Biomedical subjects

Paul Schalch

Publications and source records attributed to Paul Schalch.

9 recordsLinked to original sources

PubMed2007

Bone marrow mononuclear cells stimulate angiogenesis when transplanted into surgically induced fibrocollagenous tunnels: results from a canine ischemic hindlimb model.

Progenitor cell transplantation has been considered as a potential angiogenesis therapy for the ischemic hindlimb. In this work we performed an ischemic hindlimb model in dogs. We ligated the middle sacra and the external right iliac arteries. After 7 days, the femoral artery was ligated and removed, and three Silastic tubes were inserted into the gracilis muscle to create fibrocollagenous tunnels. After Silastic implantation, we administered saline or granulocyte colony stimulating factor (G-CSF) subcutaneously daily during 5 days. Fourteen days after device positioning we transplanted bone marrow mononuclear cells (BMMC) into the tunnels previously formed by Silastic tube reaction. Twenty-eight days later, contrasted angiographies were performed and angiographic scores were calculated. Also, vessels and endothelial cells and proliferating cells were identified by immunochemistry of muscle sections. Results demonstrated that BMMC transplantation enriched by G-CSF administration significantly stimulates angiogenesis in the ischemic hindlimb, and more than BMMC transplantation alone. Transplantation of progenitor cells in an appropriate extracellular matrix is a potential therapy for hindlimb ischemia.

Angiogenesis Inducing Agents↗

PubMed2006

Fibrin glue: an alternative technique for nerve coaptation--Part I. Wave amplitude, conduction velocity, and plantar-length factors.

The search for better surgical repair of nerve injuries should be aimed at uncovering alternatives that not only are efficient, but also enhance nerve growth. The purpose of this study was to compare functional nerve responses following repair with either a traditional microsuture technique or Quixil human fibrin sealant. Thirty female Lewis rats received transection of the right sciatic nerve. Nerve repair was achieved with either epineurial microsuture (n = 15) or Quixil fibrin glue (n = 15). Functional results were assessed at 2, 6, and 12 weeks postoperatively with walking-track analysis. Electrophysiologic nerve recordings were also performed 12 weeks postoperatively. Rats receiving Quixil nerve repair returned to baseline performance on the walking-track analysis significantly faster than those with microsuture repairs (6 and 12 weeks postoperatively; p < 0.0001). Recovery of nerve conduction velocities and wave amplitudes was also significantly better in the nerves repaired with Quixil than in those repaired with microsuture (p's < 0.0001). Quixil human fibrin sealant is a good alternative to traditional microsuture nerve repair techniques.

Animals↗

PubMed2006

Fibrin glue: an alternative technique for nerve coaptation--Part II. Nerve regeneration and histomorphometric assessment.

The results of nerve repair with fibrin glue and microsuture were evaluated in rat nerve transection models. Ninety Wistar-Furth rat median nerves were exposed, transected, and repaired in an end-to-end fashion with one of four substances/techniques: 1) human fibrin sealant (Quixil); 2) autologous graft and human fibrin sealant (Quixil); 3) bovine fibrin sealant (Tissucol); and 4) nylon microsuture, epineurial technique. Histologic analyses were performed at 3-, 6-, and 9-month postoperative intervals, and factors evaluated included: presence of inflammatory cells (i.e., macrophages and T cells); number of Schwann cells at the repair site; number of blood vessels; fibrosis; axonal regeneration; and fiber alignment. An additional group underwent histologic analysis at 3 weeks following repair with Quixil. Surgical time of repair was also measured. Nerve repairs performed with fibrin sealants produced less inflammatory response and fibrosis, and better axonal regeneration and fiber alignment than nerve repairs performed with microsuture. In addition, the fibrin sealant techniques were quicker and easier to use. The authors conclude that fibrin sealant represents a good alternative technique to microsuture for peripheral-nerve repair.

Animals↗

PubMed2006

Palatal stiffening after failed uvulopalatopharyngoplasty with the Pillar Implant System.

OBJECTIVE/HYPOTHESIS: The objective of this study was to measure subjective and objective improvement after palatal stiffening in patients after uvulopalatopharyngoplasty (UPPP) who were experiencing persistence or recurrence of snoring with or without daytime sleepiness symptoms. STUDY DESIGN: The authors conducted a prospective, nonrandomized study of 26 patients after UPPP who underwent the Pillar Implant Technique (PIT) as a revision procedure. METHODS: Patients were selected to undergo revision PIT if they presented with recurrence or persistence of snoring after UPPP. Patients had mild or moderate obstructive sleep apnea-hypopnea syndrome (OSAHS) (apnea-hypopnea index [AHI] >5 and < or =40), persistent retropalatal obstruction, and a residual palate > or =2 cm. Some patients experienced daytime somnolence as well. Patients with severe OSAHS (AHI > or =40), Friedman anatomic stage IV, and/or nasopharyngeal stenosis were excluded. Pre-/postoperative snoring levels, Epworth Sleepiness Scale (ESS), SF-36v2 Quality of Life (QOL) questionnaires, and polysomnograms were obtained. RESULTS: We completed data on 23 patients. Postoperative snoring levels (3.4 +/- 1.8) and ESS (8.7 +/- 1.8) significantly improved (P < .0001) compared with preoperative values (8.7 +/- 1.8 and 13.2 +/- 2.9). A total of 73.9% of patients improved subjectively. Seven of eight SF-36v2 QOL domains showed significant improvement (P < .05). Postoperative AHI and minimum oxygen saturation also improved significantly (P < .05). Objective cure was only achieved in 21.7% of patients. CONCLUSIONS: Revision PIT is effective in achieving subjective improvement of recurrent symptoms after UPPP. Objective cure was only obtained in 21.7% of patients. As a result of the safety and low morbidity of the procedure, it is an alternative to improve symptoms, especially snoring, in patients not willing to accept continuous positive airway pressure permanently or patients who refuse revision surgery.

Adult↗

PubMed2005

Arteriovenous access: managing common problems.

The creation and maintenance of hemoaccess occupies a significant portion of most vascular and general surgery practices. In this article, the methods used to detect hemoaccess at risk for failure and the endovascular and surgical techniques used to prolong or restore their patency are reviewed. Also, the management of hemoaccess infection, aneurysmal degeneration, false aneurysm formation, and symptomatic arterial steal syndrome are described.

Aneurysm, False↗

PubMed2004

Adenoviral-mediated transfer of vascular endothelial growth factor 121 cDNA enhances myocardial perfusion and exercise performance in the nonischemic state.

BACKGROUND: Angiogenic gene therapy has been demonstrated to enhance perfusion to ischemic tissues, but it is unknown whether the administration of angiogenic growth factors will increase blood flow to nonischemic tissues. This study investigates whether enhanced myocardial perfusion can be mediated by adenovirus-mediated transfer of vascular endothelial growth factor 121 cDNA to nonischemic myocardium. METHODS: New Zealand White rabbits received adenovirus (5 x 10(10) particle units) encoding for vascular endothelial growth factor 121 (n = 14) or a control vector without a transgene (n = 13) or saline solution (n = 9) via direct myocardial injection. Fluorescent microsphere perfusion studies and histologic analyses were performed 4 weeks later. In a parallel study, exercise treadmill testing was performed to assess the functional effects of this therapy in Sprague-Dawley rats. RESULTS: Microsphere assessment of myocardial perfusion in rabbits 4 weeks after adenovirus-encoding vascular endothelial growth factor administration was greater than that for rats injected with control vector without a transgene or saline solution (3.2 +/- 0.5 vs 2.7 +/- 0.7 and 2.4 +/- 0.4, respectively; P <.03). The endothelial cell count per high power field was increased in animals injected with adenovirus-encoding vascular endothelial growth factor versus animals injected with control vector without a transgene or saline solution (147 +/- 27 vs 123 +/- 14 and 125 +/- 16 cells, respectively), although this did not reach statistical significance (P =.12). Rats treated with adenovirus-encoding vascular endothelial growth factor also demonstrated prolonged exercise tolerance compared with rats injected with control vector without a transgene or saline solution (exhaustion time: 26 +/- 5 minutes vs 19 +/- 2 minutes and 20 +/- 3 minutes, respectively; P =.006). CONCLUSIONS: Adenovirus encoding-mediated transfer of vascular endothelial growth factor 121 induces an enhancement in regional perfusion in nonischemic myocardium that corresponds to changes in exercise tolerance. Adenovirus-encoding vascular endothelial growth factor therapy may be useful for inducing angiogenesis in the nonischemic state, such as for prophylactic therapy of early coronary artery disease.

Adenoviridae↗

PubMed2004

Angiogenic pretreatment improves the efficacy of cellular cardiomyoplasty performed with fetal cardiomyocyte implantation.

BACKGROUND: Cell implantation into areas of myocardial infarction (cellular cardiomyoplasty) may be limited in efficacy because of the lack of blood supply to these areas of myocardium, resulting in early loss of transplanted cells. We therefore tested the hypothesis that pretreatment of infarcted myocardium with angiogenic therapy, followed by cell transplant, would be more effective than the application of either strategy alone. METHODS: Fischer 344 rats underwent left coronary artery ligation and injection of an adenovirus encoding VEGF 121, an empty expression cassette control vector, or saline solution. Capillary density in the infarcted region was determined in preliminary studies. Cardiomyocytes harvested from syngeneic Fischer rat fetuses were prelabeled and then injected directly into the infarct area 3 weeks after vector administration. Exercise treadmill testing was performed 2 weeks after cell transplantation, after which a cell viability index was calculated as the number of implanted (prelabeled) nuclei divided by the number of coadministered microspheres detected in sections of implanted myocardium. RESULTS: Capillary density in the area of infarction was significantly greater in adenovirus encoding VEGF 121 compared with rats injected with saline solution (P =.001). The cell survival index was also greater in adenovirus encoding VEGF 121 compared with animals injected with empty expression cassette control or saline solution (P =.0045). Exercise tolerance was nearly doubled in animals receiving adenovirus encoding VEGF 121 3 weeks prior to cell implantation compared with animals receiving adenovirus encoding VEGF 121 or cells alone or those receiving adenovirus encoding VEGF 121 at the time of cell implantation (P <.001). CONCLUSIONS: Pretreatment of an infarcted region of the heart with angiogenic mediators such as VEGF can enhance the efficacy of cellular cardiomyoplasty, presumably by creating a more favorable environment for the survival of transplanted cells.

Animals↗

PubMed2004

Homozygous deletion of early growth response 1 gene and critical limb ischemia after vascular ligation in mice: evidence for a central role in vascular homeostasis.

BACKGROUND: The early growth response 1 gene (Egr1) encodes for an immediate to early response transcription factor that is upregulated by changes in vascular strain and hypoxia and in turn upregulates the downstream expressions of a number of angiogenic growth factors. We therefore hypothesized that early growth response 1 may be a critical early messenger governing revascularization in the setting of acute vascular occlusions. METHODS: C57 BL/6 mice deficient in the Egr1 gene (knockout) and their wild-type litter mates underwent ligation and excision of the femoral artery with or without the previous administration of 2.7 x 10(9) particle units of an adenoviral vector coding for the vascular endothelial growth factor gene (VEGF) or Egr1. Distal hind limb perfusion was serially measured in these animals with laser Doppler perfusion imaging. RESULTS: Wild-type mice (n = 9) had nearly complete restitution of hind limb perfusion by day 35 after ligation. In contrast, all noninjected Egr1 knockout mice (n = 5) had severe ipsilateral limb necrosis develop between 1 and 4 days after ligation (P <.0001). Egr1 knockout mice injected with VEGF vector (n = 4) demonstrated significantly improved perfusion relative to baseline by postligation day 28, which persisted to postligation day 35 (P <.05). Egr1 knockout animals injected with Egr1 vector (n = 7) demonstrated a partial recovery of hind limb perfusion relative to VEGF vector-treated knockout animals at postligation day 4 (P <.01), which persisted to day 35. CONCLUSIONS: These findings suggest that early growth response 1 plays a pivotal role in reperfusion responses to vascular occlusion in mice and possibly other mammals.

Adenoviridae↗

PubMed2003

Administration of bone marrow cells into surgically induced fibrocollagenous tunnels induces angiogenesis in ischemic rat hindlimb model.

We established a comparative model of angiogenic induction in previously formed fibrocollagenous tunnels in rat inner thigh muscles. A unilateral hindlimb chronic ischemia model was performed in male Sprague-Dawley rats. A device was then inserted in the central portion of the inner thigh muscles. Vascularity in the ischemic limb was determined by means of an angiographic score, capillary/fiber ratio, and endothelial proliferation by histochemistry and immunohistochemistry. Autologous transplant of bone marrow, vascular endothelial growth factor (VEGF), or collagen-polyvinylpyrrolidone plus heparin induced significant vascularization of the ischemic hindlimb when compared to saline solution. However, the bone marrow group presented a higher angiographic score than the other two. No differences among groups were observed in capillary/fiber ratio or proliferation, except for the VEGF group, where capillary proliferating cells were significantly higher than in controls. Based on these results, bone marrow-derived progenitor cells may constitute a safe and viable alternative for the induction of therapeutic angiogenesis.

Angiography↗