NobleBlocks

Harrisburg Hospital

Hospital / health systemHarrisburg, Pennsylvania, United States

Research output, citation impact, and the most-cited recent papers from Harrisburg Hospital (United States). Aggregated across the NobleBlocks index of 300M+ scholarly works.

Total works
472
Citations
22.2K
h-index
71
i10-index
353
Also known as
Harrisburg HospitalPinnacleHealth Harrisburg Hospital

Top-cited papers from Harrisburg Hospital

Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients
Michael J. Reardon, Nicolas M. Van Mieghem, Jeffrey J. Popma, Neal S. Kleiman +4 more
2017· New England Journal of Medicine3.0Kdoi:10.1056/nejmoa1700456

BACKGROUND: Although transcatheter aortic-valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative outcomes among patients with aortic stenosis who are at intermediate surgical risk. METHODS: We evaluated the clinical outcomes in intermediate-risk patients with severe, symptomatic aortic stenosis in a randomized trial comparing TAVR (performed with the use of a self-expanding prosthesis) with surgical aortic-valve replacement. The primary end point was a composite of death from any cause or disabling stroke at 24 months in patients undergoing attempted aortic-valve replacement. We used Bayesian analytical methods (with a margin of 0.07) to evaluate the noninferiority of TAVR as compared with surgical valve replacement. RESULTS: A total of 1746 patients underwent randomization at 87 centers. Of these patients, 1660 underwent an attempted TAVR or surgical procedure. The mean (±SD) age of the patients was 79.8±6.2 years, and all were at intermediate risk for surgery (Society of Thoracic Surgeons Predicted Risk of Mortality, 4.5±1.6%). At 24 months, the estimated incidence of the primary end point was 12.6% in the TAVR group and 14.0% in the surgery group (95% credible interval [Bayesian analysis] for difference, -5.2 to 2.3%; posterior probability of noninferiority, >0.999). Surgery was associated with higher rates of acute kidney injury, atrial fibrillation, and transfusion requirements, whereas TAVR had higher rates of residual aortic regurgitation and need for pacemaker implantation. TAVR resulted in lower mean gradients and larger aortic-valve areas than surgery. Structural valve deterioration at 24 months did not occur in either group. CONCLUSIONS: TAVR was a noninferior alternative to surgery in patients with severe aortic stenosis at intermediate surgical risk, with a different pattern of adverse events associated with each procedure. (Funded by Medtronic; SURTAVI ClinicalTrials.gov number, NCT01586910 .).

Effect of Torcetrapib on the Progression of Coronary Atherosclerosis
Steven E. Nissen, Jean‐Claude Tardif, Stephen J. Nicholls, James H. Revkin +4 more
2007· New England Journal of Medicine966doi:10.1056/nejmoa070635

BACKGROUND: Levels of high-density lipoprotein (HDL) cholesterol are inversely related to cardiovascular risk. Torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, increases HDL cholesterol levels, but the functional effects associated with this mechanism remain uncertain. METHODS: A total of 1188 patients with coronary disease underwent intravascular ultrasonography. After treatment with atorvastatin to reduce levels of low-density lipoprotein (LDL) cholesterol to less than 100 mg per deciliter (2.59 mmol per liter), patients were randomly assigned to receive either atorvastatin monotherapy or atorvastatin plus 60 mg of torcetrapib daily. After 24 months, disease progression was measured by repeated intravascular ultrasonography in 910 patients (77%). RESULTS: After 24 months, as compared with atorvastatin monotherapy, the effect of torcetrapib-atorvastatin therapy was an approximate 61% relative increase in HDL cholesterol and a 20% relative decrease in LDL cholesterol, reaching a ratio of LDL cholesterol to HDL cholesterol of less than 1.0. Torcetrapib was also associated with an increase in systolic blood pressure of 4.6 mm Hg. The percent atheroma volume (the primary efficacy measure) increased by 0.19% in the atorvastatin-only group and by 0.12% in the torcetrapib-atorvastatin group (P=0.72). A secondary measure, the change in normalized atheroma volume, showed a small favorable effect for torcetrapib (P=0.02), but there was no significant difference in the change in atheroma volume for the most diseased vessel segment. CONCLUSIONS: The CETP inhibitor torcetrapib was associated with a substantial increase in HDL cholesterol and decrease in LDL cholesterol. It was also associated with an increase in blood pressure, and there was no significant decrease in the progression of coronary atherosclerosis. The lack of efficacy may be related to the mechanism of action of this drug class or to molecule-specific adverse effects. (ClinicalTrials.gov number, NCT00134173 [ClinicalTrials.gov].).

Becoming an information master: a guidebook to the medical information jungle.
Allen F. Shaughnessy, D C Slawson, J H Bennett
1994· PubMed217

The medical information system is a "jungle" in which the unguided visitor can become lost or disoriented. This paper, the second in a series on becoming a medical information master, is a guidebook for traveling through this jungle. It focuses on techniques for efficiently obtaining patient-oriented evidence that matters (POEM). From original research to clinical experience, each source of medical information is valuable; the trick is to learn which source is best for the specific information being sought. Armed with this guide, clinicians can find the most appropriate source of information, evaluate it quickly, and apply it confidently in their efforts to provide the best care for their patients.

Becoming a medical information master: feeling good about not knowing everything.
David C. Slawson, Allen F. Shaughnessy, J H Bennett
1994· PubMed183

The body of knowledge in medicine is growing at a phenomenal pace. Clinicians rely on many sources of medical information--journal articles and reviews, textbooks, colleagues, continuing medical education conferences, videotapes and audiotapes, and pharmaceutical representatives--although they probably have had little formal training in assessing the clinical usefulness of the information obtained from each source. Excellent reader guides on how to evaluate clinical trials and review articles have been published, but these techniques are time-consuming and are rarely employed by busy clinicians. In this paper, we present a "user-friendly" method of managing new information in a practical and time-efficient manner. This approach allows clinicians to disregard most of the available medical information and focus on patient-oriented evidence that truly matters.

Stenting and Angioplasty with Protection in Patients at High‐Risk for Endarterectomy: SAPPHIRE Worldwide Registry First 2,001 Patients
Douglas W. Massop, Rajesh Davé, Christopher Metzger, Williams Bachinsky +4 more
2008· Catheterization and Cardiovascular Interventions170doi:10.1002/ccd.21844

BACKGROUND: Previously, the Stenting and Angioplasty with Protection of Patients with High Risk for Endarterectomy (SAPPHIRE) randomized trial showed that carotid artery stenting (CAS) was not inferior to carotid endarterectomy (CEA) in the treatment of high-surgical risk patients. OBJECTIVE: The primary objective of the SAPPHIRE Worldwide Registry is to evaluate 30-day major adverse events (MAE) after CAS performed by physicians with varied experience and utilizing a formal training program. Data will be analyzed on the overall patient population and by high-risk inclusion criteria. METHODS: SAPPHIRE Worldwide is a multicenter, prospective, postapproval registry to evaluate CAS with distal protection in patients at high-risk for surgery using the Cordis PRECISE Nitinol Stent and ANGIOGUARD XP/RX Emboli Capture Guidewire. Participating physicians are encouraged to treat patients according to their standard of practice and consistent with current Food and Drug Administration-approved labeling. RESULTS: Enrollment began in October 2006. Data are available on the first 2,001 patients enrolled and followed to 30 days. Of these patients, the mean age was 72.2 +/- 9.75 yr; 62% were male; and 27.7% were symptomatic. Entry criteria for surgical high-risk included anatomic (n = 716), physiologic (n = 918), or both risk factors (n = 327). At 30-day follow-up, the MAE was 4.4% (death 1.1%, stroke 3.2%, MI 0.7%) for the overall population. Patients with anatomic risk had a significantly lower 30-day MAE than patients with physiologic risk (2.8% vs. 4.9%, P = 0.0306), respectively. CONCLUSIONS: While the number of physicians performing CAS continues to increase, MAE rates seen in this registry (4.4%) are well within an acceptable range, as was first seen in the SAPPHIRE randomized trial (4.8%). A significant decrease in MAE was seen in patients with anatomic risk compared with physiologic risk factors. The SAPPHIRE Worldwide Registry supports the use of CAS as an alternative to CEA in patients who are at high-risk for surgery due to anatomic risk factors.

Real‐world use of the Impella 2.5 circulatory support system in complex high‐risk percutaneous coronary intervention: The USpella Registry
Brijeshwar Maini, Srihari S. Naidu, Suresh Mulukutla, Neal S. Kleiman +4 more
2011· Catheterization and Cardiovascular Interventions157doi:10.1002/ccd.23403

OBJECTIVES: We report on the real-world, multicenter experience of the Impella 2.5 circulatory support system during high-risk PCI, a subset of the larger USpella Registry. BACKGROUND: Standard of care for most patients with compromised ventricular function with multivessel or high-risk coronary lesions has been coronary artery bypass grafting. In poor operative candidates, high-risk PCI is increasingly considered, despite an increased risk for periprocedural hemodynamic compromise. METHODS: 175 consecutive patients who underwent high-risk PCI with prophylactic support of the Impella 2.5 were evaluated. The primary safety endpoint was the incidence of major adverse cardiac events (MACE) at 30 days. Secondary endpoints included safety and efficacy related to the device and patient outcomes, including survival at 12 months. RESULTS: Overall angiographic revascularization was successful in 99% of patients and in 90% of those with multivessel revascularization, resulting in a reduction of the mean SYNTAX score post-PCI from 36 ± 15 to 18 ± 15 (P < 0.0001) and an improvement of the ejection fraction (from 31 ± 15% to 36 ± 14%, P < 0.0001). In 51% of patients, the functional status improved by one or more NYHA class (P < 0.001). At 30-day follow-up, the rate of MACE was 8%, and survival was 96%, 91%, and 88% at 30 days, 6 months, and 12 months, respectively. CONCLUSIONS: The use of Impella 2.5 in high-risk PCI appeared feasible and safe in the real-world setting. The utilization of the Impella 2.5 was successful, resulting in favorable short- and midterm angiographic, procedural and clinical outcomes.

PERIODIC SOMNOLENCE AND MORBID HUNGER: A NEW SYNDROME
MAX LEVIN
1936· Brain153doi:10.1093/brain/59.4.494

Journal Article PERIODIC SOMNOLENCE AND MORBID HUNGER: A NEW SYNDROME Get access MAX LEVIN MAX LEVIN Harrisburg State HospitalHarrisburg, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar Brain, Volume 59, Issue 4, December 1936, Pages 494–504, https://doi.org/10.1093/brain/59.4.494 Published: 01 December 1936

High Total Bilirubin as a Protective Factor for Diabetes Mellitus: An Analysis of NHANES Data From 1999 - 2006
Pramil Cheriyath
2010· Journal of Clinical Medicine Research138doi:10.4021/jocmr425w

BACKGROUND: Diabetes Mellitus (DM) is a rampantly growing epidemic in the United States, affecting nearly 10% of the adult population. Studies have shown that higher levels of Total Bilirubin (TBili) convey a protective effect with regard to cardiovascular risk. In this study, we will examine the relationship between TBili level and prevalence of DM to discern whether a similar relationship exists. METHODS: The National Health and Nutrition Examination Survey (NHANES) is a comprehensive survey performed regularly to evaluate the overall health and nutrition status of the United States population. For the purpose of this study, we combined NHANES data collected between 1999 and 2006. Totally 15,876 eligible participants were selected after excluding all patients younger than twenty years, those with a history of abnormal liver function tests, or those who disclosed a history of liver disease. The data collected on these individuals was adjusted for demographic characteristics, as well as risk factors for DM, and was analyzed via multivariate logistic regression, using SAS proc survey methodology. RESULTS: After age adjustment, increased TBili was associated with 26% reduction in diabetes risk (OR 0.74, 95% CI 0.64 - 0.88). Multivariate analysis, adjusting for all diabetes risk factors assessed, confirmed this association (OR 0.80, 95% CI 0.67 - 0.95). CONCLUSIONS: Our results show that a higher level of serum TBili is associated with odds of having a lower incidence of DM. This finding supports the hypothesis that the antioxidant nature of TBili, demonstrating a protective effect with regard to the risk of stroke, atherosclerosis, and vasculitis in prior research, also extends to DM risk. Furthermore, research has shown that higher levels of TBili increase glucose mobilization into the cells, leading to more efficient, biologic glucose utilization. There is no doubt that the beneficial effect of TBili is multifactorial; thus further investigation is warranted. KEYWORDS: Bilirubin; Diabetes; Antioxidant; Protective.

Biological Significance of Aromatase Activity in Human Breast Tumors*
NANCY TILSON-MALLETT, Steven J. Santner, Peter D. Feil, Richard J. Santen
1983· The Journal of Clinical Endocrinology & Metabolism133doi:10.1210/jcem-57-6-1125

Human breast carcinomas contain aromatase, the enzyme necessary for the conversion of androgens to estrogens. If present in sufficient amounts, aromatase could catalyze the synthesis of estrogens from plasma steroid precursors and produce high breast cancer tissue concentrations. To determine the biological importance of tumor aromatase, we validated a specific and highly sensitive 3H-labeled water release assay for aromatase and used this to quantitate the amount of estrogen synthesized in vitro in breast tumors. As proof of assay validity, the [3H] water release assay detected 22.7 +/- 0.09 (+/- SEM) pmol/g . h estrogen formed vs. 24.7 pmol/g . h with the direct product isolation assay. Of 61 human breast tumors studied, 48 contained measurable aromatase activity, ranging from 5-70.5 pmol estrone formed/g . h. Three aromatase inhibitors (aminoglutethimide, testololactone, and 4-hydroxyandrostenedione) blocked this activity at concentrations similar to those affecting aromatase activity in other tissues. If biologically important, the estrogen formed locally from aromatase would be expected to stimulate production of the progesterone receptor. Under these circumstances, a positive correlation of progesterone receptor and local estrogen production should be found. In contrast, no significant correlation between aromatase activity and progesterone receptor level was observed (r = -0.27; P = NS). In addition, no correlation between estrogen receptor content and aromatase activity was detected. Finally, the amount of aromatase activity present in most tumors was insufficient to produce biologically meaningful saturation of estrogen receptors. These observations suggested that aromatase, while present in the majority of breast cancer tissues, may only be biologically important in those few tumors with very high aromatase activity.

Acetabular Labral Tears of the Hip: Examination and Diagnostic Challenges
RobRoy L. Martin, Keelan R. Enseki, Peter Draovitch, Talia Trapuzzano +1 more
2006· Journal of Orthopaedic and Sports Physical Therapy112doi:10.2519/jospt.2006.2135

The purpose of this clinical commentary is to provide an evidence-based review of the examination process and diagnostic challenges associated with acetabular labral tears of the hip. Once considered an uncommon entity, labral tears have recently received wider recognition as a source of symptoms and functional limitation. Information regarding acetabular labral tears and their association to capsular laxity, femoral acetabular impingement (FAI), dysplasia of the acetabulum, and chondral lesions is emerging. Physical therapists should understand the anatomical structures of the hip and recognize how the clinical presentation of labral tears is difficult to view isolated from other hip articular pathologies. Clinical examination should consider lumbopelvic and extra-articular pathologies in addition to intra-articular pathologies when assessing for the source of symptoms and functional limitation. If a labral tear is suspected, further diagnostic testing may be indicated. Although up-and-coming evidence suggests that information obtained from patient history and clinical examination can be useful, continued research is warranted to determine the diagnostic accuracy of our examination techniques.

Prevalence and risk factors of heart failure in the USA: NHANES 2013 – 2014 epidemiological follow-up study
Saketram Komanduri, Yogesh Jadhao, Sai Guduru, Pramil Cheriyath +1 more
2017· Journal of Community Hospital Internal Medicine Perspectives101doi:10.1080/20009666.2016.1264696

Background: Heart Failure (HF) is a progressive epidemic associated with considerable morbidity and mortality. Self-reported data from the National Health and Nutrition Examination Survey (NHANES) provides a unique representation of individuals suffering from HF. The purpose of this study is to analyze updated NHANES 2013-2014 data to identify any changes in the prevalence and current risk factors of HF, especially given the novel lifestyles and increased medical awareness of current generations.Methods: NHANES uses a multistage probability sampling design under the Centers for Disease Control and Prevention (CDC). The Student's t-test and Chi-square test/ Fisher's exact test was used for analysis of variables. A multiple logistic regression model was used to identify statistically significant risk factors for HF. Analyses were performed with the use of SAS software, version 9.4.Results: Based on our analysis, the primary risk factor was coronary artery disease followed by hypertension, diabetes mellitus, age ≥ 65 years, and obesity.Conclusion: The findings revealed that despite improved population awareness and advancements in diagnostics and therapeutics, the same risk factors continue to persist. This provided an insight into the path towards which our resources need to be directed, so as to effectively tackle the aforementioned risk factors.

Isoenzymes of Serum Alkaline Phosphatase in Hepatobiliary and Skeletal Disease
Howard F. Taswell, David M. Jeffers
1963· American Journal of Clinical Pathology96doi:10.1093/ajcp/40.4.349

Howard F. Taswell, M.D., David M. Jeffers, M.T. (ASCP); Isoenzymes of Serum Alkaline Phosphatase in Hepatobiliary and Skeletal Disease, American Journal of

Excimer Laser Recanalization of Femoropopliteal Lesions and 1-Year Patency: Results of the CELLO Registry
Rajesh Davé, Raghotham Patlola, Kenneth R. Kollmeyer, Frank Bunch +4 more
2009· Journal of Endovascular Therapy94doi:10.1583/09-2781.1

PURPOSE: To evaluate the safety and efficacy of a modified laser catheter designed for the endovascular treatment of peripheral artery disease (PAD) affecting the superficial femoral artery (SFA) and proximal popliteal artery. METHODS: The CliRpath Excimer Laser System to Enlarge Lumen Openings (CELLO) study was a single-arm, prospective registry conducted at 17 investigational sites in the United States. The primary endpoint was the reduction in index lesion percent diameter stenosis (% DS) measured by Doppler ultrasound following laser ablation prior to any adjunctive therapy. The primary safety endpoint was major adverse events at 6 months. Sixty-five patients (39 men; mean age 68.3+/-10.1 years) with intermittent claudication, stenotic lesions >70% by visual assessment, a reference vessel diameter >or=4.0 and <or=7.0 mm, and a total lesion length >or=1.0 and <or=15.0 cm underwent laser-assisted recanalization with optional balloon angioplasty (BA) or BA + stenting. Sixty-five de novo lesions (5.6+/-4.7 cm) in 13 occluded and 52 stenotic arteries were treated. RESULTS: Laser ablation reduced the % DS from 77%+/-15% at baseline to 34.7%+/-17.8%, which was reduced to 21%+/-14.5% after adjunctive therapy with BA (n = 42, 64.6%) or BA + stenting (n = 15, 23.3%). Eight (12.3%) patients did not receive post laser adjunctive therapy. Patency rates (% DS <50%) were 59% and 54% at 6 and 12 months, respectively. Target lesion revascularization was not required in 76.9% of CELLO participants within the 1-year follow-up. There were no major adverse events. The study cohort demonstrated a statistically significant improvement in the walking impairment and functional status assessments during follow-up. CONCLUSION: The data validate the safety and efficacy of the investigational device, with a high clinical success rate and 12-month data indicating freedom from reintervention in the majority of patients treated.

WSES guidelines for management of Clostridium difficile infection in surgical patients
Massimo Sartelli, Mark A. Malangoni, Fikri M. Abu‐Zidan, Ewen A. Griffiths +4 more
2015· World Journal of Emergency Surgery94doi:10.1186/s13017-015-0033-6

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.

Comparative Study of Same Sitting Hybrid Coronary Artery Revascularization versus Off‐Pump Coronary Artery Bypass in Multivessel Coronary Artery Disease
William Bachinsky, Murad Abdelsalam, Gouthami Boga, Lukasz Kiljanek +2 more
2012· Journal of Interventional Cardiology89doi:10.1111/j.1540-8183.2012.00752.x

OBJECTIVE: We compared the outcomes of same sitting robotic-assisted hybrid coronary artery revascularization (HCR) with off-pump coronary artery bypass grafting (OPCABG) in similar patients with multivessel coronary artery disease. BACKGROUND: HCR is a novel procedure in selected patients with multivessel coronary artery disease (CAD). Although there are some data on staged HCR, the data on same sitting HCR are limited. METHODS: We conducted a prospective study comparing same sitting robotic-assisted HCR patients (n = 25) to a group of consecutive low to moderate risk OPCABG patients (n = 27) during the study period. HCR patients underwent robotic internal mammary artery takedown followed by OPCABG via minithoracotomy. After confirming graft patency, immediate percutaneous coronary intervention on the nonbypass arteries was performed. Comparative analyses were performed on in-hospital and 30 day outcomes. RESULTS: The baseline characteristics were similar for both groups including the severity of CAD (Syntax score 33.5+/-8.2 vs. 34.9+/-8.2, P = 0.556). Overall MACE was similar between both groups; however, the HCR group showed improved hospital outcomes with lower need for postoperative transfusions (12% vs. 67%, P < 0.001), and shorter length of hospital stay (5.1+/-2.8 vs. 8.2+/-5.4 days, P < 0.01). Despite lower postoperative costs, the HCR group had higher overall hospital costs due to higher procedural costs ($33,984 +/-$4,806 vs. $27,816+/-$11,172, P < 0.0001). Propensity model analysis showed similar findings. The HCR group showed improved quality of life measures with shorter time to return to work (5.3+/-3.0 vs. 8.2+/- 4.6 weeks, P = 0.01). CONCLUSIONS: Same sitting HCR appears to be feasible and may offer superior outcomes to standard OPCABG, further studies are warranted.

What happened to the valid POEMs? A survey of review articles on the treatment of type 2 diabetes
Allen F. Shaughnessy, David C Slawson
2003· BMJ82doi:10.1136/bmj.327.7409.266

OBJECTIVE: To evaluate systematically the review literature on type 2 diabetes to assess transmission of the findings of the United Kingdom prospective diabetes study (UKPDS), an important source of recent valid patient oriented evidence that matters (POEMs). DESIGN: Inception cohort analysis of the recent medical literature. STUDIES REVIEWED: Thirty five reviews on treatment of type 2 diabetes. MAIN OUTCOME MEASURES: Presentation of three types of information from UKPDS in review articles: recommendations based on patient oriented outcomes of study; recommendations contradicted by patient oriented outcomes of study; and recommendations based on disease oriented outcomes for which no patient oriented evidence exists. RESULTS: Only six of the reviews included the POEM that tight blood glucose control had no effect on diabetes related or overall mortality. Just seven mentioned that metformin treatment was associated with decreased mortality. Most (30) of the reviews did not report that diabetic patients with hypertension benefit more from good blood pressure control than good blood glucose control. No review pointed out that treatment of overweight patients with type 2 diabetes with insulin or sulphonylurea drugs had no effect on microvascular or macrovascular outcomes. Thirteen reviews recommended drugs as first line treatment for which we do not have patient oriented outcomes data. The average validity assessment score was 1.3 out of a possible score of 15 (95% confidence interval 0.9 to 1.8). CONCLUSIONS: Review articles on the treatment of type 2 diabetes have not accurately transmitted the valid POEM results of the UKPDS to clinicians. Clinicians relying on review articles written by experts as a source of valid POEMs may be misled.

Retinal vascular endothelial growth factor (VEGF) mRNA expression is altered in relation to neovascularization in oxygen induced retinopathy
Margaret L. Donahue, Dale L. Phelps, Richard H. Watkins, Michael B. LoMonaco +1 more
1996· Current Eye Research82doi:10.3109/02713689608997411

The temporal and spatial expression of vascular endothelial cell growth factor (VEGF) mRNA was studied in normal developing cat retina, and in oxygen induced retinopathy. Unexposed control and oxygen-exposed animals (80 h of 80% oxygen from day 3, n = 16) were studied at 1, 2, 4, and 6 weeks after birth. India ink injected retinal flat mounts were used to study vessel progression, and in situ hybridizations using retinal cross sections were used to assess VEGF mRNA accumulation. In controls, as the retina matured, VEGF mRNA hybridization was evident in the ganglion cell layer in a scattered line of distinct cells prior to the ingrowth of vessels, involved the most cells in regions just peripheral to invading vessels and persisted in a fewer positive cells, widely spaced in the vascularized retinas of control, six week animals. In the inner nuclear layer, hybridization initially appeared diffusely and later became localized to a narrow portion of that layer and persisted there. In animals with oxygen induced retinopathy, a substantial increase in hybridization was observed in both the ganglion cell and inner nuclear layers of the avascular retina anterior to the advancing neovascularization. VEGF hybridization decreased abruptly to background levels in both layers at the point were neovascularization met avascular retina. By six weeks, when the neovascularization reached the ora, there was a return of VEGF mRNA in the inner nuclear layer which was similar to normal control expression. A low level of unchanging expression was also observed in the retinal pigment epithelium in both groups at all ages. These results indicate that VEGF mRNA abundance is regulated during retinal vascularization and is increased in relation to oxygen induced neovascularization, suggesting that VEGF may play an important role in both normal retinal vessel development and in the pathophysiology of retinopathy of prematurity.

Treatment of Left Anterior Descending Coronary Artery Disease With Sirolimus-Eluting Stents
Neil Sawhney, Jeffrey W. Moses, Martin B. Leon, Richard E. Kuntz +4 more
2004· Circulation82doi:10.1161/01.cir.0000136580.34604.b8

BACKGROUND: Revascularization strategies often hinge on the presence and degree of left anterior descending coronary artery (LAD) stenosis. A decision for bypass surgery is often based on the durability of surgical LAD revascularization compared with percutaneous approaches. By decreasing restenosis, drug-eluting stents may have reduced the "reintervention gap" between surgery and percutaneous intervention, making the percutaneous route preferable. METHODS AND RESULTS: Of the 1101 patients in the SIRIUS trial, 459 with an LAD stenosis were randomized to percutaneous intervention with either sirolimus-eluting or bare-metal stents. Baseline demographic, clinical, and angiographic data were obtained. Patients had 1-year clinical and 8-month angiographic follow-up. Baseline characteristics were similar in both groups. The majority of lesions were tubular type B lesions (69.7%) with a mean diameter of 2.73 mm and a mean length of 14.0 mm. The binary in-stent restenosis rate was 2% for the sirolimus stent group and 41.6% for the bare-metal arm (relative risk, 0.05; 95% CI, 0.02 to 0.1; P<0.001). One-year major adverse events (defined as cardiac death, Q-wave and non-Q-wave myocardial infarction, or target vessel revascularization) was decreased 59% in the sirolimus-stent group (9.8% versus 24.9%; relative risk, 0.39; 95% CI, 0.26 to 0.61; P<0.001). Subgroup analysis of 135 patients with proximal LAD lesions showed similar benefits. In-stent restenosis was 0 in the proximal LAD sirolimus-eluting group (n=67), compared with 38% in the bare-metal arm (n=68), and major adverse events demonstrated a similar trend, with a 50% decrease compared with control patients (10.4% versus 20.6%, P=NS). CONCLUSIONS: Sirolimus-eluting stents significantly decrease revascularization rates in LAD lesions. At 1 year, sirolimus-eluting stent revascularization rates are comparable to historic single vessel bypass surgery revascularization rates.

Genetic Heterogeneity of Heart-Hand Syndromes
Craig T. Basson, Scott D. Solomon, Barbara Weissman, Calum A. MacRae +4 more
1995· Circulation80doi:10.1161/01.cir.91.5.1326

BACKGROUND: Heart-hand syndromes compose a class of combined congenital cardiac and limb deformities. The proto-typical heart-hand disorder is Holt-Oram syndrome, which is characterized by cardiac septation defects and radial ray limb deformity. We have recently mapped the Holt-Oram syndrome gene defect to the long arm of human chromosome 12 in two families. The role of this disease locus in the pathogenesis of related conditions such as heart-hand syndrome type III (cardiac conduction disease accompanied by skeletal malformations) or familial atrial septal defects is unknown. METHODS AND RESULTS: Clinical evaluations and genetic linkage analyses were performed in five additional kindreds with Holt-Oram syndrome and also in one kindred with heart-hand syndrome type III and one kindred with familial atrial septal defect and conduction disease. Holt-Oram syndrome in all five kindreds mapped to chromosome 12q2. These studies and previous data provide odds of greater than 10(25):1 that the Holt-Oram syndrome disease gene is at chromosome 12q2. In contrast, neither the phenotypically similar disorder heart-hand syndrome type III nor the locus responsible for a familial atrial septal defect with atrioventricular block maps to chromosome 12q2. CONCLUSIONS: We demonstrate that heart-hand syndromes are genetically heterogeneous. Conditions that clinically appear to be partial phenocopies of Holt-Oram syndrome arise from distinct disease genes.

Screening Siblings for Vesicoureteral Reflux
Jean G. Hollowell
2002· The Journal of Urology79doi:10.1016/s0022-5347(05)64337-6

PURPOSE: Publications on screening the siblings of patients with reflux were reviewed to determine the overall incidence and severity of reflux and renal scarring in siblings, and identify factors that predict siblings more likely to have reflux. MATERIALS AND METHODS: A MEDLINE search for 1985 to the present was performed. Of 34 articles on familial reflux only 11, including 1 abstract, on sibling screening were used in this analysis. RESULTS: The mean incidence of reflux in siblings in all studies was 32% (570 of 1,768). Of the siblings with reflux approximately two-thirds had grades I to II disease. Only 22 of 1,051 siblings (2%) had reflux greater than grade III. Reflux was unilateral in 162 of 307 cases (53%). Certain factors predicted the chance of sibling reflux. Sibling age varied inversely with the incidence of reflux. A twin relationship and absent dysfunctional voiding symptoms in the index patient may predict a higher chance of reflux in a sibling. The mean incidence of renal abnormality in siblings with reflux was 11%. The incidence of reflux and renal abnormality in the sibling population undergoing screening was 3%. In more than half of the siblings with an abnormal renal evaluation there was no history of urinary tract infection. CONCLUSIONS: The studies reveal an incidence of reflux in siblings greater than in the general population. These data do not prove that screening and treating asymptomatic siblings decreases infectious renal scarring. Studies in a control group that consider sibling age are still needed to determine the benefit of screening asymptomatic siblings.