although it has had only limited psychometric assessment in one country (the UK), the Psoriasis Disability Index (PDI) is a commonly used measure of the impact of psoriasis on patients. This study's objective was to analyze the psychometric properties of the PDI in 1196 US patients. High Cronbach's alpha coefficients suggested that the PDI's internal consistency is good. The validity of the PDI was tested using a global question on disease burden and self-assessed extent of disease and both appeared to be good predictors of the PDI. Large floor effects and the suboptimal response distribution of most items, however, suggested that the PDI is insensitive to mild functional limitation. Factor analyses indicated that the current PDI subscales are suboptimal. In the Rasch analysis, the PDI and its subscales appeared to measure multiple constructs, making the validity of deriving a single overall score questionable. The frequent presence of differential item functioning related to several patient characteristics confirmed the instrument's multidimensionality. These findings suggest that the PDI is not an optimal measure for use in US study populations. The psychometric properties of instruments designed to measure the impact of psoriasis should be tested in populations in which the instrument is to be applied.

Clinical Trials as Topic↗
PubMed2005

Mitogen-activated protein kinases regulate LSF occupancy at the human immunodeficiency virus type 1 promoter.

Human immunodeficiency virus type 1 (HIV-1) establishes a persistent, nonproductive state within a small population of memory CD4(+) cells. The transcription factor LSF binds to sequences within the HIV-1 long terminal repeat (LTR) initiation region and recruits a second factor, YY1, to the LTR. These factors then cooperatively recruit histone deacetylase 1 to the LTR, resulting in inhibition of transcription. This appears to be one mechanism contributing to HIV persistence within resting CD4(+) T cells. We sought to further detail LSF binding to the HIV-1 LTR and factors that regulate LSF occupancy. We find that LSF binds the LTR as a tetramer and that binding is regulated by phosphorylation mediated by mitogen-activated protein kinases (MAPKs). In vitro, phosphorylation of LSF by Erk decreases binding to the LTR, while binding is increased by p38 phosphorylation. LSF occupancy at LTR chromatin is increased by the p38 agonist anisomycin and decreased by specific p38 inhibition. p38 inhibition also results in increased acetylation of histone H4 at the LTR nucleosome adjacent to the LSF binding site. p38 inhibition also blocked the ability of YY1 to inhibit activation of the integrated HIV promoter. Finally, HIV was recovered from the resting CD4(+) T cells of aviremic, HIV-infected donors upon treatment of these cells with specific inhibitor of p38. These data suggest that the MAPK pathway regulates LSF binding to the LTR and thereby one aspect of the regulation of HIV expression. This mechanism could be exploited as a novel therapeutic target to disrupt latent HIV infection.

Cells, Cultured↗
PubMed2004

Glucose production pathways by 2H and 13C NMR in patients with HIV-associated lipoatrophy.

Patients with HIV taking protease inhibitors were selected for the presence (five subjects) or absence (five subjects) of lipoatrophy. Following an overnight fast, subjects were given oral (2)H(2)O in divided doses (5 mL/kg body water), [U-(13)C(3)] propionate (10 mg/kg), and acetaminophen (1000 mg). Glucose (from plasma) or acetaminophen glucuronide (from urine) were converted to monoacetone glucose for (2)H NMR and (13)C NMR analysis. The fraction of plasma glucose derived from gluconeogenesis was not significantly different between groups. However, flux from glycerol into gluconeogenesis relative to glucose production was increased from 0.20 +/- 0.13 among subjects without lipoatrophy to 0.42 +/- 0.12 (P < 0.05) among subjects with lipoatrophy, and the TCA cycle contribution was reduced. Lipoatrophy was associated with an abnormal profile of glucose production as assessed by (13)C and (2)H NMR of plasma and urine.

Acetaminophen↗
PubMed2004

Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy.

Photobiomodulation by light in the red to near infrared range (630-1000 nm) using low energy lasers or light-emitting diode (LED) arrays has been shown to accelerate wound healing, improve recovery from ischemic injury in the heart and attenuate degeneration in the injured optic nerve. Recent evidence indicates that the therapeutic effects of red to near infrared light result, in part, from intracellular signaling mechanisms triggered by the interaction of NIR light with the mitochondrial photoacceptor molecule cytochrome c oxidase. We have demonstrated that NIR-LED photo-irradiation increases the production of cytochrome oxidase in cultured primary neurons and reverses the reduction of cytochrome oxidase activity produced by metabolic inhibitors. We have also shown that NIR-LED treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. Photobiomodulation improves wound healing in genetically diabetic mice by upregulating genes important in the promotion of wound healing. More recent studies have provided evidence for the therapeutic benefit of NIR-LED treatment in the survival and functional recovery of the retina and optic nerve in vivo after acute injury by the mitochondrial toxin, formic acid generated in the course of methanol intoxication. Gene discovery studies conducted using microarray technology documented a significant upregulation of gene expression in pathways involved in mitochondrial energy production and antioxidant cellular protection. These findings provide a link between the actions of red to near infrared light on mitochondrial oxidative metabolism in vitro and cell injury in vivo. Based on these findings and the strong evidence that mitochondrial dysfunction is involved in the pathogenesis of numerous diseases processes, we propose that NIR-LED photobiomodulation represents an innovative and non-invasive therapeutic approach for the treatment of tissue injury and disease processes in which mitochondrial dysfunction is postulated to play a role including diabetic retinopathy, age-related macular degeneration, Leber's hereditary optic neuropathy and Parkinson's disease.

Journal Article↗
PubMed2004

Black/White differences in pressure ulcer incidence in nursing home residents.

OBJECTIVES: To compare black and white nursing home residents with respect to the incidence of nursing home (NH)-acquired pressure ulcers (PUs) and to examine the role of resident characteristics and facility characteristics in explaining differences between the racial groups. DESIGN: Prospective cohort study conducted between 1992 and 1995. SETTING: Fifty-nine Maryland NHs. PARTICIPANTS: A total of 1,938 residents (301 black, 1,637 white) aged 65 and older newly admitted to participating NHs. MEASUREMENTS: The outcome variable was the first occurrence of a Stage 2, 3, or 4 PU as determined based on medical record review. The predictor variable was race (black, white). Eight resident characteristics (age, sex, number of activity of daily living dependencies, bedfast, PU on admission to facility, incontinence, dementia, and whether the resident was on Medicaid) and three facility characteristics (number of beds, for-profit ownership status, and urban/nonurban location) were considered as possible confounding variables. RESULTS: The incidence of PUs was 0.38 per person-year in the NH. The rate for blacks was significantly higher than for whites (0.56 vs 0.35 per person-year) (P<.001). In multivariate analysis, controlling for eight resident characteristics and three facility characteristics, race was significantly associated with PU incidence (hazard ratio comparing blacks with whites=1.31, 95% confidence interval=1.02-1.66). CONCLUSION: Blacks have a higher incidence of NH-acquired PUs than whites; resident characteristics appear to mediate the higher risk. Future research should aim to identify modifiable factors that explain differences between racial groups in PU risk and to develop solutions to prevent the suffering and cost associated with PUs.

Activities of Daily Living↗
PubMed2003

Noninvasive evaluation of liver metabolism by 2H and 13C NMR isotopomer analysis of human urine.

Mammalian liver disposes of acetaminophen and other ingested xenobiotics by forming soluble glucuronides that are subsequently removed via renal filtration. When given in combination with the stable isotopes 2H and 13C, the glucuronide of acetaminophen isolated from urine provides a convenient "chemical biopsy" for evaluating intermediary metabolism in the liver. Here, we describe isolation and purification of urinary acetaminophen glucuronide and its conversion to monoacetone glucose (MAG). Subsequent 2H and 13C NMR analysis of MAG from normal volunteers after ingestion of 2H2O and [U-13C3]propionate allowed a noninvasive profiling of hepatic gluconeogenic pathways. The method should find use in metabolic studies of infants and other populations where blood sampling is either limited or problematic.

Acetaminophen↗
PubMed2003

Pressure ulcers and the transition to long-term care.

OBJECTIVE: To estimate the prevalence of pressure ulcers among newly admitted residents of long-term-care facilities and to determine whether patients admitted from hospitals had a higher prevalence than those admitted from home or other settings. DESIGN: Prospective cohort study conducted between 1992 and 1995. SETTING: 59 long-term-care facilities in Maryland. PARTICIPANTS: 2015 residents aged 65 years and older newly admitted to participating long-term-care facilities. MAIN OUTCOME MEASURE: Stage II, III, or IV pressure ulcer, first mentioned in the long-term-care facility's chart within 2 days of admission. MAIN RESULTS: Of the 2015 residents studied, 208 (10.3%) had 1 or more pressure ulcers on admission to a long-term-care facility. The proportion of patients with 1 or more pressure ulcers was 11.9% among those admitted from a hospital and 4.7% among those not admitted from a hospital (P<.001). In multivariable analysis, admission from a hospital was significantly associated with pressure ulcer prevalence on admission (odds ratio, 2.2; 95% confidence interval, 1.3-3.7). A lower prevalence of pressure ulcers on admission was significantly associated with being white; a higher prevalence was associated with being chairbound or bedridden, being underweight, and having fecal incontinence. CONCLUSION: Admission to a long-term-care facility from a hospital is an important marker for higher pressure ulcer risk. The identification of pressure ulcer risk factors is essential to the implementation of prevention activities, ensuring that appropriate interventions are targeted to the residents who are most likely to benefit.

Activities of Daily Living↗
PubMed2003

Safety and immunogenicity of a heptavalent pneumococcal conjugate vaccine in infants with human immunodeficiency virus type 1 infection.

OBJECTIVE: Heptavalent pneumococcal conjugate vaccine (PCV) has been shown to be safe and effective in healthy infants and children. However, little is known about its use in children who have human immunodeficiency virus (HIV) infection and are known to be at increased risk of developing pneumococcal infections. This study was conducted to evaluate the safety and immunogenicity of heptavalent PCV in infants with HIV infection. METHODS: The Pediatric AIDS Clinical Trials Group Study 292 Team randomized infants with HIV infection 2:1 to receive heptavalent PCV or placebo in a double-blinded manner. Infants were vaccinated with 3 doses at 2-month intervals, starting at ages 56 to 180 days. A booster dose was given at 15 months of age. Immunogenicity was evaluated after the third dose of vaccine, before and after the booster dose, and at 24 months of age. RESULTS: Thirty infants with HIV infection received PCV, and 15 received placebo. No differences in baseline characteristics were found across arms. Five severe acute reactions were experienced by 4 subjects: 3 in the PCV arm and 1 in the placebo arm; all occurred among subjects with symptomatic disease at study entry. No differences were found in the 2 arms with respect to the number or timing of new diagnoses through 24 months of age, including diagnoses of otitis media. However, when symptomatic subjects were examined separately, the first new diagnosis occurred more rapidly among PCV recipients. Three deaths, all judged to be unrelated to study vaccine, occurred during follow-up: 2 in the PCV arm and 1 in the placebo arm. The primary immunogenicity measures were based on composites of 4-fold changes in serotype-specific immunoglobulin G titers from preimmunization levels. We found a highly significant difference between the vaccine and placebo arms, with the PCV arm showing higher rates of response. Asymptomatic and symptomatic subjects who received PCV had similar immunologic responses for all serotypes. CONCLUSIONS: This study demonstrates that heptavalent PCV was well tolerated and not associated with vaccine-associated adverse reactions. Most important, this vaccine was immunogenic in the infant with HIV infection. However, additional studies of this vaccine (or others) must pay special attention to patients with symptomatic HIV disease, as they seem to be at higher risk for adverse events to any antigen.

Antibodies, Bacterial↗
PubMed2002

GCAP1 rescues rod photoreceptor response in GCAP1/GCAP2 knockout mice.

Visual transduction in retinal photoreceptors operates through a dynamic interplay of two second messengers, Ca(2+) and cGMP. Ca(2+) regulates the activity of guanylate cyclase (GC) and the synthesis of cGMP by acting on a GC-activating protein (GCAP). While this action is critical for rapid termination of the light response, the GCAP responsible has not been identified. To test if GCAP1, one of two GCAPs present in mouse rods, supports the generation of normal flash responses, transgenic mice were generated that express only GCAP1 under the control of the endogenous promoter. Paired flash responses revealed a correlation between the degree of recovery of the rod a-wave and expression levels of GCAP1. In single cell recordings, the majority of the rods generated flash responses that were indistinguishable from wild type. These results demonstrate that GCAP1 at near normal levels supports the generation of wild-type flash responses in the absence of GCAP2.

Animals↗
PubMed2002

NASA light-emitting diodes for the prevention of oral mucositis in pediatric bone marrow transplant patients.

OBJECTIVE: The purpose of this study was to determine the effects of prophylactic near-infrared light therapy from light-emitting diodes (LEDs) in pediatric bone marrow transplant (BMT) recipients. BACKGROUND DATA: Oral mucositis (OM) is a frequent side effect of chemotherapy that leads to increased morbidity. Near-infrared light has been shown to produce biostimulatory effects in tissues, and previous results using near-infrared lasers have shown improvement in OM indices. However, LEDs may hold greater potential for clinical applications. MATERIALS AND METHODS: We recruited 32 consecutive pediatric patients undergoing myeloablative therapy in preparation for BMT. Patients were examined by two of three pediatric dentists trained in assessing the Schubert oral mucositis index (OMI) for left and right buccal and lateral tongue mucosal surfaces, while the patients were asked to rate their current left and right mouth pain, left and right xerostomia, and throat pain. LED therapy consisted of daily treatment at a fluence of 4 J/cm(2) using a 670-nm LED array held to the left extraoral epithelium starting on the day of transplant, with a concurrent sham treatment on the right. Patients were assessed before BMT and every 2-3 days through posttransplant day 14. Outcomes included the percentage of patients with ulcerative oral mucositis (UOM) compared to historical epidemiological controls, the comparison of left and right buccal pain to throat pain, and the comparison between sides of the buccal and lateral tongue OMI and buccal pain. RESULTS: The incidence of UOM was 53%, compared to an expected rate of 70-90%. There was also a 48% and 39% reduction of treated left and right buccal pain, respectively, compared to untreated throat pain at about posttransplant day 7 (p < 0.05). There were no significant differences between sides in OMI or pain. CONCLUSION: Although more studies are needed, LED therapy appears useful in the prevention of OM in pediatric BMT patients.

Adolescent↗
PubMedDate not supplied

Risk factors for pressure ulcers among elderly hip fracture patients.

The purpose of this study was to estimate the incidence of hospital-acquired pressure ulcers among elderly patients hospitalized for hip fracture surgery and to identify extrinsic factors that are associated with increased risk. We conducted a secondary analysis of data abstracted from medical records at 20 hospitals in Pennsylvania, Texas, New Jersey, and Virginia. Participants were patients aged 60 years and older admitted with hip fracture to the study hospitals between 1983 and 1993. The incidence of hospital-acquired pressure ulcers was 8.8% (95% confidence interval 8.2%-9.4%). After adjusting for confounding variables, longer wait before surgery, intensive care unit stay, longer surgical procedure, and general anesthesia were significantly associated with higher pressure ulcer risk. Extrinsic factors may be important markers for high pressure ulcer risk in hospitalized hip fracture patients. Although it is not possible to eliminate factors such as requiring an intensive care unit stay or having a long surgical procedure, it may be possible to develop interventions that minimize pressure ulcer risk in patients who experience these factors.

Aged↗