COMPANY: Crown Laboratories, Inc. provides pharmaceutical and ethical OTC products to the medical marketplace. Crown competes in the $3 billion world pharmaceutical industry. Crown markets its products under the names of Del-Ray Dermatologicals and Med-Derm Pharmaceuticals. Crown also provides contract manufacturing to the pharmaceutical industry. MISSION STATEMENT: To continue to b
Sasg.cnof the resistance arteries decrease with age.3 It has The Authors Reply: We agree with Duran and
been suggested that endothelium-dependent dila- Taffet that coronary microvascular function chang- tation of the resistance coronary arteries evoked by es significantly with aging. Indeed, we stated, acetylcholine may decrease with age in humans.4 “In healthy persons, however, coronary flow re- The mechanisms underlying the age-associat- serve varies according to age and sex. Therefore, ed reduction in the ability of the coronary micro- it is essential to compare data on coronary flow vasculature to dilate in response to acetylcholine reserve in patients with data obtained in age- are controversial. With advancing age, nitrous matched and sex-matched control subjects.” Using oxide–dependent mechanical and agonist-medi- positron-emission tomography, Uren et al.1 and ated endothelial vasodilatation is reduced in Chareonthaitawee et al.2 have shown that resting humans and animals.5 Coronary microvascular and hyperemic myocardial blood flow remain un- dysfunction due to aging should not be underes- changed in persons up to 60 years of age. After timated. Although pharmacologic treatment has 60 years of age, there is a significant increase in been shown to restore coronary blood reserve in resting myocardial blood flow, associated with endothelial dysfunction due to aging, its effect on an increase in systolic blood pressure. After 70 the clinical outcome remains to be determined. years of age, there is a significant reduction in J. Roberto Duran III, M.D. hyperemic myocardial blood flow and in coronary flow reserve. There are probably multiple causes of these age-related changes, and they remain in- 1. Camici PG, Crea F. Coronary microvascular dysfunction.
2. Lakatta EG, Yin FCP. Myocardial aging: functional alterations London W12 0NN, United Kingdom
and related cellular mechanisms. Am J Physiol 1982;242:H927- firstname.lastname@example.org H941.
3. Toma BS, Wangler RD, DeWitt DF, Sparks HV Jr. Effect of Filippo Crea, M.D.
development on coronary vasodilator reserve in the isolated guinea Catholic University 4. Egashira K, Inou T, Hirooka Y, et al. Effects of age on endo-
thelium-dependent vasodilation of resistance coronary artery by 1. Uren NG, Camici PG, Melin JA, et al. Effect of aging on myo-
acetylcholine in humans. Circulation 1993;88:77-81.
cardial perfusion reserve. J Nucl Med 1995;36:2032-6.
5. Csiszar A, Ungvari Z, Edwards JG, et al. Aging-induced pheno-
2. Chareonthaitawee P, Kaufmann PA, Rimoldi O, Camici PG.
typic changes and oxidative stress impair coronary arteriolar Heterogeneity of resting and hyperemic myocardial blood flow in healthy humans. Cardiovasc Res 2001;50:151-61.
To the Editor: In his review of perioperative tension was more likely after regional anesthesia.
stroke, Selim (Feb. 15 issue)1 states that regional The differences that have been identified may not anesthesia may pose less risk of perioperative have a great clinical impact and require further complications than general anesthesia and that study.
“isoflurane and thiopentone may provide neuro- Turner et al.3 reviewed the literature on agents protection.” However, the references that he cites2,3 for induction of general anesthesia and conclude do not provide support for these contentions. that thiopental, propofol, and etomidate have Breen and Park’s2 review of the literature showed similar effects on intracranial pressure, cerebral that no conclusions could be drawn about the blood flow, and cerebral oxygen consumption, risk of stroke associated with general as compared so the selection of an agent should be based on with regional anesthesia for carotid endarterec- other considerations. They did not discuss isoflu- tomy. In fact, the results of the randomized tri- rane. The most one can conclude from the extant als reviewed indicated that postoperative hypo- literature is that there are a number of hypotheses n engl j med 356;22 www.nejm.org may 31, 2007 Downloaded from www.nejm.org on July 25, 2007 . Copyright 2007 Massachusetts Medical Society. All rights T h e n e w e ng l a n d j o u r na l o f m e dic i n e to test with robust methods before clinical recom- tion in 160 consecutive high-risk patients (mean age, 66 years) who were scheduled for surgery with dynamic magnetic resonance angiography and flow analysis. Unsuspected hypoplastic ver- tebral-artery flow of less than 50 ml per second Milwaukee, WI 53226-3596 email@example.com was present in 40 patients (25%). Reduced basilar- artery flow was noted with increased microinfarc- 1. Selim M. Perioperative stroke. N Engl J Med 2007;356:706-13.
tions on magnetic resonance imaging (77% vs. 2. Breen P, Park KW. General anesthesia versus regional anes-
38% in patients with normal basilar-artery flow). thesia. Int Anesthesiol Clin 2002;40:61-71.
3. Turner BK, Wakim JH, Secrest J, Zachary R. Neuroprotective Patients with unsuspected carotid occlusion (six
effects of thiopental, propofol, and etomidate. AANA J 2005;73: patients) and those with vertebral-artery occlusion (two patients) also had reduced basilar-artery flow.
Carotid ultrasonography, although less costly, To the Editor: Selim emphasizes that atrial fi- is also less accurate, with incomplete imaging of
brillation is an important cause of perioperative the vertebral arteries. Flow velocities and vessel stroke, and he outlines its predictors. The current diameters tend to be lower on the right side, with literature, however, does not provide support for lower net flow volume, and they are significantly including high magnesium levels among the risk lower in women than in men.3 Ultrasonography factors for postoperative atrial fibrillation, as Selim is 80% as accurate as angiography in detecting does in Table 5 of his review. In fact, magnesium vertebral-artery size and only 90% as accurate in supplementation has been shown to have varying determining the direction of flow.4 degrees of benefit in reducing the incidence of Michael I. Weintraub, M.D.
postoperative atrial fibrillation.1-4 Selim notes that New York Medical College beta-blockers and amiodarone are effective as pro- Valhalla, NY 10595 phylaxis against the development of postopera- firstname.lastname@example.org tive atrial fibrillation. Magnesium supplementa- Andre Khoury, M.D.
White Plains Hospital White Plains, NY 10601 Amitabh Parashar, M.D.
Carilion Clinic 1. Weintraub MI, Khoury A. Cerebral hemodynamic changes
induced by simulated tracheal intubation: a possible role in peri- operative stroke? Magnetic resonance angiography and flow analysis in 160 cases. Stroke 1998;29:1644-9.
1. Burgess DC, Kilborn MJ, Keech AC. Interventions for preven-
2. Idem. Critical neck positioning as an independent risk factor
tion of post-operative atrial fibrillation and its complications after for posterior circulation stroke: a magnetic resonance angio- cardiac surgery: a meta-analysis. Eur Heart J 2006;27:2846-57.
graphic analysis. J Neuroimaging 1995;5:16-22.
2. Mitchell LB. Prophylactic therapy to prevent atrial arrhyth-
3. Seidel E, Eicke BM, Tettenborn B, Krummenauer F. Reference
mia after cardiac surgery. Curr Opin Cardiol 2007;22:18-24.
values for vertebral artery flow volume by duplex sonography in 3. Henyan NN, Gillespie EL, White CM, Kluger J, Coleman CI. young and elderly adults. Stroke 1999;30:2692-6.
Impact of intravenous magnesium on post-cardiothoracic surgery 4. Davis PC, Nilsen B, Braun IF, Hoffman JC. A prospective
atrial fibrillation and length of hospital stay: a meta-analysis. comparison of duplex sonography vs. angiography of the verte- bral arteries. AJNR Am J Neuroradiol 1986;7:1059-64.
4. Naito Y, Nakajima M, Inoue H, Hibino N, Mizutami E,
Tsuchiya K. Prophylactic effect of magnesium infusion against postoperative atrial fibrillation. Kyobu Geka 2006;59:793-7. (In The Author Replies: When I chose the refer-
ences for this review, my intent was not to high- light the specific results of a particular study but To the Editor: With regard to the article by Se- rather to direct the reader to a balanced discus-
lim, the unique anatomy of the vertebral arteries sion of the topic, given the limited space for the and their vulnerability to mechanical compression article. With regard to local as compared with at the atlantoaxial and atlanto-occipital junction general anesthesia, various studies have had mixed during neck angulation and hyperextension consti- results. A Cochrane meta-analysis of 41 nonran- tute an overlooked cause of perioperative stroke.1,2 domized and 7 small randomized studies showed We designed a study to simulate tracheal intuba- that the use of local anesthesia was associated n engl j med 356;22 www.nejm.org may 31, 2007 Downloaded from www.nejm.org on July 25, 2007 . Copyright 2007 Massachusetts Medical Society. All rights with significant reductions in the odds of death appropriate to point to “disturbances of serum and stroke within 30 days after carotid surgery in magnesium” instead of high magnesium levels. the nonrandomized studies.1 In the randomized He also correctly suggests that magnesium sup- studies, the use of local anesthesia was associated plementation may be beneficial in reducing the with a significant reduction in hemorrhagic com- incidence of atrial fibrillation. The effects of mag- plications, but there was insufficient evidence of nesium seem to be independent of serum magne- a reduction in perioperative stroke. Therefore, my sium concentrations, and they are probably medi- statement that “regional anesthesia is less likely ated through its direct effects on sinoatrial-node than general anesthesia to result in perioperative conduction. Most guidelines for the management complications” is not inconsistent with the liter- of postoperative atrial fibrillation provide level A evidence of the efficacy of beta-blockers and amio- Kettler points to postoperative hypotension as darone, in contrast to level B evidence for mag- a complication of regional anesthesia. I reiterate nesium.5 that most perioperative strokes are embolic. Hypo- Finally, I thank Weintraub and Khoury for perfusion is responsible for only a small number sharing their findings on the pathophysiological of such strokes. Regional anesthesia facilitates basis of some perioperative strokes.
neurologic assessments during surgery, thus per- Magdy Selim, M.D., Ph.D.
mitting timely detection and treatment of stroke, Beth Israel Deaconess Medical Center and it is associated with less blood loss and Boston, MA 02215 shorter hospital stays,2 thereby decreasing post- email@example.com operative thromboembolic complications. A quick 1. Rerkasem K, Bond R, Rothwell PM. Local versus general
literature search (www.pubmed.com) shows sev- anaesthesia for carotid endarterectomy. Cochrane Database Syst eral reports that provide support for the neuro- Rev 2004;2:CD000126.
2. Mofidi R, Nimmo AF, Moores C, Murie JA, Chalmers RT.
protective properties of isoflurane,3 but I concur Regional versus general anaesthesia for carotid endarterectomy: that the choice of the anesthetic agent should not impact of change in practice. Surgeon 2006;4:158-62.
be based solely on its putative neuroprotective 3. Zheng S, Zuo Z. Isoflurane preconditioning induces neuro-
protection against ischemia via activation of P38 mitogen-acti- vated protein kinases. Mol Pharmacol 2004;65:1172-80.
Parashar questions whether a high level of mag- 4. Parikka H, Toivonen L, Pellinen T, Verkkala K, Jarvinen A,
nesium is a risk factor for postoperative atrial fi- Nieminen MS. The influence of intravenous magnesium sulphate on the occurrence of atrial fibrillation after coronary artery by-pass brillation. Although several studies suggest that operation. Eur Heart J 1993;14:251-8.
hypomagnesemia is associated with postoperative 5. Dunning J, Treasure T, Versteegh M, Nashef SA, EACTS Audit
atrial fibrillation, there are conflicting data in the and Guidelines Committee. Guidelines on the prevention and management of de novo atrial fibrillation after cardiac and tho- literature.4 Therefore, it would have been more racic surgery. Eur J Cardiothorac Surg 2006;30:852-72.
Medical Mystery: Skin Discolorations — The Answer
To the Editor: The medical mystery in the April 5 and microanalysis with x-rays showed that some of
issue1 involved a 34-year-old bank employee who the bills the patient had been counting (Fig. 1D) presented with black discolorations of the skin were prepared with a combination of silver nitrate (Fig. 1A) on all her fingers. The discolorations had and petroleum jelly, a method often used to find developed in the evening after work. A skin-biopsy a thief. Silver nitrate diffuses into the epidermis specimen of the black spots revealed brownish and reacts with chloride from sweat to form silver deposits of elemental silver in the corneal layer chloride, which is photochemically reduced by ul- (Fig. 1B), with a fluorescent aspect on the dark- traviolet light to form colloidal particles of me- field microscopical examination (Fig. 1C), which is tallic silver; these appear black and persist in the typical of elemental silver. Infrared spectroscopy epidermis. An advantage of this method of trap- n engl j med 356;22 www.nejm.org may 31, 2007 Downloaded from www.nejm.org on July 25, 2007 . Copyright 2007 Massachusetts Medical Society. All rights
SPARC 2004 The Doped Vanadium Oxides Prepared by Liquid Injection MOCVD Atmospheric pressure liquid injection MOCVD was used for the deposition of tungsten doped vanadium (IV) oxide coatings. The deposition was carried out on commercial SiO2-precoated glass using 0.1 M solution of vanadyl acetylacetonate (VO(acac)2) in methanol (CH3OH) at 0.02 L min-1 and 0.04 L min-1 oxygen flo