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Biomedical subjects

Arie Orenstein

Publications and source records attributed to Arie Orenstein.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of human tumor-infiltrating lymphocyte effector functions by the homophilic carcinoembryonic cell adhesion molecule 1 interactions.

Efficient antitumor immune response requires the coordinated function of integrated immune components, but is finally exerted by the differentiated effector tumor-infiltrating lymphocytes (TIL). TIL cells comprise, therefore, an exciting platform for adoptive cell transfer (ACT) in cancer. In this study, we show that the inhibitory carcinoembryonic Ag cell adhesion molecule 1 (CEACAM1) protein is found on virtually all human TIL cells following preparation protocols of ACT treatment for melanoma. We further demonstrate that the CEACAM1 homophilic interactions inhibit the TIL effector functions, such as specific killing and IFN-gamma release. These results suggest that CEACAM1 may impair in vivo the antitumor response of the differentiated TIL. Importantly, CEACAM1 is commonly expressed by melanoma and its presence is associated with poor prognosis. Remarkably, the prolonged coincubation of reactive TIL cells with their melanoma targets results in increased functional CEACAM1 expression by the surviving tumor cells. This mechanism might be used by melanoma cells in vivo to evade ongoing destruction by tumor-reactive lymphocytes. Finally, CEACAM1-mediated inhibition may hinder in many cases the efficacy of TIL ACT treatment of melanoma. We show that the intensity of CEACAM1 expression on TIL cells constantly increases during ex vivo expansion. The implications of CEACAM1-mediated inhibition of TIL cells on the optimization of current ACT protocols and on the development of future immunotherapeutic modalities are discussed.

Animals↗
PubMed2006

Ex vivo activated human macrophages improve healing, remodeling, and function of the infarcted heart.

BACKGROUND: Activated macrophages have a significant role in wound healing and damaged tissue repair. We sought to explore the ability of ex vivo activated macrophages to promote healing and repair of the infarcted myocardium. METHODS AND RESULTS: Human activated macrophage suspension (AMS) was prepared from a whole blood unit obtained from young donors in a closed sterile system and was activated by a novel method of hypo-osmotic shock. The AMS (approximately 4 x 10(5) cells) included up to 43% CD14-positive cells and was injected into the ischemic myocardium of rats (n=8) immediately after coronary artery ligation. The control group (n=9) was treated with saline injection. The human cells existed in the infarcted heart 4 to 7 days after injection, as indicated by histology, human growth hormone-specific polymerase chain reaction, and magnetic resonance imaging (MRI) tracking of iron oxide-nanoparticle-labeled cells. After 5 weeks, scar vessel density (+/-SE) (25+/-4 versus 10+/-1 per mm2; P<0.05), myofibroblast accumulation, and recruitment of resident monocytes and macrophages were greater in AMS-treated hearts compared with controls. Serial echocardiography studies, before and 5 weeks after injection, showed that AMS improved scar thickening (0.15+/-0.01 versus 0.11+/-0.01 cm; P<0.05), reduced left ventricular (LV) diastolic dilatation (0.87+/-0.02 versus 0.99+/-0.04 cm; P<0.05), and improved LV fractional shortening (31+/-2 versus 20+/-4%; P<0.05), compared with controls. CONCLUSIONS: Early after myocardial infarction, injection of AMS accelerates vascularization, tissue repair, and improves cardiac remodeling and function. Our work suggests a novel clinically relevant option to promote the repair of ischemic tissue.

Adolescent↗
PubMed2006

Nitrous oxide administered by the plastic surgeon for repair of facial lacerations in children in the emergency room.

BACKGROUND: The purpose of this study was to investigate a means of providing pain relief during repair of facial lacerations in children in the emergency room. METHODS: This study was conducted in the emergency room of a tertiary care, university-affiliated hospital. Fifty percent nitrous oxide was administered by the surgeon who sutured the laceration. A nurse monitored the child throughout the procedure. At the end of the procedure, pain scores were evaluated by the surgeon and nurse using the FLACC (face, legs, activity, cry, and consolability) scale, a structured observational-behavioral scale for measurement of pain. RESULTS: Sixty patients between the ages of 1 and 16 years participated in the study. Of these, 15 were sutured using standard care (lidocaine infiltration), and 45 children received nitrous oxide in addition to lidocaine infiltration. Nitrous oxide was administered for an average of 11.9 +/- 5.1 minutes (range, 4 to 30 minutes). Forty-three children recovered to preprocedure activity in less than 1 minute. Two children recovered in less than 3 minutes. Average FLACC scores during infiltration and suturing were significantly lower in the nitrous oxide group compared with controls (infiltration, 1.9 of 10 versus 9.7 of 10; suturing, 2 of 10 versus 8.8 of 10). Forceful restraining was necessary in all the controls, whereas in the nitrous oxide group mild force was required in only 15 percent. Seventy percent of the children receiving nitrous oxide had no side effects. Vomiting and nausea were the most common (17 percent), transient side effects. No respiratory or cardiovascular side effects occurred. CONCLUSIONS: Nitrous oxide can be safely administered by plastic surgeons while suturing facial lacerations in the emergency room. The fast onset and rapid recovery characteristics of nitrous oxide provide a convenient environment for performing short surgical procedures. This safe method for provision of analgesia and anxiolysis may be appealing to plastic surgeons for ambulatory procedures (e.g., suture removal, expander inflation, Botox injection, injection of various fillers) in pediatric and adult populations.

Adolescent↗
PubMed2006

Stensen duct rupture (sialocele) and other complications of the Aptos thread technique.

BACKGROUND: The Aptos thread technique is a mode of uplifting the flabby soft tissue of the aging face. Permanent suture material made of polypropylene monofilament with dents is used in this technique. This procedure is gaining popularity throughout the world. According to the literature, several hundred Aptos procedures have been performed, and no major complications have been reported yet. METHODS: Two adult women presented shortly after the Aptos thread insertion. They sustained devastating results. A close study was performed to understand and learn the potential complications. RESULTS: The authors present two major complications, a rare case of Stensen's duct laceration and a case of chronic inflammation mandating surgical treatment. CONCLUSIONS: Describing complications may teach plastic surgeons more about this method and how to avoid similar devastating side effects in the future.

Diagnosis, Differential↗
PubMed2006

Laser treatment of venous malformations.

Venous malformations (VM) are developmental errors comprised of enlarged dysplastic blood vessels. Clinically they manifest as either a faint blue patch or a soft blue vascular mass. Treatment options include a sclerosing agent (such as alcohol or ethiblock), surgery or laser therapy. A review of the literature concerning VM and laser treatment yielded a few sporadic reports describing series of 3 to 46 cases. In this retrospective study we reviewed the files of the relevant cases. The data included the extent of the lesion, the different anatomical sites, age of patient and the extent of clearance of the lesion as the treatment's end point. This study includes 56 cases which makes it the largest series presented. The success rate of laser treatment was 92.8%. The immediate complication rate was very low (approximately 3.57%) including minimal scarring and deformity. No long term complications were noted. Our study concludes that treatment of VM is a difficult task due to the nature of the lesions. Laser treatment of these lesions enables one to obtain good results with a very low incidence of complications. Surgery and other treatment modalities are not always satisfactory, yield similar or less efficient results and have a higher complication rate. Laser treatment can play an important role in the treatment of VM and in fact may be the treatment of choice in some settings.

Arteriovenous Malformations↗
PubMed2006

Terror-inflicted thermal injury: A retrospective analysis of burns in the Israeli-Palestinian conflict between the years 1997 and 2003.

BACKGROUND: Terror attacks have changed in the past decade, with a growing tendency toward explosives and suicide bombings, which led to a rise in the incidence of thermal injuries among victims. The Israeli-Palestinian conflict of October 2000 marked a turning point when an organized terror campaign commenced. This article presents data of terror-associated burns from the Israeli National Trauma Registry (ITR) during the years 1997 to September 2000 and October 2000 to 2003. METHODS: We analyzed demographic and clinical characteristics of 219 terror-related burn patients and 6,546 other burn patients admitted to hospitals in Israel between 1997 and 2003. Data were obtained from the ITR. RESULTS: Burns contributed about 9% of all terror related trauma and about 5% of all other trauma (p < 0.0001). These percentages have not changed significantly before and after October 2000. Terror-related burns afflict Jewish males more than predicted by their percentage in the population, whereas other burns afflict non-Jewish males more than predicted. Adults and young adults (15-59 years) are the predominant group in terror-related burns (80%), whereas children younger than 15 years are the predominant group in other burns (50%). Large burns (20% to 89% total body surface area) are more common in terror casualties, with greater mortality (6.4% in terror-related versus 3.4% in others; p = 0.0258). CONCLUSION: Although the incidence of burns has risen because of an organized campaign, this change was noticeable in other trauma forms as well in similar proportions. Terror-related burns afflict a targeted population, and generally take on a more severe course with greater mortality rates, thus requiring appropriate medical treatment.

Adolescent↗
PubMed2006

Vascular wall maturation and prolonged angiogenic effect by endothelial-specific platelet-derived growth factor expression.

BACKGROUND: The implementation of angiogenic gene therapy at clinics is hindered by the transience of the therapeutic effect. Recruiting vascular wall smooth muscle cells, a process termed 'maturation', can stabilize newly formed vessels. OBJECTIVE: To induce angiogenesis followed by vessel maturation in a murine ischemic limb model by endothelial cell-specific promoter regulated expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB). METHODS: We constructed adenoviral vectors containing angiogenic factors VEGF and PDGF-B regulated by a modified preproendothelin-1 (PPE-1-3x) promoter and investigated their angiogenic effect in a murine ischemic limb model. RESULTS: VEGF gene therapy increased perfusion and the vessel density in the limb shortly after expression with PPE-1-3x promoter or cytomegalovirus (CMV) promoter vectors, but only PPE-1-3xVEGF treatment exhibited a sustained effect. Expression of PDGF-B by PPE-1-3x promoter resulted in morphological maturation of the vasculature and further increased the perfusion, while nonspecific expression of PDGF-B with CMV promoter had no therapeutic effect. Regulation of dual therapy with VEGF and PDGF-B by PPE-1-3x promoter resulted in an early-onset, sustained angiogenic effect accompanied by vessel maturation. CONCLUSIONS: Systemic gene therapy with the angiogenic factors VEGF and PDGF-B under angiogenic- endothelial cell-specific regulation was effective in inducing functionally and morphologically mature vasculature.

Adenoviridae↗
PubMed2005

Targeting small-cell lung cancer with novel fluorescent analogs of somatostatin.

Early, accurate detection of small-cell lung cancer (SCLC), before it becomes systemic, is essential for successful treatment. Fluorescence-based imaging provides safe, sensitive detection of malignancies. Targeted delivery of fluorophores increases sensitivity of endoscopic imaging. We synthesized novel somatostatin analogs, based on backbone cyclic peptides, and conjugated them with fluorescent agents. Nineteen conjugates differing in core peptide, length of alkyl linker and fluorescence moiety (rhodamine and fluorescein) were tested in vitro, using a receptor binding assay, and nine of the more promising conjugates were tested in vivo by fiber-optic spectrofluorimetry and quantitative spectral imaging, on an H69 human SCLC tumor mouse xenograft model. The lead compound showed exceptional tumor/normal tissue ratios, ranging from 9 to 90, and has potential for targeting SCLC overexpressing somatostatin receptors.

Amino Acid Sequence↗
PubMed2005

Convection-enhanced drug delivery: increased efficacy and magnetic resonance image monitoring.

Convection-enhanced drug delivery (CED) is a novel approach to directly deliver drugs into brain tissue and brain tumors. It is based on delivering a continuous infusion of drugs via intracranial catheters, enabling convective distribution of high drug concentrations over large volumes of the target tissue while avoiding systemic toxicity. Efficient formation of convection depends on various physical and physiologic variables. Previous convection-based clinical trials showed significant diversity in the extent of convection among patients and drugs. Monitoring convection has proven to be an essential, yet difficult task. The current study describes the application of magnetic resonance imaging for immediate assessment of convection efficiency and early assessment of cytotoxic tissue response in a rat brain model. Immediate assessment of infusate distribution was obtained by mixing Gd-diethylenetriaminepentaacetic acid in the infusate prior to infusion. Early assessment of cytotoxic tissue response was obtained by subsequent diffusion-weighted magnetic resonance imaging. In addition, the latter imaging methodologies were used to establish the correlation between CED extent and infusate's viscosity. It was found that low-viscosity infusates tend to backflow along the catheter track, whereas high-viscosity infusates tend to form efficient convection. These results suggest that CED formation and extent may be significantly improved by increasing the infusate's viscosities, thus increasing treatment effects.

Animals↗
PubMed2005

Monitoring PDT-induced damage using spectrally resolved reflectance imaging of tissue oxygenation.

Photodynamic therapy (PDT) with chlorin e6 (Chl) was monitored in vivo using vital microscopy and Fourier transform spectral imaging (FT-SI). Mammary C26 colon carcinoma, implanted intradermally in a mouse, was irradiated at 650 nm with various radiant exposures, 3 h after administration of 5 mg/kg Chl. The photodynamic response (PDR) in the skin flap with tumor was expressed as microcirculation disturbances (thrombi formation, multiple embolizations, arteriolar occlusion and venous stasis) and, dependent on the radiant exposure, was transient or permanent. These biological manifestations were accompanied by a change in hemoglobin (Hb)/oxyhemoglobin (HbO2) absorption spectra obtained in vivo by FT-SI. False-color mapping of hemoglobin oxygen saturation (OS) visualized the alteration of tissue oxygenation. The results demonstrate, for the first time, that FT-SI can serve as a sensitive non-invasive tool for OS monitoring of PDT effects.

Animals↗
PubMed2005

Improved pharmacokinetics, biodistribution and necrosis in vivo using a new near infra-red photosensitizer: tetrahydroporphyrin tetratosylat.

The search for better photosensitizers for photodynamic therapy of malignancies has led to the investigation of a new water-soluble, positively charged, and chemical stable tetrahydroporphyrin tetratosylat (THPTS) with a strong absorption at 760.5 nm, belonging to the bacteriochlorophyll family. THPTS undergoes a rapid uptake by human choroidal melanoma (CM) cells with a weak dark toxicity after a 24-h incubation (LD10 = 150 microM, LD50 = 6.0 mM). In response to laser light at 760+/-3 nm and doses of 10, 15 and 30 J/cm2, around 71%, 76%, and 92% of the CM cells were killed, respectively. Studies of pharmacokinetics and biodistribution in vivo (living mice) and ex vivo (excised organs) were made in a Balb/c mice bearing subcutaneously inoculated C26 colon carcinoma using fiber-optic spectrofluorimetry (FOS). Tumours were irradiated 3 h after intraperitoneal (i.p.) injection of 5.0 mg/kg THPTS with an incoherent light source at 750+/-20 nm and an intensity of 100 mW/cm2 and fluences of 60, 90 and 120 J/cm2. THPTS demonstrated preferential accumulation in C26 colon carcinoma in comparison with most normal tissues except kidneys. For the tissues of liver, colon, muscle, and spleen the tumour/normal tissue ratio (TNTR) ranged from 8.0 to 50. After irradiation with 120 J/cm2 the depth of tumour necrosis reached 15 mm. Histological examination of the tumour samples 24 h after THPTS-PDT, revealed severe stasis in the blood vessels and coagulative necrosis. These results suggest that THPTS-PDT may be of particular importance in the treatment of accessible malignancies.

Animals↗
PubMed2005

Use of mitomycin C for treatment of keloid: a preliminary report.

OBJECTIVES: Mitomycin C (MC) is an anti-neoplastic agent with an anti-proliferative effect on fibroblasts. We set out to evaluate the effect of MC application following keloid excision. STUDY DESIGN AND SETTING: Patients with keloid in a tertiary referral center were enrolled in a prospective study. The scar was excised and prior to skin closure, a pledget with 1 cc of MC 0.4 mg/mL was applied for 5 minutes. Patient satisfaction and keloid thickness were assessed. RESULTS: All patients were satisfied with the results, although complete disappearance of the keloid was evident only in two. Keloid thickness was measured and ranged from 5 to 26 mm. Following surgery and treatment at 2 months thickness ranged from 0 to 8 mm. CONCLUSIONS: MC application following scar resection appears to be effective in treatment of keloid. SIGNIFICANCE: As no specific effective treatment for keloid is currently available, utilization of this readily available therapeutic agent may improve treatment outcome.

Adolescent↗
PubMed2005

Competitive quenching: a possible novel approach in protecting RPE cells from damage during PDT.

PURPOSE: The purpose of this study is to demonstrate feasibility of using our novel concept, termed competitive quenching, for protecting the choroidal extravascular compartment and retinal pigment epithelium (RPE) from verteporfin (VP)-induced phototoxicity using hypericin. Furthermore, we aim to achieve partitioning of the quencher, hypericin, in the extravascular space and VP within the microvascular compartment of the chorio-retinal complex in vivo. METHODS: We protect RPE cells from damage inflicted by photoactivated VP by introducing hypericin into these cells prior to photosensitization to quench the photosensitizing activity of VP. Cell protection levels were measured by MTT and Hemacolor viability assays. Wavelength range used for VP photoexcitation (700 +/- 40 nm) excludes the absorption range of hypericin, preventing the latter from photoactivation. Pharmacokinetic conditions, in which hypericin spreads throughout the choroidal and retinal extravascular space while VP is confined to the vasculature, are delineated using double-fluorescence imaging. RESULTS: Cell viability increased 3- to 5-fold when 10-20 microM hypericin were present in RPE cells during photosensitization with 0.1-0.5 microM VP. VP fluorescence intensity was unchanged by the presence of hypericin in the cells. Hypericin administered intravenously to rats was confined to the choroidal vasculature after 15 min to 2 hr. Subsequently, hypericin partitioned to the choroidal and retinal extravascular space. VP administered at this time was confined to the microvasculature. CONCLUSIONS: RPE and choroid may potentially be protected by compartmentalizing hypericin to the extravascular compartment while VP administered shortly before photosensitization is confined to the microvasculature. Adverse photodynamic therapy (PDT) damage to choroidal tissues adjacent to neovasculature targeted for photoablation have the potential of being prevented by competitive quenching with hypericin.

Animals↗
PubMed2005

[Ultrasonic apocrine suction-lipolysis under endoscopic guidance for axillary osmidrosis].

There are several modalities to treat axillary hyperhydrosis. None of these eliminates the sweat-associated odor (Osmidrosis), which is sometimes present even despite local hygiene and use of deodorants. A technique to dissolve the axillary apocrine glands under endoscopic guidance has been described to be highly efficient, without compensatory hyperhydrosis. We describe our experience with the first 18 patients who were treated by this technique. A 1.5 cm axillary incision was used to introduce both the endoscope and the ultrasonic suction-lipolysis device. Complete disappearance of axillary sweat and odor was achieved immediately after treatment. Superficial hematoma was the only complication encountered. One-sided recurrence was observed in one patient over an 8 month follow-up period.

Adult↗
PubMed2004

Antimetastatic activity of the photodynamic agent hypericin in the dark.

A unique property of the photodynamic signal transduction inhibitor hypericin (HY) is high functionality in the dark, which has been shown to result in portfolio of anticancer activities both in vitro and in vivo. Here we show that treatment with HY significantly reduces growth rate of metastases in 2 murine models: breast adenocarcinoma (DA3) and squamous cell carcinoma (SQ2). Focus on metastases was achieved by resection of primary tumors at stages in which micrometastases exist in lungs. Long-term animal survival in DA3 tumor-excised groups increased from 15.6% in controls to 34.5% following supplementary treatment with HY. In mice bearing SQ2 tumor metastases, therapy with HY increased animal survival from 17.7% in controls to 46.1%. Using Laser-induced fluorescence and multipixel spectral image analyses, we demonstrate that HY has a high tendency to accumulate in primary and metastatic tumors; HY content in lungs bearing metastases was approximately 2-fold higher than in the lungs of healthy animals. The tendency of HY to preferentially concentrate in lung metastases, combined with its potent antiproliferative activities, may render HY as a useful supplementary modality in the treatment of metastatic cancer irrespective of photoactivation.

Animals↗