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Biomedical subjects

Arie Orenstein

Publications and source records attributed to Arie Orenstein.

33 records · Page 2Linked to original sources

High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice.

PURPOSE: To evaluate the use of diffusion-weighted magnetic resonance (MR) imaging with standard and high b values for pretreatment prediction and early detection of tumor response to various antineoplastic therapies in an animal model. MATERIALS AND METHODS: Mice bearing C26 colon carcinoma tumors were treated with doxorubicin (n = 25) and with aminolevulinic acid-based photodynamic therapy (n = 23). Fourteen mice served as controls. Conventional T2-weighted fast spin-echo and diffusion-weighted MR images were acquired once before therapy and at 6, 24, and 48 hours after treatment. Pretreatment and early (1-2 days) posttreatment water diffusion parameters were calculated and compared with later changes in tumor volumes measured on conventional MR images by using the Pearson correlation test. RESULTS: In chemotherapy-treated tumors, a significant correlation (P <.002, r = 0.6) was observed between diffusion parameters that reflected tumor viability, measured prior to treatment, and changes in tumor volumes after therapy. This correlation implies that tumors with high pretreatment viability will respond better to chemotherapy than more necrotic tumors. In tumors treated with photodynamic therapy, no such correlation was found. Changes observed in water diffusion 1-2 days after treatment significantly correlated with later tumor growth rate for both therapies (P <.002, r = 0.54 for photodynamic therapy; P <.0003, r = 0.61 for chemotherapy). CONCLUSION: High-b-value diffusion-weighted MR imaging has potential use for the early detection of response to therapy and for predicting treatment outcome prior to initiation of chemotherapy.

Animals↗

Ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) sensitizes tumors to chemotherapy by inhibiting the tumor interleukin 10 autocrine loop.

Cancer cells of different solid and hematopoietic tumors express growth factors in respective stages of tumor progression, which by autocrine and paracrine effects enable them to grow autonomously. Here we show that the murine B16 melanoma cell line and two human primary cultures of stomach adenocarcinoma and glioblastoma multiforme (GBM) constitutively secrete interleukin (IL)-10 in an autocrine/paracrine manner. This cytokine is essential for tumor cell proliferation because its neutralization decreases clonogenicity of malignant cells, whereas addition of recombinant IL-10 increases cell proliferation. The immunomodulator ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) decreased cell proliferation by inhibiting IL-10. This activity was abrogated by exogenous addition of recombinant IL-10. IL-10 inhibition by AS101 results in dephosphorylation of Stat3, followed by reduced expression of Bcl-2. Moreover, these activities of AS101 are associated with sensitization of tumor cells to chemotherapeutic drugs, resulting in their increased apoptosis. More importantly, AS101 sensitizes the human aggressive GBM tumor to paclitaxel both in vitro and in vivo by virtue of IL-10 inhibition. AS101 sensitizes GBM cells to paclitaxel at concentrations that do not affect tumor cells. This sensitization can also be obtained by transfection of GBM cells with IL-10 antisense oligonucleotides. Sensitization of GBM tumors to paclitaxel (Taxol) in vivo was obtained by either AS101 or by implantation of antisense IL-10-transfected cells. The results indicate that the IL-10 autocrine/paracrine loop plays an important role in the resistance of certain tumors to chemotherapeutic drugs. Therefore, anti-IL-10 treatment modalities with compounds such as AS101, combined with chemotherapy, may be effective in the treatment of certain malignancies.

Animals↗

Parry-Romberg syndrome and sympathectomy--a coincidence?

Parry-Romberg syndrome is a clinical entity consisting of progressive hemifacial atrophy appearing at a young age. Animal studies indicate that sympathectomy can produce hemifacial atrophy. To our knowledge, this is the first report of a patient with a possible association between Parry-Romberg syndrome and thoracoscopic sympathectomy.

Adolescent↗

Genetics in melanoma.

Melanoma is the leading cause of death from skin tumors worldwide, with an annual increase in incidence over the past decade. The molecular mechanisms involved in melanoma pathogenesis are beginning to be unraveled. While a family history of melanoma and exposure to ultraviolet irradiation have been known for years as risk factors in melanoma development, the precise genes involved in inherited predisposition were defined only in the past decade. Germline mutations in two genes that play a pivotal role in controlling cell cycle and division--CDKN2A and cyclin-dependent kinase 4 (CDK4)--have been detected in autosomal, dominant, high penetrance familial melanoma cases. In addition to these two highly penetrant genes, germline mutations and polymorphisms in a few low penetrance genes have been reported in familial melanoma cases: melanocortin-1 receptor, epidermal growth factor, glutathione s-transferase M1, cytochrome p450 debrisoquine hydroxylase locus (CYP2D6) and vitamin D receptor.

Cytochrome P-450 CYP2D6↗

[Sex reassignment surgery].

Israel is among the few countries in the world where sex reassignment surgery (SRS) is performed in public hospitals. Today, the only center performing SRS in Israel is the Sheba Medical Center. A multidisciplinary committee grants authorization permitting surgery after a follow-up period of two years. We found that this multidisciplinary approach leads to the best therapeutic results. We briefly present the pre-operative evaluation, operative approach, post-operative course, final results and complications of sex reassignment surgery. This article aims to inform physicians of this therapeutic option, and the indications for referral.

Elective Surgical Procedures↗

Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging.

PURPOSE: To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. PATIENTS AND METHODS: Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. RESULTS: One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. CONCLUSION: The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

Brain↗

Dermatobia hominis myiasis among travelers returning from South America.

Dermatobia hominis is the most common cause of myiasis in Central and South America, affecting mammals and humans, causing nonhealing furuncle-like lesions. During the years 1994 to 1999, 14 Israeli travelers returning from South America were diagnosed with D hominis myiasis. The approach consists of correct diagnosis and a proper removal of the larvae, after which the patients heal with no complications.

Adult↗

[Silicone breast implants with silicone gel and autoimmune disease--are they related?].

Silicone breast implants are used for breast reconstruction and breast augmentation. In the late 80's anecdotal literature describing a possible connection between silicone gel filled breast implants and autoimmune disease accumulated. Emerging concern about the safety of silicone gel implants had led the FDA to restrict their use. The continued use of the implants in postmastectomy reconstruction was allowed, as was their use in a small number of breast augmentation patients who were willing to enroll in long-term studies. In recent years, large meta-analyses established the fact that there is no association between silicone gel breast implants and autoimmune disease. We review the current literature, emphasizing the most important epidemiologic studies.

Autoimmune Diseases↗

Positive changes in sun-related behavior in Israel (1994-1998).

BACKGROUND: Current preventive measures against skin cancer focus on individual sun protection and early detection. Solar radiation in Israel is powerful, and about one-half of its population is fair skinned. We investigated whether public awareness efforts yielded changes in sun-related behaviors in Israel from 1994 to 1998. METHODS: The Department of Health Promotion in the Ministry of Health in Israel has been conducting an ongoing research on health knowledge, attitude, and practice, including six closed questions about sun-related behaviors in a general questionnaire. Independent samples of about 3,000 people representing the adult Jewish population (18 years old and above) were surveyed in 1994, 1996, and 1998. Response rates in 1994 and 1996 were about 85 and 80% in 1998. RESULTS: The number of people reporting sun protection behaviors increased from 34% in 1994 to 41% in 1996 and to 46% in 1998. Periodic medical skin examination increased from 9% of the responders in 1994, to 13% in 1996 and to 16% in 1998. The number of people reporting having fair skin increased from 28% in 1994 to 41% in 1996 and to 43% in 1998. CONCLUSIONS: There were positive changes in sun-related awareness and behaviors in Israel between 1994 and 1998. These findings support the conclusion that positive gains were associated with the health promotion efforts conducted by the Israel Cancer Society, Ministry of Health, and other Israeli organizations throughout these years.

Adolescent↗

Wavelength-dependent properties of photodynamic therapy using hypericin in vitro and in an animal model.

Wavelength effects in photodynamic therapy (PDT) with hypericin (HY) were examined in a C26 colon carcinoma model both in vitro and in vivo. Irradiation of HY-sensitized cells in vitro with either 550 or 590 nm caused the loss of cell viability in a drug- and light-dose-dependent manner. The calculated ratio of HY-based PDT (HY-PDT) efficiencies at these two wavelengths was found to correlate with the numerical ratio of absorbed photons at each wavelength. In vivo irradiation of C26-derived tumors, 6 h after intraperitoneal administration of HY (5 mg/kg), caused extensive vascular damage and tumor necrosis. The depth of tumor necrosis (d) was more pronounced at 590 than at 550 nm and increased when the light dose was raised from 60 to 120 J/cm2. The maximal depths of tumor necrosis (at 120 J/cm2) were 7.5+/-1.5 mm at 550 nm and 9.9+/-0.8 mm at 590 nm. Both values are rather high in view of the limited penetration of green-yellow light into the tissue. Moreover, the depth ratio, d590/d550 = 1.3 (P < 0.001), is smaller than expected considering the 2.2-fold lower HY absorbance and the 1.7-fold lower tissue penetration of radiation at 550 than at 590 nm. This finding indicates that in vivo the depth at which HY-PDT elicits tumor necrosis is not only determined by photophysical considerations (light penetration, number of absorbed photons) but is also influenced significantly by other mechanisms such as vascular effects. Therefore, despite the relatively short-wavelength peaks of absorption, our observations suggest that HY is an effective photodynamic agent that can be useful in the treatment of tumors with depths in the range of 1 cm.

Animals↗

Measuring alterations in intra-abdominal pressure during abdominoplasty as a predictive value for possible postoperative complications.

The purpose of this study was to measure the changes in Intra-Abdominal Pressure (IAP) during abdominoplasty and the relevance of these changes to the immediate postoperative recovery period. Eighteen patients (17 females and one male) who underwent abdominoplasty for aesthetic reasons participated in the study. The data collected included measurements of height, weight, and measurements of the intra-urinary bladder pressure prior to surgery, immediately post operative, and 18-24 hours postoperative. Changes in tidal volume and ventilation pressures were also measured prior to surgery and immediately postoperative. The weight of the excised tissue ranged between 1150 g-6500 g with an average of 2700 g. Three patients had significant diasthesis recti repair during surgery. In these patients the measured intra-vesicular pressure was above 24 cm of H(2)O by the end of the operation and above 20 cm of H(2)O the day following surgery. Two out of the three patients were treated with anticoagulants and the symptoms subsided within a week. The third patient recovered spontaneously by the third day. In conclusion, patients with an intra-urinary bladder pressure above 20 cm of H(2)O following abdominoplasty were felt to be at significant risk for development of respiratory distress in the immediate postoperative period.

Abdomen↗

The use of video capture virtual reality in burn rehabilitation: the possibilities.

We independently explored the use of the Sony PlayStation II EyeToy (Sony Corporation, Foster City, CA) as a tool for use in the rehabilitation of patients with severe burns. Intensive occupational and physical therapy is crucial in minimizing and preventing long-term disability for the burn patient; however, the therapist faces a difficult challenge combating the agonizing pain experienced by the patient during therapy. The Sony PlayStation II EyeToy is a projected, video-capture system that, although initially developed as a gaming environment for children, may be a useful application in a rehabilitative context. As compared with other virtual reality systems the EyeToy is an efficient rehabilitation tool that is sold commercially at a relatively low cost. This report presents the potential advantages for use of the EyeToy as an innovative rehabilitative tool with mitigating effects on pain in burn rehabilitation. This new technology represents a challenging and motivating way for the patient to immerse himself or herself in an alternate reality while undergoing treatment, thereby reducing the pain and discomfort he or she experiences. This simple, affordable technique may prove to heighten the level of patient cooperation and therefore speed the process of rehabilitation and return of functional ability.

Burns↗

Treatment of deep sternal wound infections post-open heart surgery by application of activated macrophage suspension.

Postoperative sternal wound infection remains a significant complication and generally causes considerable morbidity and mortality. Macrophages play a major role in the process of wound healing. In order to evaluate the efficacy of local injection of activated macrophage suspensions into open infected sternal wound space, a retrospective case-control study was conducted. Sixty-six patients with deep sternal wound infection treated by activated macrophages (group 1) and 64 patients with deep sternal wound infection treated by sternal reconstruction surgery with various regional flaps (group 2), were matched for gender, age, and risk index. In up to 54 months of follow-up of group 1, 60 patients (91%) achieved complete wound closure. Two (3%) late deaths occurred unrelated to the procedure. Mortality rate in group 2 was 29.7% (19/64). Duration of hospitalization was 22.6 days in group 1 vs. 56.2 days in group 2. Patients with deep sternal wound infection following open heart surgery that were treated by activated macrophages had significantly less mortality as well as significant reduction of hospitalization in comparison to the surgically treated group. These results illustrate the advantages of using a biologically based activated macrophage treatment.

Adoptive Transfer↗

Pretreatment prediction of brain tumors' response to radiation therapy using high b-value diffusion-weighted MRI.

Diffusion-weighted magnetic resonance imaging (DWMRI) is sensitive to tissues' biophysical characteristics, including apparent diffusion coefficients (ADCs) and volume fractions of water in different populations. In this work, we evaluate the clinical efficacy of DWMRI and high diffusion-weighted magnetic resonance imaging (HDWMRI), acquired up to b = 4000 sec/mm(2) to amplify sensitivity to water diffusion properties, in pretreatment prediction of brain tumors' response to radiotherapy. Twelve patients with 20 brain lesions were studied. Six ring-enhancing lesions were excluded due to their distinct diffusion characteristics. Conventional and DWMRI were acquired on a 0.5-T MRI. Response to therapy was determined from relative changes in tumor volumes calculated from contrast-enhanced T1-weighted MRI, acquired before and a mean of 46 days after beginning therapy. ADCs and a diffusion index, R(D), reflecting tissue viability based on water diffusion were calculated from DWMRIs. Pretreatment values of ADC and R(D) were found to correlate significantly with later tumor response/nonresponse (r = 0.76, P <.002 and r = 0.77, P <.001). This correlation implies that tumors with low pretreatment diffusion values, indicating high viability, will respond better to radiotherapy than tumors with high diffusion values, indicating necrosis. These results demonstrate the feasibility of using DWMRI for pretreatment prediction of response to therapy in patients with brain tumors undergoing radiotherapy.

Brain↗

Ten commandments for minimal pain during administration of local anesthetics.

Local anesthetic agents are administered before many ambulatory cutaneous operations. The injection of the local anesthetic agent is often the only painful aspect of the procedure. There are various factors that determine how painful the anesthetic administration may be. These include the preparation used, the size of the needle and syringe used, injection technique, depth of injection, attitude of the physician, and more. In this article, we present the different techniques we apply to achieve minimal pain during the injection of local anesthetics.

Administration, Cutaneous↗