Publications by authors named "Kenneth Park"

21 Publications

  • Page 1 of 1

A Financial Plot to Reduce the Burden of Medical School Tuition Fees.

J Emerg Med 2021 Feb 4;60(2):e27-e30. Epub 2020 Nov 4.

Department of Emergency Medicine, American University of Beirut, Beirut, Lebanon; Department of Emergency Medicine, University of California, Irvine, California.

Tuition fees for medical school are continuously and riotously increasing. This upsurge is amassing debts on the backs of students. In the class of 2018, 75% finished medical school with an outstanding balance of $196,520, on average-a $5826 increase from 2017. Tuition fees differ in terms of the ownership of the medical school (public vs. private) and according to the medical student residence status (in-state or out-of-state). It is critical that students arrange a long-term budget that shows them where they stand: in surplus or in deficit. Students may classify expenditures into two groups: "fixed" and "variable," where they can manipulate the variable expenses to fit into their budget. To pay for their tuition, medical students have four possibilities: cash, scholarships and grants, service-obligation scholarships, and loans. Loans are the most common alternatives, and so there are Traditional Repayment Plans and Income-Driven Repayment Plans. This article serves to provide medical students with attainable alternatives for funding their education and for repaying their debts.
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February 2021

Feasibility and safety study of 22-gauge endoscopic ultrasound (EUS) needles for portal vein sampling in a swine model.

Endosc Int Open 2020 Nov 22;8(11):E1717-E1724. Epub 2020 Oct 22.

Cedars-Sinai Medical Center, Division of Digestive Diseases, Los Angeles, California.

 Endoscopic ultrasound (EUS) has been used for portal vein sampling in patients with pancreaticobiliary cancers for enumerating circulating tumor cells but is not yet a standard procedure. Further evaluation is needed to refine the methodology. Therefore, we evaluated the feasibility and safety of 19-gauge (19G) versus a 22-gauge (22 G) EUS fine-needle aspiration needles for portal vein sampling in a swine model.  Celiotomy was performed on two farm pigs. Portal vein sampling occurred transhepatically. We compared 19 G and 22 G needles coated interiorly with saline, heparin or ethylenediaminetetraacetic acid (EDTA). Small- (10 mL) and large- (25 mL) volume blood collections were evaluated. Two different collection methods were tested: direct-to-vial and suction syringe. A bleeding risk trial for saline-coated 19 G and 22 G needles was performed by puncturing the portal vein 20 times. Persistent bleeding after 3 minutes was considered significant.  All small-volume collection trials were successful except for 22 G saline-coated needles with direct-to-vial method. All large-volume collection trials were successful when using suction syringe; direct-to-vial method for both 19 G and 22 G needles were unsuccessful. Collection times were shorter for 19 G vs. 22 G needles for both small and large-volume collections (  < 0.05). Collection times for saline-coated 22 G needles were longer compared to heparin/EDTA-coated (  < 0.05). Bleeding occurred in 10 % punctures with 19 G needles compared to 0 % with 22 G needles.  The results of this animal study demonstrate the feasibility and the safety of using 22 G needles for portal vein sampling and can form the basis for a pilot study in patients.
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November 2020

Is Increased Sleep Responsible for Reductions in Myocardial Infarction During the COVID-19 Pandemic?

Am J Cardiol 2020 09 20;131:128-130. Epub 2020 Jun 20.

Pulmonary Critical Care Section, Veterans Affairs (VA) San Diego Healthcare System, La Jolla, California; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego (UCSD), La Jolla, California. Electronic address:

The COVID-19 pandemic caused by the highly contagious SARS-CoV-2 virus has had devastating consequences across the globe. However, multiple clinics and hospitals have experienced a decrease in rates of acute myocardial infarction and corresponding cardiac catheterization lab activations, raising the question: Has the risk of myocardial infarction decreased during COVID? Sleep deprivation is known to be an independent risk factor for myocardial infarction, and sleep has been importantly impacted during the pandemic, possibly due to the changes in work-home life leading to a lack of structure. We conducted a social media-based survey to assess potential mechanisms underlying the observed improvement in risk of myocardial infarction. We used validated questionnaires to assess sleep patterns, tobacco consumption and other important health outcomes to test the hypothesis that increases in sleep duration may be occurring which have a beneficial impact on health. We found that the COVID-19 pandemic led to shifts in day/night rhythm, with subjects waking up 105 minutes later during the pandemic (p <0.0001). Subjects also reported going to sleep 41 minutes later during the pandemic (p <0.0001). These shifts led to longer duration of sleep during the COVID-19 pandemic. Before the pandemic, subjects reported sleeping 6.8 hours per night, which rose to 7.5 hours during the pandemic, a 44 minute or 11% increase (p <0.0001). We acknowledge the major negative health impact of the global pandemic but would advocate for using this crisis to improve the work and sleep habits of the general population, which may lead to overall health benefits for our society.
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September 2020

Cherry pits causing colonic obstruction.

Gastrointest Endosc 2020 05 18;91(5):1212-1213. Epub 2019 Dec 18.

Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, California, USA.

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May 2020

Balloon Aortic Valvuloplasty Using a Non-Occlusive Balloon Catheter: First Animal Experience.

Cardiovasc Eng Technol 2020 02 18;11(1):59-66. Epub 2019 Nov 18.

Division of Cardiology, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa.

Background: Transcatheter aortic valve implants (TAVI) have revolutionised the treatment of elderly patients requiring aortic valve replacement. These patients often do not tolerate balloon valvuloplasty well, and a valvuloplasty balloon that would allow a degree of continued cardiac output during expansion would be beneficial. We tested such a balloon and describe our results in the sheep model.

Methods And Results: We developed a non-occlusive balloon (NOB) catheter. An acute experiment was performed where the NOB was inflated in six sheep in the aortic valve position without any attempt to arrest cardiac output. Two inflations were performed per animal: the first for 30 s and the second for 2-3 min. Standard occlusive balloons were inflated in two animals under rapid ventricular pacing to serve as controls. Mean pressure gradient across the NOB was 9.7 ± 5 mmHg during the inflations and all animals remained hemodynamically stable during NOB inflations.

Conclusions: The novel non-occlusive balloon catheter, which permitted uninterrupted cardiac output for a prolonged period without the need for pacing-induced temporary cessation of cardiac output, is both feasible and well tolerated in the acute sheep model.
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February 2020

Outcomes of endoscopic treatment of leaks and fistulae after sleeve gastrectomy: results from a large multicenter U.S. cohort.

Surg Obes Relat Dis 2019 Jun 17;15(6):850-855. Epub 2019 Apr 17.

Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri.

Background: Sleeve gastrectomy is the most commonly performed bariatric surgery in the United States. Leaks after sleeve gastrectomy (SGL) occur in 1% to 3% of patients. Endoscopic therapies are increasingly used for treatment of SGLs, but few data exist on their outcomes.

Objectives: The aim of this study was to assess technical success, leak resolution, and reoperation rates of patients undergoing endoscopic therapy for repair SGLs.

Setting: Eight high-volume academic endoscopy centers.

Methods: Patients undergoing endoscopic therapy for SGLs from 2007 to 2017 were identified. Patients were excluded if the index endoscopic therapy for SGL was performed elsewhere or if no follow-up data were available. Leaks were classified as acute (≤7 d of SG), early (1-6 wk), late (7-12 wk), and chronic (>12 wk). Leak resolution was defined as lack of extraluminal air, extravasation on oral contrast radiography, cross-sectional imaging, or resolution of percutaneous drain output. Demographic and procedural data were recorded as rates of additional therapy, adverse events, and surgical revision.

Results: A total of 85 patients met criteria for analysis (70 women, age 42.6 ± 10.8 yr). A total of 295 endoscopic sessions (median 3, range 1-14) were performed across the cohort. SGLs resolved after index endoscopic therapy in 43 (50.1%) patients. The primary outcome of endoscopic resolution of SGL was observed in 62 patients (72.9%). There were 34 (11.5%) PRAE (the majority occurring with self-expandable metal stents), all but 1 of which were managed endoscopically. Surgical revision was required in 23 (21.7%) patients. On univariate analyses independent variables associated with the need for surgical revision included both acute and chronic SGLs (P = .028), loculated subphrenic collections/abscesses (P = .03), and intraabdominal sepsis (P = .03). On multivariable logistic regression using statistically significant predictors from the univariate analyses, acute SGLs were significantly associated with a need for surgical revision (odds ratio 4.8, 95% confidence interval 1.2-18.9, P = .025).

Conclusion: Endoscopic therapy for SGLs is associated with good clinical success, avoiding the need for surgical revision in 73% of patients, with an acceptable adverse event profile. Patients with acute or chronic SGLs and those with loculated abscesses or intraabdominal sepsis are more likely to undergo surgical revision. Endoscopic therapy is an appropriate first-line modality for the management of SGLs, especially those not classified as acute or chronic.
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June 2019

Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria.

Clin Gastroenterol Hepatol 2019 08 22;17(9):1763-1769. Epub 2018 Nov 22.

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.

Background & Aims: In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US.

Methods: We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% white) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999, through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined.

Results: The mean size of gastric adenocarcinomas was 23.0 ± 16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI, 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively.

Conclusions: The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases.
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August 2019

Prognostic Value of Computed Tomography: Measured Parameters of Body Composition in Primary Operable Gastrointestinal Cancers.

Ann Surg Oncol 2017 Aug 21;24(8):2241-2251. Epub 2017 Mar 21.

University Department of Surgery, Aberdeen Royal Infirmary, Aberdeen, UK.

Background: Previous reports suggest that body composition parameters can be used to predict outcomes for patients with gastrointestinal (GI) cancers. However, evidence for an association with long-term survival is conflicting, with much of the data derived from patients with advanced disease. This study examined the effect of body composition on survival in primary operable GI cancer.

Methods: Patients with resectable adenocarcinoma of the GI tract (esophagus, stomach, colon, rectum) between 2006 and 2014 were identified from a prospective database. Computed tomography (CT) scans were analyzed using a transverse section at L3 to calculate sex-specific body composition indices for skeletal muscle, visceral fat, and subcutaneous fat. Kaplan-Meier and log-rank analysis were used to compare unadjusted survival. Multivariate survival analyses were performed using a proportional hazards model.

Results: The study enrolled 447 patients (191 woman and 256 men) with esophagogastric (OG) (n = 108) and colorectal (CR) (n = 339) cancer. Body composition did not predict survival for the OG cancer patients. Among the CR cancer patients, survival was shorter for those with sarcopenia (p = 0.017) or low levels of subcutaneous fat (p = 0.005). Older age (p = 0.046) and neutrophilia (p = 0.013) were associated with sarcopenia in patients with CR. Tumor stage (p = 0.033), neutrophil count (p = 0.011), and hypoalbuminemia (p = 0.023) were associated with sarcopenia in OG cancer patients. In the multivariate analysis, no single measure of body composition was an independent predictor of reduced survival.

Conclusion: Sarcopenia and reduced subcutaneous adiposity are associated with reduced survival for patients with primary operable CR cancer. However, in this study, no parameter of body composition was an independent prognostic marker when considered with age, tumor stage, and systemic inflammation.
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August 2017

Ultrasound-guided, percutaneous peripheral nerve stimulation: technical note.

Neurosurgery 2010 Sep;67(3 Suppl Operative):ons136-9

Columbia University Medical Center, New York, New York, USA.

Background: Peripheral nerve stimulation is a form of neuromodulation that applies electric current to peripheral nerves to induce stimulation paresthesias within the painful areas.

Objective: To report a method of ultrasound-guided, percutaneous peripheral nerve stimulation. This technique utilizes real-time imaging to avoid injury to adjacent vascular structures during minimally invasive placement of peripheral nerve stimulator electrodes.

Material And Methods: We describe a patient that presented with chronic, bilateral foot pain following multiple foot surgeries, for whom a comprehensive, pain management treatment strategy had failed. We utilized ultrasound-guided, percutaneous tibial nerve stimulation at a thigh level to provide durable pain relief on the right side, and open peripheral nerve stimulation on the left.

Results: The patient experienced appropriate stimulation paresthesias and excellent pain relief on the plantar aspect of the right foot with the percutaneous electrode. On the left side, we were unable to direct the stimulation paresthesias to the sole of the foot, despite multiple electrode repositionings. A subsequent, open placement of a left tibial nerve stimulator was performed. This revealed that the correct electrode position against the tibial nerve was immediately adjacent to the popliteal artery, and was thus not appropriate for percutaneous placement.

Conclusion: We describe a method of ultrasound-guided peripheral nerve stimulation that avoids the invasiveness of electrode placement via an open procedure while providing excellent pain relief. We further describe limitations of the percutaneous approach when navigating close to large blood vessels, a situation more appropriately managed with open peripheral nerve stimulator placement. Ultrasound-guided placement may be considered for patients receiving peripheral nerve stimulators placed within the deep tissues, and not easily placed in a blind fashion.
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September 2010

F-18-FDG and C-11-Choline Positron Emission Tomography in Human Esophago-Gastric Cancer: Prediction of Response to Therapy.

World J Oncol 2010 Apr 30;1(2):66-67. Epub 2010 Apr 30.

Department of Surgery, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK, AB25 2ZN.

Background: To determine the utility of F-18-FDG and C-11-Choline uptake, in patients with esophageal and esophago-gastric junction tumors who are to undergo either neo-adjuvant or palliative chemotherapy, in predicting response (pathological and survival).

Methods: Eighteen patients with biopsy proven cancer were recruited prospectively. Patients underwent PET imaging before and during the first cycle of chemotherapy (seven and 14 days) with both F-18-FDG and C-11-Choline. Tracer uptake was quantified using Standardized Uptake Values. Pathological tumor response was determined using the Mandard criteria. Cellular proliferation was determined using ki-67 immunohistochemistry. Relationships between tracer uptake and response, one-year survival and cellular proliferation were determined.

Results: All 18 tumors were imaged by F-18-FDG PET compared to 16/18 with C-11-Choline. Change in uptake of either tracer did not correlate with pathological response. Pathological response did not influence survival (median-survival, responders = 16.1 months; non-responders = 19.0 months, = 0.978). There was no significant correlation of change in tracer uptake with survival. C-11-Choline tumor uptake did not correlate with cellular proliferation.

Conclusion: F-18-FDG PET is superior for imaging of the primary tumor. Neither F-18-FDG nor C-11-Choline PET was able to predict response accurately.
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April 2010

Needs analysis for the development of a preoperative clinic protocol for perioperative beta-blocker therapy.

J Clin Anesth 2008 Dec;20(8):580-8

Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Study Objective: To study the development and implementation of a hospital-wide protocol regarding preoperative beta-blocker therapy.

Design: Prospective, observational clinical study.

Setting: Preoperative test center at a university hospital.

Patients: 1,000 consecutive patients presenting for a preoperative visit and scheduled for same-day admit surgery.

Interventions: An algorithm of indications and contraindications for beta-blocker therapy was designed. Data were collected prospectively on 1,000 consecutive patients between June 1, 2004 and August 31, 2004.

Measurements: Data collected included patient demographics, medication history, risk factors, indications and contraindications to beta-blocker therapy, as well as surgical risk stratification and postoperative complications.

Main Results: 960 of the 1,000 patients underwent surgery and had complete information for the study collected. 169 patients (17.6%) were receiving beta blockers prior to evaluation. Of the patients having high-risk surgery, 72% had a major or minor indication for beta-blocker therapy without contraindication. Of the patients having intermediate or low-risk surgery, 10% had a major indication for beta blockers without contraindication. Overall, 52% (409/791) of the patients who were candidates for perioperative beta blockers were not receiving them. Some type of complication was experienced by 59 (6.1%) patients.

Conclusions: Development, implementation, and monitoring of perioperative beta-blocker therapy protocols is necessary, as a significant number of appropriate patients do not receive this therapy.
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December 2008

Optimal gastric pouch reconstruction post-gastrectomy.

Gastric Cancer 2008 29;11(1):33-6. Epub 2008 Mar 29.

Department of Upper Gastrointestinal Surgery, Aberdeen Royal Infirmary, Grampian University Hospital Trust, Aberdeen, UK.

Background: Gastric pouches have the potential to improve nutrition following total gastrectomy, compared with standard reconstruction. However, a consensus view of clinical benefit is not available, at least partly due to a lack of standardization of pouch design or size. This study was undertaken to identify optimal conditions for pouch design.

Methods: A mathematical model was established and a porcine model constructed to evaluate the pressure/volume dynamics of the pouch. A "J" pouch was constructed at anastomotic lengths of 5, 10, 15, and 20 cm. Each pouch was distended with saline and the pressure/volume relationship established.

Results: Mathematically, increasing the anastomotic length of the pouch to 15 cm increases the volume significantly; thereafter, there is minimal benefit of increasing the pouch length further. For smaller pouches (5 and 10 cm) a 350-to 400-ml volume (approximate meal volume in the elderly) is never achieved until higher pressures (45 cmH(2)O) are applied. However, in the larger pouches (15 and 20 cm) a 350-to 400-ml volume is readily achieved at basal pressures of 15 cmH(2)O.

Conclusion: Smaller pouches never achieve adequate volumes at basal pressures; accordingly, it is unlikely that they will lead to any clinical benefit. Further in-vivo studies should therefore be based upon 15-cm pouch designs.
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June 2008

The impact of operative approach on outcome of surgery for gastro-oesophageal tumours.

World J Surg Oncol 2007 Aug 20;5:95. Epub 2007 Aug 20.

Department of Surgery, Ward 33, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB25 2ZN, UK.

Background: The choice of operation for tumours at or around the gastro-oesophageal junction remains controversial with little evidence to support one technique over another. This study examines the prevalence of margin involvement and nodal disease and their impact on outcome following three surgical approaches (Ivor Lewis, transhiatal and left thoraco-laparotomy) for these tumours.

Methods: A retrospective analysis was conducted of patients undergoing surgery for distal oesophageal and gastro-oesophageal junction tumours by a single surgeon over ten years. Comparisons were undertaken in terms of tumour clearance, nodal yield, postoperative morbidity, mortality, and median survival. All patients were followed up until death or the end of the data collection (mean follow up 33.2 months).

Results: A total of 104 patients were operated on of which 102 underwent resection (98%). Median age was 64.1 yrs (range 32.1-79.4) with 77 males and 25 females. Procedures included 29 Ivor Lewis, 31 transhiatal and 42 left-thoraco-laparotomies. Postoperative mortality was 2.9% and median survival 23 months. Margin involvement was 24.1% (two distal, one proximal and 17 circumferential margins). Operative approach had no significant effect on nodal clearance, margin involvement, postoperative mortality or morbidity and survival. Lymph node positive disease had a significantly worse median survival of 15.8 months compared to 39.7 months for node negative (p = 0.007), irrespective of approach.

Conclusion: Surgical approach had no effect on postoperative mortality, circumferential tumour, nodal clearance or survival. This suggests that the choice of operative approach for tumours at the gastro-oesophageal junction may be based on the individual patient and tumour location rather than surgical dogma.
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August 2007

Toxic vessel reaction to an absorbable polymer-based paclitaxel-eluting stent in pig coronary arteries.

J Invasive Cardiol 2006 Aug;18(8):383-90

American Cardiovascular Research Institute/Saint Joseph's Hospital of Atlanta, Georgia, USA.

Objectives: The goal of this study was to evaluate a new drug-eluting stent (DES) comprising a bioabsorbable polymer eluting a moderate dose of paclitaxel in a clinically relevant animal model.

Background: Although DES limit restenosis, adverse vascular pathologies and toxicities continue to be of major concern. Optimization of DES components, especially completely absorbable polymers, may reduce these toxicities.

Methods: Bare-metal (BM), absorbable polymer coating only (POLY), and polymer-based paclitaxel-eluting (PACL) stents were implanted in porcine coronary arteries using intravascular ultrasound (IVUS) to optimize stent apposition. The dose density of paclitaxel was 0.30-0.35 mcg/mm2, with in vitro elution studies demonstrating a gradual elution over 6-8 weeks. The animals were terminated at 1 week, 1 month and 3 months. Histopathologic and histomorphometric analyses were perform.

Results: The arteries with PACL showed extensive smooth muscle cell necrosis at 1 week and poor apposition of stent struts at 1 month (malapposition measured as gap width between strut and internal elastic lamina), with greater gap width compared to the BM and POLY groups (0.22 mm +/- 0.02 vs. 0.03 mm +/- 0.02 and 0.02 mm +/- 0.01, respectively; p < 0.001). At 3 months, the PACL group showed rebound neointimal thickness and histological percent stenosis compared to the BM group (0.48 mm +/- 0.14 vs. 0.07 mm +/- 0.02, respectively; p < 0.001 and 59% +/- 11 vs. 17% +/- 2, respectively; p < 0.001).

Conclusions: Despite in vitro data showing slow, sustained release of paclitaxel from a bioabsorbable polymer, the porcine coronary artery model demonstrated a sequence of medial necrosis, stent malapposition and late neointimal thickening. Since the therapeutic window for paclitaxel may be narrower than currently inferred, thorough preclinical testing coupled with the polymer development process for stents eluting paclitaxel is needed.
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August 2006

Multiple laparotomies are a predictor of fascial dehiscence in the setting of severe trauma.

Am Surg 2005 May;71(5):402-5

Department of Surgery, Section of Trauma, Washington Hospital Center, Washington, DC 20010, USA.

The purpose of this study was to determine the incidence of wound dehiscence after repeat trauma laparotomy. We performed a retrospective analysis of adult trauma patients who underwent laparotomy at an urban level 1 trauma center during the past 5 years. Patients were divided into single (SL) and multiple laparotomy (ML) groups. Demographic, clinical, and outcome data were collected. Data were analyzed using chi2, t testing, and ANOVA. Overall dehiscence rate was 0.7 per cent. Multiple laparotomy patients had damage control, staged management of their injuries, or abdominal compartment syndrome as the reason for reexploration. SL and ML patients had similar age and sex. ML patients had a higher rate of intra-abdominal abscess than SL patients (13.7% vs 1.2% P < 0.0001), but intra-abdominal abscess did not predict wound dehiscence in the ML group (P = 0.24). This was true in spite of the fact that ML patients had a significantly higher Injury Severity Score (ISS) than SL patients (21.68 vs 14.35, P < 0.0001). Interestingly, wound infection did not predict dehiscence. Patients undergoing repeat laparotomy after trauma are at increased risk for wound dehiscence. This risk appears to be associated with intraabdominal abscess and ISS, but not wound infection. Surgeons should leave the skin open in the setting of repeat trauma laparotomy, which will allow serial assessment of the integrity of the fascial closure.
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May 2005

Medullary N-type and P/Q-type calcium channels contribute to neuropathy-induced allodynia.

Neuroreport 2005 Apr;16(6):563-6

Department of Pharmacology, Merck Research Laboratories, San Diego, CA 92121, USA.

The present study was designed to determine the contribution of N-type, P/Q-type and L-type calcium channels in the rostral ventromedial medulla to tactile allodynia following peripheral nerve injury. L5/L6 spinal nerve ligation in rats produced tactile allodynia, which was dose-dependently inhibited by intrarostral ventromedial medulla microinjection of the N-type calcium channel antagonist omega-conotoxin MVIIA. Similarly, intrarostral ventromedial medulla microinjection of the P/Q-type calcium channel antagonist omega-agatoxin IVA inhibited spinal nerve ligation-induced tactile allodynia, whereas intrarostral ventromedial medulla microinjection of the L-type calcium channel antagonist nimodipine had no effect. These results demonstrate that N-type and P/Q-type calcium channels in the rostral ventromedial medulla contribute to tactile allodynia following peripheral neuropathy, likely via neurotransmitter-mediated activation of descending facilitatory systems from the rostral ventromedial medulla.
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April 2005

Clinical experience with the S-Flex coronary stent.

Cardiovasc J S Afr 2005 Jan-Feb;16(1):9-14. Epub 2004 Sep 10.

Cardiac Clinic, Groote Schuur Hospital, and Department of Medicine, University of Cape Town, Cape Town.

Objective: Restenosis and the risk of sub-acute thrombosis still compromise the advantages of coronary stenting. This report aims to present a clinical audit of the first 100 patients to receive the South African-developed 'low injury' S-Flex coronary stent at Groote Schuur Hospital.

Methods: From September 1999 to March 2001, 102 patients received one or more S-Flex stents. There were no special criteria for the use of the S-Flex and the stents were used routinely with stents from other manufacturers. Procedural and patient demographic information was obtained through a retrospective examination of patient records. All but two patients were followed up through clinical interview or telephone contact six months or more after the procedure. The primary endpoint was clinical restenosis, defined as angiographic restenosis (> 50% diameter narrowing), or recurrence of significant symptoms of ischaemic heart disease or target lesion revascularisation (TLR) after discharge from the hospital, unless shown angiographically that the S-Flex was not implicated.

Results: Device success was achieved in all cases. There were five cases of in-hospital major adverse cardiac events (MACE), including the deaths of two patients who had initially presented with cardiogenic shock. The six-month MACE rate was 7.9%, the six-month TLR rate was 3.0% and the total six-month mortality was 4.0%. The clinical restenosis rate after six months was 7.1% and the total event-free survival (i.e. survival without MACE or clinical restenosis) at six months was 86.1%.

Conclusion: The S-Flex stent has a low clinical restenosis rate in a non-selective population undergoing stenting for coronary artery disease.
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August 2005

The use of quantitative end-tidal capnometry to avoid inadvertent severe hyperventilation in patients with head injury after paramedic rapid sequence intubation.

J Trauma 2004 Apr;56(4):808-14

Department of Emergency Medicine, University of California, San Diego, CA 92103-8676, USA.

Background: This study aimed to determine whether field end-tidal carbon dioxide CO2 (ETCO2) monitoring decreases inadvertent severe hyperventilation after paramedic rapid sequence intubation.

Methods: Data were collected prospectively as part of the San Diego Paramedic Rapid Sequence Intubation Trial, which enrolled adults with severe head injuries (Glasgow Coma Score, 3-8) that could not be intubated without neuromuscular blockade. After preoxygenation, the patients underwent rapid sequence intubation using midazolam and succinylcholine. A maximum of three intubation attempts were allowed before Combitube insertion was mandated. Tube confirmation was accomplished by physical examination, qualitative capnometry, pulse oximetry, and syringe aspiration. Standard ventilation parameters (tidal volume, 800 mL; 12 breaths/minute) were taught. One agency used portable ETCO2 monitors, with ventilation modified to target ETCO2 values of 30 to 35 mm Hg. Trial patients transported by aeromedical crews also underwent ETCO2 monitoring. The primary outcome measure was the incidence of inadvertent severe hyperventilation, defined as arterial blood gas partial pressure of CO2 (pCO2) of less than 25 mm Hg at arrival, for patients with and those without ETCO2 monitoring. These groups also were compared in terms of age, gender, clinical presentation, Abbreviated Injury Score, Injury Severity Score, arrival arterial blood gas data, and survival.

Results: The study enrolled 426 patients and administered neuromuscular blocking agents to 418 patients. Endotracheal intubation was successful for 355 of these patients (85.2%). Another 58 patients (13.6%) underwent Combitube insertion. For 291 successfully intubated patients, arrival pCO2 values were documented, with continuous ETCO2 monitoring performed for 144 of these patients (49.4%). Patients with ETCO2 monitoring had a lower incidence of inadvertent severe hyperventilation than those without ETCO2 monitoring (5.6% vs. 13.4%; odds ratio, 2.64; 95% confidence interval, 1.12-6.20; p = 0.035). There were no significant differences in terms of age, gender, clinical presentation, Abbreviated Injury Score, Injury Severity Score, arrival partial pressure of oxygen (PO2) and pH, or survival. The patients in both groups with severe hyperventilation had a significantly higher mortality rate than the patients without hyperventilation (56 vs. 30%; odds ratio, 2.9; 95% confidence interval, 1.3-6.6; p = 0.016), which could not be explained solely on the basis of their injuries.

Conclusions: The use of ETCO2 monitoring is associated with a decrease in inadvertent severe hyperventilation.
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April 2004

Synthesis and biological evaluation of 6-aryl-6H-pyrrolo[3,4-d]pyridazine derivatives: high-affinity ligands to the alpha 2 delta subunit of voltage gated calcium channels.

Bioorg Med Chem Lett 2004 Mar;14(5):1295-8

Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA.

A novel class of 6-aryl-6H-pyrrolo[3,4-d]pyridazine ligands for the alpha2delta subunit of voltage-gated calcium channels has been described. Substitutions in the aryl ring of the molecule were generally not tolerated, and resulted in diminished binding to the alpha2delta subunit. Modifications to the pyridazine ring revealed numerous permissive substitutions, and detailed SAR studies were carried out in this portion of the molecule. Replacement of the pyridazine ring methyl group with an aminomethyl functionality provided greatly improved potency over the initial lead. The initial lead compound displayed good rat pharmacokinetic properties, and was shown to be efficacious in the Chung model for neuropathic pain in rats.
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March 2004