Showing papers by "Jewish Hospital published in 2001"

Oxidative stress and diabetic cardiomyopathy: a brief review.

Abstract: Diabetes is a serious public health problem. Improvements in the treatment of noncardiac complications from diabetes have resulted in heart disease becoming a leading cause of death in diabetic patients. Several cardiovascular pathological consequences of diabetes such as hypertension affect the heart to varying degrees. However, hyperglycemia, as an independent risk factor, directly causes cardiac damage and leads to diabetic cardiomyopathy. Diabetic cardiomyopathy can occur independent of vascular disease, although the mechanisms are largely unknown. Previous studies have paid little attention to the direct effects of hyperglycemia on cardiac myocytes, and most studies, especially in vitro, have mainly focused on the molecular mechanisms underlying pathogenic alterations in vascular smooth-muscle cells and endothelial cells. Thus, a comprehensive understanding of the mechanisms of diabetic cardiomyopathy is urgently needed to develop approaches for the prevention and treatment of diabetic cardiac complications. This review provides a survey of current understanding of diabetic cardiomyopathy. Current consensus is that hyperglycemia results in the production of reactive oxygen and nitrogen species, which leads to oxidative myocardial injury. Alterations in myocardial structure and function occur in the late stage of diabetes. These chronic alterations are believed to result from acute cardiac responses to suddenly increased glucose levels at the early stage of diabetes. Oxidative stress, induced by reactive oxygen and nitrogen species derived from hyperglycemia, causes abnormal gene expression, altered signal transduction, and the activation of pathways leading to programmed myocardial cell deaths. The resulting myocardial cell loss thus plays a critical role in the development of diabetic cardiomyopathy. Advances in the application of various strategies for targeting the prevention of hyperglycemia-induced oxidative myocardial injury may be fruitful.

An essential role of the JAK-STAT pathway in ischemic preconditioning.

Abstract: The goal of this study was to determine the role of the Janus tyrosine kinase (JAK)–signal transducers and activators of transcription (STAT) pathway in the late phase of ischemic preconditioning (PC). A total of 230 mice were used. At 5 min after ischemic PC (induced with six cycles of 4-min coronary occlusion/4-min reperfusion), immunoprecipitation with anti-phosphotyrosine (anti-pTyr) antibodies followed by immunoblotting with anti-JAK antibodies revealed increased tyrosine phosphorylation of JAK1 (+257 ± 53%) and JAK2 (+238 ± 35%), indicating rapid activation of these two kinases. Similar results were obtained by immunoblotting with anti-pTyr-JAK1 and anti-pTyr-JAK2 antibodies. Western analysis with anti-pTyr-STAT antibodies demonstrated a marked increase in nuclear pTyr-STAT1 (+301 ± 61%) and pTyr-STAT3 (+253 ± 60%) 30 min after ischemic PC, which was associated with redistribution of STAT1 and STAT3 from the cytosolic to the nuclear fraction and with an increase in STAT1 and STAT3 γ-IFN activation site DNA-binding activity (+606 ± 64%), indicating activation of STAT1 and STAT3. No nuclear translocation or tyrosine phosphorylation of STAT2, STAT4, STAT5A, STAT5B, or STAT6 was observed. Pretreatment with the JAK inhibitor AG-490 20 min before the six occlusion/reperfusion cycles blocked the enhanced tyrosine phosphorylation of JAK1 and JAK2 and the increased tyrosine phosphorylation, nuclear translocation, and enhanced DNA-binding activity of STAT1 and STAT3. The same dose of AG-490 abrogated the protection against myocardial infarction and the concomitant up-regulation of inducible NO synthase (iNOS) protein and activity observed 24 h after ischemic PC. Taken together, these results demonstrate that ischemic PC induces isoform-selective activation of JAK1, JAK2, STAT1, and STAT3, and that ablation of this response impedes the up-regulation of iNOS and the concurrent acquisition of ischemic tolerance. This study demonstrates that the JAK-STAT pathway plays an essential role in the development of late PC. The results reveal a signaling mechanism that underlies the transcriptional up-regulation of the cardiac iNOS gene and the adaptation of the heart to ischemic stress.

Hypofibrinolysis, thrombophilia, osteonecrosis.

Abstract: In the context of additional characterization of the pathoetiologic associations of heritable hypofibrinolysis and thrombophilia with osteonecrosis of the hip, the authors assessed 15 women and 21 men at entry to a 12-week treatment study of the amelioration of Ficat Stages I or II osteonecrosis by low molecular weight heparin (Enoxaparin). All 36 patients had osteonecrosis of the hip; four patients had unifocal osteonecrosis, 25 patients had two joints affected, five had three affected joints, and two had four affected joints. In 11 of 15 women (73%), hyperestrogenemia of pregnancy (20%) or exogenous estrogen supplementation (53%) were associated with the development of osteonecrosis. Five gene mutations affecting coagulation and nine serologic coagulation tests were studied. Compared with control subjects, patients were more likely to have heterozygosity and homozygosity for the hypofibrinolytic 4G polymorphism of the plasminogen activator inhibitor-1 gene. Moreover, the plasminogen activator inhibitor-1 gene product, plasminogen activator inhibitor activity, the major determinant of hypofibrinolysis, was 10 times more likely to be high (> 21.1 U/mL) in patients than in control subjects (31% versus 3%), with a median of 15.7 versus 6.3 U/mL. Compared with controls, patients were more likely to have the thrombophilic methylenetetrahydrofolate reductase gene mutation. In addition, the thrombophilic methylenetetrahydrofolate reductase gene product, homocysteine, was four times more likely to be high (>13.5 umol/L) in patients than in control subjects (20% versus 5%), with a median of 9.1 versus 7 umol/L. Twenty-three percent of patients had low levels (< 65%) of the thrombophilic free protein S versus 3% of control subjects. Patients were more likely than control subjects to have hypofibrinolytic high lipoprotein (a) (≥ 35 mg/dL), 33% versus 13%. Median lipoprotein (a) was higher in patients than in control subjects, 15 versus 5 mg/dL. Heritable hypofibrinolysis and thrombophilia, often augmented in women by hyperestrogenemia, seem to be major pathoetiologies of osteonecrosis. If the association between coagulation disorders and osteonecrosis reflects cause and effect, as postulated, then anticoagulation with Enoxaparin should be a promising therapy for patients with osteonecrosis.

Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30.

Abstract: We studied 31 nondiabetic, habitually (> or =5 years) morbidly obese subjects (mean +/- SD body mass index [BMI] 43 +/- 8.7, median 43). Our specific aim was to determine whether metformin (2.55 g/d for 28 weeks) would ameliorate morbid obesity and reduce centripetal obesity; lipid and lipoprotein cholesterol, insulin, and leptin levels; and plasminogen activator inhibitor activity (PAI-Fx), risk factors for coronary heart disease (CHD). The patients were instructed to continue their prestudy dietary and exercise regimens without change. After 2 baseline visits 1 week apart, the 27 women and 4 men began receiving metformin, 2.55 g/d, which was continued for 28 weeks with follow-up visits at study weeks 5, 13, 21, and 29. Daily food intake was recorded by patients for 7 days before visits then reviewed with a dietitian. Kilocalories per day and per week were calculated. At each visit, fasting blood was obtained for measurement of lipid profile, insulin, leptin, and PAI-Fx. The mean +/- SD kilocalories consumed per day, 1,951 +/- 661 at entry, fell by week 29 to 1,719 +/- 493 (P =.014) but did not differ at weeks 5, 13, and 21 from that at week 29 (P >.2). Weight fell from 258 +/- 62 pounds at entry to 245 +/- 54 pounds at week 29 (P =.0001). Girth was reduced from 51.8 +/- 6.2 to 49.2 +/- 4.5 inches (P =.0001). Waist circumference fell from 44.0 +/- 6.4 inches to 41.3 +/- 5.9 (P =.0001). The waist/hip ratio fell from 0.85 +/- 0.09 to 0.84 +/- 0.09 (P =.04). Fasting serum insulin, 28 +/- 15 microU/mL at entry, fell to 21 +/- 11 microU/mL at week 29 (P =.0001), and leptin fell from 79 +/- 33 ng/mL to 55 +/- 27 ng/mL (P =.0001). On metformin, there were linear trends in decrements in weight, girth, waist circumference, waist/hip ratio, insulin, and leptin throughout the study period (P 30, probably by virtue of its insulin-sensitizing action.

Taking the "ouch" out of injections for children. Using distraction to decrease pain.

Abstract: Purpose:This research compared the effect of two forms of distraction on injection pain in a convenience sample of preschool children.Design:A quasi-experimental study of 105 children (53 girls and 52 boys) ages 4 to 6 years needing DPT immunizations. Data were collected at three sites: two

Nitroglycerin Induces Late Preconditioning Against Myocardial Infarction in Conscious Rabbits Despite Development of Nitrate Tolerance

Abstract: Background— Recent studies suggest that the late phase of ischemic preconditioning (PC) can be mimicked by pretreatment with NO donors. The ability of clinically relevant NO donors to induce PC against infarction, however, has not been evaluated. Furthermore, it is unknown whether tolerance to the hemodynamic actions of nitrates also extends to their PC effects. Methods and Results— Conscious rabbits underwent a 30-minute coronary occlusion and 3 days of reperfusion. A 60-minute intravenous (IV) infusion of nitroglycerin (NTG) ending 1 hour before occlusion reduced infarct size, indicating an early PC effect. When the time interval between NTG infusion and occlusion was extended to 24 or 72 hours, the infarct-sparing action of NTG became even more pronounced, indicating a robust late PC effect. Transdermal NTG patches elicited a late PC effect that was (1) equivalent to that induced by IV NTG, demonstrating the efficacy of transdermal NTG as an alternative form of NTG delivery for inducing late PC, and (2...

Problem behaviour, caregiver reactions, and impact among caregivers of persons with Alzheimer’s disease

Abstract: Problem behaviour, caregiver reactions, and impact among caregivers of persons with Alzheimer’s disease Background. Problem behaviours that occur during Alzheimer’s disease (AD) can have major impact on caregivers. How caregivers react to these behaviours may determine the total impact experienced from caregiving. Purpose. This study examined the relationships between problematic behaviours and caregiving impact in 30 primary caregivers of persons with AD. The first question explored the relationship between frequency of problem behaviour and impact; the second explored the relationship between caregiver reactions to problem behaviours and impact from caregiving. Methods. The frequency of problem behaviour and the caregiver reaction was measured using The Revised Memory and Behaviour Problem Checklist (Teri et al. 1992). The impact from caregiving was operationalized using the Cost of Care Index developed by Kosberg and Cairl (1986). Results. Significant associations were found for 11 of the 20 subscales that measured the association between the frequency of problem behaviour in the client and the impact from caregiving experienced by the caregiver. In comparison, the association between caregiver’s reaction to problem behaviours and impact from caregiving was even more significant in value with 15 subscales of 20 being significant. Female caregivers experienced a greater reaction to disruptive and depressive behaviour when compared with male caregivers even though both genders reported similar frequencies of problem behaviours. In regard to findings about the impact from caregiving, four of the six indicators were higher for women than for men. Conclusions. Caregiver reaction to problem behaviours was more highly associated with impact from caregiving than the actual frequency of the behaviours. These findings have great implications for intervention programs. Caregivers, especially females, need to receive individualized, specific education/training on how to understand and manage disruptive and depressive behaviour in persons with AD.

Neurostimulation of the ventral intermediate thalamic nucleus in inherited myoclonus-dystonia syndrome.

Abstract: We report on the effects of bilateral neurostimulation of the ventral intermediate thalamic nucleus (VIM) in a patient with medically intractable and progressing inherited myoclonus dystonia syndrome (IMDS). Postoperatively, the patient improved by approximately 80% on the modified version of a myoclonus score without any significant change in the dystonic symptoms. This suggests that neurostimulation of the VIM may be an effective treatment for myoclonus in pharmacologically intractable IMDS.

Inhibition of hypoxia/reoxygenation-induced apoptosis in metallothionein-overexpressing cardiomyocytes.

Abstract: To study possible mechanisms for metallothionein (MT) inhibition of ischemia-reperfusion-induced myocardial injury, cardiomyocytes isolated from MT-overexpressing transgenic neonatal mouse hearts and nontransgenic controls were subjected to 4 h of hypoxia (5% CO2-95% N2, glucose-free modified Tyrode's solution) followed by 1 h of reoxygenation in MEM + 20% fetal bovine serum (FBS) (5% CO2-95% air), and cytochrome c-mediated caspase-3 activation apoptotic pathway was determined. Hypoxia/reoxygenation-induced apoptosis was significantly suppressed in MT-overexpressing cardiomyocytes, as measured by both terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling and annexin V-FITC binding. In association with apoptosis, mitochondrial cytochrome c release, as determined by Western blot, was observed to occur in nontransgenic cardiomyocytes. Correspondingly, caspase-3 was activated as determined by laser confocal microscopic examination with the use of FITC-conjugated antibody against active caspase-3 and by enzymatic assay. The activation of this apoptotic pathway was significantly inhibited in MT-overexpressing cells, as evidenced by both suppression of cytochrome c release and inhibition of caspase-3 activation. The results demonstrate that MT suppresses hypoxia/reoxygenation-induced cardiomyocyte apoptosis through, at least in part, inhibition of cytochrome c-mediated caspase-3 activation.

Founder BRCA1 and BRCA2 mutations in early-onset French Canadian breast cancer cases unselected for family history.

Abstract: Recently, founder BRCA1 and BRCA2 mutations were identified in Canadian breast cancer and breast-ovarian cancer families of French ancestry. The presence of a breast cancer case diagnosed at younger than 36 years of age was strongly predictive of the presence of any founder mutation screened. Here we report the occurrence of founder BRCA1 and BRCA2 mutations in a series of 61 French Canadian women with invasive breast cancer diagnosed at age 40 or younger, unselected for family history of breast and ovarian cancer. Germline mutations in BRCA1 (n = 4) and BRCA2 (n = 4) were identified in 8 of 61 (13%) cases. All BRCA1 mutations were found in invasive ductal carcinomas, the most common histologic type of tumor in this series. In contrast, the BRCA2 mutations were found in tumors of various histologic types: two ductal carcinomas, a tumor containing both ductal and lobular histologic types and an invasive lobular carcinoma. Of the 37 women with at least one first-, second- or third-degree relative with breast or ovarian cancer and the 24 women with no history of these cancers, 7 (19%) and 1 (4%), respectively, were mutation carriers. The seven mutation carriers with a family history of cancer had at least one first-, second- or third-degree relative with a breast cancer diagnosis at less than 51 years of age. The identification of founder BRCA1 and BRCA2 mutations in young-onset breast cancer cases unselected for family history can facilitate carrier detection when the expected yield of a comprehensive screen may be low.

Partial Left Ventriculectomy: The 2nd International Registry Report 2000

Abstract: Background: Partial left ventriculectomy (PLV) has been performed without standardized inclusion or exclusion criteria. Methods: An international registry of PLV was expanded, updated, and refined to include 287 nonischemic cases voluntarily reported from 48 hospitals in 11 countries. Results: Gender, age, ventricular dimension, etiology, ethnology, myocardial mass, operative variation, presence or absence of mitral regurgitation, and transplant indication had no effects on event-free survival, which was defined as absence of death or ventricular failure that required a ventricular assist device or listing for transplantation. Preoperative patient conditions, such as duration of symptoms (> 9 vs 12%; p = 0.001), and refractory decompensation that required emergency procedure (p < 0.001) were associated with reduced event-free survival. Five or more cases in each hospital led to significantly better outcomes then the initial four cases. Rescue procedures for 14 patients nonsignificantly improved patient survival (2-year survival 52%) over event-free survival (2-year survival 48%; p = 0.49), with improved NYHA class among survivors (3.6 to 1.8; p < 0.001). Outcome was better in 1999 then in all series before 1999 (p = 0.02) most likely due to patient selection, which was refined to avoid known risk factors such as reduced proportion of patients in NYHA Class IV, FS < 5%, and hospitals with experience in 10 or less cases. A combination of these risk factors could have stratified 17 high-risk patients with 0% 1-year survival and 26 low-risk patients with 75% 2-year event-free survival. Conclusion: Avoidance of risk factors appears to improve survival and might help stratify high- or low-risk patients. Although less symptomatic patients with preserved contractility had better results after PLV, change of indication requires prospective randomized comparison with medical therapies or other approaches.

Anticoagulant therapy for osteonecrosis associated with heritable hypofibrinolysis and thrombophilia.

Abstract: Osteonecrosis develops as the end-result of reduced blood flow to the femoral head. We postulate that venous thrombosis leads to increased intraosseus venous pressure, reduced arterial flow and hypoxic bone death. Hypofibrinolysis (reduced ability to lyse thrombi) and thrombophilia (increased tendency to form thrombi) appear to play an important role in osteonecrosis. If coagulation disorders cause osteonecrosis, then anticoagulation might ameliorate osteonecrosis. In subjects with coagulation disorders and osteonecrosis of the hip, provided that anticoagulant therapy is started before irreversible segmental collapse of the head of the femur, osteonecrosis may be arrested or, speculatively, sometimes reversed. This has the potential of preventing femoral head collapse which usually leads to total hip replacement.

Interaction of heritable and estrogen-induced thrombophilia: possible etiologies for ischemic optic neuropathy and ischemic stroke.

Abstract: Our specific aim was to assess how thrombophilic exogenous estrogens interacted with heritable thrombophilias leading to nonarteritic ischemic optic neuropathy (NAION) and ischemic stroke. Coagulation measures were performed in a 74 year old patient and her immediate family. The proband had a 47 year history of 9 previous thrombotic episodes, and developed unilateral NAION 4 years after starting estrogen replacement therapy (ERT). The proband was heterozygous for two thrombophilic gene mutations (G20210A prothrombin gene, platelet glycoprotein IIIa PlA1/A2 polymorphism), and homozygous for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Of 238 normal controls, none had these 3 gene mutations together. The proband’s mother and brother had deep venous thrombosis (DVT). The proband’s brother, sister, nephew, daughter, and two granddaughters were homozygous for the C677T MTHFR mutation. The proband’s brother was heterozygous for the G20210A prothrombin gene mutation. The proband’s niece was heterozygous for the G20210A prothrombin gene mutation, homozygous for the C677T MTHFR mutation, homozygous for the hypofibrinolytic 4G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene, and heterozygous for the platelet glycoprotein IIIa PlA1/A2 polymorphism. Of 238 normal controls, none had the niece’s combination of 4 gene mutations. When ERT-mediated thrombophilia was superimposed on the proband’s heritable thrombophilias, unilateral ischemic optic neuropathy developed, her tenth thrombotic event over a 5 decade period. When estrogenprogestin oral contraceptives were given to the proband’s niece, she had an ischemic stroke at age 22. Exogenous estrogen-mediated thrombophilia superimposed on heritable thrombophilia and hypofibrinolysis is associated with arterial and venous thrombi, and appears to be a preventable, and potentially reversible etiology for ischemic optic neuropathy and ischemic stroke.

Double dose-intensive chemotherapy with autologous stem cell support for relapsed and refractory testicular cancer: the University of Michigan experience and literature review.

Abstract: Testicular cancer patients refractory or in relapse after primary chemotherapy have < or =25% 5-year progression-free survival with salvage. To improve prognosis, patients entered a phase I/II tandem dose-escalation trial of carboplatin (1500-2100 mg/m(2)) and etoposide (1200-2250 mg/m(2)) with ABMT. Patients were eligible for a second cycle if disease progression was absent and performance status allowed. From August 1990 to June 1998, 29 males (25 NSGCT) were treated. At the time of ABMT, 10 were chemosensitive, four were chemoresistant, and 10 were absolutely refractory to platinum. Disease status (no. patients) at transplant: primary refractory disease (six), first relapse (10), second relapse (eight), third relapse (five). Fifteen (52%) received both transplants. Treatment-related mortality was 10%. Best response after ABMT included: two CR, one CR surgically NED, five PR, three PR surgically NED, seven SD, and eight PD. Eight (28%) patients are continuously progression-free a median 60 months (range, 31-93) from first ABMT. Three seminoma patients remain progression-free. Of five long-term NSGCT survivors, four were treated in first relapse with platinum-sensitive disease. Eighteen relapses occurred a median of 4 months after ABMT I (two late relapses at 28 and 44 months). The median PFS and OS for the whole group are 4 and 14 months, respectively. Patients with relapsed/ refractory testicular cancer benefit most from ABMT if they have platinum-sensitive disease in first relapse. Patients who do poorly despite ABMT have a mediastinal primary site, true cisplatin-refractory disease, disease progression prior to ABMT, and/or markedly elevated betaHCG at ABMT. New treatment modalities are needed for the latter group.

Chlamydia pneumoniae in atherosclerotic carotid artery plaques: high prevalence among heavy smokers.

Abstract: This study was designed to determine the prevalence of Chlamydia pneumoniae in carotid artery plaques. Although there have been numerous studies evaluating coronary plaques for this bacterium fewer studies have assessed noncoronary vasculature. In addition we wished to evaluate whether correlation exists between the presence of C. pneumoniae in carotid plaques and established risk factors for atherosclerosis. Sixty intact carotid artery plaques removed during surgery (carotid endarterectomy) were formalin-fixed and paraffin-embedded according to conventional techniques. These samples were evaluated by polymerase chain reaction analysis to detect presence of C. pneumoniae DNA. Results were tabulated and compared against established risk factors for atherosclerosis: diabetes, hypertension, hyperlipidemia, age, and smoking. Forty-two (70.0%) of the 60 plaques that were evaluated tested positive for the presence of C. pneumoniae DNA by polymerase chain reaction analysis. In the sample defined as being from heavy smokers (greater than 15-pack-year history) 33 (94.3%) of 35 plaques tested positive whereas two (5.7%) tested negative. This correlation demonstrated statistical significance (p = 1.36 x 10 -6 , two-tailed Fisher exact test). Presence of C. pneumoniae in carotid plaques demonstrated no statistically significant correlation with diabetes, hypertension, or hyperlipidemia. Age as a risk factor was examined but not statistically evaluated because of the narrow range within our patient sample. Analysis of the data reveals that C. pneumoniae is present in large numbers of atheromatous plaques as is consistent with emerging data. What is interesting though is that 33 (94.3%) of the 35 smokers had plaques that tested positive for the bacterium as opposed to only nine (36.0%) of the 25 nonsmokers. Identification of specific populations exhibiting a high prevalence of C. pneumoniae may serve to focus future studies. Ongoing investigation will seek to determine whether C. pneumoniae plays an active role in the pathogenesis of atherosclerosis.

Interaction of estrogen replacement therapy with the thrombophilic 20210 G/A prothrombin gene mutation for atherothrombotic vascular disease: a cross-sectional study of 275 hyperlipidemic women.

Abstract: In a consecutive case series, cross-sectional study of 275 women referred for therapy of hyperlipidemia, (75 [27%] on estrogen replacement therapy [ERT]), our specific aim was to determine whether ERT-mediated thrombophilia and heterozygosity for the thrombophilic 20210 G/A prothrombin gene mutation interacted as risk factors for atherothrombotic cardiovascular disease (ATCVD). Of the 275 women, 100 (36%) had ATCVD; 10 (3.6%) were heterozygous for the 20210 G/A prothrombin gene mutation. In women without the 20210 G/A prothrombin gene mutation, 15 of 71 (21%) on ERT had ATCVD versus 78 of 194 (40%) not on ERT (X 2 = 8.31, P = .004). By stepwise logistic regression, in 261 women with ATCVD risk factor data, positive explanatory variables for ATCVD included the 20210 G/A prothrombin mutation (risk odds ratio, 5.8; 95% confidence intervals [CI], 1.4 to 30.2; P = .021) and a 20210 G/A prothrombin gene mutation*ERT interaction term (risk odds ratio, 2.70; 95% CI, 1.4 to 5.4; P = .004). ATCVD events were more likely in 2 subgroups of women (ERT minus [−] and 20210 G/A prothrombin gene mutation −) or (ERT plus [+] and 20210 G/A prothrombin gene mutation +), P = .004. Other positive explanatory variables for ATCVD events included age ( P = .004), triglycerides ( P = .012), lipoprotein (a) ( P = .03), and homocysteine ( P = .032). ERT may be protective against ATCVD when the thrombophilic 20210 G/A prothrombin gene mutation is absent, whereas the 20210 G/A prothrombin gene mutation may increase risk for ATCVD, particularly in the presence of ERT. We suggest that the 20210 G/A prothrombin gene mutation be measured in all women on ERT or before beginning ERT to identify those heterozygous for the thrombophilic prothrombin gene mutation (4%) in whom ERT is contraindicated because of increased risk for ATCVD and thromboembolism, and a second, much larger group of women without the 20210 G/A prothrombin gene mutation (96%) in whom ERT may possibly reduce risk for ATCVD.

The advantages of the Harmonic Scalpel for the harvesting of radial arteries for coronary artery bypass.

Abstract: Background Improvements in replacement vessel harvesting techniques and antispasmodic agents since the 1970s have led to a resurgence of interest in the radial artery (RA) as a conduit for coronary revascularization. Methods This randomized study compared the Ultra Cision Harmonic Scalpel (HS) (Ethicon Endo-Surgery, Inc., Cincinnati, OH) and the cold steel scalpel (CSS) for harvesting radial arteries to be used in coronary artery bypass grafting (CABG) procedures. Men and non-pregnant women, aged 21 to 79 years, with myocardial ischemia or coronary stenosis who were scheduled to undergo coronary bypass were enrolled in the study. Results Harvesting of the radial artery by the Harmonic Scalpel required a significantly lower number of clips to control bleeding. There was no significant difference between the times required to harvest the artery with either device. There were no complications, malfunctions, or serious adverse events associated with the use of either device. Conclusions The Harmonic Scalpel provides excellent control of bleeding compared to the cold steel scalpel, and its use permits bleeding to be controlled without the need for potentially damaging electrocautery. No clinically significant adverse events were associated with the use of the Harmonic Scalpel.

Pediatric Lung Transplantation: Families’ Need for Understanding

Abstract: Fifteen parents of 12 children who had undergone lung transplantation described their relationships with others, such as members of their extended family, coworkers, and friends prior to, during, and following the transplantation. We conducted a content analysis to formulate a narrative description of the parents’ relationships with others. The parents described their relationships in terms of the support they received from them. Some parents described diminishing support in the posttransplantation period, which they attributed, in part, to a lack of understanding. This finding may reflect the influence that living with a physical condition with long-term consequences, such as lung transplantation, may have on some interpersonal relationships. Pediatric lung transplantation is an increasingly common treatment regimen for children with end-stage lung or pulmonary vascular disease. Promoting understanding of what it is like to live with a lung transplantation may help to maintain support for these families.

The Use of Autogenous Bone Grafting to Reconstruct a Mandibular Knife Edge Ridge Before Implant Surgery: A Case Report

Abstract: Patients can present some anatomic limitations that prevent ideal implant placement, and it might be necessary to reconstruct the alveolar ridge. Intraoral autogenous bone grafts are the ideal source for the reconstruction of small deficiencies. Mandibular symphysis or mandibular ramus area (or both) may be used for bone harvesting. Use of intraoral sites has many advantages compared with the use of extraoral sites.

Application of data mining for examining polypharmacy and adverse effects in cardiology patients.

Abstract: This article comments upon the use of data mining tools to examine clinical data. Many cardiovascular patients have co-morbid diseases that put them at risk for polypharmacy, or severe adverse reactions from the interactions of multiple medications. Clinical trials typically use too few patients with stringent inclusion/exclusion criteria that prevent an examination of the issue of polypharmacy. However, clinical data collected in the course of patient treatment can be used in conjunction with data mining to find meaningful results.

Estrogen Replacement in a Protein S Deficient Patient Leads to Diarrhea, Hyperglucagonemia, and Osteonecrosis

Abstract: Context Protein S deficiency and mesenteric venous thrombosis have been described in association with ischemic and/or necrotic bowel. Thrombophilic familial protein S deficiency is known to be amplified by estrogen replacement therapy. Pancreatic ischemia studies have revealed elevated amylase and lipase levels but not hyperglucagonemia. We postulate that estrogen replacement therapy leading to mesenteric and pancreatic ischemia not only caused symptoms of ischemic bowel, but also pancreatic oversecretion of glucagon in a patient with protein S deficiency. Our specific aim was to assess thrombophilic interactions of estrogen replacement therapy and familial protein S deficiency leading to osteonecrosis, hyperglucagonemia, and diarrhea. Case Report Premarin (2.5 mg/day) was begun following bilateral oophrectomy at age 37. At age 56, hip replacement was done for osteonecrosis of the femoral head. Subsequently, severe epigastric pain and diarrhea developed, which persisted despite conservative measures. iagnostic evaluation revealed hyperglucagonemia (1420 pg/mL). Although abdominal sonograms, CT scans, and endoscopy failed to document a glucagon-secreting tumor, octreotide (50 μg/day) was begun. Normalization of glucagon levels and improvement of abdominal pain was achieved; diarrhea (5-6 episodes/day) persisted. Serologic and genetic testing revealed thrombophilic familial protein S. After stopping estrogen replacement therapy and octreotide, diarrhea and abdominal pain disappeared, glucagon remained normal (normal after 30 months follow-up), and free and functional protein S remained low. Conclusions Estrogen induced reduction of protein S, superimposed on familial protein S deficiency, led to osteonecrosis and then, speculatively, to thrombotic mesenteric and pancreatic ischemia with resultant diarrhea, abdominal pain, and hyperglucagonemia. Diarrhea, abdominal pain, and yperglucagonemia normalized when estrogen was discontinued, and have remained normal over 30 months follow-up.

Anesthetic and Perioperative Considerations in Patients Undergoing Placement of Totally Implantable Replacement Hearts

Abstract: The recent successful implantation of the AbioCor im plantable replacement heart at the Rudd Heart-Lung Institute, Jewish Hospital, Louisville, KY, has renewed clinical interest in the use of the mechanical replace ment heart as therapy for intractable heart failure Al though the number of orthotopic heart transplants has plateaued in the past decade, the number of patients requiring transplantation continues to increase This supply/demand discrepancy continues to be the main catalyst for the research and development of other therapies for the failing heart This review addresses perioperative considerations, monitoring modalities, and perioperative therapeutic interventions that may help guide the cardiac anesthesiologist through the challenges presented by implantation of total replace ment hearts in end-stage cardiac patients

Take the wind out of asthma.

Abstract: Learn how to take a team approach to managing your patient's asthma. Strategies focus on preventing acute attacks, relieving acute attacks when they occur, and preventing complications.