'Hot Joints' infection protocol reduces unnecessary post-operative re-admissions following total hip and knee arthroplasty.

AIMS: To evaluate the effectiveness of an institutionally developed algorithm for evaluation and diagnosis of prosthetic joint injection and to determine the impact of this protocol on overall hospital re-admissions.p PATIENTS AND METHODS: We retrospectively evaluated 2685 total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients prior to (1263) and following (1422) the introduction of an infection detection protocol. The protocol used conservative thresholds for C-reactive protein to direct the medical attendant to aspirate the joint. The protocol incorporated a clear set of laboratory and clinical criteria that allowed a patient to be discharged home if all were met. Patients were included if they presented to our emergency department within 120 days post-operatively with concerns for swelling, pain or infection and were excluded if they had an unambiguous infection or if their chief complaint was non-orthopaedic in nature. RESULTS: Concern for infection was the single most common (32%) reason for presentation. A total of 296 patients made an emergency visit and were included following THA or TKA. In the pre-protocol cohort, 11 of 27 patients were formally re-admitted to the hospital with concern for infection but only five (45%) patients had actual infections and received additional treatment. In comparison, in the post-protocol cohort, 11 patients were admitted for suspected infection, nine (82%) of whom were truly infected (p = 0.04). Sensitivity increased from 83% to 100% and specificity increased from 71% to 96%. Implementation of this protocol did not miss any infections. CONCLUSION: A standardised protocol for evaluation of THA and TKA infections significantly reduced unnecessary hospital re-admissions. The protocol was both sensitive and specific and did not compromise quality of care. Cite this article: Bone Joint J 2017;99-B:1603-10.

Effects of therapeutic recreation on adults with ASD and ID: a preliminary randomized control trial.

BACKGROUND: The purpose of this research was to examine effects of a therapeutic recreation (TR) program designed to increase executive function (EF), social skills, adaptive behaviours and well-being of adults with autism spectrum disorder (ASD) and intellectual disability (ID). METHOD: A preliminary pre-test, post-test randomized control group experimental design was used to measure effects of a 40-week TR program designed to increase EF (TR-EF). The TR-EF used instructional electronically based games delivered during 200 1-h sessions (5/week). RESULTS: Participants (experimental group, n = 19; wait-list group, n = 18) were evaluated at baseline and 10 months later. There was a positive and direct impact of the program on several EF and indirect effect on social skills, adaptive behaviour and personal well-being. CONCLUSIONS: Findings provide support for inclusion of EF enrichment as a way to enhance effects of TR interventions for adults with ASD and ID. Preliminary results of this study can be considered in planning TR services in the future. In addition to TR-EF program primary effects on EF, there were indirect benefits on adaptive behaviours, personal well-being and social skills.

Medical student appraisal: electronic resources for inpatient pre-rounding.

BACKGROUND: Pre-rounding is essential to preparing for morning rounds. Despite its importance, pre-rounding is rarely formally taught within the medical school curriculum and more often informally learned by modeling residents. The evolution of mobile applications provides opportunities to optimize this process. OBJECTIVES: To evaluate three options available to medical students while pre-rounding and promote adoption of mobile resources in clinical care. METHODS: Six medical students formed the evaluation cohort. Students were surveyed to assess pre-rounding practices. Participants utilized paper-based pre-rounding templates for two weeks followed by two weeks of the electronic note-taking service Evernote. A review of mobile applications on the iTunes and Google Play stores was performed, with each application informally reviewed by a single student. The application Scutsheet was selected for formal review by all students. Data was collected from narrative responses supplied by students throughout the evaluation periods and aggregated to assess strengths and limitations of each application. RESULTS: Pre-study responses demonstrated two consistent processes: verbal sign-out of overnight events and template use to organize patient information. The paper-based template was praised for its organization and familiarity amongst residents, but perceived as limited by the requirement of re-copying data into the hospital's electronic medical record (EMR). Evernote excelled due to compatibility across multiple operating systems, including accessibility from clinical workstations and ability to copy notes into the hospital's EMR. Scutsheet allowed for retention of data across multiple hospital days, but was limited by inability to export data or modify the electronic template. Aggregated user feedback identified the abilities to customize templates and copy information into the EMR as two prevailing characteristics that enhanced the efficiency of pre-rounding. DISCUSSION: Mobile devices offer the potential to enhance pre-rounding efficiency for medical students and residents. A customizable Evernote-based system is described in sufficient detail for reproduction by interested students.

Medical student appraisal: applications for bedside patient education.

BACKGROUND: Medical students are often afforded the privilege of counselling patients. In the past resources were limited to pen and paper or anatomic models. The evolution of mobile applications allows for limitless access to resources that facilitate bedside patient education. OBJECTIVES: To evaluate the utility of six applications in patient education and promote awareness of implementing mobile resources in clinical care. METHODS: Six medical students rotating on various clerkships evaluated a total of six mobile applications. Strengths, limitations, and suggested uses in clinical care were identified. Applications included Meditoons™, VisiblePatient™, DrawMD™, CardioTeach™, Visual Anatomy™, and 360° Patient Education Suite™. Data was generated from narrative responses supplied by each student during their evaluation period. RESULTS: Bedside teaching was enhanced by professional illustrations and animations depicting anatomy and pathophysiology. Impromptu teaching was facilitated, as resources were conveniently available on a student's smartphone or tablet. The ability to annotate and modify images and subsequently email to patients was an extraordinary improvement in provider-patient communication. Universal limitations included small smartphone screens and the novelty of new technology. DISCUSSION: Mobile applications have the potential to greatly enhance patient education and simultaneously build rapport. Endless opportunities exist for their integration in clinical practice, particularly for new diagnoses, consent for procedures, and at time of discharge. Providers should be encouraged to try new applications and utilize them with patients.

Medical student appraisal: searching on smartphones.

BACKGROUND: The rapidly growing industry for mobile medical applications provides numerous smartphone resources designed for healthcare professionals. However, not all applications are equally useful in addressing the questions of early medical trainees. METHODS: Three popular, free, mobile healthcare applications were evaluated along with a Google(TM) web search on both Apple(TM) and Android(TM) devices. Six medical students at a large academic hospital evaluated each application for a one-week period while on various clinical rotations. RESULTS: Google(TM) was the most frequently used search method and presented multimedia resources but was inefficient for obtaining clinical management information. Epocrates(TM) Pill ID feature was praised for its clinical utility. Medscape(TM) had the highest satisfaction of search and excelled through interactive educational features. Micromedex(TM) offered both FDA and off-label dosing for drugs. DISCUSSION: Google(TM) was the preferred search method for questions related to basic disease processes and multimedia resources, but was inadequate for clinical management. Caution should also be exercised when using Google(TM) in front of patients. Medscape(TM) was the most appealing application due to a broad scope of content and educational features relevant to medical trainees. Students should also be cognizant of how mobile technology may be perceived by their evaluators to avoid false impressions.

Effects of a leisure programme on quality of life and stress of individuals with ASD.

BACKGROUND: Even though there is research demonstrating a positive relationship between leisure participation and the two constructs of quality of life and stress reduction, current conceptualisation of leisure as a contributor to quality of life is limited. In addition, in spite of improvements in accurate diagnosis of autism spectrum disorder (ASD) at increasingly earlier ages and proliferation of interventions, research associated with leisure and quality of life for people with ASD is lacking. METHODS: Therefore, a study using a repeated measures design was used to measure effects of a 1-year group leisure programme intended to facilitate interaction with media, engagement in exercise, playing games and doing crafts, attending events, and participating in other recreation activities on quality of life and stress of 37 participants (22 male, 15 female), ages 17-39 (M = 31.49) years at the beginning of the programme) diagnosed with an ASD and a group of 34 adults with ASD as control group (waiting list) (19 male, 15 female), ages 24-38 (M = 30 at programme initiation) years. RESULTS: There was a significant decrease in overall scores of stress levels for participants over the course of the study and there was a significant increase in the four factors of quality of life that were measured (satisfaction, independence, competence and social interaction) as well as the total score for quality of life from baseline to the end of the intervention 12 months later. In contrast, the control group demonstrated no significant improvements related to stress or quality of life. Implications of these findings to leisure services and the quality of life of individuals with ASD are discussed. CONCLUSION: Findings support the contention that participation in recreation activities positively influenced the stress and quality of life of adults with ASD.

Impact on physician workload and revenue following the creation of a specialty vein clinic within an academic vascular practice.

OBJECTIVE: To evaluate the impact of creating a new specialty vein clinic within an academic-based vascular practice on clinical volume, physician workload and financial parameters. METHODS: All patients evaluated and treated for varicose vein related problems within an academic vascular surgery practice were identified from institutional billing databases. Data were stratified according to the time period prior to establishing a vein clinic (PRE-VC) (1999-2001) and after creation of a vein clinic (POST-VC) (2002-2004). Clinical volume, physician workload and financial parameters were evaluated. Comparisons were made between vein (VEIN) and overall vascular (VASC) practice trends. RESULTS: Comparison of clinical volume, physician workload and financial parameters in both the clinic and operative settings showed larger and more rapid expansion of the VEIN practice than VASC practice between PRE-VC and POST-VC time periods (VEIN vs.VASC growth, respectively: new patient clinic volume +162 vs. +18%; clinic relative value units (RVUs) +131 vs. +1%, clinic revenue +201 vs. +44%; procedure volume +348 vs. +19%; procedure RVUs +129 vs. +11%; procedure revenue +93 vs. +10%). Comparing the beginning of PRE-VC to the end of POST-VC time periods, an increasing trend was also present for the percentage of VEIN practice accounting for the total VASC practice (%VEIN PRE-VC to POST-VC, respectively: new patient clinic volume 11.6-30.2%; clinic RVUs 3.2-48.2%; clinic revenue 17.6-31.2%; procedure volume 3.1-14.3%; procedure RVUs 2.8-9.8%; procedure revenue 3.3-11.7%). CONCLUSION: Establishing a specialty vein clinic within an academic vascular practice can lead to a rapid expansion of clinical volume with associated increase in physician workload and reimbursement at a rate greater than that for the overall vascular practice.

A long-term study of patient outcomes with pelvic muscle re-education for urinary incontinence.

PURPOSE: The purpose of this study was to determine the level of continence, satisfaction, and compliance with a maintenance pelvic muscle exercise program 12 months or more after discharge from a clinician-supervised pelvic floor muscle rehabilitation program. SETTING AND SUBJECTS: Forty-nine female patients diagnosed with stress, urge, and mixed etiology urinary incontinence were treated with pelvic muscle re-education and biofeedback. Treatment was performed in a urology clinic setting with sessions supervised by a registered nurse. METHODS: A retrospective chart review was performed for all female patients trained in pelvic muscle exercises from March 1997 through November 1997. Telephone interviews were conducted and questionnaires were administered to determine long-term efficacy of and compliance with pelvic muscle exercises 13 to 20 months after treatment. RESULTS: Fifty-three percent of patients maintained their posttreatment level of continence, and 38% had improved when evaluated 13 to 20 months following treatment (x macro = 16.6 months). Sixty-nine percent continued to perform pelvic muscle exercises once weekly or several times per week. CONCLUSIONS: Clinician-supervised pelvic floor muscle rehabilitation is effective in improving stress and urge incontinence in community-dwelling women with stress, urge, and mixed urinary incontinence. This effect is durable for a period of 16 months, and the majority of women continue to perform pelvic muscle exercises one or more times per week.

The effect of combined arterial hemodynamics on saphenous venous endothelial nitric oxide production.

INTRODUCTION: Evidence exists that an ideal bypass conduit should have a functional endothelial cell surface combined with mechanical properties similar to those of native arteries. We hypothesized that the effect of combined arterial levels of pulsatile shear stress, flow, and cyclic strain would enhance saphenous venous endothelial cell nitric oxide (NO) production, and that variations in these "ideal" conditions could impair this function. We studied NO production as a measure of endothelial function in response to different hemodynamic conditions. METHODS: Human adult saphenous venous endothelial cells were cultured in 10-cm silicone tubes, similar in diameter (5 mm) and compliance (6%) to a medium-caliber peripheral artery (eg, popliteal). Tube cultures were exposed to arterial conditions: a combined pressure (120/80 mm/Hg; mean, 100 mm/Hg), flow (mean, 115 mL/min) and cyclic strain (2%), with a resultant pulsatile shear stress of 4.8 to 9.4 dyne/cm2 (mean, 7.1). Identical tube cultures were used to study variations in these conditions. Modifications of the system included a noncompliant system, a model with nonpulsatile flow, and a final group exposed to pulsatile pressure with no flow. NO levels were measured with a fluorometric nitrite assay of conditioned media collected at 0, 0.25, 0.5, 1, 2, and 4 hours. Experimental groups were compared with cells exposed to nonpulsatile, nonpressurized low flow (shear stress 0.1 dyne/cm2) and static cultures. RESULTS: All experimental groups had greater rates of NO production than cells under static conditions (P <.05). Cells exposed to ideal conditions produced the greatest levels of NO. Independent decreases in compliance, flow, and pulsatility resulted in significantly lower rates of NO production than those in the group with these conditions intact (vs noncompliant P <.05, vs nonflow P <.05, and vs nonpulsatile P <.05). CONCLUSIONS: Our results show that in the absence of physiologically normal pulsatility, cyclic strain, and volume flow, endothelial NO production does not reach the levels seen under ideal conditions. Pulsatile flow and compliance (producing flow with cyclic stretch) play a key role in NO production by vascular endothelium in a three-dimensional hemodynamically active model. This correlates biologically with clinical experience linking graft inflow and runoff and the mechanical properties of the conduit to long-term patency.

Intrathoracic herniation and perforation 18 years after open Nissen fundoplication.

Nissen fundoplication is the most commonly performed surgical procedure in the management of gastroesophageal reflux disease. Esophageal and gastric perforations most commonly occur in the perioperative period and carry significant morbidity. We describe a unique case of intrathoracic gastric wrap perforation and its suspected pathophysiology almost two decades after the original procedure.

Decreased expression of tissue inhibitor of metalloproteinase 1 in stunned myocardium.

Ultrastructural studies of stunned myocardium have shown disorganization and loss of extracellular collagen and increased collagenase activity early after ischemia and reperfusion. The interplay between matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) regulates the turnover of cardiac extracellular matrix fibrillar collagens. However, the gene expression of MMP-1 and TIMP-1 in stunned myocardium is not known. Here, we determined whether altered expression of MMP-1 and TIMP-1 occurs in globally stunned hearts. An isolated nonworking rabbit heart preparation, perfused with a bovine erythrocyte suspension in modified Krebs solution, was used. Two groups were studied: the stunned group was subjected to 20 min of normothermic global ischemia followed by 120 min of normal reperfusion (n = 8), and the control group underwent 140 min of uninterrupted perfusion (n = 7). The developed pressures at the end of reperfusion for ischemic and control hearts were 67.0 +/- 2.73 and 83.1 +/- 1.52 mm Hg (P < 0. 006) respectively. Ribonuclease protection assays of total left ventricular RNA using riboprobes for MMP-1, TIMP-1, and 18S rRNA were performed. A significant decrease (twofold, P < 0.03) in TIMP-1 gene expression was found in the stunned hearts, while MMP-1 mRNA expression was unchanged. Thus, in early stunning, the decrease in TIMP-1 expression could tip the balance favoring enhanced metalloproteinase activity, promoting collagen turnover, and initiating extracellular matrix remodeling. This may contribute to delayed recovery from myocardial stunning.

The nitric oxide precursor L-arginine reduces expression of hyaluronan synthase in experimental vein bypass grafts.

BACKGROUND: The success of vascular bypass procedures is limited by the development of intimal hyperplasia (IH). The nitric oxide (NO) precursor, L-arginine (L-ARG) significantly reduces IH in both arteries and experimental vein grafts; however, the precise mechanism has yet to be elucidated. Hyaluronan synthase-1 (HAS-1) is one of the two enzymes believed to be responsible for making hyaluronan, a key component extracellular matrix composition. PURPOSE: To determine how L-ARG supplementation affects the gene expression of HAS-1 in experimental vein grafts. METHODS: Thirty-four male New Zealand white rabbits were divided into three groups: control (no operation, regular chow and water, n = 4); L-ARG supplemented (n = 15); and no L-ARG (n = 15). The latter two groups underwent a right interposition carotid bypass using jugular vein. Vein grafts were harvested at 7, 14, and 21 days after surgery. Ribonuclease protection assays were performed using 32P-labeled riboprobes for HAS-1 and 18S rRNA as an internal control and expressed as a ratio (HAS-1/rRNA). RESULTS: There was a significant rise in HAS-1 expression in the vein grafts 7 (1.57 +/- 0.5), 14 (0.7 +/- 0.2), and 21 days (2.82 +/- 0.7) after grafting compared to control (0.14 +/- 0.08) (P < 0.05). L-ARG-supplemented animals had a significant decrease in HAS-1 expression at 21 days (0.65 +/- 0.1) compared to nonsupplemented vein grafts (2.82 +/- 0.7) (P < 0.02). CONCLUSIONS: These results demonstrate for the first time a significant rise in HAS expression in the early experimental vein grafts. Furthermore, L-ARG supplementation significantly diminishes the expression of HAS at 21 days. These results may represent a potential mechanism by which augmentation of the L-ARG/NO pathway inhibits IH in experimental vein grafts and may ultimately provide for improved therapeutic interventions in alleviating IH.

Should vein be saved for future operations? A 15-year review of infrainguinal bypasses and the subsequent need for autogenous vein.

The decision to use prosthetic or autogenous vein as the initial conduit for first-time vascular bypass of the lower extremity depends in part on the likelihood of subsequent need for autogenous conduit for another leg or heart bypass. The true frequency of these later events is not known. To answer this question, we analyzed a database of infrainguinal and coronary artery bypasses (CABG) performed at one institution between January 1980 and July 1995, to determine how many patients required subsequent infrainguinal bypass or CABG after their initial leg bypass. Five hundred and seventy-two infrainguinal bypasses were performed on 440 patients (mean age 63.9); average follow-up was 5.6 years. The clinical philosophy favored autogenous vein for first bypass, which was used in 84% of first operations performed during the study period while prosthetic material was used in 16%. For patients in which vein was used for the first operation, and who went on to have a second operation, the use of prosthetic conduit rose from 16% of operations to 27% (p < 0.05). The rate of subsequent CABG after leg bypass was very low, 2% at 5 years, 3% at 10 years. The cumulative probability of requiring a subsequent infrainguinal bypass was 27% at 5 years, 32% at 10 years. Of these, 46% were ipsilateral and 54% were contralateral. Considering only subsequent tibial bypasses (where vein might be considered obligatory), the cumulative 5-year rate of subsequent leg bypass was only 13%. Another bypass was most likely to occur within the first 3 years, rarely thereafter. In summary, after primary infrainguinal bypass, additional procedures using vein may arise in 1/4 to 1/3 of patients, mostly in the first 3 years. However, only 13% will definitely need vein for tibial bypass in 5 years, and subsequent CABG is uncommon.

Hypercholesterolemia alters the gene expression of novel components of the extracellular matrix in experimental vein grafts.

The success rate of vascular bypass procedures is limited by the development of intimal hyperplasia (IH). Hypercholesterolemia has been shown to accelerate IH in both arteries and experimental vein grafts; however the mechanism remains uncertain. Hyaluronic acid synthase (HAS-1) is a transmembrane enzyme responsible for the formation of hyaluronan; an important constituent of extracellular matrix (ECM). The integrin receptor for hyaluronan is CD-44. Both CD-44 and HAS-1 have been studied in the development of ECM of wounds but have yet to be examined in the ECM of IH within vein grafts. The purpose of this study was to determine if the expression of CD-44 and HAS-1 is increased during the early stages of IH and how cholesterol supplementation affects these genes. Forty white male New Zealand rabbits were divided into two groups: cholesterol supplemented (1% cholesterol chow) and noncholesterol supplemented. Each set of 20 rabbits was then divided into four additional groups (n = 5); a nonoperative group (control) and three operative groups that underwent a right interposition carotid bypass using jugular vein. Grafts were harvested at 3, 7, and 21 days after surgery for molecular studies and histology. Ribonuclease protection assays were performed using 32P-labeled riboprobes for HAS-1, CD-44, and 18s rRNA. Densitometric analysis is expressed as a ratio (riboprobe/rRNA). Cholesterol levels differed significantly between cholesterol supplemented and nonsupplemented groups (1419 +/- 130 mg/dl and 48 +/- 12 mg/dl) (p < 0.01). There was a significant increase in the expression of HAS-1 and CD-44 in the vein grafts compared to normal jugular vein. Cholesterol supplementation caused a further increase in CD-44 gene expression versus nonsupplemented vein grafts. These data demonstrate a role for CD-44 and HAS-1 transcription in vein graft intimal hyperplasia, which is further altered by cholesterol supplementation. Lastly, these results could explain differences seen in the development of IH with hypercholesterolemia and ultimately provide for improved therapies in alleviating this process.

Prognostic signs in the surgical management of plexiform neurofibroma: the Children's Hospital of Philadelphia experience, 1974-1994.

OBJECTIVES: To estimate the rate of progression of plexiform neurofibroma after surgery and to identify prognostic factors that predict progression. STUDY DESIGN: A retrospective review of the inpatient and outpatient records of 121 patients, who had 302 procedures on 168 tumors over a 20-year period at a single large pediatric referral center. Data on age, location, indication for surgery, and extent of resection was analyzed for prognostic significance. RESULTS: The overall freedom from progression was 54%. Children < 10 years old had a shorter interval of tumor control than older children (p = 0.0004). Tumors of the head/neck/face fared worse than tumors of the extremities (p = 0.0003). Less extensive resection predicted shorter interval to progression (p < 0.0001). Indication for surgery was not of prognostic importance. In multivariable analysis older age and location in the extremities were predictors of a better outcome. CONCLUSIONS: Tumor progression is a serious problem for children with plexiform neurofibroma. Younger children, children with tumors of the head/neck/face, and tumors that cannot be nearly completely removed are at particular risk. These data may be useful in helping clinicians decide which patients and which tumors are most likely to benefit from surgical intervention.

The limits of generalized cardiac screening tests for predicting cardiac complications after infrainguinal arterial reconstruction.

We examined the relative efficacies of different cardiac screening strategies for infrainguinal arterial bypass. The outcomes of 205 elective leg bypass procedures over a 10-year period, including myocardial infarction (MI), total cardiac complications, and mortality were tallied. Clinical risk factors popularized by Goldman and Eagle, and the results of dipyridamole thallium myocardial imaging (DThal) were recorded. The overall mortality rate was 3.4%, with a 3.4% incidence of MI and a 5.4% total cardiac complication rate. Both abnormal DThal (p = 0.011) and Goldman class II-IV (p = 0.030) were significant predictors of MI and cardiac death, but both suffered from poor specificity and positive predictive value. Because logistic regression analysis identified a correlation between angina, CHF, and an abnormal DThal, a customized screening strategy was developed to include the presence of angina, CHF and an abnormal DThal. Eighty-eight percent of patients suffering MI or death met these criteria, while only 11% of the complication-free group did. This screening strategy provided a superior sensitivity of 88%, specificity of 89%, positive predictive value of 25%, and 99% negative predictive value. A customized screening strategy (angina, CHF, abnormal DThal), developed from a 10-year experience with a single patient group, provided better predictive accuracy than any generalized screening formula.

Inducible nitric oxide synthase expression in human vein grafts.

BACKGROUND: The patency of vascular reconstructive procedures is limited by the development of intimal hyperplasia (IH). Nitric oxide (NO) seems to be beneficial in abrogating this process. Currently, there is little information concerning inducible nitric oxide synthase (iNOS), the enzyme responsible for NO synthesis, and human vein grafts. The purpose of this study was to examine iNOS gene expression in human aortocoronary vein grafts (ACVG) and infrainguinal vein bypass grafts (IVG). METHODS: Nonthrombosed sections from ACVG (n = 5), IVG (n = 5), and control saphenous vein (SV; n = 4) were harvested and processed for RNA isolation. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed on samples using 32P radioactively end labeled primers. Glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) was the internal control, and results were expressed as iNOS pmol/GAPDH pmol. RESULTS: There was a significant increase in the iNOS gene expression in the ACVG (0.049 +/- 0.01) when compared with IVG (0.019 +/- 0.001) or normal SV (0.011 +/- 0.002; P < or = 0.05). There was no significant difference between normal vein and the infrainguinal grafts. Sequencing of a fragment of the amplified 428 bp gene product confirmed 84% homology with the available gene bank human sequence. CONCLUSIONS: This study proves that iNOS is expressed in human vein bypass grafts. Additionally, there is a significant elevation of iNOS message in human ACVGs compared with IVG or normal SV. This difference may be the result of the unique vascular beds supplied by these grafts. Ultimately, manipulation of iNOS expression may lead to therapies to alleviate IH in these grafts.

The temporal expression of transforming growth factor-beta 1 in early aortocoronary vein grafts.

The success of coronary reconstructive procedures is limited by the high incidence of restenosis secondary to intimal hyperplasia (IH). Transforming growth factor-beta 1 (TGF-beta 1) is a growth factor which has been shown to be important in the early development of IH in arteries and peripheral vein grafts. To date, there is little information concerning the early remodeling in aortocoronary vein grafts (ACVG). The purpose of this study was to characterize the expression of TGF-beta 1 expression in early aortocoronary vein grafts. Eighteen mongrel dogs underwent aortocoronary vein bypass grafting. Vein grafts were excised at 2 hr, 4 hr, and 7 days after implantation, snap frozen, and processed for ribonuclease protection assays (RPA) using 32P-labeled riboprobes for TGF-beta 1 and 18 S rRNA. TGF-beta 1 expression was quantified by densitometric analysis of autoradiographs which were expressed as a ratio TGF-beta 1/rRNA. Representative vessel rings were also collected for histology. There was a significant rise in TGF-beta 1 expression in the 2-hr vein grafts (0.42 +/- 0.04 compared to control saphenous vein (0.21 +/- 0.05, P < 0.02). In addition, there was significant downregulation of TGF-beta 1 at 4 hr (0.28 +/- 0.05) and at 7 days (0.18 +/- 0.01) when compared to 2 hr (P < 0.05). Histological specimens showed minimal intimal hyperplasia at 7 days. These results show for the first time an acute rise in TGF-beta 1 expression in ACVG. This upregulation quickly subsides by 4 hr and gene expression approaches control values by 7 days. By understanding this temporal relationship of expression one could better target potential therapeutic modalities to attenuate IH.