David Rott

Effects of MF-tricyclic, a selective cyclooxygenase-2 inhibitor, on atherosclerosis progression and susceptibility to cytomegalovirus replication in apolipoprotein-E knockout mice ☆

OBJECTIVES We examined whether selective cyclooxygenase-2 (COX-2) inhibition in apolipoprotein-E (apoE) deficient mice reduces cytomegalovirus (CMV) replication, and determined whether COX-2 anti-inflammatory activity leads to decreased atherosclerosis. BACKGROUND Evidence suggests that CMV infection contributes to atherosclerosis and that this occurs in part through inflammatory mechanisms. Cyclooxygenase-2 inhibitors are potent anti-inflammatory agents. They also inhibit CMV replication in vitro. METHODS The apoE deficient mice were either treated or not treated with a selective COX-2 inhibitor, and either infected or not infected with CMV. Viral deoxyribonucleic acid load in salivary glands was determined by quantitative polymerase chain reaction. Atherosclerotic lesion analysis was performed by standard methods. RESULTS In vivo COX-2 inhibition, unexpectedly increased viral load: in the CMV-infected animals viral load was 2.58 +/- 1.0 in the nontreated group, 4.74 +/- 1.38 in the group treated with 12 mg/kg/day MF-tricyclic, and 6.51 +/- 1.64 in the group treated with 24 mg/kg/day MF-tricyclic (p trend = 0.050). This increased viral load was paralleled by increased anti-CMV antibody titers. Most surprisingly, COX-2 inhibition significantly increased early atherosclerotic lesion area, independent of viral infection. CONCLUSIONS Our study demonstrates that selective inhibition of COX-2 in vivo increases viral load. The finding that inhibition of COX-2 increases atherosclerosis development in apoE deficient mice suggests, unexpectedly, that this enzyme exerts antiatherosclerosis activity, at least in this model.

Brain Natriuretic Peptide Levels Predict Perioperative Events in Cardiac Patients Undergoing Noncardiac Surgery: A Prospective Study

Objectives: Brain natriuretic peptide (BNP) levels correlate with prognosis in patients with cardiac disease and may be useful in the risk stratification of cardiac patients undergoing noncardiac surgery (NCS). The objective of this study was to examine whether BNP levels predict perioperative events in cardiac patients undergoing NCS. Methods: Patients undergoing NCS with at least 1 of the following criteria were included: a clinical history of congestive heart failure (CHF), ejection fraction <40%, or severe aortic stenosis. All patients underwent echocardiography and measurement of BNP performed using the ADVIA-Centaur BNP assay (Bayer HealthCare). Clinical endpoints were death, myocardial infarction or pulmonary congestion requiring intravenous diuretics at 30 days of follow-up. Results: Forty-four patients were entered into the study; 15 patients (34%) developed cardiac postoperative complications. The mean BNP level was 1,366 ± 1,420 pg/ml in patients with events and 167 ± 194 pg/ml in patients without events, indicating a highly significant difference (p < 0.001). The ROC area under the curve was 0.91 (95% CI 0.83–0.99) with an optimal cutoff of >165 pg/ml (100% sensitivity, 70% specificity). Conclusions: BNP levels may predict perioperative complications in cardiac patients undergoing NCS, and the measurement of BNP should be considered to assess the preoperative cardiac risk.

Effects of acute metabolic stress on the peripheral vasopressinergic system in schizophrenia

Although both vasopressin and stress have been implicated in the course of schizophrenia, it is unknown whether schizophrenic patients have altered stress-induced function of the vasopressinergic system. We examined the effects of acute metabolic stress induced by pharmacological doses (40 mg/kg) of 2-deoxyglucose (2DG) on plasma concentrations of vasopressin in 13 patients with schizophrenia (with no history of polydipsia and hyponatremia) and 12 healthy control subjects. Baseline vasopressin levels were lower in the schizophrenic patients and progressively increased in both groups throughout the 60 min following 2DG administration to a similar absolute amount, thus remaining lower in the schizophrenic group. Concomitantly, patients with schizophrenia had significantly higher 2DG-induced plasma homovanillic acid (HVA) and 5-hydroxyindoleacetic acid levels. Vasopressin responses correlated positively and significantly with the HVA responses in schizophrenics and with the pituitary-adrenal axis responses in controls. These results suggest two different patterns of neuroendocrine alterations in schizophrenia, namely a relatively normal vasopressin response to 2DG despite significantly decreased baseline levels and exaggerated responses of the peripheral dopaminegic and serotonergic systems in the face of normal baseline concentrations.

The incidence and haemodynamic significance of gas emboli during operative hysteroscopy: a prospective echocardiographic study

AIMS Operative hysteroscopy is associated with complications including the development of gas embolism. The aim of this study was to utilize continuous echocardiographic imaging during operative hysteroscopy to assess the extent and the haemodynamic effects of gas embolism in these patients. METHODS AND RESULTS Women undergoing operative hysteroscopy under general anaesthesia without a history of cardiac disease were eligible. Transthoracic echocardiography (TTE) was performed continuously in all study participants with assessment of the extent and frequency of gas embolism, right ventricular function and pulmonary hypertension. Twenty-three women (mean age: 48.0 +/- 9.4 years) participated in the study. All subjects had evidence of bubble embolism in the right atrium (RA) and 20 of 23 (85%) had evidence of continuous flow of bubbles. In the 17 patients with adequate assessment, estimated pulmonary artery systolic pressure was 19.1 +/- 3.7 mmHg prior to the procedure and 23.3 +/- 3.4 following the procedure, a statistically significant difference (P < 0.05). There were no significant changes between the two groups in right ventricular end-diastolic area, end-systolic area, or fractional area change. CONCLUSION Our study demonstrates a high frequency of continuous gas embolism during hysteroscopy, which is associated with a small but statistically significant increase in pulmonary artery systolic pressure without affecting right ventricular function.

Seasonal Variation in Myocardial Infarction Is Limited to Patients with ST‐Elevations on Admission

Previous studies have demonstrated seasonal variation in the incidence of acute myocardial infarction (AMI) with an increase in cases during the winter months. However, they did not assess whether ST‐elevation MI (STEMI) and non‐ST‐elevation MI (NSTEMI) exhibit similar changes. The object of this study was to compare the seasonal variation of STEMI and NSTEMI. All patients who presented with AMI and underwent coronary angiography within seven days of admission were identified via the institutional database. STEMI diagnosis required admission ECG demonstrating ST elevation in at least two continguous leads. All AMIs not meeting criteria for STEMI were defined as NSTEMI. Patients were divided into monthly and seasonal groups based on the date of admission with MI. A total of 784 patients were included: 549 patients with STEMI and 235 with NSTEMI. When STEMI patients were analyzed by season, there were 170 patients (31%) in the winter months, a statistically significant difference of excess MI (p<0.005). When NSTEMI patients were analyzed, there were 62 patients (26%) in the winter with no statistically significant difference in the seasonal variation. Our findings suggest that the previously noted seasonal variation in the incidence of AMI is limited to patients presenting with STEMI, and that there are important physiological differences between STEMI and NSTEMI, the nature of which remains to be elucidated.

The efficacy of cardiac shock wave therapy in the treatment of refractory angina: A pilot prospective, randomized, double-blind trial

Refractory angina pectoris (RAP) is a growing clinical problem [1]. Prognosis in these patients is poor and conventional medical therapy is frequently inadequate for symptom relief. The aim of this pilot prospective, double-blind, placebo-controlled study was to test the hypothesis that low-energy extracorporeal shockwave myocardial revascularization (ESMR) can reduce clinical symptoms and improve exercise tolerance in patients with RAP. Patients over the age of 18 with at least three months of RAP with ischemia on SPECT-thallium testing, coronary disease not amenable for revascularization, and stable medical therapy for at least 6 weeks were eligible for inclusion in the study. Patients who experienced an acute coronary syndrome or who underwent revascularization within three months were excluded. The study was approved by the institutional review board and informed consent was obtained from all participants prior to inclusion. All candidates underwent exercise testing and filled out a Seattle Angina Questionnaire (SAQ) within two weeks of beginning shock wave therapy. Patients were randomized in a 2:1 fashion to treatment with active therapy or placebo. Following ESMR therapy, exercise testing was repeated at one-month and threemonth follow-up. SAQ was repeated at 3-month follow-up. The primary study endpoints were change in exercise treadmill duration and SAQ score from baseline to three months. Shockwaves were applicated with a commercially available cardiac shock wave generator system (CardiospecTM, Medispec, Germantown, MD, USA) under echocardiographic guidance. The placebo patients were treated with a placebo applicator created by placing a shield internally which did not alter the external appearance of the applicator. Real shockwaves were generated and heard by the patient and treating physician but were blocked inside the applicator. The initial step of ESMR is to locate the ischemic region of interest after which, a full cardiac cycle is recorded with the echocardiography system. These measurements are calibrated into the shockwave applicator head to ensure the position of the focal treatment zone on the ischemic zone and shockwaves were then applied. The treatment schedule was divided into three sessions with three treatments per week every 4 weeks. The ischemic area of interest was divided into 3 zones, corresponding to the 3 weeks of treatments. SW application started at the border zone and then progressed to the interior zones. Each treatment for each target spot consisted of 100 pulses gated by R wave trigger. Up to 5 target spots (total of 500 pulses) were treated at each individual session. The authors of this manuscript certify that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. As data was not normally distributed, results are presented as medians±interquartile ranges. Differences between patient groups were analyzed using chi-square or Fishers exact tests for categorical variables and unpaired t-tests for normally distributed continuous variables with Kruskal–Wallis test for non-normally distributed continuous values. A p-value of b0.05 was considered statistically significant. 28 patients were included and clinical characteristics of the two groups are displayed in Table 1. There were no significant differences in any of the parameters examined. All patients tolerated the treatment well without any arrhythmias, chest pain or skin discomfort/reactions. One patient in the placebo group developedmild peripheral edema and one patient in the treatment group developed bradycardia on beta blocker therapy several weeks after completion of the treatment protocol and underwent pacemaker implantation. In the active treatment group (n=18) baseline exercise time rose from 394 (25–75% IQR 294.5–510.25) seconds at baseline to 423 (368–745) seconds at one-month follow-up and then fell to 381 (359– 639.5) seconds at three-month follow-up. Corresponding figures for the placebo group were 523.5 (363–573.25) seconds at baseline to 596 (511–636.5) seconds at one month follow-up and 554 (449.25– 624.75) seconds at three-month follow-up. The degree of physical limitation as assessed by the SAQ significantly improved in the treatment group as compared to placebo (34±23% versus 6±20%; pb0.04) (Table 2). The overall composite SAQ score including all 5 parameters improved by 19.1±18.6% in the treatment group as opposed to 2.7±15.1% in the placebo group, a difference that was close to statistical significance (pb0.07). The study demonstrates the potential efficacy of ESMR for the treatment of refractory angina pectoris in a prospective, randomized, and placebo-controlled double-blind trial. Previous studies have demonstrated that ESMR can induce the development of collateral arteries, increase capillary density and facilitate recruitment of endothelial progenitor cells in an animal model of hindlimb ischemia [2,3]. In animal models of myocardial ischemia ESMR reduced remodeling, and improved left ventricular systolic function as well as regional myocardial blood flow [4–6].

Carbon monoxide poisoning in Jerusalem: epidemiology and risk factors

Objectives. To describe the epidemiology of carbon monoxide (CO) poisoning in Jerusalem and identify risk factors for such poisoning. Design. A retrospective descriptive analysis of patients with CO poisoning who presented to the Hadassah hospitals in Jerusalem from 1994 to 2006. Patients. All patients with suspected CO poisoning were examined and those with confirmed cases [carboxyhemoglobin (COHb) level >5%] were included. Sources of exposure, seasonal variation, and demographic characteristics were analyzed. Results. There were 292 patients (49% males) with 40 family clusters that accounted for 149 patients (51%); 230 patients (79%) presented during the winter months. All but one had unintentional CO intoxication. The main sources of exposure were faulty gas heaters (n = 135), fire (n = 102), and other residential heating systems (n = 40). The estimated annual incidence of CO poisoning decreased from 6.45 per 100,000 in 1994–2000 to 3.53 per 100,000 in 2001–2006. High-risk intoxication (COHb level >25%) occurred in 84 patients (29%). Factors associated with severe intoxication were male gender, individual patients (compared with those in clusters), and faulty gas heaters (compared with other sources). Conclusions. Males exposed to CO may have a more severe intoxication. The lower risk in patients presenting in clusters could be explained by the assumption that severe presentation in one patient alerts the others who are less severely affected. The implementation of safer standards for residential heating systems and CO detectors together with the public education may explain the decline in the incidence of CO poisoning.

Optic nerve head drusen mimicking papilledema and malignant hypertension

A 41 years old manwith a history of mild hypertensionwas seen at an ophthalmology clinic for routine visual acuity testing. Fundoscopy revealed papilledema and the patient was referred to the emergency room. The patient was not taking any medications on a regular basis. In the emergency room the patient was anxious with a blood pressure of 160/100 mm Hg and a pulse of 75/min. He was afebrile, neck was supple, lungs were clear, heart sounds were normal and neurological exam was unremarkable. Fundoscopy confirmed the presence of papilledema. The patient was transferred to the intensive care unit with a provisional diagnosis of malignant hypertension. Treatment with IV nitroprusside was initiated but discontinued few minutes later due to a significant decrease in blood pressure. Treatment with captopril 12.5mg Q8hwas instituted. The next morning the patient was asymptomatic with a blood pressure of 120/80 mm Hg. The clinical picture of papilledema with only mildly elevated blood pressure that quickly responded to oral treatment put the provisional diagnosis of malignant hypertension in question and a head CT scan was ordered. The CT was unremarkable except for calcification of the optic nerves head bilaterally (Fig. 1), a finding typical of optic disc drusen. The diagnosis was changed accordingly and the patient was discharged.

Elevation of Cardiac Troponin T after Running Is Not Limited to Marathon Runners

A 40-year-old male was brought to the emergency room (ER) after an episode of syncope. The syncope occurred at the end of a 10-km running competition; the patient described a sensation of dizziness that was followed by fainting. He was unconscious for a few seconds and was brought to the hospital by a medical team. He received no specific treatment before arriving at the ER. The patient denied chest pain, shortness of breath or palpitations at any time during the race. The syncope occurred after the patient had finished the race, and no signs of epileptic activity were reported by the medical team. The patient was a healthy young man with no significant medical history. He had reported a similar episode a few months earlier, also following a race. The patient was not a professional athlete. He reported regular training runs of 10 km a few times a week over the last 6 months. He was not a smoker and denied consumption of alcohol or drugs. Upon arrival to the ER the patient was feeling well, with no complaints. His pulse was 87 beats/min, and his blood pressure

ST deviation pattern and infarct related artery in acute myocardial infarction.

Myocardial infarction (MI) may be classified as ST‐elevation MI (STEMI) or non‐ST‐elevation MI (NSTEMI). There is little data regarding the relationship between the infarct related artery (IRA), clinical characteristics of the patients, and the ST deviation pattern (ie, STEMI or NSTEMI).