BRIEF CLINICAL OBSERVATIONS

ATRIAL NATRIURETIC PEPTIDE IN THE RECOVERY FROM HIGH- OUTPUT CONGESTIVE HEART FAILURE

Large a r t e r iovenous f i s tu las (AVFs) increase venous return, preload, and cardiac output and may eventually lead to congestive heart failure (CHF) with severe fluid and sodium retention [1]. Clo- sure of an AVF induces a charac- teristic diuretic and natriuretic re- sponse in experimental animals as well as reversal of the clinical signs of CHF in patients. The mecha- nism of this response is poorly un- derstood, although involvement of the renin-angiotensin system and the renal sympathetic nerves has been proposed [2]. The potential role of atrial natriuretic peptide (ANP) in the natriuresis following closure of a fistula and in the recov- ery from CHF has not been studied previously. We report here the plasma levels of ANP in two pa- tients with CHF due to a large AVF, both before and after surgical repair, and in two patients with small AVFs, for comparison.

A 67-year-old patient was re- ferred with a large iatrogenic femo- ral AVF. He exhibited dyspnea on exertion, distended jugular veins, enlarged liver, marked peripheral edema, a pulsating mass in his right groin, and oliguria. Plasma ANP concentration was increased to 407 pg/mL (versus 32 4- 5 pg/mL in 10 controls, measured by radioimmu- noassay). Surgical closure of the fistula by lateral repair of the fem- oral artery and vein was followed by a polyuric phase and gradual improvement in the signs of heart failure. Plasma ANP levels re- mained high immediately after surgery (390 pg/mL), then de- creased gradually and returned to normal over a week (283, 205, and 23 pg/mL at 2, 4, and 6 days post- operatively, respectively).

Another 70-year-old patient pre- sented with a spontaneous large AVF between an atherosclerotic il- iac aneurysm and the inferior vena cava. He had severe congestive heart failure, dyspnea, engorged jugular veins, enlarged liver, a pul- sating abdominal mass, peripheral edema, hypotension, and oliguria that progressed to anuria. Plasma

ANP levels were increased about 300% (91 pg/mL). He underwent urgent operation, the AVF was re- paired, and the aneurysm was re- sected and grafted. ANP levels re- mained high immediately after and 1 day after surgery (82 and 78 pg/ mL, respectively). The patient did not recover from surgery and later died of multisystem organ failure.

In contrast to these two patients with large AVFs, in two young pa- tients with small AVFs caused by shrapnel wounds (one femoral and one brachial), and with no signs of heart failure or renal failure, plas- ma ANP levels were normal both before (5 and 23 pg/mL) and 1 day after surgery (13 and 26 pg/mL, re- spectively).

These data demonstrate marked increases in plasma ANP levels in patients with high-output CHF caused by large fistulas, similar to that reported in other forms of CHF [3] as well as in animal models of AVF [4]. Moreover, a rather slow decrease in plasma ANP levels over several days after surgical closure of a large AVF was observed, in contrast to reportedly immediate decreases in ANP levels after re- pair of mitral stenosis [5]. Circulat- ing levels of ANP were very high even after surgical closure of an AVF, and were associated with polyuria and a reduction in the signs of CHF. Similar results were recently obtained in an experimen- tal correlate of an aortocaval fistula model in rats [6].

The natriuresis that follows re- lief of bilateral ureteral obstruction or supraventricular tachycardia has been attributed to ANP [7,8]. Similarly, the pattern of plasma ANP changes in our patients sug- gests that ANP is not only a marker of the severity of fluid retention [9], but may also play a role in the re- covery from CHF by facilitating di- uresis and natriuresis after the pri- mary cause of CHF is removed.

AARON HOFFMAN, M.D. JOSEPH WINA VER, M.D.

Rambam Medical Center and The Technion

Haifa, Israel A VIAD HARAMATI, Ph.D. Georgetown Universi ty

Washington, D.C.

1. Alexander J J, Imbembo AL: Aorta-vena cava fistu- la. Surgery 1989; 105: 1-12.

2. Humphreys MH, AI-Bander H, Eneas JF, Schambe- lan M: Factors determining electrolyte excretion and renin secretion after closure of an arteriovenous fistu- la in the dog. J Lab Clin Med 1981; 98: 89-98. 3. Burnett JC, Kao PC, Hu DC, etahAtrial natriuretic peptide i n congestive heart failure in the human. Sci- ence 1986; 231: 1145-1147. 4.Winaver J, Hoffman A, Burnett JC, Haramati A: Hormonal determinants of sodium excretion in rats with experimental high-output heart failure. Am J Physiol 1988; 254: R776-R784. 5. Ishikura F, Nagata S, Hirata Y, et ak Rapid reduc- tion of plasma atrial natriuretic peptide levels during percutaneous mitral commissurotomy. Circulation 1989; 79: 47-50. 6. Hoffman A, Grossman E, Keiser HR: Role of atrial natriuretic peptide in the natriuresis after closure of a large arteriovenous fistula (abstr). Circulation 1989; 80 (suppl): 11-361. 7. Purkerson ML, Blaine EH, Stokes T J, Klahr S: Role of atrial peptide in the natriuresis and diuresis that follows relief of obstruction in rat. Am J Physio11989; 256: F583-F598. 8. Yamaji T, Ishibashi M, Nakaoka H, Imataka K, Amano M, Fujii J: Possible role for atrial natriuretic peptide in polyuria associated with paroxysmal atrial arrhythmias. Lancet 1985; 1: 1211. 9. Singer DR, Shore AC, Markandu AD, eta/.' Atrial natriuretic peptide levels in treated congestive heart failure. Lancet 1986; 1: 851.

Submitted November 29, 1989, and accepted De- cember 6, 1989

ACUTE TUMOR LYSIS SYNDROME IN PROLYMPHOCYTIC LEUKEMIA

Chemotherapeutic treatment of large volume, rapidly proliferating tumors may result in acute tumor lysis syndrome (TLS) [1,2]. This occurs most commonly after com- bination chemotherapy of Bur- kitt's lymphoma. Prolymphocytic leukemia (PL), a B-cell neoplasm that is relatively nonresponsive to agents with activity against other lymphoproliferative malignancies, has been associated with TLS after combination chemotherapy in one report [3]. We describe a case of TLS developing in a patient treat- ed with dexamethasone alone.

A 70-year-old man presented to an outside hospital with fatigue, lassitude, and hepatosplenomega- ly. Examination of the peripheral blood smear revealed a lymphocy- tosis with 30% prolymphocytes. He received three courses of cyclo- phosphamide, vincristine, and daunomycin with short-lived re- sponses, and subsequently was transferred to our facility. On ad- mission, the following values were noted: white blood cell count (WBC) 71,200/#L with 41% pro-

May 1990 The American Journal of Medicine Volume 88 547

BRIEF CLINICAL OBSERVATIONS

lymphocytes, hemoglobin 11.2 g/ dL, platelets 82,000/#L, potassium 3.2 mmol/L, bicarbonate 22 mmol/ L, uric acid 22.2 mg/dL, lactate de- hydrogenase (LDH) 12,360 IU/L, calcium 10.6 mg/dL, and phospho- rus 1.3 mg/dL.

Bone marrow examina t i on showed the marrow to be packed with prolymphocytes. An abdomi- nal computed tomographic (CT) scan revealed impressive hepato- sp lenomega ly and per iaor t i c lymphadenopathy.

We initiated t reatment with VAD, a regimen consisting of vin- cristine 0.4 mg/day by a 4-day con- t inuous intravenous infusion, Adriamycin TM (doxorubicin) 15 mg/ day by a 4-day continuous intrave- nous infusion, and dexamethasone 40 mg orally daily for 4 days. Be- cause of a clinical error, the patient received only dexamethasone for 2 days. Within 2 days the organome- galy was no longer detectable, and the following values were noted: WBC 7,800/#L, platelets 48,000/ #L, bicarbonate 15 mg/dL, uric acid 1.8 mg/dL, LDH 313 IU/L, and calcium 5.8 mg/dL. Over the same period the potassium, phos- phorus, and creatinine levels rose to 5.6 mmol/L, 10.0 mg/dL, and 1.6 mg/dL, respectively.

Over the ensuing 2 weeks, tumor progression was again noted with recurrent hepatosplenomegaly, a WBC of 82,000/#L, LDH of 3,541 IU/L, calcium of 9.4 mg/dL, and phosphorus of 5.6 mmol/L. Subse- quent abdominal CT scan demon- strated hepatosplenomegaly with- out adenopathy, and he received a full course of VAD chemotherapy with gratifying response and no further complications.

There are several unique aspects to this case. PL is a slow-growing B-cell neoplasm with a large tumor burden, and rapid changes in tu- mor burden with therapy are not characteristic. This case involved rapid tumor progression and im- pressive therapeutic responses, a pattern typical of more aggressive acute leukemias. Although it is es- tablished that steroids demon- strate activity against other lym- phoproliferat ive malignancies [1,2], this is the first time to our knowledge that PL has responded to dexamethasone alone.

The previously reported case of TLS associated with PL [3] in- volved therapy with vincristine and high-dose prednisone. It was not possible from that report to as-

certain the role of prednisone alone, as both agents have antitu- mor activity [4].

In this case, the total dexameth- asone delivered had one fourth the glucocorticoid activity reported in the previously cited prednisone- vincristine combination, yet re- sulted in biochemical changes con- sistent with acute TLS. Therefore, the use of dexamethasone alone i n this disease should be cautiously approached.

ROY E. SMITH, M.D. THOMAS R. STOIBER, M.D.

The Medical College of Wisconsin Milwaukee, Wisconsin

1. Cadman EC, Lundber WB, Bertino JR: Hyperphos- phatemia and hypocalcemia accompanying rapid cell lysis in a patient with Burkitt's lymphoma and Bur- kitt's cell leukemia. Am J Med 1977; 62: 283-290. 2. Gomez GA, Stutzman L, Chu TM: Xanthine ne- phropathy during chemotherapy in deficiency of hy- poxanthine:guanine phosphoribosyltransferase. Arch Intern Med 1978; 138: 1017-1019. 3. Gomez GA, Han T: Acute tumor lysis syndrome in prolymphocytic leukemia. Arch Intern Med 1987; 147: 375-376. 4. Livingston RB, Carter SK: Single agents in cancer chemotherapy. New York: IF J/Plenum, 1970; 337- 358.

Submitted September 11, 1989, and accepted in re- vised form November 10, ],989

PNEUMOCOCCAL MENINGITIS DURING INTRAVENOUS CIPROFLOXACIN THERAPY

Cooper and Lawlor (Am J Med 1989; 87: 475) report a case of pneu- mococcal bacteremia occurring during oral therapy with ciproflox- acin. I wish to report an even more alarming clinical case in which pneumococcal meningitis devel- oped during treatment with intra- venous ciprofloxacin.

A 77-year-old woman was admit- ted in septic shock. Chest radiogra- phy showed left lobe consolidation and a large pleural effusion. Re- sults of neurologic examination were normal. The patient was ad- mitted to the intensive care unit and resuscitated, and underwent ventilation. Past medical history included mild hypertension requir- ing no treatment, and polymyalgia rheumatica for which she received prednisone 5 mg daily. As part of an open trial, she was treated with ciprofloxacin 200 mg intravenously every 12 hours. Clinical improve- ment was rapid and she was extu- bated on Day 3. Multiple blood cul- tures taken on admission grew Streptococcus pneumoniae. Two days later she became obtunded;

548 May 1990 The American Journal of Medicine Volume 88

examination revealed neck stiff- ness. A lumbar puncture yielded cloudy fluid; glucose was undetect- able, the protein value was 258 mg/ dL, the red blood cell count was 91/ mm 3, the white blood cell count was 21/mm 3, and Gram-stained smear revealed large numbers of gram-positive diplococci. Culture grew S. pneumoniae of the same serotype as the blood isolate. Treatment was changed to ampicil- lin and the pat ient ul t imately made a complete recovery.

Both isolates of S. pneumoniae were susceptible to ciprofloxacin by Kirby-Bauer disk diffusion; the minimal inhibitory concentration was 2 #g/mL using an agar dilution method. The activity of ciprofloxa- cin against S. pneumoniae is only moderate; a concentration of 2 #g/ mL is needed to inhibit 90% of iso- lates [1]. Nevertheless, response rates for chronic bronchitis and pneumonia range from 70% to 90%, although persistence of the organ- ism has been reported [2]. Spinal fluid concentrations in the range of 0.35 to 0.56 #g/mL [3] discourage ciprofloxacin use if pneumococcal meningitis is suspected.

Intravenous ciprofloxacin thera- py would be expected to effectively control bacteremia. Meningeal seeding in this setting is very alarming. Use of oral ciprofloxacin for the empiric treatment of com- munity-acquired pneumonia is probably unwise.

JULIE RIGHTER, M.D., F.R.C.PoC. Toronto East General and

Orthopaedic Hospital Toronto, Canada

1. Davies BI, Maesen FPV: Quinolones in chest infec- tions. J Antimicrob Chemother 1986; 18: 296-299. 2. Ball AP: Overview of clinical experience with cipro- floxacin. Eur J Clin Microbiol 1986; 5: 214-219. 3. Wolff M, Boutron L, Singlas E, Clair B, Decazes JM, Regnier B: Penetration of ciprofloxacin into cerebro- spinal fluid of patients with bacterial meningitis. Anti- microb Agents Chemother 1987; 31: 899-902.

Submitted November 29, 1989, and accepted De- cember 6, 1989

DESENSITIZATION TO SULFONAMIDES IN PATIENTS WITH HIV INFECTION

Sulfonamides are the agents most frequently incriminated in the de- velopment of a variety of presumed immunologic skin reactions [1]. Al- though these eruptions may be a source of considerable morbidity and occasional mortality, with- holding the offending agent and al-