Biomedical subjects
A Park
Publications and source records attributed to A Park.
The case for David Ho.
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Closing in on cancer.
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Development of poly-(D,L-lactide--coglycolide) microsphere formulations containing recombinant human vascular endothelial growth factor to promote local angiogenesis.
Although preclinical animal studies have demonstrated the utility of recombinant human vascular endothelial growth factor (rhVEGF) in promoting neovascularization in regions of ischemia, rhVEGF systemic administration did not provide clinical benefit to patients in recent placebo-controlled Phase II clinical trials. The amount of rhVEGF localized in the ischemic region after systemic administration is minimal and does not persist for more than 1 day. A greater persistence of rhVEGF at the region of ischemia may provide an increased angiogenesis with the eventual formation of patent blood vessels to restore nourishment to the tissues. We sought to develop a formulation of rhVEGF in poly(D,L-lactide--co-glycolide) (PLG) microspheres that would provide a continuous local delivery of intact protein. A stable formulation of rhVEGF for encapsulation contained a small amount of a stabilizing sugar, trehalose. Addition of excess trehalose increased the rate of release from the PLG. In addition, PLG with free acid end groups appeared to retard the initial release of rhVEGF by associating with it through ionic interactions at the positively charged heparin binding domain. rhVEGF was released continuously for 21 days with a very low (less than 10%) initial burst. The released rhVEGF aggregated and hydrolyzed over time and lost heparin affinity but not receptor affinity. The compression molding of rhVEGF PLG microspheres into disks yielded formulations with a low initial release and a lag of 10 days followed by complete release. The PLG microsphere formulations were assessed in the corneal implant model of angiogenesis and generated a dose-dependent angiogenic response. These formulations were also administered intravitreally and subretinally, generating local neovascularization comparable to the human disease states, vitroretinopathy and age-related macular degeneration, respectively. The rhVEGF PLG formulations may increase local angiogenesis without systemic side effects and may also be useful in the development of ocular disease models.
The nun study. How one scientist and 678 sisters are helping unlock the secrets of Alzheimer's.
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Your A to Z guide to the year in medicine.
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AIDS. Still no vaccine, but better antiviral drugs are on the way.
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Inhibition of neutrophil elastase prevents cathelicidin activation and impairs clearance of bacteria from wounds.
The host defense roles of neutrophil elastase in a porcine skin wound chamber model were explored. Analysis of wound fluid by acid-urea polyacrylamide gel electrophoresis, Western blot, and bacterial overlay confirmed that the neutrophil-derived protegrins constituted the major stable antimicrobial polypeptide in the wound fluid. The application to the wound of 0.10 and 0.25 mM N-methoxysuccinyl-alanine-alanine-proline-valine (AAPV) chloromethyl ketone, a specific neutrophil elastase inhibitor (NEI), blocked the proteolytic activation of protegrins and diminished the associated antimicrobial activity as detected by radial diffusion assay against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans or by bacterial gel overlay against S epidermidis and E coli. The application of the related cathepsin G inhibitor (CGI), benzyloxycarbonyl-glycine-leucine-phenylalanine (ZGLF) chloromethyl ketone, had no effect. In wound chambers that received 10(6) colony-forming unit (CFU)/mL of S epidermidis, the presence of NEI significantly decreased the 24-hour clearance of bacteria from the wound compared to wounds treated with CGI or solvent only. Neither inhibitor, at 0.10 or 0.25 mM concentration, affected leukocyte accumulation or degranulation in the wound chambers. The in vitro microbicidal decrement due to NEI was restored by an amount of the specific protegrin (PG-1), which was equivalent to the measured difference of protegrin between control and inhibited chambers. Administration of 1 microg/mL exogenous PG-1 4 hours after chamber preparation was sufficient to normalize in vivo antimicrobial activity. Although pharmacologic NEIs are promising candidates as anti-inflammatory drugs, they may impair host defense in part by inhibiting the activation of cathelicidins by neutrophil elastase.
Laparoscopic surgery of the spleen: state of the art.
INTRODUCTION: Laparoscopic splenectomy (LS) offers superior visualization and access to the spleen and avoids the major laparotomy incision necessary in open splenectomy (OS). This review summarizes the current knowledge of laparoscopic techniques for splenectomy from the perspective of surgeons whose combined experience now totals 340 cases. BACKGROUND AND DISCUSSION: While LS has been applied across the spectrum of splenic diseases, it is most indicated in treatment of a benign hematologic condition with a normal or slightly enlarged spleen as seen in autoimmune thrombocytopenic purpura (ITP), autoimmune deficiency syndrome-related ITP, hemolytic anemia, or spherocytosis. Both anterior and lateral approaches have been used for LS. While benefits of the anterior approach include access to the splenic artery along the superior border of the pancreas within the lesser sac, thus securing vascular control early in the procedure, the lateral approach allows for improved exposure of and access to the splenic pedicle. Also, mechanics and sequence of dissection are enhanced and more intuitive to the surgeon using the lateral approach, and the tail of the pancreas is more easily identified. Potential perioperative complications of LS include hemorrhage, injury to the tail of the pancreas, and deep vein thrombosis. The most common criticisms facing LS are the potential for missed accessory spleens, longer operating time, and greater operating room costs compared to OS. However, while LS requires a longer operating time than OS, studies indicate shorter postoperative hospital stays for LS versus OS patients in comparable cases, which can, in turn, reduce the total hospital cost for the procedure. CONCLUSION: Although LS continues to pose certain technical challenges--such as management of the massive spleen, specimen extraction, and identification of remotely located accessory spleens--its advantages over OS in terms of faster postoperative recovery, shorter hospital stay, and equivalent or lower perioperative morbidity are now well established. Indications for LS and more laparoscopic spleen-conserving surgery are likely to broaden.
Laparoscopic splenectomy.
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Laparoscopic management of Crohn's disease.
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Laparoscopic-assisted panenteroscopy.
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Protease inhibitor therapy is associated with markedly prolonged time to relapse and improved survival in AIDS patients with cytomegalovirus retinitis.
Prior to the use of highly active antiretroviral therapy (HAART), cytomegalovirus retinitis (CMV-R) in AIDS patients was characterized by multiple relapses and decreased survival. Recent data suggest that CMV-R in patients treated with HAART may remain relapse-free for long periods. We performed a study of the effects of HIV protease inhibitors (PIs) on the incidence of relapse and time to death in AIDS patients with CMV-R treated with anti-CMV therapy. Medical records of all AIDS patients with CMV-R at Parkland Memorial Health and Hospital System treated with anti-CMV agents were reviewed for date of diagnosis of CMV-R, date of CMV-R relapse, type and duration of anti-CMV therapy, and duration of PI therapy. Relapse rates in subjects treated with PIs were compared with the relapse rates in those who were not treated with PIs. The primary endpoint was the time to relapse and death as determined by Kaplan-Meier analysis. Multivariate analysis was performed by Cox proportional hazard model. One hundred and nine cases of CMV-R were identified in 75 patients. Median follow-up time was 247 days (range 31-1818 days). There were 0.54 relapses per 1000 patient days in the group treated with PIs compared with 1.83 relapses per 1000 patient days in the non-PI treatment group (relative risk [RR]=0.29, P<0.01). Time to relapse was increased in the PI treatment group compared with the non-PI treatment group (endpoint not reached vs 182 days, P<0.001, log-rank). Similarly, the time to relapse or death was increased in the PI group compared with the non-PI group (543 days vs 103 days, P<0.001, log-rank). Multivariate analysis utilizing the Cox proportional hazards model demonstrated that only PI therapy but not anti-CMV therapy was associated with decreased risk of CMV-R relapse or death. Only 3 patients with an undetectable HIV viral load and one patient with a CD4 count >120 cells/microl had a relapse. We conclude that patients with CMV-R treated with HAART containing a PI have increased time to relapse and have prolonged survival.
Using immersive VR as a tool for preoperative planning for minimally invasive donor nephrectomy.
For surgeons approaching minimally invasive donor nephrectomy it is important to identify variant anatomy preoperatively since this anatomy can vary significantly from patient to patient. The goal of this operation is to preserve the architecture and function of the organ so it can be transplanted and function successfully. The ability of the surgeon to navigate through an individual patient's anatomy in a virtual three-dimensional (3D) immersive environment augments understanding of anatomical relationships particular to that individual patient and facilitates conveying that information to other physicians and students. Utilizing automated 3D reconstruction of high contrast computed tomography (CT) scan files viewed in this way, surgeons reported a better preoperative understanding of the anatomical variations and encountered fewer surprises at the time of surgery.
Laparoscopic splenectomy in patients with normal-sized spleens versus splenomegaly: does size matter?
Laparoscopic resection has become the standard means for removal of normal-sized spleens in many medical centers. The application of minimally invasive techniques in the setting of splenomegaly is less well defined and was previously considered a contraindication to the laparoscopic approach. The purpose of this prospective study of consecutive patients was to compare the outcomes of patients undergoing laparoscopic splenectomy for normal-sized spleens (150 g or less) versus those with clear evidence of splenomegaly (500 g or greater). One hundred forty-two patients met the inclusion criteria. The most common diagnosis in the normal-sized spleen group was idiopathic thrombocytopenia purpura (67 of 82, 82%). Malignant hematologic diseases (lymphoma and leukemia) were the most common diagnoses in the splenomegaly group (35 of 60, 58%). Mean operative times (127 vs 172 minutes) and estimated blood loss (123 vs 173 cm3) were lower for those patients with normal-sized spleens (P < 0.05). There were no statistical differences in conversion rates, lengths of stay, or complications between the two groups. We conclude that laparoscopic splenectomy is safe and effective in the setting of splenomegaly despite modest but statistically longer operative times and increased operative blood loss when compared with laparoscopic splenectomy for normal-sized spleens.