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Biomedical subjects

L Silver

Publications and source records attributed to L Silver.

At least 19 recordsLinked to original sources
PubMed2001

Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: This study evaluated the safety and intraocular pressure-lowering efficacy of two concentrations of travoprost (0.0015% and 0.004%) compared with latanoprost 0.005% and timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. METHODS: Eight hundred one patients with open-angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.0015%, travoprost 0.004%, latanoprost 0.005%, or timolol 0.5%. The efficacy and safety of travoprost (0.0015% and 0.004%) daily was compared with latanoprost daily and timolol twice daily for a period of 12 months. RESULTS: Travoprost was equal or superior to latanoprost and superior to timolol with mean intraocular pressure over visits and time of day ranging from 17.9 to 19.1 mm Hg (travoprost 0.0015%), 17.7 to 19.1 mm Hg (travoprost 0.004%), 18.5 to 19.2 mm Hg (latanoprost), and 19.4 to 20.3 mm Hg (timolol). For all visits pooled, the mean intraocular pressure at 4 PM for travoprost was 0.7 mm Hg (0.0015%, P =.0502) and 0.8 mm Hg (0.004%, P =.0191) lower than for latanoprost. Travoprost 0.004% was more effective than latanoprost and timolol in reducing intraocular pressure in black patients by up to 2.4 mm Hg (versus latanoprost) and 4.6 mm Hg (versus timolol). Based on a criterion of 30% or greater intraocular pressure reduction from diurnal baseline or intraocular pressure 17 mm Hg or less, travoprost 0.0015% and 0.004% had an overall response to treatment of 49.3% and 54.7%, respectively, compared with 49.6% for latanoprost and 39.0% for timolol. Iris pigmentation change was observed in 10 of 201 of patients (5.0%) receiving travoprost 0.0015%, six of 196 of patients (3.1%) receiving travoprost 0.004%, 10 of 194 of patients (5.2%) receiving latanoprost, and none of the patients receiving timolol (0 of 196). The average ocular hyperemia score was less than 1 on a scale of 0 to 3, indicating that on average patients experienced between none/trace and mild for all treatment groups. There were no serious, unexpected, related adverse events reported for any therapy. CONCLUSIONS: Travoprost (0.0015% and 0.004%), a highly selective, potent prostaglandin F (FP) receptor agonist, is equal or superior to latanoprost and superior to timolol in lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. In addition, travoprost 0.004% is significantly better than either latanoprost or timolol in lowering intraocular pressure in black patients. Travoprost is safe and generally well tolerated in the studied patient population.

Adult↗
PubMed2000

Accelerated flap prefabrication with vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a potent promoter of angiogenesis that has been shown to enhance revascularization of ischemic tissues, including skin flaps. This study was designed to investigate the value of a single topical application of recombinant human VEGF to accelerate flap viability in a rat model of a non-ischemic prefabricated flap. Prefabricated flaps were created in 48 Sprague-Dawley rats. An autologous tail artery loop was anastomosed to the femoral artery and vein, and implanted subcutaneously in the lower abdomen. Flaps were divided into two groups of 24 each. At the time of loop implantation the control group received 0.9 percent NaCl or a 16 percent vol/wet polyvinyl alcohol (PVA) solution: the treatment group received VEGF in 0.9 percent NaCl or VEGF in PVA. The PVA gel was used to facilitate topical application In each group, 3- x 4-cm flaps nurtured by the tail artery pedicle were elevated and resutured into place after 3, 4, and 5 weeks. The percentage of surviving skin of each flap was determined by planimetry 7 days after flap elevation. Mean skin survival areas at 3, 4, and 5 weeks were control group 0 percent. 8 percent and 17.5 percent; and VEGIF-treated group, 6 percent, 40 percent, and 66.7 percent respectively VEGF significantly improved flap survival by 5 weeks (p = 0.02). These results suggest that VEGF can accelerate maturation of prefabricated flaps. This approach could expand the application of flap prefabrication as a resource for reconstructive surgery.

Animals↗
PubMed2000

Salvage of ear replantation using the temporoparietal fascia flap.

The authors report a case involving a 46-year-old man who sustained a traumatic amputation of approximately 60% of his ear from a human bite. The ear was replanted microsurgically without the benefit of venous anastomosis. Blood transfusion was not required despite the use of leech therapy and systemic anticoagulation. The replantation appeared to be a success at the time of his discharge from the hospital, but during the late postoperative period the replanted ear became progressively necrotic. The failing ear replantation was rescued successfully with the use of temporoparietal fascia flap reconstruction.

Amputation, Traumatic↗
PubMed2000

Plastic surgical perspectives on vascular endothelial growth factor as gene therapy for angiogenesis.

The practice of plastic surgery has always remained at the frontier of medical science. Over the past few decades, this frontier has been marked by significant developments in the field of gene therapy. Gene therapy serves to replace, supplement, or manipulate a patient's genetic makeup to restore function that has been lost or to correct function that is aberrant. Recent technology may allow surgeons to augment the processes of wound healing and angiogenesis by transfecting genes encoding desirable proteins, such as vascular endothelial factor (VEGF), into ischemic tissues. VEGF is a vital growth factor in the development of blood vessels. Although its mechanisms of action are numerous, its sole function seems to be the augmentation of angiogenesis. VEGF is active in growth and development, in wound healing, and in various pathologic conditions, such as psoriasis and rheumatoid arthritis. The role of VEGF in the field of plastic surgery is just beginning to be explored; it may someday prove to be very rewarding.

Animals↗
PubMed1999

Reduced immunotoxicity and preservation of antibacterial activity in a releasable side-chain carbapenem antibiotic.

A carbapenem antibiotic, L-786,392, was designed so that the side chain that provides high-affinity binding to the penicillin-binding proteins responsible for bacterial resistance was also the structural basis for ameliorating immunopathology. Expulsion of the side chain upon opening of the beta-lactam ring retained antibacterial activity while safely expelling the immunodominant epitope. L-786,392 was well tolerated in animal safety studies and had significant in vitro and in vivo activities against methicillin- and vancomycin-resistant Staphylococci and vancomycin-resistant Enterococci.

Animals↗
PubMed1999

Staging arteriovenous fistula loops for lengthening of free-flap pedicles.

The authors investigated the optimal period of maturation following the creation of arteriovenous (AV) loops using polyterafluoroethylene (PTFE) in a white rat model, which were subsequently used to support free-tissue transfer The AV loops in Group 1 (n = 17) were allowed to mature for 3 days prior to creation of the flap, while those from Group 2 (n = 14) were allowed to mature for 5 days. Results were compared to those from a previous study in which the authors reported an 80 percent initial patency rate (n = 30) and a 67 percent viability rate, based on 12 patent loops after 7 days. In the present study, patency rates were 59 percent for the 3-day group and 79 percent for the 5-day group; viability rates were 50 and 64 percent, respectively. Considering both patent and nonpatent loops, the overall viability rates were 29 and 50 percent respectively. Maturation periods longer than 3 days for AV loops constructed from PTFE micrografts were determined to be preferable for subsequent free-tissue transfer.

Anastomosis, Surgical↗
PubMed1998

Effect of time on the viability of ischemic skin flaps treated with vascular endothelial growth factor (VEGF) cDNA.

This study examined the efficacy of gene therapy on wound healing. The authors investigated whether delivery of the gene encoding a particular cytokine, known to be important in angiogenesis, could affect ischemic skin flaps. Anterior abdominal skin flaps, based solely on the epigastric artery and vein, were created in the Sprague-Dawley rat model. At the time of elevation, the arterial pedicle supplying each flap was infused either with the gene for vascular endothelial growth factor (VEGF) or physiologic saline alone. The flaps were resutured into place and observed for a period of either 4 or 3 days, at which time the pedicle was ligated. Twenty minutes following ligation, blood flow in the flaps was measured by dye fluorescence. Tissue viability of the flaps was subsequently measured by planimetry after a period of 7 days. Flaps that received the VEGF gene and were ligated at 4 days had an average dye fluorescence index (DFI) of 31.1 following ligation, and 93.9 percent viable tissue after 7 days. Flaps that received saline alone, and were ligated following a similar interval, had an average DFI of 14.0 and 31.9 percent viable tissue. Among the subjects that were ligated at 3 days, only a single, gene-infused flap had any noticeable viable tissue after 7 days. The DFI of these groups was 11.0 for the gene-infused group and 22.1 for the saline-infused group. The results suggest that delivery of the gene for VEGF can improve the survival of ischemic skin flaps, but that the effect of gene therapy is not limitless.

Analysis of Variance↗
PubMed1998

Locally administered vascular endothelial growth factor cDNA increases survival of ischemic experimental skin flaps.

Microvascular surgery has emerged as an attractive area for recent advances in the field of gene therapy. The present study investigated the survival of ischemic, experimental skin flaps after treatment with the gene encoding vascular endothelial growth factor (VEGF). In 30 Sprague-Dawley rats, anterior abdominal skin flaps supplied by the epigastric artery and vein were created. Ten animals were treated with a mixture of liposomes and the cDNA encoding the 121-amino acid isoform of VEGF. Another 10 animals were treated with control plasmid DNA and liposome transfection medium; a third group of 10 animals was given physiologic saline. Each solution was injected directly into the femoral artery distal to the origin of the epigastric pedicle supplying the flap. Four days after injection, the pedicle was ligated and blood flow in the flap was approximated using dye fluorescence. Seven days later, the amount of viable tissue within the flap was measured by planimetry. After the animals were killed, specimens from both the operated and nonoperated sides of the abdomen were harvested for immunohistologic evidence of VEGF protein expression. Average dye fluorescence indices of the three groups (VEGF cDNA, control plasmid, and saline) 2 hours after pedicle ligation were 35.9, 23.9, and 53.9 percent, respectively (p < 0.05). Compared with the two control groups, flaps receiving VEGF cDNA had significantly greater tissue viability at the end of 7 days: 93.9 versus 28.1 percent for the control plasmid DNA group and 31.9 percent for the saline group (p < 0.05). Immunohistochemical staining documented increased deposition of VEGF protein in flaps that were infused with the VEGF cDNA versus saline alone (p < 0.05). The results indicated that the survival of ischemic tissues can be enhanced by administration of a cDNA encoding VEGF, a protein known to be important in the process of angiogenesis and wound healing.

Animals↗
PubMed1997

Isolation and characterization of a gene from the DiGeorge chromosomal region homologous to the mouse Tbx1 gene.

DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and isolated and familial forms of conotruncal cardiac defects have been associated with deletions of chromosomal region 22q11.2. This report describes the identification, cloning, and characterization of the human TBX1 gene, which maps to the center of the DiGeorge chromosomal region. Further, we have extended the mouse cDNA sequence to permit comparisons between human and mouse Tbx1. TBX1 is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes are transcription factors involved in the regulation of developmental processes. There is 98% amino acid identity between human and mouse TBX1 proteins overall, and within the T-box domain, the proteins are identical except for two amino acids. Expression of human TBX1 in adult and fetal tissues, as determined by Northern blot analysis, is similar to that found in the mouse. Additionally, using 3 'RACE, we obtained a differentially spliced message in adult skeletal muscle. Mouse Tbx1 has been previously shown to be expressed during early embryogenesis in the pharyngeal arches, pouches, and otic vesicle. Later in development, expression is seen in the vertebral column and tooth bud. Thus, human TBX1 is a candidate for some of the features seen in the 22q11 deletion syndrome.

Adult↗
PubMed1997

Documenting wife abuse: a guide for physicians.

An estimated 12% to 30% of women are assaulted by their male partners at least once during the relationship. Therefore, in their everyday practice, physicians are likely to encounter women who have suffered domestic abuse. The authors define wife abuse, outline epidemiologic aspects and discuss common signs and symptoms. In cases of suspected or confirmed abuse, it is very important for physicians to document the details of the injuries, the patient visit, any treatment and follow-up as well as to screen for associated conditions and ensure that any samples taken are not tampered with. When asked to disclose information by police or courts, physicians need to know when they are obliged to submit copies of their patients' medical records, when patient consent is required, what information should be divulged and how to defend this information in court. The authors present information about the necessary, relevant and appropriate evidence to be collected and documented for both medical and legal purposes. They also discuss the criminal justice system and the role of physicians in legal proceedings concerning wife abuse.

Adult↗
PubMed1997

Initiation of murine embryonic erythropoiesis: a spatial analysis.

Hematopoiesis in the mouse conceptus begins in the visceral yolk (VYS), with primitive erythroblasts first evident in blood islands at the headfold stage (E8.0). VYS erythropoiesis is decreased or abrogated by targeted disruption of the hematopoietic transcription factors tal-1, rbtn2, GATA-1, and GATA-2. To better understand the potential roles of these genes, and to trace the initial temporal and spatial development of mammalian embryonic hematopoiesis, we examined their expression patterns, and that of betaH1-globin, in normal mouse conceptuses by means of in situ hybridization. Attention was focused on the 36-hour period from mid-primitive streak to early somite stages (E7.25 to E8.5), when the conceptus undergoes rapid morphologic changes with formation of the yolk sac and blood islands. Each of these genes was expressed in extraembryonic mesoderm, from which blood islands are derived. This VYS expression occurred in a defined temporal sequence: tal-1 and rbtn2 transcripts were detected earlier than the others, followed by GATA-2 and GATA-1, and then by betaH1-globin. Transcripts for all of these genes were present in VYS mesoderm cell masses at the neural plate stage (E7.5), indicating commitment of these cells to the erythroid lineage before the appearance of morphologically recognizable erythroblasts. By early somite stages (E8.5), GATA-2 mRNA expression is downregulated in VYS blood islands as terminal primitive erythroid differentiation proceeds. We conclude that primitive mammalian erythropoiesis arises during gastrulation through the ordered temporal expression of tal-1, rbtn2, GATA2, and GATA-1 in a subset of extraembryonic mesoderm cells. During the stages analyzed, tal-1 and rbtn2 expression was also present in posterior embryonic mesoderm, while GATA-1 and GATA-2 expression was evident in extraembryonic tissues of ectodermal origin.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Clinical and histologic behavior of exposed porous high-density polyethylene implants.

Reconstruction in the head and neck is difficult and often requires complex solutions to restore functional and aesthetic form. While autogenous tissue is preferred, many alloplasts have been investigated. These materials, however, are foreign bodies, and most alloplasts tolerate exposure and infection poorly. An alloplast's in vivo behavior is a function not only of its composition but also of its form and macrostructure, as well as the interaction at the host-implant interface. Porous high-density polyethylene is well tolerated by surrounding tissue, and its porous core is rapidly infiltrated by host tissue. In order to further investigate the response of porous high-density polyethylene under adverse conditions, we implanted three porous high-density polyethylene disks and one silicone disk underneath the dorsal skin in each of 12 rats. The implants were exposed at differing times after implantation. After 7 days, the exposed areas were either skin grafted or allowed to close by secondary intention. Silicone implants all tolerated exposure poorly. Porous high-density polyethylene implants exposed soon after implantation also tolerated exposure poorly; however, none of these extruded. Porous high-density polyethylene implants exposed after the host tissue had invaded the pores tolerated exposure well, healing either by secondary intention or by skin grafting. Porous high-density polyethylene is a safe and reliable material for use in aesthetic and functional reconstruction of the head and neck. Porous high-density polyethylene and possibly other porous alloplasts tolerate exposure well once host fibrovascular tissue has invaded the implant pores. Further investigation of differing clinical settings and implant behavior is currently in progress.

Animals↗
PubMed1997

Continuous tissue oxygen tension measurement as a monitor of free-flap viability.

Early recognition of vascular compromise within microvascular free-tissue transfers is essential if reexploration is to prove successful. Tissue oxygen tension is increasingly recognized to be a sensitive and reliable index of tissue perfusion, and preliminary studies suggest that it may be of value in the assessment of free-flap viability. We describe our investigation into the application of an implantable microcatheter oxygen sensor in the monitoring of free flaps used in head and neck and extremity reconstruction. In a preliminary study using the rabbit model, we sought to evaluate the response of oxygen tension as an index of tissue perfusion in myocutaneous (n = 20) and osteomyocutaneous flaps (n = 5) under conditions of arterial and venous occlusion. A clinical study was then undertaken to evaluate the role of this method in the monitoring of surface and buried free flaps. In 30 heterogeneous free-tissue transfers, sensors placed intraoperatively were used to provide continuous information about flap oxygen tension (mean monitoring period 3.2 +/- 0.8 days). The data generated were correlated with changes in clinical parameters and routine flap observations. Results for experimental and clinical data have confirmed the efficacy of continuous tissue oxygen measurements using this device as a method that provides an objective, recordable index of free-tissue transfer viability in a variety of circumstances and vascular events. Tissue oxygen tension is a suitable index by which to evaluate flap viability with the probe placed in muscle or bone but is unreliable when used for the monitoring of revascularized cutaneous flaps.

Animals↗
PubMed1997

Evaluation of experimental therapeutics in a new mouse model of Helicobacter felis utilizing 16S rRNA polymerase chain reaction for detection.

BACKGROUND: A new mouse model of Helicobacter felis infection, which mimics the human infection observed with H. pylori, has recently been developed utilizing polymerase chain reaction (PCR) based on the 16S rRNA gene sequence for detection of infection. METHODS: We tested several therapeutic regimens in this model, including some currently utilized in the clinic and some shown ineffective in the clinic. RESULTS: The therapeutic results obtained by PCR with this model are consistent with results observed in the published human H. pylori clinical trials and also with results obtained in another H. felis mouse model utilizing culture and histology. CONCLUSIONS: These results support further use of this new model in screening for new therapeutic regimens for the management of Helicobacter disease.

Animals↗
PubMed1997

Erythropoietin-receptor expression and function during the initiation of murine yolk sac erythropoiesis.

Although erythropoietin is necessary for definitive (fetal liver and bone marrow) erythropoiesis, the role of erythropoietin signaling in primitive (yolk sac) hematopoiesis has not been well defined. In situ hybridization studies have revealed that erythropoietin-receptor (EPOR) mRNA accumulation begins in mesoderm cell masses of the developing yolk sac of the neural plate stage embryo (E7.5) before the development of morphologically recognizable erythroblasts. EPOR mRNA is also present in yolk sac blood islands at early somite stages (E8.5). These findings suggest that EPOR functions during early stages of yolk sac erythropoiesis. We have used a serum-free murine yolk sac explant system (Palis et al., Blood 86:156, 1995) to investigate the initial differentiation of primitive erythroblasts from extraembryonic mesoderm cells. Exogenous erythropoietin increased both erythroblast numbers and betaH1-globin accumulation in yolk sac explants, suggesting that primary yolk sac erythroblasts are directly responsive to erythropoietin. An antisense oligodeoxynucleotide (ODN) experimental approach was used to examine the functional role of erythropoietin signaling during the initiation of yolk sac hematopoiesis in yolk sac explants. Antisense EPOR ODN produced a >50% reduction (p < 0.005) in the number of differentiating primitive erythroblasts, >95% reduction in betaH1-globin accumulation (p < 0.001), and a >50% reduction (p < 0.01) in the number of CFU-E and BFU-E compared with missense EPOR ODN-treated and untreated control explants. Antisense EPOR ODN also blocked the increase in primitive erythroblast number induced by exogenous erythropoietin. We conclude that erythropoietin/EPOR signaling is functionally active during the initial proliferation and differentiation of primary yolk sac erythroblasts. These results also suggest that other growth factor signaling cascades are active during the onset of mammalian erythropoiesis.

Animals↗
PubMed1996

Increased patency of artificial microvascular grafts using arteriovenous fistula loops: a two-stage procedure for lengthening the pedicle of free-tissue transfer.

The effect of a high-flow system on the patency of artificial microvascular grafts (AMG) was investigated using arteriovenous (A-V) fistula loops made of polytetrafluoroethylene (PTFE) in a clinically useful longer length. At a second stage, the A-V loops, matured for 7 days, were used as recipient conduits for free-tissue transfer. The patency rates of 5-cm long PTFE A-V fistula loops were compared with 5-cm and 1-cm long interpositional micrografts in a rat model. The patency rate of the loops at 7 days was 80 percent, compared to 0 percent for both the 5-cm and 1-cm interpositional grafts. A-V fistula loops matured for 7 days in vivo were divided in their midsections and used as arterial and venous conduits (each 2.5 cm long) for free epigastric flaps (3 x 6 cm) raised from the contralateral groin. Sixty-seven percent (8/12) of the free flaps were viable at 7 days. The A-V fistula loop in a high-flow system has a beneficial effect in maintaining patency of AMGs. PTFE fistula loops matured for 7 days can be used as arterial and venous conduits for microsurgical tissue transfer in rats.

Animals↗