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Biomedical subjects

M Zilberman

Publications and source records attributed to M Zilberman.

At least 19 recordsLinked to original sources

Molecular and cellular characterization of mesenchymal progenitors for skeletal biomedical devices.

Mesenchymal cells are successfully used to create cell-loaded devices in tissue engineering. Molecular properties of the cells and interaction with polymer scaffolds regulate the development of desired tissues. The present study compared the molecular markers in mesenchymal pleuripotent C3H10T1/2 and osteogenic MBA-15 cells. The cells express transcription factors (TF) of chondro-ostegenic pathway (cbfa-1 and c-fos) and MyoD - TF of muscle differentiation pathway, but not myogenin. Analyzed cells expressed receptors for glucocorticoids, growth hormone, prolactin, and PTH, which indicates their potential responsiveness to systemic signals. Analysis of mRNA encoding for receptors of TGFbeta, TNF, and various interleukins revealed differential expression of IL-2r and TGFbeta-1r receptors, which were expressed by MBA-15 but not by C3H10T1/2 cells. Expression of functional genes indicates differences in the stages of cell differentiation: ALK was present in MBA-15 only, while both cell types expressed collagen-I. Furthermore, we evaluated the expression of adhesion proteins that mediate cell-polymer interactions by flow cytometry analysis. Cell adhesion molecules (CAMs) analyzed were integrinalpha-M (CD11b), selectin-E (CD62E), and PECAM-1 (CD31), which have shown differential expression on cells cultured on plastic, poly(L-lactic acid) (PLLA) or poly(DL-lactide-glycolide acid) (PDLGA) polymer films. Detailed molecular characterization of mesenchymal cells will enable optimization of culture conditions for successful creation of implantable cell-loaded constructs.

Animals↗

Adhesion molecule expression by osteogenic cells cultured on various biodegradable scaffolds.

Design of tissue-engineered cell-loaded device involves cells seeding onto scaffolds in vitro, allowing them to settle and grow before in vivo transplantation. Interaction between scaffold and cells is important in the development of desired tissues. The present study aimed to investigate the effect of cell-polymer interactions on cell morphology and expression of surface markers of osteogenic MBA-15 cells cultured on various bioresorbable polymers. In this study, we used various polymers: poly(L-lactic acid) (PLLA), poly(DL-lactic acid) (PDLLA), poly(L-lactic-glycolic acid) (PLGA), and poly(DL-lactide-glycolide acid) PDLGA1 and PDLGA2. Expression of integrinalpha-M (CD11b), selectin-E (CD62E), and PECAM-1 (CD31), important in cell-cell and cell-matrix interactions, were quantified by flow-cytometry analysis. Cells grown on PDLGA1 films demonstrated fivefold increase in CD62E expression and two-folds increase in CD11b expression. None of the polymers affected the levels of CD31. Identified differential effect of polymers on the expression of cell-adhesion molecules by osteoprogenitors in vitro might help to choose optimal parameters for successful engraftment of cell-loaded constructs.

Animals↗

Dexamethasone loaded bioresorbable films used in medical support devices: structure, degradation, crystallinity and drug release.

Bioresorbable polymer films containing dexamethasone (DM) were prepared using a solution processing technique. Investigation of the films focused on cumulative DM release as affected by film morphology (drug location/dispersion in the film) and degradation processes. Two film structures were studied: A-type, a polymer film with large drug crystals located on the film's surface, and B-type, a polymer film with small drug particles and crystals distributed within the bulk. The effect of the polymer's degree of crystallinity on the drug release profile was also studied. Prototypical applications of these films are biodegradable medical support devices which combine mechanical support with drug release. In most of our studied systems the drug release profile from the film is determined mainly by both drug location/dispersion in the film and the polymer's weight loss rate. All release profiles from A-type films exhibited a burst effect of approximately 30%, accompanied by a second release phase at a constant rate, whereas the release profiles from B-type films were determined mainly by the degradation profile of the host polymer, and did not exhibit any burst effect. A high degree of crystallinity is important for the current application, since good mechanical properties are required. This contributes to slower drug release rates, mainly at relatively low weight losses, whereas at high weight losses, where a porous structure is created, the crystallinity almost does not affect the rate of drug release. The shape of the porous structure that develops with degradation also affects the drug release profile from the B-type films.

Absorbable Implants↗

In vitro study of drug-loaded bioresorbable films and support structures.

Bioresorbable films can serve simultaneously as anatomic support structures and as drug delivery platforms. In the present study, bioresorbable poly(L-lactic acid) (PLLA) films containing dexamethasone were prepared by solution processing methods. Their in vitro studies focused on the mechanical properties with respect to morphology and degradation and erosion processes. Novel expandable support devices (stents) developed from these films were studied. Such a stent would support conduits, such as the neonatal trachea to treat tracheal malacia, until the airway matures, and would then be totally resorbed, obviating the need for a removal operation. The PLLA films showed good initial mechanical properties. They can accommodate drug incorporation on the film surface and also in the bulk. Water incubation of the films results in a decrease in their tensile mechanical properties, due to chain scission and morphological changes. These changes can vary from degradation and small changes in morphological features to erosion, leading to a microporous structure, depending on the polymer. The cumulative release of dexamethasone from the films is linear. The rate of release is determined by the film's structure (drug location/dispersion). The stents demonstrated good mechanical properties. The initial radial compression strength of the stent is determined mainly by the polymer structure. Drug incorporation has a minor effect on the initial stent strength. Exposure to radial compression stress results in elastic reversible deformation or a sudden brittle fracture, depending on the polymer. A 20-week in vitro study of the stents showed that they are applicable for supporting body conduits, such as the trachea.

Absorbable Implants↗

Structured drug-loaded bioresorbable films for support structures.

Bioresorbable films can serve simultaneously as anatomic support structures and as drug delivery platforms. In the present study, bioresorbable PLLA films containing dexamethasone were developed through solution processing. The effect of processing parameters on the film morphology and the resulting mechanical properties was studied. A model describing the structuring of these films is suggested. Generally, the solvent evaporation rate determines the kinetics of drug and polymer crystallization and thus, both the mode of drug dispersion in the polymer and the resulting mechanical properties. Two types of structured films were studied: (1) a polymer film with drug located on its surface, obtained due to drug skin formation accompanied by a later polymer core formation; and (2) a polymer film with small drug particles and crystals distributed within the bulk, obtained by parallel solidification of the two components. A prototypical application of these films is an expandable biodegradable support structure (stent). which we have developed. This stent demonstrated good initial mechanical properties. The film structure has only a minor effect on the stent radial compression strength, but more significantly affects the tensile mechanical properties.

Biocompatible Materials↗

Transabdominal pelvic sonography in the preoperative evaluation of patients with congenital adrenal hyperplasia.

PURPOSE: We assessed the clinical value of transabdominal pelvic sonography in the preoperative evaluation of patients with congenital adrenal hyperplasia (CAH) who required feminizing genitoplasty. METHODS: From 1987 to 1998, 31 patients with female pseudohermaphroditism due to CAH underwent feminizing genitoplasty. The median age of the patients was 9 months (range, 1-18 years). Radiologic evaluation performed before surgical reconstruction included retrograde genitography in the first 10 patients and sonographic examination in all 31 patients. Imaging was used to evaluate the anatomic positions and the length of the vagina, whether the junction of the vagina and the urogenital sinus occurred distal or proximal to the pelvic floor, and the presence of internal genitalia. RESULTS: Abdominal sonography identified internal female genitalia in all 31 patients, identified the anatomic shape and position of the vagina in 30 patients (97%), and confirmed the site of communication between the vagina and the urogenital sinus relative to the pelvic floor in 28 patients (90%). Sonographic findings were confirmed by intraoperative panendoscopy. Genitography was less useful than sonography, identifying the site of communication between the vagina and urogenital sinus in only 6 (60%) of 10 patients. CONCLUSIONS: In patients with CAH undergoing vaginal reconstruction, sonography provides adequate information about the anatomy of the vagina and urogenital sinus for surgical decision-making.

Adolescent↗

Laser prostatectomy. Long-term follow-up of 303 patients.

OBJECTIVE: This retrospective study was undertaken to evaluate results and complications in 303 patients with symptomatic bladder outlet obstruction due to benign prostatic hyperplasia (BPH) who underwent laser prostatectomy focusing on the long-term follow-up, 57 patients had a follow-up of more than 3 years. MATERIALS AND METHODS: A total of 303 patients were treated with the neodymium:YAG laser system for 1993 to 1997, of whom 57 patients were followed up for at least 3 years. All of the patients have been evaluated after 3 months, 6 months and 2 years. 57 patients were evaluated after 3 years. Pre- and postoperative American Urological Association (AUA) symptom score, uroflowmetry (UF), and immediate and long-term complications were assessed. RESULTS: The mean AUA symptom scores of 303 patients decreased over the 24 months follow-up from 16.9 to 7.6. In 57 patients after 36 months the mean AUA symptom score was 7.1. The mean maximal UF increased over the 24 months from 9 to 14.1 cm3/s in 303 patients. In 57 patients at 3 years the mean UF was 13. 9 cm3/s. The overall complications of 303 patients included two perforations of the bladder wall and two perforations of the prostatic capsule. Six (1.9%) patients had postoperative febrile UTI and 28 (9.2%) patients had acute urinary retention after catheter removal. Early bleeding occurred in 3 (0.9%) patients, late bleeding in 8 (2.4%), 4 (1.2%) had urethral stricture, and 1 had stricture of the bladder neck. The overall reoperation rate for symptomatic residual tissue was 1.9% (6 patients). CONCLUSION: Neodymium:YAG laser ablation of prostate represents an efficacious surgical intervention for symptomatic bladder outlet obstruction due to BPH with minimal associated morbidity.

Aged↗

[Tension-free vaginal tape--a new surgical treatment of female urinary stress incontinence].

Female urinary stress incontinence diminishes the quality of life of about 5% of women. It is usually dealt with by surgery to correct the relaxed pelvic floor, the cause of the incontinence. Tension-free vaginal tape is used in a newly described procedure. It consists of the vaginal introduction of a prolene needle-guided mid-urethral sling. The procedure is easy to perform under local anesthesia, recovery is rapid, and results are similar to those of other effective operations. We report 44 patients who underwent this type of surgery. There were no significant complications. The early results were good and although the follow-up has been short, we believe that experience with this operation will play an important role in the treatment of urinary stress incontinence.

Adult↗

Reactivity patterns of antiphospholipid antibodies and endothelial cells: effect of antiendothelial antibodies on cell migration.

Antiphospholipid syndrome (APS) is characterized by the presence of a heterogeneous class of antibodies directed against phospholipids and associated with high occurrence of thrombotic complications. Antiendothelial cell antibodies (AECAs) have been identified in various autoimmune disorders including APS, but their reactivity patterns remain unclear. We used eluted endothelial membrane-bound antibodies (EC eluates) to investigate possible cross-reactivity of AECAs and their pathogenic effects on endothelial cell integrity. The heterogeneous and nonspecific nature of AECAs was confirmed by our finding that they cross-react with fibroblasts and platelets and bind to cardiolipin. In addition, platelet-bound antibodies from sera of patients with APS reacted with endothelial cells. A dose-dependent binding of human monoclonal anticardiolipin antibody was demonstrated, but this antibody did not compete with AECAs in EC eluates, indicating that only small portion of AECAs are directed against cardiolipin. Although sera from APS patients prolonged coagulation tests, EC eluates did not affect coagulation, suggesting that AECAs may belong to antiphospholipid antibodies subsets that does not interfere with coagulation. Vascular damage is a common feature of autoimmune disorders associated with AECAs. Possible effects of AECAs on vascular perturbance were investigated by cytotoxicity, attachment, and migration assays. Although AECAs were not shown to be cytotoxic or to affect cell attachment, sera from APS patients caused reduced cellular migration (by 30%), and EC eluates caused even more significant inhibition (by 50%). These findings suggest possible interference of AECAs in vascular repair mechanisms and provide an explanation for the thrombotic complications frequently seen in APS patients.

Antibodies, Antiphospholipid↗

One-stage repair of hypospadias--experience with 856 cases.

OBJECTIVES: 856 cases of hypospadias, operated over a period of 7 years, using various methods of one-stage repair, are reviewed in order to assess their functional and cosmetic results and their rate of complications. PATIENTS AND METHODS: 856 boys with an average age of 3.5 years were classified according to the classification proposed by Duckett (anterior, middle and posterior hypospadias). Magpi, Mathieu's (flip-flap technique) and pedicled flaps tubularized or as onlay were utilized, depending upon the severity of the anomaly. RESULTS: Satisfactory functional and cosmetic results without complications were obtained in 736 cases (85.9%). We had early complications with 72 cases consisting of 64 fistulas (7. 5%) and 8 cases of breakdown (0.93%), and 48 cases of delayed complications consisting of 26 meatal retractions (3.1%) and 22 cases of meatal stenosis (2.5%).

Child↗

The importance of the early detection of varicocele in adolescent males.

Varicocele is a common finding in adult and adolescent males and may lead to potential infertility. Many methods are available to the practitioner for evaluation of the problem. The least invasive is color duplex imaging of the spermatic vein, to visualize the presence of reflux (backflow) in the vein, as well as to define flow characteristics. It is recommended that adolescent males be screened using this modality beginning at age 10-15 years if they appear to have physical findings indicating a varicocele or if there is a family history of male fertility problems or varicocele. If a varicocele is found, then referral can be made for intervention if needed.

Adolescent↗

A comparative study of radioligand (DCC) and modified immunoperoxidase anti-estrogen receptor techniques in breast carcinoma.

This study deals with the pattern of estrogen receptors in 52 cases of invasive breast carcinoma by comparing the ligand-binding assays with dextran-coated charcoal (DCC) to an immunoperoxidase assay (IPE) technique in paraffin-embedded material from the same tumor. A modification of the IPE by adding cobalt chloride in the final reaction and counter-staining with eosin instead of hematoxylin was introduced. A significantly high correlation was found between the two compared methods (80.8% positivity by the DCC method and 80% by the IPE method). The correlation was very significant in cases where the immunohistochemical grading was higher than 4 (according to our semi-quantitative evaluation scale of 0-8), and for these cases we suggest the IPE method as highly specific and precise.

Breast Neoplasms↗

Evaluation and treatment of iatrogenic ureteral injuries during obstetric and gynecologic operations for nonmalignant conditions.

Twenty-one iatrogenic ureteral injuries (20 patients) as a result of obstetric and gynecologic operations are presented. All injuries occurred during operations for benign conditions, such as Cesarean section and transabdominal hysterectomy. Pelvic adhesions as a result of repeat Cesarean section, markedly enlarging the uterus at the time of abdominal hysterectomy, and massive hemorrhage during surgical treatment were the main causes of ureteral injury. Nine ureters were transected (eight patients) and 12 ureters had postoperative obstruction. Fistulas occurred between the affected ureter and the vagina (five patients), uterus (one patient) and skin (one patient). The existence and the site of such a fistula is clearly demonstrated roentgenographically using intravenous urograms while a urethral catheter filled with contrast media is inserted into the bladder. Only a few ureteric injuries (two patients) were diagnosed and managed during the initial gynecologic operation. The remainder underwent delayed repair procedures. In most patients, the upper urinary tract was protected by percutaneous nephrostomy. The preferred operation for definitive correction was ureteroneocystostomy using the psoas hitch procedure. Direct localization by difficult dissection of the injured ureteral site was unnecessary with ureteroneocystostomy because this procedure bypasses the site of the injury to the ureter. This procedure can be applied in most injuries to the ureter, distal or proximal, which occur during gynecologic and obstetric operations. Renal salvage was achieved in all instances, with no operative or postoperative complications.

Adult↗

Experience with the immediate treatment of iatrogenic bladder injuries and the repair of complex vesico-vaginal fistulae by the transvesical approach.

We describe our experience in treating 16 established cases of vesicovaginal fistulae in non-irradiated bladders which followed obstetric and gynecological procedures. The fistulae, most of which were large and complex, were successfully repaired surgically after two to three months intervals, using the O'Connor transvesical technique. The advantages of late correction using the transvesical approach in such cases are discussed. Thirteen additional cases of accidental bladder injuries during obstetric and gynecological procedures are presented. These injuries were successfully treated by immediate primary sutures. Our experience shows that bladder injuries mainly occur in women who had previously had a Cesarean section.

Adult↗

Paravesical granulomas masquerading as bladder neoplasms: late complications of inguinal hernia repair.

Paravesical granuloma formation after inguinal herniorrhaphy is a rare complication due to infected suture material. We present 8 cases of large paravesical granulomas masquerading as bladder tumors. Irritable symptoms predominate the symptom complex and accurate diagnosis can be obtained with multiple, sonographically guided, needle biopsies of the mass. An operation results in complete resolution of the symptoms, while nonoperative management may help to improve but not resolve the symptoms.

Diagnosis, Differential↗

[Multiple enteral fistulas in peritoneal tuberculosis].

A 40-year-old Ethiopian man had abdominal pain for a year and a half, diarrhea and weight loss. Multiple enteral fistulas were diagnosed by X-ray and colonoscopy. During investigation, the differential diagnosis was between Crohn's disease, intestinal lymphoma and intestinal tuberculosis. Therapeutic trial with corticosteroids was unsuccessful. At operation peritoneal tuberculosis was diagnosed and several entero-enteric fistulas were found, but there were no other intestinal lesions nor other foci of tuberculosis. Intestinal fistulas complicating peritoneal tuberculosis are rare in comparison with enteral tuberculosis, lymphoma or Crohn's disease. After the fistulas were closed surgically and antitubercular treatment given, the patient recovered, returned to his normal weight, and had no complaints.

Adult↗

Active antireflux mechanism induced by micturition. Experimental study in awake sheep.

The influence of increased bladder pressure on ureteral peristalsis is described in the literature. All experiments were done on anesthetized animals and vesical contractions were electrically induced. We present an experiment on awake sheep. The animals voided spontaneously while a recording of the peristaltic pressure of the lower ureter was recorded. A rise in the peristaltic pressure in both ureters was observed during micturition. We suggest that the rise in ureteral pressure participates in the antireflux mechanism.

Animals↗

Bacteremia in anal dilatation.

One hundred patients underwent anal dilatation for acute or chronic anal fissure during the period 1983-1984; white blood count, serum, muscle enzymes, and blood cultures were done. Positive blood cultures were found following the procedure in eight patients. A correlation based on serum enzymes, bacteremia, and trauma can be made. Prophylactic broad-spectrum antibiotics are recommended for patients at risk.

Adult↗