Oren P. Schaefer

Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema.

BACKGROUND Hereditary angioedema due to C1 inhibitor deficiency is characterized by recurrent acute attacks of swelling that can be painful and sometimes life-threatening. METHODS We conducted two randomized trials to evaluate nanofiltered C1 inhibitor concentrate in the management of hereditary angioedema. The first study compared nanofiltered C1 inhibitor concentrate with placebo for treatment of an acute attack of angioedema. A total of 68 subjects (35 in the C1 inhibitor group and 33 in the placebo group) were given one or two intravenous injections of the study drug (1000 units each). The primary end point was the time to the onset of unequivocal relief. The second study was a crossover trial involving 22 subjects with hereditary angioedema that compared prophylactic twice-weekly injections of nanofiltered C1 inhibitor concentrate (1000 units) with placebo during two 12-week periods. The primary end point was the number of attacks of angioedema per period, with each subject acting as his or her own control. RESULTS In the first study, the median time to the onset of unequivocal relief from an attack was 2 hours in the subjects treated with C1 inhibitor concentrate but longer than 4 hours in those given placebo (P=0.02). In the second study, the number of attacks per 12-week period was 6.26 with C1 inhibitor concentrate given as prophylaxis, as compared with 12.73 with placebo (P<0.001); the subjects who received the C1 inhibitor concentrate also had significant reductions in both the severity and the duration of attacks, in the need for open-label rescue therapy, and in the total number of days with swelling. CONCLUSIONS In subjects with hereditary angioedema, nanofiltered C1 inhibitor concentrate shortened the duration of acute attacks. When used for prophylaxis, nanofiltered C1 inhibitor concentrate reduced the frequency of acute attacks. (Funded by Lev Pharmaceuticals; ClinicalTrials.gov numbers, NCT00289211, NCT01005888, NCT00438815, and NCT00462709.)

Tracheoarterial Fistula: An Unusual Complication of Tracheostomy

The tracheoarterial fistula is an unusual but devastating complication of tracheostomy. It occurs with a frequency of approximately 0.7%, and it is uniformly fatal if not recognized and surgically corrected. Mucosal damage from the tracheal cannula, pressure necrosis from high cuff pressure, or mucosal trauma from an improperly positioned cannula tip results in erosion through the tracheal wall into the vascular structures that lie in the pretracheal space. Bleeding from this complication almost always occurs late (> 48 hours postprocedure). It is often preceded by sentinel hemoptysis. A paucity of signs and symptoms that precede or are associated with this complication require a high index of clinical suspicion to make the diagnosis. In addition to bleeding, other potential clues include a low-lying tracheostomy tube, pulsation of the tracheostomy tube, and the presence of infection, hypotension, malnutrition, and corticosteroid use. Unfortunately, there are no consistently useful diagnostic tools for tracheoarterial fistula. Fiberoptic bronchoscopy and angiography have been performed with mixed results. Should no other cause be found to explain the hemorrhage from or around the tracheostomy, or from disease distal to the primary carina, the patient must be taken to the operating room for a more definitive examination and possible vascular repair. Management is divided into acute stabilization and support, with protection of the airway and restoration of circulating blood volume, followed by definitive repair should the patient survive. Measures to prevent tracheal damage by the tracheostomy tube, such as proper surgical technique and proper inflation of the tracheostomy tube cuff, may go a long way to avoid this potentially lethal complication. Early consideration of this entity may be what saves the life of its victim.

Linezolid-Associated Serotonin Syndrome After Concomitant Treatment With Citalopram and Mirtazepine in a Critically Ill Bone Marrow Transplant Recipient

Linezolid was initially discovered as an antidepressant because of its effect on blocking intracellular metabolism of serotonin, norepinephrine, and other biogenic amines. As time passed, it was realized that linezolid possessed antibacterial activity, and linezolid has been developed and marketed as such. In medicine we are quick to categorize drugs into specific classes as a mechanism to recall indication and use. By classifying linezolid as an antibacterial, it is common to forget about its antidepressant roots. A case report involving linezolid with citalopram and mirtazepine in the precipitation of serotonin syndrome in a critically ill bone marrow transplant patient is described in this article.

Unsuspected bacterial suppurative disease of the airways presenting as chronic cough

dependent Estrogen-mediated coronary relaxation after acute estrogen withdrawal. Circulation. 1994;90:1964 –1968. 15. Collins P, Rosano GMC, Sarrel PM, et al. 17 -estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease. Circulation. 1995;92:24 –30. 16. Rosano GMC, Sarrel PM, Poole-Wilson PA, Collins P. Beneficial effect of oestrogen on exercise-induced myocardial ischaemia in women with coronary artery disease. Lancet. 1993;342:133–136. 17. Moran VH, Leathard HL, Coley J. Cardiovascular functioning during the menstrual cycle. Clin Physiol. 2000;20:496 –504. 18. Cunningham FG, Gant NF, Leveno KJ, et al. The endometrium and decidua. Menstruation and pregnancy. In: Cunningham FG, Gant NF, Leveno KJ, et al., eds. Williams Obstetrics. New York, New York: McGraw-Hill; 2001:65-83. 19. Kawano H, Motoyama T, Ohgushi M, et al. Menstrual cyclic variation of myocardial ischemia in premenopausal women with variant angina. Ann Intern Med. 2001;135:977–981. 20. The North American Menopause Society. Normal physiology. In: Menopause Core Curriculum Study Guide. 2nd ed. Cleveland, Ohio: North American Menopause Society; 2002:15-20. 21. Polderman KH, Stehouwer CD, van Kamp GJ, et al. Modulation of plasma endothelin levels by the menstrual cycle. Metabolism. 2000; 49:648 –650. 22. Webb CM, Ghatei MA, McNeill JG, et al. 17beta-estradiol decreases endothelin-1 levels in the coronary circulation of postmenopausal women with coronary artery disease. Circulation. 2000;102:1617– 1622. 23. Wilcox JG, Hatch IE, Gentzschein E, et al. Endothelin levels decrease after oral and nonoral estrogen in postmenopausal women with increased cardiovascular risk factors. Fertil Steril. 1997;67: 273–277. 24. Dubey RK, Jackson EK, Keller PJ, et al. Estradiol metabolites inhibit endothelin synthesis by an estrogen receptor-independent mechanism. Hypertension. 2001;37:640 –644. 25. Rosselli M, Imthurm B, Macas E, et al. Circulating nitrite/nitrate levels increase with follicular development: indirect evidence for estradiol mediated no release. Biochem Biophys Res Commun. 1994; 202:1543–1552. 26. Kharitonov SA, Logan-Sinclair RB, Busset CM, Shinebourne EA. Peak expiratory nitric oxide differences in men and women: relation to the menstrual cycle. Br Heart J. 1994;72:243–245. 27. Lloyd GW, Patel NR, McGing E, et al. Does angina vary with the menstrual cycle in women with premenopausal coronary artery disease? Heart. 2000;84:189 –192.

Applicability of Prediction Rules in Patients With Community-Acquired Pneumonia Requiring Intensive Care: A Pilot Study

Little attention has been paid to developing prediction rules that could assist in deciding which patients with community-acquired pneumonia (CAP) need intensive care. Four existing prediction rules were examined to determine if any could predict the need for intensive care in these patients. The prediction rules studied were British Thoracic Society (BTS), Conte et al, Leroy et al, and Fine et al. Thirty-two patients admitted to the medical or coronary intensive care unit (ICU) during 1 year with pneumonia Diagnosis Related Group 079 or 089 were evaluated. The sensitivity of each rule for identifying a need for ICU admission in our group was BTS .72 using both rules together, Conte et al .47, Leroy et al .56, and Fine et al .84. It was concluded that these rules poorly identify the need for ICU admission for patients with severe CAP. Of the 4 rules tested, the BTS rule was the simplest, and the Fine et al rule was the most sensitive. None of them performed well enough to be used for decision making in individual patients.

Coronary artery bypass grafting and aortic valve replacement with cold cardioplegia in a patient with cold-induced urticaria

BACKGROUND Cold-induced urticaria is an uncommon but well described phenomenon in which a spectrum of responses may result from exposure to a cold stimulus. Patients with cold-induced urticaria who require cold cardiopulmonary bypass are at risk for hypotensive episodes. OBJECTIVE To describe the case of a 69-year-old man with documented cold-induced urticaria who required aortic valve replacement and coronary artery bypass surgery. METHODS After receiving a prophylactic anti-inflammatory regimen, the patient underwent cold cardiopulmonary bypass. After systemic cooling to 32 degrees C, cold blood cardioplegia was administered at 4 degrees C to obtain initial cardiac standstill. Thirty minutes before anticipated rewarming, anti-inflammatory medications were again administered. After rewarming to 37 degrees C for more than 33 minutes, he was successfully weaned from cardiopulmonary bypass without inotropic or pressor support and with normal pulmonary compliance. The prophylactic regimen was continued postoperatively. RESULTS The patient was extubated 11 hours after surgery, and with the exception of a brief, self-limited episode of atrial fibrillation, his course was uneventful. He experienced no urticaria, angioedema, or hypotension and was discharged home on the fourth postoperative day. CONCLUSIONS Although it is likely that the need for cold cardiopulmonary bypass surgery in patients with cold-induced urticaria is uncommon, it is encouraging that such a regimen may allow for the successful completion of the surgery.

Effects of salmeterol on muscarinic inhibition of adenylyl cyclase in bovine trachealis cells.

The goal was to assess whether salmeterol, a potent and long-acting beta-2-adrenergic agonist used in the treatment of asthma, also has non-beta-2-adrenergic effects on the stimulation or inhibition of adenylyl cyclase activity. Salmeterol (100 nM) maximally stimulated cAMP accumulation in enzyme dispersed bovine trachealis cells and this was entirely inhibited by propranolol, as expected for beta-adrenergic stimulation. However, the same concentration of salmeterol also antagonized carbachol inhibition of cAMP accumulation and altered binding of carbachol to muscarinic receptors. These effects of salmeterol were sensitive to washing of the cells and this was not consistent with a beta-2-adrenergic mechanism. The findings suggested that the maximal, beta-2-adrenergic stimulation of cAMP accumulation by salmeterol was accompanied by a non-beta-2-adrenergic interaction of salmeterol with muscarinic receptors that attenuated muscarinic inhibition of adenylyl cyclase.

Empyema in a Woman with Cystic Fibrosis: A Cautionary Tale

Cystic fibrosis (CF) is a disease which predisposes individuals to recurrent infective exacerbations of suppurative lung disease; however, empyema is a rare complication in these patients. Empyemas secondary to Staphylococcus aureus and Burkholderia cepacia have been described in patients with CF. We report the case of pleural empyema with mixed S. aureus and Pseudomonas aeruginosa infection in a 34-year-old woman with CF, which was managed with ultrasound-guided pigtail catheter insertion, fibrinolysis, and antibiotic therapy. Physicians should be aware of this unusual complication in CF patients, especially those receiving an immunosuppressive therapy.