Biomedical subjects
Publications and source records attributed to S E Wilson.
Minimally invasive esophagectomy is emerging as an alternative option to open esophagectomy for benign and malignant esophageal diseases. This article provides a detailed review of the history of minimally invasive esophagectomy and an update on the currently accepted techniques for minimally invasive esophagectomy and its outcomes.
Effective stiffness of the musculoskeletal system was examined as a function of the characteristics of an external load. Thirteen healthy subjects provided active contraction of the ankle plantarflexion musculature in a neutral ankle posture to support an external load. Musculoskeletal stiffness was computed from kinetic data recorded in response to dorsiflexion/plantarflexion perturbations. Ankle dynamics were recorded while supporting external loads of 19 and 38 kg with and without antagonistic co-contraction. External loads were applied using pure gravitational mass. In separate trials external loads were applied from stretch of steel springs in parallel with the plantarflexion musculature that also provided added parallel stiffness to the system. Adding external stiffness of 4.9 and 8.1 kN/m surprisingly failed to significantly change the stiffness of the ankle-plus-spring system. This suggests contributions from intrinsic muscle stiffness and reflex stiffness declined in response to added external stiffness. This could not be explained by load magnitudes, ankle postures, or co-activation as these were similar between the inertial and elastic loading conditions. However, non-linear parametric analyses suggest mean intrinsic stiffness of 35.5 kN/m and reflex gain of 11.6 kN/m with a constant reflex delay of 70 ms accurately described the empirical results. The phase response between the mechanical dynamics of the musculoskeletal system and delayed neuromotor feedback combine to provide robust control of system behavior.
Leg stiffness was compared between age-matched males and females during hopping at preferred and controlled frequencies. Stiffness was defined as the linear regression slope between the vertical center of mass (COM) displacement and ground-reaction forces recorded from a force plate during the stance phase of the hopping task. Results demonstrate that subjects modulated the vertical displacement of the COM during ground contact in relation to the square of hopping frequency. This supports the accuracy of the spring-mass oscillator as a representative model of hopping. It also maintained peak vertical ground-reaction load at approximately three times body weight. Leg stiffness values in males (33.9+/-8.7 kN/m) were significantly (p<0.01) greater than in females (26.3+/-6.5 kN/m) at each of three hopping frequencies, 3.0, 2.5 Hz, and a preferred hopping rate. In the spring-mass oscillator model leg stiffness and body mass are related to the frequency of motion. Thus male subjects necessarily recruited greater leg stiffness to drive their heavier body mass at the same frequency as the lighter female subjects during the controlled frequency trials. However, in the preferred hopping condition the stiffness was not constrained by the task because frequency was self-selected. Nonetheless, both male and female subjects hopped at statistically similar preferred frequencies (2.34+/-0.22 Hz), therefore, the females continued to demonstrate less leg stiffness. Recognizing the active muscle stiffness contributes to biomechanical stability as well as leg stiffness, these results may provide insight into the gender bias in risk of musculoskeletal knee injury.
Biological diversity in the wound healing response is thought to be a major factor limiting the predictability of the outcome of refractive surgical procedures such as laser in situ keratomileusis and photorefractive keratectomy. Corneal wound healing is critical to the success of topography-linked or wave front-linked excimer laser ablation to optimize visual performance. This is because of the importance of retaining subtle features of custom ablation and the tendency of epithelial hyperplasia and stromal remodeling to obscure these features following either procedure. The corneal wound healing response is exceedingly complex. Keratocyte apoptosis, which occurs in response to epithelial injury, is the earliest observable event in the wound healing cascades and is therefore an excellent target for pharmacological intervention. Alterations of surgical technique can be designed to limit keratocyte apoptosis and the subsequent events in corneal wound healing. Abnormalities of the cascades could contribute to the pathogenesis of corneal diseases. For example, recent data have suggested that perturbation of the keratocyte apoptosis/mitosis balance could underlie the development of keratoconus in a proportion of patients.
Threats to the current form of surgical training in the academic medical center include financial pressures from the government and managed care organizations. A diminishing medical student interest in surgical careers has been noted. The constraints of managed care hold the potential to introduce weaknesses in surgical training in the academic medical center.
HYPOTHESIS: Patency after primary percutaneous transluminal angioplasty (PTA) and stenting of superficial femoral artery (SFA) occlusions is better than historical experience with PTA alone. DESIGN: Consecutive case series of primary PTA with stenting, and follow-up with duplex imaging every 6 months (mean +/- SD follow-up, 32 +/- 15 months). SETTING: Veterans Affairs medical center. PATIENTS AND METHODS: Patients were 57 previously untreated men with 71 limbs having chronic atherosclerotic SFA occlusion with suprageniculate reconstitution and patent tibial runoff. Critical ischemia (Society for Vascular Surgery [SVS] category, 4-6) was present in 7 (10%), the remainder had intermittent claudication only (SVS, 1-3). INTERVENTIONS: Guidewire recanalization followed by PTA, Wallstent deployment, and adjunctive thrombolysis as necessary; 19 limbs (27%) required thrombolysis to manage periprocedural thrombosis. MAIN OUTCOME MEASURES: Cumulative patency, limb salvage, and complications. RESULTS: Length (mean +/- SD) of occlusion was 14.4 +/- 9.9 cm. Length of stented artery was 24.3 +/- 11.1 cm. Ankle brachial index increased from 0.59 +/- 0.14 to 0.86 +/- 0.16 (P<.001) after stenting. One- and 3-year patencies were as follows: primary, 54.6% +/- 6.3% and 29.9% +/- 6.6%; assisted primary, 72.3% +/- 5.6% and 59.0% +/- 6.8%; and secondary, 81.6% +/- 4.8% and 68.3% +/- 6.5%. Three-year secondary patency when periprocedural thrombolysis was required was 35.7% +/- 12.5% compared with 70.6% +/- 7.4% for limbs not requiring periprocedural thrombolysis (P=.02); the differences in occlusion length and severity of ischemia were not significant between these 2 groups. Limbs undergoing adjunctive PTA during angiography 6 to 12 months after initial stenting had 63.0% +/- 13.3% patency at 3 years compared with 100% patency in limbs not requiring PTA at 6 to 12 months angiography (P=.046). Periprocedural mortality and morbidity were 2.8% and 15.5%, respectively. Three of the 7 limbs with critical ischemia underwent amputation during follow-up compared with 2 (3%) of 64 limbs with functional ischemia (chi(2) test, P<.006). A mean of 1.8 endovascular interventions per limb were performed. CONCLUSIONS: Percutaneous transluminal angioplasty and stenting yielded higher patency rates than historical controls undergoing PTA alone. When periprocedural thrombolysis is required, subsequent patency appears to be significantly worse. Poor results after PTA and stenting of limbs with critical ischemia and the need for additional endovascular therapy limit the technique's utility.
BACKGROUND AND OBJECTIVE: Intimal hyperplasia (IH) leading to restenosis is a major complication of arterial revascularization. The purpose of this study was to investigate the effect of photodynamic therapy (PDT) using mono-L-aspartyl chlorin e6 (NPe6) as a photosensitizer and intraluminal radial irradiation for inhibition of IH experimentally. STUDY DESIGN/MATERIALS AND METHODS: Study of laser transmission through the blood indicated that exclusion of blood is a prerequisite for intraluminal PDT. For homogeneous radial laser irradiation to the vessel wall, we used a newly developed cylindrical diffusing balloon laser fiber. Injuries were induced by pulling a balloon catheter through the right iliac artery of rabbits. One and 6 hours after the NPe6 injection (5mg/kg i.v.), drug distribution was examined by fluorescence microscopy. Nineteen rabbits received NPe6 at the time of injuries and PDT was performed with 664-nm laser at 30 and 10 J/cm(2) (20, 30, 40 mW/cm(2)) 1 hour after the injuries. The arteries were harvested at 2 days. In a second group of rabbits, PDT was given at 30 mW/cm(2) (30 J/cm(2)). Two weeks after treatment, the arteries were removed and examined histologically. RESULTS: NPe6 was found to be distributed selectively in the injured media. Endovascular NPe6-PDT showed complete depletion of smooth muscle cells even with 10 J/cm(2) at 2 days. IH was significantly inhibited at 14 days after PDT. CONCLUSIONS: Endovascular PDT of injured artery using NPe6 can prevent IH in this model of arterial wall injury and may become clinically useful for the prophylaxis of IH.
Discoidin domain receptor (DDR) 1 and 2 have recently been found to serve as receptors for several collagen types. These receptors have been found to modulate cell proliferation and metalloprotease expression in response to collagen stimulation. The purpose of this study was to examine expression of DDR1 and DDR2 in the cornea and to determine the effect of several collagen types on proliferation and response to pro-apoptotic cytokines by corneal fibroblasts. DDR1 and DDR2 mRNAs were detected by RT-PCR. Proteins were detected by immunocytochemistry and immunoprecipitation with Western blotting. Cell proliferation in response to acetic acid-solubilized collagen type I, II, IV, IX or X was determined by cell counting. The effect of these collagen types on Fas-stimulating antibody-induced cell death was determined by trypan blue assay. DDR1 and DDR2 mRNAs were detected in each major human cell type of the cornea. Both were also detected in ex vivo human corneal epithelium. DDR1 and DDR2 proteins were detected in all three major cell types in culture and in human corneal tissue. Collagen types I, II, IV, IX and X stimulated proliferation, but had no effect on Fas-mediated apoptosis, of corneal fibroblasts. DDR1 and DDR2 tyrosine kinase receptors are expressed in the cornea. Collagen-stimulated mitosis of corneal fibroblasts in culture is likely mediated by the DDR receptors. Collagen had no effect on Fas-mediated apoptosis of corneal fibroblasts.
PURPOSE: To report two cases of laser in situ keratomileusis-induced neurotrophic epitheliopathy with punctate epitheliopathy and rose bengal staining of the corneal flap. METHODS: Interventional case reports. RESULTS: A 42-year-old woman and a 37-year-old man with no preoperative symptoms or signs of dry eye developed dry eye symptoms and bilateral punctate epithelial erosions as well as rose bengal staining of the corneal flaps after laser in situ keratomileusis. Neither patient had less than 12 mm of wetting with the Schirmer test without anesthesia at any time point between development and resolution of the flap surface abnormalities. The flap surface abnormalities resolved approximately 6 months after laser in situ keratomileusis. CONCLUSIONS: Laser in situ keratomileusis-induced neurotrophic epitheliopathy may be attributable to loss of trophic influence from severed corneal nerve trunks. The condition typically resolves approximately 6 months after laser in situ keratomileusis or laser in situ keratomileusis retreatment.
BACKGROUND: Common bile duct injuries occur in 0.2% to 0.8% of laparoscopic cholecystectomies (LC). Intraoperative cholangiograms (IOCG) are a useful means of detecting common bile duct injuries in the operating room. METHODS: Data were retrospectively reviewed for patients referred for management of common duct injuries from 1996 to 2000. Cost data were obtained from hospital records. Legal settlements were obtained from published sources. RESULTS: Twenty-one patients (0.133%) were found to have bile duct injuries and incurred median hospital stays of 11.5 days at an average cost of $587,491. The average cost of those requiring reoperation was $669,134. The 21 cases in our sample had total charges of $10,819,767. Performing IOCG during each LC in Orange County would have cost $10,669,725. If extrapolated to state and nationwide levels, the savings is far greater. CONCLUSIONS: IOCG during LC is a cost-effective means of preventing the costs of delayed recognition of bile duct injuries.
OBJECTIVE: To evaluate tear production, corneal topography, accuracy of refractive correction, and best spectacle-corrected visual acuity in eyes that had moderate to severe rose bengal staining develop on the flap compared with eyes with little or no staining on the flap, the first few months after laser in situ keratomileusis (LASIK). None of the eyes in this study had significant preoperative dry eye disease. DESIGN: Retrospective case control study. PARTICIPANTS: Individual eyes of 19 consecutive patients with moderate to severe punctate epithelial erosions and rose bengal staining on the flap 1 to 3 months after LASIK were compared with eyes of 19 concurrent patients who did not have punctate epithelial erosions or more than trace staining on the flap develop. METHODS: Nonparametric statistical analyses were used to compare tear secretion, corneal topographic irregularity, spherical equivalent, and visual acuity 3 and 6 months after surgery. Some eyes in both groups also had analysis of tear secretion 1 month after surgery. MAIN OUTCOME MEASURES: Schirmer's test without anesthesia, the topographic corneal irregularity measurement (CIM), the difference between attempted and achieved spherical equivalent, and the loss of best spectacle-corrected visual acuity. RESULTS: There was no difference in tear production 1, 3, or 6 months after LASIK in patients who had punctate epithelial erosions and rose bengal staining on the flap develop and those who did not. There was no significant difference in the CIM or mean accuracy of the refractive correction in the two groups, but some patients had a transient decrease in best spectacle-corrected visual acuity. Flap rose bengal staining resolved by 6 months after LASIK in most affected patients. CONCLUSIONS: LASIK-induced rose bengal staining in patients without preexisting dry eye is likely neurotrophic epitheliopathy, because there is no difference in mean tear production between patients who have significant punctate epithelial erosions and rose bengal staining develop on the flap and those who do not. The signs and symptoms of LASIK-induced (presumed) neurotrophic epitheliopathy tend to resolve approximately 6 months after surgery. This disorder tends to be more common and severe in patients with pre-existing dry eye disease.
OBJECTIVE: The influence of trunk posture on musculoskeletal stability of the spine was investigated. DESIGN: A biomechanical model was developed to evaluate the influence of posture on spinal stability. Model performance was assessed by comparing predicted muscle recruitment patterns with measured EMG activity from the trunk muscles during static lifting exertions. METHOD: An inverted double-pendulum model of the spine controlled by 12 muscle equivalents of the trunk was implemented to determine spinal load and stability. Model input included trunk posture and lifted mass, output included muscle recruitment patterns necessary to achieve stability of the spine and spinal load. EMG activity recorded from the trunk muscles of 10 subjects were recorded during static exertions in various trunk flexion and asymmetric postures to compare with model output. Stable spinal load was examined as a function of trunk flexion and asymmetry during the lifting exertions. RESULTS: Antagonistic co-contraction was necessary to achieve spinal stability, particularly in upright postures. Stable spinal load was increased in asymmetric postures as a result of antagonistic muscle recruitment, suggesting greater neuromuscular control is necessary to maintain stability in asymmetric lifting postures. As trunk flexion angle increased, stability improved but spinal load was greater. CONCLUSIONS: Results illustrate that muscle recruitment patterns are more accurately explained by stability than by equilibrium alone. Spinal stability is influenced by posture. Specifically, control of spinal stability is reduced in asymmetric postures associated with low-back disorder risk. RELEVANCE: Traditional assessment of low-back disorder risk have focussed on spinal loading. Results illustrate that postural risk factors for low-back pain may be partially attributable to stability considerations.
The corneal wound healing cascade is complex and involves stromal-epithelial and stromal-epithelial-immune interactions mediated by cytokines. Interleukin-1 appears to be a master modulator of many of the events involved in this cascade. Keratocyte apoptosis is the earliest stromal event noted following epithelial injury and remains a likely target for modulation of the overall wound healing response. Other processes such as epithelial mitosis and migration, stromal cell necrosis, keratocyte proliferation, myofibroblast generation, collagen deposition, and inflammatory cell infiltration contribute to the wound healing cascade and are also likely modulated by cytokines derived from corneal cells, the lacrimal gland, and possibly immune cells. Many questions remain regarding the origin and fate of different cell types that contribute to stromal wound healing. Over a period of months to years the cornea returns to a state similar to that found in the unwounded normal cornea.
OBJECTIVE: The purpose of this study was to compare abdominal aortic aneurysm (AAA) associations in men and women. METHODS: Veterans aged 50 to 79 years without a previous history of AAA underwent ultrasound screening for AAA after completing a questionnaire on demographic information and potential risk factors. RESULTS: A total of 122,272 men and 3450 women were successfully screened. An AAA of 3.0 cm or greater in diameter was found in 4.3% of men and 1.0% of women (P <.001). Contrary to a previous report, we did not find suprarenal aortic enlargement accompanying AAA to be more common in women. The principal associations that we have previously reported for AAA in this cohort (age, smoking, family history of AAA, and a negative association with diabetes) were all similar in women compared with men. In age- and smoking-adjusted models, the interaction terms indicated that black race and cancer were more strongly associated with AAA in women than men (P <.05). Height and cerebral vascular disease were also more strongly associated with AAA in women than in men, but these interaction terms did not reach statistical significance (P <.10). Although the other differences were unexpected and require confirmation, the trend toward a stronger association of cerebral vascular disease with AAA in women is consistent with two previous reports. CONCLUSIONS: Despite the much lower prevalence of AAA in women, the most important associations with AAA are similar to those seen in men. Our data provide some support for a previous finding that cerebrovascular disease may be more closely associated with AAA in women than in men.
PURPOSE: To identify and differentiate cell cycle and differentiation genes that are up-regulated or down-regulated in human corneal epithelial cells in response to alternative epithelium-modulating cytokines epidermal growth factor (EGF), hepatocyte growth factor (HGF) or keratinocyte growth factor (KGF). METHODS: Primary cultures human corneal epithelial cell (HCE) were treated with 25 ng/ml of EGF, 25 ng/ml HGF, 25 ng/ml KGF, or vehicle for 8 hours. Complementary DNA (cDNA) probes were synthesized from total cellular RNA isolated from the HCE cells. The cDNA probes were hybridized to the Atlas human cell cycle/differentiation array membrane. RNAse protection assay was used to confirm up-regulation of the serine/threonine-protein kinase PITALRE gene by EGF, KGF, and HGF. RESULTS: The expression of one hundred and eleven cell cycle and differentiation genes was monitored with the gene array system. It was found that these epithelial cell-modulating cytokines shared similar effects on some of the cell cycle and differentiation genes that were monitored, but had specific effects on some cytokines. Up-regulation of PITALRE gene expression was confirmed using RNAse protection assay. CONCLUSION: EGF, HGF and KGF had differential effects on cell cycle- and differentiation-related gene expression in corneal epithelial cells. For example, all three mitogenic growth factors up-regulated the expression of cyclin D1 (BCL-1 oncogene) and serine/threonine-protein kinase PITALRE in the primary cultured human corneal epithelial cells. However, EGF and KGF, but not HGF, up-regulated expression of the E2F-1 pRB-binding protein gene. Thus, while these three epithelial mitogens have similar effects on many genes that were analyzed, important differences were noted that may relate to differing effects of these growth factors on corneal epithelial cells. Studies to analyze the significance of the identified differences among these growth factors are in progress.
BACKGROUND: Acinetobacter baumannii is a gram-negative coccobacillus that causes outbreaks of nosocomial infections in ICUs. Due to resistance to multiple antibiotics, management of clusters of A. baumannii is useful as a model in eradication of multi-drug resistant infections. We outline the evolution of an A. baumannii outbreak, focusing on methods of transmission and multidisciplinary measures aimed at eliminating it from the ICU. METHODS: Patients in an urban, tertiary care medical center from November 1996 to December 1997 having positive cultures for multi-drug resistant A. baumannii are included in this study. A. baumannii was isolated on blood agar and MacConkey cultures and identified by Vitek panel. Disk diffusion including amikacin, imipenem, polymyxin B, and sulbactam were used to determine resistance. RESULTS: An outbreak of 52 patients (27 infected, 25 colonized) with 68 positive sites began with the transfer of a colonized >50% total body surface area burn patient from an outside hospital. Within 3 days, the index patient was in the burn ICU, coronary care unit, and medical ICU. Soon, clusters of patients with A. baumannii infections sensitive only to polymyxin B were seen in those units and, ultimately, the surgical ICU. On typing, 2 strains were found, PFGE B and C. Given the level of antibiotic resistance, patients with colonization or infection were cohorted and placed on contact isolation. Strict antiseptic measures, such as hand-washing, barrier isolation, equipment and room cleaning, sterilization of ventilator equipment, and dedication of medical equipment to each patient were instituted. Still, positive environmental cultures were found in ventilator water traps, sinks, and bedrails. Sporadic cases continued for a total of 13 months, with 10 deaths resulting from the infections. CONCLUSION: A. baumannii is a mildly virulent organism that becomes resistant to antimicrobials. Because of multiple antibiotic resistance, strict contact isolation cohorting and antiseptic technique are the primary modes of containment. This outbreak serves as a model of eradication of multi-drug resistant organisms from ICUs. These measures will become of greater importance as nosocomial organisms develop increasing resistance to antimicrobials.
BACKGROUND: Infectious complications encountered after major surgery include operative site infections and nosocomial pneumonia. Recent infection surveillance programs have identified the increasing pathogenic role of gram-positive bacteria in these infections and the high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the United States and abroad. Surgical site infections and nosocomial pneumonia, often serious infections, are associated with adverse clinical outcomes including bacteremia and its resultant complications, as well as the socioeconomic consequences of excess hospitalization and discharge to nursing care. METHODS: The essential triad for management of postoperative soft tissue infection consists of thorough appraisal of the infection site for reintervention, culture of drainage or infected tissue, and prompt initiation of empiric antimicrobial therapy designed to cover the most probable causative pathogens. Broad-spectrum antimicrobial regimens are often necessary for empiric therapy of skin and soft tissue infections or nosocomial pneumonia; however, regimens should be tailored to the most effective and clinically appropriate agent based on results of susceptibility testing. RESULTS: Results of the clinical trial experience with the first United States Food and Drug Administration (FDA)-approved antimicrobial in the new class of oxazolidinones, linezolid, are reviewed. CONCLUSION: In randomized, controlled trials, linezolid 600 mg twice daily (intravenously or orally) provided effective antimicrobial therapy for gram-positive soft tissue infections, including MRSA, and nosocomial pneumonia in which S. aureus was a causative pathogen.
BACKGROUND: Infection of vascular prosthetics implanted for arterial occlusive disease occurs in approximately 1-5% of patients, including early and late clinical presentation. The incidence of infection depends on the anatomical site, with the highest rate occurring in vascular access grafts placed for hemodialysis and in inguinal and lower extremity incisions in patients undergoing bypass procedures for femoropopliteal tibial occlusion. Treatment of prosthetic graft infection has traditionally included antimicrobials, excision of the infected prosthesis, and extraanatomical bypass. With the recognition that prosthetic infection secondary to Staphylococcus epidermidis can be managed with less extensive procedures, clinical data have been reported on in situ replacement with antibiotic-bonded prostheses. Patients who have S. aureus isolated, including methicillin-resistant S. aureus, or gram-negative pathogens, still require conventional graft excision and extraanatomical bypass. METHODS: Selective review of the English-language literature. RESULTS: Recent clinical series show that management by graft excision of infected infrarenal aortic prosthetics and axillofemoral bypass results in 2- and 5-year survival rates of 67% and 47%, and limb salvage rates in survivors of 93% and 82% at 2 and 5 years. In situ replacement with a rifampicin-bonded prosthesis has been accomplished successfully in smaller numbers of patients and shows promising early results. Other methods under study include cryopreserved arterial and femoral vein allografts and autogenous femoral vein grafts, but data are limited when used as replacement for infected prosthetics. CONCLUSION: Advances in the management of infected vascular prostheses over the last decade have led to improved mortality and decreased amputation rates with conventional excision and extraanatomical bypass. Newer methods including in situ graft replacement with antibiotic-impregnated prosthetics appear suitable for low-virulence S. epidermidis infection. Early results are promising for cryopreserved allografts and autogenous femoral vein in situ grafts; however, more clinical experience and longer follow-up will be needed to confirm their durability in a contaminated field.