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Kenneth J Woodside

Publications and source records attributed to Kenneth J Woodside.

31 records · Page 2Linked to original sources
PubMed2003

Altered expression of vascular endothelial growth factor and its receptors in normal saphenous vein and in arterialized and stenotic vein grafts.

BACKGROUND: Myointimal thickening is a major cause saphenous vein graft failure. The prominence of medial and adventitial microvessels in stenotic vein grafts and the known angiogenic effects of vascular endothelial growth factor (VEGF) lead us to investigate the expression of VEGF and its receptors in vein graft arterialization and stenosis. METHODS: Normal and arterialized vein graft segments were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) for expression of VEGF-R1 (flt), VEGF-R2 (KDR), and neuropilin-1. The cells expressing VEGF, VEGF-R1, VEGF-R2, and neuropilin-1 were identified in normal, stenotic, and arterialized vein graft segments by immunohistochemistry. RESULTS: Vascular endothelial growth factor, detected in the wall in endothelial cells and adventitial microvessels in normal vein, localized to smooth muscle cells, endothelial cells and adventitial microvessels in arterialized and stenotic vein. VEGF-R1 and VEGF-R2 were expressed infrequently on endothelial cells, macrophages, and smooth muscle cells in arterialized and stenotic vein. Neuropilin-1 was detected in all specimens. RT-PCR demonstrated significantly greater expression of neuropilin-1 in normal vein compared with arterialized vein (P <0.05). CONCLUSIONS: The differential expression of VEGF and its receptors in normal, arterialized, and stenotic vein grafts suggests that alterations in VEGF/VEGF-R2/neuropilin-1 interactions may be important determinants of the adaptive response of vein grafts to arterialization.

Graft Occlusion, Vascular↗
PubMed2003

Morphologic characteristics of varicose veins: possible role of metalloproteinases.

BACKGROUND: Although varicose veins are a common cause of morbidity, etiologic factors predisposing to dilatation, elongation, and tortuosity of the saphenous vein and its tributaries are poorly understood. We compared histologic features of normal and varicose saphenous veins and investigated the role of enzyme or inhibitor imbalance in development of varicosities. METHODS: Eight normal and 10 varicose (C(2,3)E(P,S)A(S)P(R,O)) vein segments were used for this analysis. Matrix metalloproteinase (MMP) expression and activity were analyzed with Western blotting and zymography. Venous architecture and protein localization were determined with histology and immunohistochemistry. RESULTS: Western blot analysis demonstrated the presence of MMP- 1, MMP-2, MMP-9, and MMP-12, as well as small quantities of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 in protein isolates from normal and varicose veins. Both vein types demonstrated MMP-2, MMP-9, and MMP-12 activity by gelatin zymography, although varicose vein expressed less MMP-9 activity than normal vein did. Compared with normal veins, changes in varicose veins were not uniformly distributed along the circumference; areas of intimal thickening were often interspersed with focal areas of dilatation. Fragmentation of elastic lamellae and loss of circular and longitudinal muscle fibers were evident in the varicosities. Focal aggregates of macrophages were detected within the media and adventitia of both normal and varicose veins. MMP-1 and MMP-9 were expressed in both types of vein segments; however, their immunohistochemical localization was distinctly different. In normal vein, endothelial cells, occasional smooth muscle cells (SMC), and adventitial microvessels expressed MMP-1, whereas its expression was localized to fibroblasts, SMC, and endothelial cells throughout involved portions of varicose veins. MMP-9 was localized to endothelial cells, medial SMC, and adventitial microvessels in both normal and varicose veins, although varicose veins demonstrated increased medial smooth muscle cell staining. MMP-12 was found in SMC and fibroblasts in both normal and varicose veins. Neither TIMP-1 nor TIMP-2 were detected with immunohistochemistry in any specimens examined. CONCLUSIONS: There are distinct differences in the structural architecture and localization of MMP expression in normal and varicose veins. Although the changes observed are not sufficiently definitive to enable a causal relationship, they do suggest a possible mechanism for the alterations in matrix composition observed between normal and varicose veins.

Aged↗
PubMed2003

Deep venous thrombosis prophylaxis in trauma: improved compliance with a novel miniaturized pneumatic compression device.

OBJECTIVE: Intermittent pneumatic compression (IPC) devices prevent lower-extremity deep venous thrombosis (LEDVT) when used properly, but compliance remains an issue. Devices are frequently discontinued when patients are out of bed, and they are rarely used in emergency departments. Trauma patients are at high risk for LEDVT; however, IPCs are underused in this population because of compliance limitations. The hypothesis of this study was that a new miniaturized, portable, battery-powered pneumatic compression device improves compliance in trauma patients over that provided by a standard device. METHODS: This was a prospective trial in which trauma patients (mean age, 46 years; revised trauma score, 11.7) were randomized to DVT prophylaxis with a standard calf-length sequential IPC device (SCD group) or a miniaturized sequential device (continuous enhanced-circulation therapy [CECT] group). The CECT device can be battery-operated for up to 6 hours and worn during ambulation. Timers attached to the devices, which recorded the time each device was applied to the legs and functioning, were used to quantify compliance. For each subject in each location during hospitalization, compliance rates were determined by dividing the number of minutes the device was functioning by the total minutes in that location. Compliance rates for all subjects were averaged in each location: emergency department, operating room, intensive care unit, and nursing ward. RESULTS: Total compliance rate in the CECT group was significantly higher than in the SCD group (77.7% vs. 58.9%, P =.004). Compliance in the emergency department and nursing ward were also significantly greater with the CECT device (P =.002 and P =.008 respectively). CONCLUSIONS: Previous studies have demonstrated that reduced compliance with IPC devices results in a higher incidence of LEDVT. Given its ability to improve compliance, the CECT may provide superior DVT prevention compared with that provided by standard devices.

Aged↗
PubMed2003

Use of kidneys from hepatitis C seropositive donors shortens waitlist time but does not alter one-yr outcome.

Utilization of hepatitis C seropositive kidney donors remains controversial. We examined the use of hepatitis C seropositive donors for renal transplantation. Data for creatinine, liver function tests, cold ischemia time, and graft and patient survival were analyzed from 20 hepatitis C seropositive recipients receiving cadaveric renal allografts from seropositive donors and were compared with 20 hepatitis C seropositive recipients receiving allografts from seronegative donors. Recipients receiving a kidney from a hepatitis C seropositive donor were on the waitlist for 9.9 +/- 1.8 months, compared with 17.8 +/- 3.3 months for those receiving a kidney from a seronegative donor (p < 0.05). There were no significant differences in graft or patient survival. Incidences of acute cellular rejection and acute tubular necrosis were similar. There were no significant differences in creatinine, alanine aminotransferase, alkaline phosphatase, or bilirubin values. While there was a significant difference in aspartate aminotransferase at 2 wk and 6 months, these differences were of questionable clinical importance. In conclusion, donor seropositivity for hepatitis C should not preclude renal transplantation into a hepatitis C seropositive recipient and utilization of these organs decreases waitlist time for hepatitis C seropositive recipients.

Adult↗
PubMed2003

Decreased lymphocyte apoptosis by anti-tumor necrosis factor antibody in Peyer's patches after severe burn.

Severe burn results in immunosuppression, with increased lymphocyte apoptosis in both the central and peripheral immune system. As atrophy of the small intestine has been described in mouse models and intestinal lymphocytes have been implicated in the burn inflammatory response, we examined the effects of burn and tumor necrosis factor (TNF)-alpha on lymphocytes in intestinal Peyer's patches. Anesthetized C57BL6 mice received a 30% full-thickness scald burn on the upper back. Sham-burned animals served as controls. Anti-TNF or control immunoglobulin (Ig) G antibody (200 microg) was given immediately after the burn. The animals were initially resuscitated with 2 mL of normal saline, and were then sacrificed 12 h postburn. Terminal deoxyuridine nick-end labeling (TUNEL) and proliferative cell nuclear antigen (PCNA) staining was performed. Apoptosis was quantified as apoptotic lymphocytes/high-powered field (hpf). Results, expressed as mean +/- SEM, were compared using analysis of variance (ANOVA) and the Student-Newman-Keuls test. All mice survived the burn. An initial time-course experiment demonstrated maximal Peyer's patch apoptosis 12 h after the burn. Sham mice had 25 +/- 7 TUNEL-stained cells/hpf in Peyer's patches, whereas burned mice had 93 +/- 18 cells/hpf (P < 0.05). In contrast, burned mice receiving anti-TNF antibody had 28 +/- 8 TUNEL-stained cells/hpf (P < 0.05 vs. burn), whereas sham mice receiving anti-TNF antibody had 20 +/- 4 cells/hpf. There were no significant differences in PCNA staining between the groups. Scald burn results in lymphocyte apoptosis in Peyer's patches. This apoptosis can be abrogated by the addition of anti-TNF antibody. Apoptotic changes may lead to the failure of the intestinal immunological barrier and increased risk of sepsis.

Animals↗
PubMed2003

Renal cortical adenoma incidentally found during living donor nephrectomy.

We report a living related kidney donor incidentally found to have a renal cortical adenoma at nephrectomy. The patient is a 53-year-old man accepted for living related kidney donation. Predonation workup revealed a solitary left renal artery and, on the right kidney, a main artery with a small accessory artery in theupper pole. No other abnormalities were found in the medical history, physical examination, or laboratory and radiological studies. A left laparoscopic nephrectomy was planned. However, during dissection of the upper pole, a 5-mm mass was noted. The nephrectomy was completed, and the organ was preserved in cold University of Wisconsin solution. Permanent section histology showed that the lesion was mostly likely a renal cortical adenoma. As the risk of malignant transformation with immunosuppression could not be adequately determined, the kidney was not transplanted into the recipient. The donor elected not to have the kidney replaced, and the organ was discarded.

Adenoma↗
PubMed2002

Safe administration of a humanized murine antibody after anaphylaxis to a chimeric murine antibody.

BACKGROUND: Basiliximab and daclizumab are potent and relatively safe immunosuppressive induction agents used in transplantation. These chimeric or humanized monoclonal antibodies, respectively, act by binding to the alpha chain of interleukin-2 receptors on activated T lymphocytes. Herein, the authors describe successful transplant induction therapy with a humanized murine antibody in a patient with a history of anaphylaxis to a chimeric murine antibody. METHODS: The authors report a 42-year-old woman who received a dose of basiliximab without adverse reaction before an anticipated renal transplant that was canceled. Two weeks later, she received a second dose of basiliximab. Within 10 min of receiving the second dose, she developed chest tightness, shortness of breath, tongue swelling, diffuse pruritic rash, and skin flushing. RESULTS: The authors hypothesized that her anaphylaxis was mediated by immunoglobulin (Ig) E antibodies to basiliximab. Consistent with this hypothesis, intradermal administration of a 1:100 dilution of basiliximab induced a 10 x 10-mm flare. The authors sought to find an alternative immunosuppressive agent for this patient. The patient elicited prick and intradermal skin testing responses to horse and rabbit polyclonal antithymocyte antibody preparations. However, she mounted neither a prick nor an intradermal response to daclizumab. The patient was administered daclizumab without any adverse effects. CONCLUSIONS: The negative skin test and safe administration of daclizumab is surprising because the similarity of these hybrid antibodies would have predicted similar IgE responsiveness and clinical outcome. The authors propose that patients who develop anaphylaxis to basiliximab or other chimeric antibodies may be candidates for treatment with a humanized antibody preparation such as daclizumab in the presence of a negative skin test to the humanized agent.

Adult↗
PubMed2002

Predictors of alveolar air leaks.

Persistent air leaks are caused by the failure of the postoperative lung to achieve a configuration that is physiologically amenable to healing. The raw pulmonary surface caused by the dissection of the fissure often is separated from the pleura, and the air leak fails to close. Additionally, higher air flow thorough an alveolar-pleural fistula seems to keep the fistula open. Other factors that interfere with wound healing, such as steroid use, diabetes, or malnutrition, can result in persistence of the leak. A thoracic surgeon can minimize the incidence of air leak through meticulous surgical technique and can identify patients in whom the balance of risks (Table 1) and benefits warrant operative intervention based on an understanding of the underlying pathophysiology.

Air↗
PubMed2002

A potential role for CD69 in thymocyte emigration.

The early activation marker, CD69, is transiently expressed on activated mature T cells and on thymocytes that are undergoing positive or negative selection in the thymus. CD69 is a member of the NK gene complex family of C-type lectin-like signaling receptors; however, its function is unknown. In this report, we describe the characterization of mice that constitutively express high levels of surface CD69 on immature and mature T cells throughout development. Constitutive surface expression of CD69 did not affect T cell maturation, signaling through the TCR or thymocyte selection. However, phenotypically and functionally mature thymocytes accumulated in the medulla of CD69 transgenic mice and failed to be exported from the thymus. The retention of mature thymocytes correlated with transgene dose and CD69 surface levels. These results identify a potential role for CD69 in controlling thymocyte export, and suggest that the transient expression of CD69 on thymocytes and T cells may function to regulate thymocyte and T cell trafficking.

Animals↗
PubMedDate not supplied

Current management of gastrointestinal carcinoid tumors.

Gastrointestinal carcinoid tumors are rare neuroendocrine tumors arising from the embryologic primitive gut. Depending on the location in the gastrointestinal tract, these tumors may secrete a variety of hormonally active substances. However, many of these tumors are found incidentally, or the diagnosis is made postoperatively. Also, there is a significant incidence of multicentric carcinoid tumors and synchronous noncarcinoid malignancies in these patients. Treatment is usually based on the size of the tumor. Surgical resection remains the cornerstone of therapy. For advanced metastatic disease, somatostatin analog therapy and surgical debulking provide the best symptomatic relief and may improve survival. Recent studies have demonstrated a benefit from radiolabeled somatostatin analogs for carcinoid tumor localization. In contrast, radiolabeled somatostatin analogs have shown little therapeutic benefit. Future directions include somatostatin receptor profiling of carcinoid tumors, with somatostatin analog therapy targeting the specific receptors.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Pneumothorax in patients with acute respiratory distress syndrome: pathophysiology, detection, and treatment.

Pneumothorax is a frequent and potentially fatal complication of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). Prompt recognition and treatment of pneumothoraces is necessary to minimize morbidity and mortality. The radiologic and clinical signs of pneumothoraces in ARDS patients may have unusual and subtle features. Furthermore, small pneumothoraces in these patients can cause severe hemodynamic or pulmonary compromise. Sparse clinical literature exists on when or how to treat pneumothoraces once they develop in patients with ARDS. In this article, the authors review the pathogenesis, radiologic signs, clinical significance, and treatment of pneumothoraces in ARDS patients. Treatment options include traditional tube thoracostomy, open thoracotomy, and image-guided percutaneous catheters.

Causality↗