Biomedical subjects

Alberto Gobbi

Publications and source records attributed to Alberto Gobbi.

At least 19 recordsLinked to original sources

PubMed2006

Patellofemoral full-thickness chondral defects treated with Hyalograft-C: a clinical, arthroscopic, and histologic review.

BACKGROUND: Tissue engineering has emerged as a potential therapeutic option for cartilage regeneration. HYPOTHESIS: Hyaluronan-based scaffolds seeded with autologous chondrocytes are a viable treatment for damaged articular surface of the patellofemoral joint. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Thirty-two chondral lesions with a mean size of 4.7 cm(2) were treated with Hyalograft-C. Twenty-two lesions were located in the patella and 10 in the trochlea. Sixteen patients had previous trauma, 3 had osteochondritis dissecans, and 13 had degenerative changes. Transplantations were carried out arthroscopically or through a miniarthrotomy incision. Eight patients had concomitant procedures, including patellar realignment (2), lateral release (3), and meniscectomy (3). Results were evaluated using the International Cartilage Repair Society-International Knee Documentation Committee scale, EuroQol EQ-5D form, and magnetic resonance imaging scans at 12 and 24 months. Six patients had second-look arthroscopy and biopsies. Statistical analysis was performed using the paired t test and Wilcoxon signed rank test. RESULTS: The International Cartilage Repair Society-International Knee Documentation Committee and EuroQol EQ-5D scores demonstrated a statistically significant improvement (P < .0001). Objective preoperative data improved from 6/32 (18.8%) with International Knee Documentation Committee A or B to 29/32 (90.7%) at 24 months after transplantation. Mean subjective scores improved from 43.2 points preoperatively to 73.6 points 24 months after implantation. Magnetic resonance imaging studies at 24 months revealed 71% to have an almost normal cartilage with positive correlation to clinical outcomes. Second-look arthroscopies in 6 cases revealed the repaired surface to be nearly normal with biopsy samples characterized as hyaline-like in appearance. CONCLUSION: Biodegradable scaffolds seeded with autologous chondrocytes can be a viable treatment for chondral lesions. The type of tissue repair achieved demonstrated histologic characteristics similar to normal articular cartilage. Long-term investigations are needed to determine the durability of the repair produced with this technique.

Adjuvants, Immunologic↗

PubMed2006

Factors affecting return to sports after anterior cruciate ligament reconstruction with patellar tendon and hamstring graft: a prospective clinical investigation.

In athletes, anterior cruciate ligament (ACL) reconstruction is recommended after injury to restore the normal knee function and allow subsequent return to sport. Successful ACL reconstruction with patellar tendon (PT) and hamstring tendon (HT) grafts combined with a well-structured rehabilitation program could bring athletes back to their previous level of sport activities. We prospectively followed-up 100 athletes who underwent ACL reconstruction with either PT (n=50) or HT grafts (n=50). Evaluation was done pre-operatively and post-operatively (3, 6, 12, and 24 months) using International Knee Documentation Committee (IKDC), Lysholm, Noyes, and Tegner scales. Subjective assessment numeric evaluation (SANE), knee activity rating scale (Marx) and a psychological profile questionnaire (psychovitality) were also utilized. Objective evaluations included isokinetic tests and computerized knee motion analysis. Data gathered were statistically analyzed using the Mann-Whitney non-parametric U-test. Among the 100 patients who have undergone ACL reconstruction, 65% returned to the same level of sports, 24% changed sports and 11% ceased sport activities. No significant difference (P>0.05) in outcome between PT and HT grafts were observed. No significant differences (P>0.05) were noted between athletes who "returned" to their previous sport and those who "did not return" to sports at the same level when using the IKDC, Lysholm, Noyes, and Tegner knee evaluation scales. However, significant difference was observed with the knee scores obtained by those who returned and those who completely ceased participation in sport activities. Computerized laxity test revealed that 90% of these patients have less than 3 mm side-to-side difference with no significant difference between HT and PT groups. Patients who "returned to sports" obtained significantly better scores with the Marx scale (P=0.001) and the psychovitality questionnaire (P=0.001) than those who did not. Conventional knee scales including IKDC, Lysholm, Noyes, and Tegner remain as reliable means of evaluating outcome of ACL reconstruction. However, the data obtained from these are not sufficient to determine which among the patients who had knee reconstruction can successfully return to sport. The use of the Marx knee activity rating scale and the evaluation of the athletes' psychological profile are additional scales that can be useful in determining which among the patients treated have a better chance of returning to their pre-injury activity levels.

Adolescent↗

PubMed2006

Osteochondral lesions of the talus: randomized controlled trial comparing chondroplasty, microfracture, and osteochondral autograft transplantation.

PURPOSE: The purpose of this study was to compare outcomes of chondroplasty versus microfracture versus osteochondral autologous transplantation (OAT) in patients with osteochondral lesions of the talus (OLT). METHODS: After prospective sample size analysis, patients with symptomatic, recalcitrant Ferkel class 2b, 3, and 4 OLT were randomized to chondroplasty, microfracture, or OAT treatment groups. Outcomes were measured with use of the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (AHS), the Subjective Assessment Numeric Evaluation (SANE) rating, Numeric Pain Intensity (NPI), and magnetic resonance imaging (MRI). RESULTS: Eleven patients had chondroplasty, 10 ankles (9 patients) had microfracture, and 12 patients had OAT. Mean time to follow-up was 53 months (range, 24 to 119 months). AHS scores showed no differences at 12 and 24 months, and SANE ratings showed no differences at final follow-up. NPI was significantly lower (P < .001) in chondroplasty and microfracture cases as compared with OAT at 24 hours postoperatively. Pearson's correlation analysis demonstrated an inverse relation between microfracture and OAT groups in that better outcome was associated with smaller lesions, compared with the chondroplasty group, which revealed mixed results with no particular trend. MRI revealed incomplete fill and edema after chondroplasty or microfracture and chondral gaps after OAT. CONCLUSION: Our results demonstrate no difference between chondroplasty, microfracture, and OAT with regard to AHS and SANE ratings in patients with OLT. However, NPI at 24 hours postoperatively was significantly lower in patients who had chondroplasty and microfracture. LEVEL OF EVIDENCE: Level I, Therapeutic study, high-quality randomized controlled trial with no statistically significant differences but narrow confidence interval.

Adolescent↗

PubMed2005

Hamstring anterior cruciate ligament reconstruction: is it necessary to sacrifice the gracilis?

PURPOSE: The purpose of this study was to determine if there was a difference in the clinical results of anterior cruciate ligament (ACL) reconstruction when using the semitendinosus tendon (ST) alone versus the semitendinosus and gracilis (STG) construct. TYPE OF STUDY: Prospective randomized study. METHODS: We prospectively followed up a group of 97 patients who underwent reconstruction with either an ST graft (50 patients) or STG graft (47 patients). The patients were evaluated according to standard knee scales (IKDC, Noyes, Lysholm, Tegner), self-evaluation score (SANE), clinical findings, computerized knee laxity analysis, and functional tests. Isokinetic flexion, extension, and internal rotation-external rotation testing were also performed. The results were subjected to statistical analysis. RESULTS: We did not find any significant difference between the 2 groups according to the standard knee scores; self-evaluation score; clinical findings; computerized knee laxity analysis; flexion, extension, and external rotation strengths; or functional tests. However, we did note that the internal rotation torque deficit was significantly higher in the STG group (P = .039). Likewise, the external-to-internal rotation ratio was significantly greater in the STG group (P = .006). CONCLUSIONS: Although there is not much clinical difference when using the ST alone versus the STG construct, internal rotation weakness following harvest of 2 tendons may need to be evaluated further. We suggest that, whenever possible, only 1 tendon should be used when performing anterior cruciate ligament reconstruction with hamstring tendons. LEVEL OF EVIDENCE: Level I, Randomized Controlled Study.

Adult↗

PubMed2005

Articular cartilage engineering with Hyalograft C: 3-year clinical results.

UNLABELLED: The use of tissue engineering for cartilage repair has emerged as a potential therapeutic option and has led to the development of Hyalograft C, a tissue-engineered graft composed of autologous chondrocytes grown on a scaffold entirely made of HYAFF 11, an esterified derivative of hyaluronic acid. Here we present the results of an ongoing multicenter clinical study conducted with the primary objective to investigate the subjective symptomatic, functional and health-related quality of life outcomes of patients treated with Hyalograft C. Clinical results on the cohort of 141 patients with followup assessments ranging from 2 to 5 years (average followup time: 38 months), are reported. At followup 91.5% of patients improved according to the International Knee Documentation Committee subjective evaluation; 76% and 88% of patients had no pain and mobility problems respectively assessed by the EuroQol-EQ5D measure. Furthermore, 95.7% of the patients had their treated knee normal or nearly normal as assessed by the surgeon; cartilage repair was graded arthroscopically as normal or nearly normal in 96.4% of the scored knees; the majority of the second-look biopsies of the grafted site histologically were assessed as hyaline-like. Importantly, a very limited complication rate was recorded in this study. The positive clinical results obtained indicate that Hyalograft C is a safe and effective therapeutic option for the treatment of articular cartilage lesions. LEVEL OF EVIDENCE: Therapeutic study, Level III-2 (retrospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Adult↗

PubMed2004

The Rai (Shc C) adaptor protein regulates the neuronal stress response and protects against cerebral ischemia.

Rai (Shc C or N-Shc) is a neuron-specific member of the family of Shc-like adaptor proteins. Rai functions in the cytoplasmic propagation of Ret-dependent survival signals and regulates, in vivo, the number of sympathetic neurons. We report here a function of Rai, i.e., the regulation of the neuronal adaptive response to environmental stresses. We demonstrate that (i) primary cultures of cortical neurons from Rai-/- mice are more sensitive to apoptosis induced by hypoxia or oxidative stress; (ii) in Rai-/- mice, ischemia/reperfusion injury induces severe neurological deficits, increased apoptosis and size of the infarct area, and significantly higher mortality; and (iii) Rai functions as a stress-response gene that increases phosphatidylinositol 3-kinase activation and Akt phosphorylation after hypoxic or oxidation insults. These data suggest that Rai has a functional neuroprotective role in brain injury, with possible implications in the treatment of stroke.

Animals↗

PubMed2004

Comparison of anterior cruciate ligament reconstruction in male and female athletes using the patellar tendon and hamstring autografts.

Despite the higher incidence of anterior cruciate ligament (ACL) injuries in female than in male athletes few authors have studied the effects of gender on the outcome of ACL reconstruction. This prospective study compared the results of ACL reconstruction using the patellar tendon and hamstring techniques in men and women. We prospectively followed 80 comparable athletes (46 males, 32 females) from a population of 287 patients operated on at our institution for ACL reconstruction using either patellar tendon or hamstring graft. There were 26 males and 14 females in the patellar tendon group, and 22 males and 18 females in the hamstring group. All patients were operated on by the same surgeon within 6 months from injury and underwent the same rehabilitation program at the same center. After an average of 36 months the patients were assessed by clinical evaluation, computerized knee laxity analysis, and isokinetic and functional strength tests; standard knee scores were also used. Among patellar tendon patients there were no significant differences between males and females regarding knee evaluation form, laxity, or isokinetic and functional tests. Females in the hamstring group had significantly greater laxity, and isokinetic tests at 1 year revealed a significantly higher deficit of peak torque at 60 degrees /s in flexion and extension. We suggest further studies on the clinical significance of these findings particularly on their possible ramifications in the areas of return to sports and rehabilitation of female athletes.

Adult↗

PubMed2004

Treatment of full thickness chondral lesions of the knee with microfracture in a group of athletes.

This prospective outcomes study was designed to prospectively investigate the outcome of the microfracture technique when applied to full thickness chondral lesions of the knee in a group of athletes. From 1991 to 1999, 109 patients were treated using the microfracture technique. We prospectively followed up 53 athletes who satisfied our inclusion criteria. Average age was 38 years (range 19-55) and mean follow-up was 72 months (range 36-120). Etiology, clinical signs, symptoms and activity level were noted preoperatively and at final follow-up. Lysholm, Tegner, IKDC and functional tests were utilized. Intraoperatively, location, size of the lesions and associated pathologies were recorded. Roentgenograms, MRI or CT scan were done before treatment and at final follow-up. Etiologic factors were mostly related to sports microtrauma (37.5%) and macrotrauma (21%), while 37.5% of our patients did not report any traumatic etiology and 4% showed patellar malalignment. The most common location was medial femoral condyle (61%). Knee pain and swelling improved in 70%, tibiofemoral crepitus in 60%. Hop test was normal in 70% at final follow-up. Subjective evaluation was 40/100 preoperatively and 70/100 at final follow-up. Lysholm was 56.8 preoperatively and 87.2 final. IKDC revealed: 0 A, 3 B, 40 C and 10 D preoperatively while at final follow-up 70% scored A or B. Tegner improved at 2 years from 3.2 to 6; however, at final follow-up 80% showed a decline in sport activity level (Tegner 5). Microfracture technique can offer clinical, functional and subjective improvement in athletically active patients. However because of the decline in sports participation over time, microfracture may not be the definitive procedure for the athlete's knee and other procedures may be indicated in the future.

Adult↗

PubMed2004

The incidence of motocross injuries: a 12-year investigation.

Off-road motorcycling is one of the most popular sports activities practiced by millions of people in the world but little has been written on motocross traumatology and its prevention. This paper aims to evaluate motocross injuries in terms of injury ratio, location, causes, and possible prevention in a series of competitions organized by Motorcyclistic Federations over a 12-year period. We retrospectively evaluated 1,500 accidents with 1,870 rider injuries out of a group of 15,870 athletes participating in European off-road competition from 1980 to 1991. Data were collected from race medical reports, insurance declarations and follow-up forms filled up by riders involved in accidents. We then classified the type and location of the injury, modality of the accident, the protective gear used and the recovery of the riders. We compared our data to lesions noted in motorcycle road races using the chi-square test and the z-test. The overall incidence of motocross injuries in our study was 94.5 per thousand, while stadium cross competitions had a 150 per thousand rate and outdoor motocross a rate of 76 per thousand representing a risk of accident of 22.72 per thousand hours of riding. Among the total of 1,870 injuries, 1076 were bruises; 27.9% of these were in the upper extremities, 26.9% on the lower, 21.2% on the trunk, and 16% on the face. There were 450 fractures recorded, 50.9% in the upper extremities, 38% in the lower, and the rest were on the spine, chest, and skull. The 26 spine fractures (5.8%) produced permanent neurologic sequelae in eight patients. Ligamentous lesions accounted for 344 cases with 206 (59.9%) occurring in the lower extremities especially on the knee (42.4%). Head trauma was noted in 86 cases (5.7% of accidents) producing coma in 3%, and loss of consciousness in 14%. Limb involvement for all types of injuries were more frequent on the left side (60%). Motocross is a high-risk sport: our study revealed the most common modalities and types of lesions sustained by the riders. Despite the reduction of some injuries by better protective gears, the occurrence of knee sprain, and wrist and clavicular fractures are still high. Furthermore, the high number of spine lesions with subsequent neurologic deficit noted in indoor races raises doubts about the safety of these events.

Chi-Square Distribution↗

PubMed2004

Skeletal muscle differentiation potential of human adult bone marrow cells.

Murine bone marrow (BM) cells have been shown to undergo myogenic differentiation and participate in muscle repair in different muscle regeneration models. In the present paper, we report on a subset of cells (CD45+/desmin+) with myogenic potential being present at very low frequencies in human adult BM. By a simple culture method, we were able to obtain in vitro multinucleated myotubes in up to 20% of the cultures. Myotubes were generated using both BM flushed from rib fragments obtained during thoracotomy and BM derived from iliac crest aspirates. Cells of the different adherent and non-adherent fractions expressed numerous muscle specific markers by immunocytochemistry, real-time RT-PCR, flow cytometry, and Western blot analyses. Moreover, direct injection of whole BM into the right tibialis anterior muscle of immunodeficient mice (NOD/RAG) that had previously been treated with cardiotoxin to induce muscle degeneration, showed a variable but significant level of human cell engraftment (from 0.06 to 0.26% Dys+/FISH+ fibers). These data suggest that cells with skeletal muscle differentiation potential are present in adult human BM can differentiate in vitro and give rise to myogenic cells in vivo in immunodeficient mice after muscle damage. Further improvements might allow new approaches to cell-mediated therapies for muscular diseases.

Alkaline Phosphatase↗

PubMed2004

Amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity.

Human tumors are believed to harbor a disabled p53 tumor suppressor pathway, either through direct mutation of the p53 gene or through aberrant expression of proteins acting in the p53 pathway, such as p14(ARF) or Mdm2. A role for Mdmx (or Mdm4) as a key negative regulator of p53 function in vivo has been established. However, a direct contribution of Mdmx to tumor formation remains to be demonstrated. Here we show that retrovirus-mediated Mdmx overexpression allows primary mouse embryonic fibroblast immortalization and leads to neoplastic transformation in combination with HRas(V12). Furthermore, the human Mdmx ortholog, Hdmx, was found to be overexpressed in a significant percentage of various human tumors and amplified in 5% of primary breast tumors, all of which retained wild-type p53. Hdmx was also amplified and highly expressed in MCF-7, a breast cancer cell line harboring wild-type p53, and interfering RNA-mediated reduction of Hdmx markedly inhibited the growth potential of these cells in a p53-dependent manner. Together, these results make Hdmx a new putative drug target for cancer therapy.

Animals↗

PubMed2003

Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells.

There is growing evidence that vasculogenesis (progenitor cell-derived generation of new blood vessels) is required for the growth of some neoplastic diseases. Here we show that the administration of cyclophosphamide (CTX) at the maximum tolerable dose with 21-day breaks or at more frequent low-dose (metronomic) schedules have opposite effects on the mobilization and viability of circulating endothelial progenitors (CEPs) in immunodeficient mice bearing human lymphoma cells. Animals treated with the maximum tolerable dose CTX experienced a robust CEP mobilization a few days after the end of a cycle of drug administration, and tumors rapidly became drug resistant. Conversely, the administration of metronomic CTX was associated with a consistent decrease in CEP numbers and viability and with more durable inhibition of tumor growth. Our findings suggest that metronomic low-dose chemotherapy regimens are particularly promising for avoiding CEP mobilization and, hence, to potentially reduce vasculogenesis-dependent mechanisms of tumor growth.

Animals↗

PubMed2003

Circulating endothelial cells as a novel marker of angiogenesis.

Measurement of tumor angiogenesis to predict and/or to assess the efficacy of antiangiogenic therapies is mainly based on the evaluation of microvessel density (MVD). We developed a novel flow cytometry procedure to measure circulating endothelial cells (CECs) and circulating endothelial cells progenitors (CECPs) in either preclinical and clinical studies. Preclinical studies were performed on an animal model of human lymphoma. A trend toward higher CECs values was observed on day 7 and 14 after transplant, and differences vs controls were highly significant on day 21 (p = 0.0061). A strong correlation was found between CECs and tumor volume (r = 0.942, p = 0.004) and between CECs and tumor-generated VEGF (r = 0.669, p = 0.02). In mice given cyclophosphamide, most of circulating apoptotic cells were hematopoietic and not endothelial. Conversely, in mice given endostatin, all of the increase in apoptotic cells was in the endothelial cell compartment. In a parallel study, we looked for CECs in the peripheral blood of 20 healthy controls and 76 newly diagnosed cancer patients by means of four-color flow cytometry. In breast cancer (n = 46) and lymphoma (n = 30) patients, both resting and activated CECs were increased by 5 fold (P < 0.0008 vs control). CECs significantly correlated with plasma levels of VCAM-1 and VEGF. Resting and activated CECs were similar to healthy controls in 7 lymphoma patients achieving complete remission after chemotherapy, and activated CECs were found to decrease in 13 breast cancer patients evaluated before and 24h after quadrantectomy. In conclusion, our findings indicate a close relation between CEC increase and tumor progression, and support CECs evaluation as a clinically relevant, non invasive angiogenesis marker. Furthermore, this assay offers insight into anti-angiogenic activity of different drugs.

Angiogenesis Inhibitors↗

PubMed2003

Quadrupled bone-semitendinosus anterior cruciate ligament reconstruction: a clinical investigation in a group of athletes.

PURPOSE: The hypothesis of our study was that a quadrupled bone-semitendinosus (STB) graft could provide a clinically stable construct, allow recovery of normal limb strength, give high patient satisfaction with early return to active sports, and involve low donor-site morbidity. TYPE OF STUDY: Outcomes study. METHODS: Anterior cruciate ligament (ACL) reconstruction with an STB graft was performed on 80 athletes with isolated ACL injury from January 1996 to December 1999. Femoral fixation was obtained with EndoButton (Smith & Nephew, Andover, MA) and tibial fixation with Fastlok (Neoligaments, Leeds, England). At a mean follow-up time of 36 months (range, 24-52 months), patients were evaluated using standard knee scores (Noyes, Lysholm, Tegner, and International Knee Documentation Committee [IKDC] rating) and functional strength tests; postoperative pain rating; knee radiographs performed after surgery and at final follow-up; magnetic resonance imaging (MRI) at 3 to 6 months; isokinetic flexion-extension and internal-external rotation tests at 3, 6, and 12 months; and computed laxity analysis at final evaluation. RESULTS: At final evaluation, subjective knee rating was 87%, kneeling test was positive in 7%, and Werner score was 44 of 50 (range, 30-48). Lachman test was negative in 90% at final evaluation. Sensory changes were present in 30% at 3 months, and 10% had definite hyposthesia. Computed laxity analysis revealed 90% with less than 3 mm side-to-side difference. Isokinetic testing showed normal hamstring and quadriceps peak torques at 12 months. The one-leg hop test and vertical jump were normal by 6 months. At final evaluation, average Noyes score was 88 (range, 65-100); Lysholm score, 91 (range, 70-100); postoperative Tegner rating, 6.5 (range, 5-9); and preinjury Tegner rating, 7.5 (range, 7-10). IKDC score showed 72 knees normal or nearly normal, 7 abnormal, and 1 severely abnormal. Sixty-five percent of patients returned to the same preinjury sports level. CONCLUSIONS: The quadrupled bone-semitendinosus graft is a viable graft for ACL reconstruction and should be considered, especially for patients with extensor mechanism problems.

Adult↗

PubMed2003

Continuous infusion of endostatin inhibits differentiation, mobilization, and clonogenic potential of endothelial cell progenitors.

PURPOSE: We investigated the effect of endostatin on differentiation, mobilization, and clonogenic potential of circulating endothelial cell (EC) progenitors, and whether the effect of endostatin was improved by continuous infusion (CI) versus bolus administration. EXPERIMENTAL DESIGN: Four-color flow cytometry and clonogenic EC cultures were used to study EC progenitors in tumor-free mice, tumor-bearing immunodeficient mice, and immunodeficient mice xenotransplanted with human bone marrow (BM) cells. RESULTS: Endostatin significantly reduced the number of circulating EC progenitors in tumor-free BALB/c mice. The effect of endostatin on EC progenitors was enhanced significantly in mice treated with CI drug treatment. When immunodeficient mice xenotransplanted with human BM cells were treated with CI of endostatin we observed a significant decrease in the engraftment and differentiation of human BM-derived EC progenitors. Numbers of circulating EC progenitors increased 7-fold in immunodeficient mice bearing human lymphoma. In this preclinical model, treatment with CI of endostatin inhibited host murine EC progenitor mobilization and human tumor growth. Furthermore, the clonogenic potential of EC progenitors was impaired severely. CONCLUSIONS: Endostatin is a potent inhibitor of the mobilization and clonogenic potential of human and murine EC progenitors, and its preclinical activity is increased significantly in CI compared with bolus administration. These observations might be useful in the design of future clinical trials.

Animals↗

PubMed2002

Hamstring graft tibial fixation: biomechanical properties of different linkage systems.

This biomechanical study analyzed the mechanical properties of different linkage systems commonly used in hamstring tendon ACL reconstruction. Two kinds of tapes, 5-mm braided polyester (Mersilene) and 3-mm woven polyester (Orthotape), were connected to a particular staple in bovine bone sections in single- and double-loop constructs with five replicates of each. These constructs underwent straight pull tensile tests, residual tensile tests, and fatigue tests at a loading regime of 540,000 cycles at 25 Hz frequency, using an Instron tensile test machine. Protrusion heights of the constructs were measured. The double-loop Mersilene-Fastlok construct was weaker than either single-loop or double-loop Orthotape-Fastlok construct. The mean failure strength of double-loop Orthotape-Fastlok was 93% higher and its mean stiffness was 40% greater at failure than that of Mersilene-Fastlok. At a 150-N load Mersilene-Fastlok was stiffer, while at 300 N Orthotape-Fastlok was stiffer. The thickness of Orthotape-Fastlok resulted in 1 mm more device protrusion. In hamstring tendon ACL reconstructions with indirect fixation we advocate the use of woven polyester (Orthotape) with Fastlok as a linkage material over braided polyester (Mersilene) with Fastlok because of its superior strength and stiffness.

Animals↗

PubMed2002

PML-RAR induces promyelocytic leukemias with high efficiency following retroviral gene transfer into purified murine hematopoietic progenitors.

Acute promyelocytic leukemia (APL) is associated with chromosomal translocations resulting in fusion proteins of the retinoic acid receptor (RAR). Here, we report a novel murine model system for APL, based on the transduction of purified murine hematopoietic progenitors (lin(-)) using high-titer retroviral vectors encoding promyelocytic leukemia-RAR (PML-RAR), and the green fluorescent protein (GFP) as a marker. PML-RAR-expressing lin(-) cells were impaired in their ability to undergo terminal myeloid differentiation and showed increased proliferative potential in vitro. Inoculation of transduced lin(-) cells into syngeneic, irradiated mice resulted in the development of retinoic acid-sensitive promyelocytic leukemias at high frequency (> 80%) and short latency (approximately 4 months). Morphologic and immunophenotypic analysis revealed no gross abnormalities of the preleukemic bone marrows. However, hematopoietic progenitors from PML-RAR preleukemic mice showed a severe impairment in their ability to undergo myeloid differentiation in vitro. This result, together with the monoclonality or oligoclonality of the leukemic blasts, supports a "multiple-hit" model, where the fusion protein causes a "preleukemic" phase, and leukemia occurs after additional genetic lesions. This model system faithfully reproduces the main characteristics of human APL and represents a versatile tool for the in vitro and in vivo study of mechanisms of leukemogenesis and the design of protocols for differentiation treatment.

Animals↗

PubMed2002

CXCR4 neutralization, a novel therapeutic approach for non-Hodgkin's lymphoma.

The chemokine stromal cell-derived factor-1 (CXCL12/SDF-1) and its monogamous receptor CXCR4 are involved in trafficking of B cells and hematopoietic progenitors. CXCR4 expression was found in the large majority of non-Hodgkin's lymphoma (NHL) cell lines and primary cells, and CXCR4 neutralization by monoclonal antibodies had profound in vitro effects on NHL cells including inhibition of transendothelial/stromal migration, enhanced apoptosis, decreased proliferation, and inhibition of pseudopodia formation. In a nonobese diabetes/severe combined immunodeficiency (NOD/SCID) mouse model of human high-grade NHL, CXCR4 neutralization had an impressive efficacy. In a first tumor-challenge trial, CXCR4 neutralization of Namalwa cells injected i.p. delayed tumor growth and reduced tumor weight. In a second tumor-challenge trial, NOD/SCID mice received Namalwa cells i.v. All of the controls died of neoplasia within day 36, whereas 83% of mice injected with cells incubated with anti-CXCR4 were still alive and disease-free >150 days after transplant. The crucial role of CXCR4 in tumor cell extravasation was confirmed by the finding that CXCR4 neutralization before i.v. injection of Namalwa cells in NOD/SCID mice increased the number of cancer cells circulating 24 h after injection. In additional preclinical trials, the therapeutic effect of anti-CXCR4 antibodies was evaluated in mice bearing Namalwa cells injected 3 days before. Tumor growth was abrogated in the majority of treated mice and significantly delayed in the remaining group. Taken together, these data support clinical studies on CXCR4 neutralization in NHL patients by monoclonal antibodies or CXCR4 antagonists.

Animals↗