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Article Excerpt
Letters to the Editor are welcomed. They may report new clinical or laboratory observations and new developments in medical care or may contain comments on recent contents of the Journal. They will be published, if found suitable, as space permits. Like other material submitted for publication, letters must be typewritten, double-spaced, and submitted in duplicate. They must not exceed two typewritten pages in length. No more than five references and one figure or table may be used. See "Information for Authors" for format of references, tables, and figures. Editing, possible abridgment, and acceptance remain the prerogative of the Editors.
Non-Q-Wave Acute Anterior Myocardial Infarction Associated with 5-Fluorouracil And Cisplatin Chemotherapy
To the Editor: It is known that the toxic effects of chemotherapeutic agents used in cancer therapy affect mainly the bone marrow and the digestive tract, and to a lesser extent they can cause cardiotoxicity. We report the case of a patient with squamous cell carcinoma of neck who presented with an acute anterior non-Q myocardial infarction after combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin.
A 66-year-old man with no history of cardiac disease was admitted to the oncology department because of left neck swelling. Pathologic assessment of the biopsy specimen revealed squamous cell carcinoma, and combination chemotherapy consisting of 5-FU and cisplatin was administered (cisplatin, 20 mg/[m.sup.2]/d infused intravenously over 4 hours; and 5-FU, 1,000 mg/[m.sup.2]/d continuous infusion over 24 h). The patient had typical chest pain lasting 30 minutes that did not resolve despite sublingual nitrate administered on the second day of therapy 5 hours after beginning cisplatin infusion. Acute anterior myocardial infarction was diagnosed on the basis of typical ST-segment elevations on the electrocardiogram and elevated creatinine kinase level. Chest pain resolved and ST-segment elevations became normal after the cessation of 5-FU infusion and the infusion of intravenous nitroglycerin. The angina did not recur during the course of his hospitalization, and pathologic Q-wave was not seen on the electrocardi ogram. Thus, the patient was diagnosed as having acute anterior non-Q-wave myocardial infarction.
The chemotherapeutic agents 5-FU and cisplatin are widely accepted as part of many cancer treatment protocols; both agents have rare potential cardiac toxicity. The incidence of cardiac toxicity due to treatment with 5-FU is reported to be from 1.2 to 18%. (1) The risk of cardiotoxicity is greater in patients who have underlying coronary artery disease. Patients with angina and even myocardial infarction have also been reported to have normal coronary angiograms. Although the cardiotoxicity of these drugs occurs most often at the time during the first course of treatment, regardless of dose, it may also occur at the time of treatment for recurrence. It has been reported that the frequency of cardiotoxicity induced by 5-FU does not seem to be influenced by age, sex, or route of administration. (2) Coronary spasm visualized at angiography during continuous intravenous 5-FU infusion has been reported. (3)
The mechanism of cardiotoxicity induced by 5-FU and cisplatin is unknown, but some hypotheses have been put forward: a coronary spasm directly induced by the drug or due to the release of vasopressive substances; direct toxic effect on the myocardium and the pericardium; an immunoallergic reaction after a sensitization period; drug-induced endothelial damage; an abnormality of thromboxaneprostacyclin hemostasis; and pertubation of clotting systems. It was reported that infusion of 5-FU increased levels of plasma endothelin-1 and fibrinopeptide A and decreased protein C levels. (4,5) These effects may contribute to the cardiotoxicity induced by these drugs.
In conclusion, myocardial ischemia and infarction induced by antineoplastic agents such as 5-FU and cisplatin are rare but potentially serious when they do occur. We think that oncologists should be aware of this side effect. Prophylaxis with calcium antagonists or nitrates may be useful in selected patients who are at high risk, such as those with underlying coronary artery disease.
Mustafa Kemal Erol, MD
Mahmut Acikel, MD
Huseyin Senocak, MD
Department of Cardiology
Ataturk University Medical School
Erzurum, Turkey
References
(1.) Becker K, Erckenbrecht JF, Haussinger D, Frieling T. Cardiotoxicity of the antiproliferative compound fluorouracil. Drugs 1999;57:475-484.
(2.) Clavel M, Simeone P, Grivet B. Cardiac toxicity of 5-fluorouracil: Review of the literature, 5 new cases [in French]. Presse Med 1988;17:1675-1678.
(3.) Luwaert RJ, Descamps O, Majois F, Chaudron JM, Beauduin M. Coronary artery spasm induced by 5-fluorouracil. Eur Heart J 1991;12:468-470.
(4.) Kuzel T, Esparaz B, Green D, Kies M. Thrombogenicity of intravenous 5-fluorouracil alone or in combination with cisplatin. Cancer 1990;65:885-889.
(5.) Porta C, Moroni M, Ferrari S. Nastasi G. Endothelin-1 and 5-fluorouracil-induced cardiotoxicity. Neoplasma 1998;45:81-82.
Spontaneous Pneumothorax as the First Manifestation of Lymphoma: A Rare Presentation and the Importance of Diagnostic Biopsy
To the Editor: Spontaneous pneumothorax as the first presentation of non-Hodgkin's lymphoma (NHL) is extremely rare and may be attributed to a direct effect of disease or a complication of therapy. (1,2) We found only two other reported instances of spontaneous pneumothorax occurring in untreated lung lymphoma. (2,3) We describe a case of recurrent pneumothoraces secondary to NHL, diagnosed by performing an open lung biopsy.
A 55-year-old man presented with a second episode of progressive dyspnea associated with left-sided chest discomfort. He had been admitted 2 weeks before for similar complaints. At that time, a chest radiograph showed a 50% left pneumothorax that required three consecutive chest tube insertions for complete resolution. A routine preoperative chest radiograph 2 years earlier was normal. He had a 30 pack-year smoking history but had not smoked in 13 years.
At the time of admission, his temperature was 100.5[degrees]F, pulse rate was 104 beats/mm, respiratory rate was 30 breaths/min, and blood pressure level was 110/70 mm Hg. Chest examination revealed absent breath sounds over the left hemithorax. The examination was otherwise unremarkable. White blood count was 18,200/ml with a normal differential count, and hemoglobin and platelet counts were normal. Chest radiograph showed a large left hydropneumothorax, with extensive bullae in the collapsed lung (Fig. 1). A chest tube was inserted with partial resolution of the pneumothorax. A computed tomographic scan of the chest showed pleural thickening and multiple large, thick-walled bullae. Open biopsy of the pleura and several bullae revealed an extensive, diffuse infiltrate of atypical small lymphocytes. Light-chain restriction was documented by [lambda] light-chain immunoreactivity and lack of k immunoreactivity by immunohistochemical tests. The atypical lymphocytes were also immunoreactive for CD20 (a B-cell mar ker). The pathologic findings were diagnostic of a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Staging workup revealed no evidence of distant disease. The patient underwent chemotherapy with six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone, with significant reduction of pleural and bullous wall thickening. Consolidative radiotherapy to the left lower hemithorax was administered after the completion of radiotherapy. He is doing well 1 [1/2] years later with no clinical or radiologic evidence of recurrent disease.
Spontaneous pneumothoraces in association with pulmonary lymphoma are usually attributed to the lymphom itself or to a complication of radiotherapy, chemotherapy, or infection. (1) Primary pulmonary NEIL is frequently indolent, confined to the lung, and diagnosed coincidentally after a screening chest radiograph. Forty-four percent of patients are asymptomatic; others have extrathoracic lymphadenopahty and/or systemic symptoms. Respiratory symptoms are frequently absent. (4) Definitive diagnosis can be made by a variety of biopsy or cytologic modalities, often requiring immunohistochemical, flow cytometric, and genetic techniques. (5)
In patients with a smoking history that predates a normal chest radiograph, subsequent lung bullae are unlikely to be complications of chronic obstructive pulmonary disease, and alternate explanations should be sought. It is reasonable to consider diagnostic biopsy in selected cases. This case demonstrates that non-Hodgkin's lymphoma may initially present as spontaneous pneumothorax and should be considered in the differential diagnosis in patients with recurrent episodes. Diagnostic biopsy may rule out this potentially treatable underlying cause of recurrent pneumothorax.
Maureen Okam, MD
Mohammad Alsolaiman, MD
Alan Brau, MD
Mariette Austin, MD
Department of Internal Medicine
Easton Hospital
Easton, PA
Matthew Plymyer, MD
Department of Pathology
Easton Hospital
Easton, PA
References
(1.) Yellin A, Benfield JR. Pneumothorax associated with lymphoma. Am Rev Respir Dis 1986; 134;590-592.
(2.) Wolf KM. Inclement weather, pneumothorax, and a cavitary apical infiltrate. Am J Med 1990;89:828-830.
(3.) Chia BL, Chiang SC, Lee SK, Chew CH. Massive bilateral consolidation and recurrent spontaneous pneumothorax due to primary lymphosarcoma of the lung. Med J Aust 1971;1:327-329.
(4.) Berkman N, Breuer R, Kramer MR, Polliack A. Pulmonary involvement in lymphoma. Leuk Lymphoma 1996;20:229-237.
(5.) Pietra G, Saihany K. Lymphoproliferative and hematologic diseases involving the lung, in Fishman AP, Elias JA, Fishman J, Kaiser LR (eds): Fishman's Pulmonary Diseases and Disorders. New York, McGraw-Hill Health Professions Division, 1998, vol II, ed 3, pp 1861-1879.
Treatment of Acute Isoniazid Toxicity of Unknown Dose
To the Editor: Isoniazid is a bactericidal antituberculosis agent. (1) Overdose of isoniazid is characterized by seizures, metabolic acidosis, and coma. (2) Because it can result in death if untreated, early consideration of the possibility of isoniazid poisoning is important. We describe a patient treated with pyridoxine after an isoniazid overdose.
A 20-year-old woman was admitted to the emergency department with complaints of spasm, cyanosis, and frothy salivation. She had a generalized seizure and was admitted to the intensive care unit (ICU) with a possible diagnosis of drug intoxication. The patient was unconscious, with spontaneous breathing and a Glasgow Coma Scale (GCS) score of 7. Blood pressure was 100/60 mm Hg, heart rate was 110 beats/mm, and respiratory rate was 24 breaths/min. Pupils were 5 mm and reactive to light bilaterally. Physical and funduscopic examinations were normal. Arterial blood gas sample showed metabolic acidosis: pH, 7.16; [PCO.sub.2], 30 mm Hg; [PO.sub.2], 70 mm Hg, base excess (BE), - 15.6; bicarbonate, 12.3 mmol/L. Serum lactate level was not measured. Serum glucose and electrolyte levels were normal. Cranial computed tomography was normal. Gastric lavage was performed, followed by the administration of activated charcoal. Because she had a family member receiving treatment for tuberculosis and her symptoms were similar to those of isoniazid intoxication, the patient was administered a solution of 5% pyridoxme intravenously by slow infusion at approximately 0.5 g/min (5 g per 10 mm in a 50 ml volume). The seizures stopped within 5 minutes and did not recur. Thirty minutes after treatment, the patient regained consciousness. She was cooperative and oriented. Her GCS score was 15. On the second hospital day, arterial blood gas values were normal, but an increase in the patient's aspartate aminotransferase and alanine aminotransferase levels was seen. Therefore, the patient was transferred to the gastroenterology service with a diagnosis of hepatitis due to isoniazid toxicity.
A dose of 1.5 g of isoniazid acutely ingested can induce toxicity in an adult; 2 to 3 g ingested at one time is usually toxic; 6 to 10 g acutely ingested can cause severe toxicity and death; 10 to 15 g or more ingested acutely by an adult is often fatal if not treated. (3) A dose of 35 to 40 mg/kg produces seizures in some patients, and a dose of 80 to 150 mg/kg induces seizures and a high mortality rate. Isoniazid produces toxic effects by inhibiting the activity of brain pyridoxal-5-phosphate, the active form of pyridoxine (vitamin [B.sub.6]). Pyridoxal-5-phosphate is necessary for the synthesis of [gamma]-aminocbutyric acid (GABA). (1) Since GABA is the major inhibitory neurotransmitter of the central nervous system, impairment of this neurotransmitter is undoubtedly one of the most important mechanisms in the pathophysiology of seizures induced by isoniazid. (1.4) The clinical triad of isoniazid overdose consists of repetitive seizures refractory to the usual anticonvulsants; metabolic acidosis, often ref ractory to treatment with sodium bicarbonate; and coma. The diagnosis of isoniazid overdose should be considered in any patient exhibiting otherwise unexplained metabolic acidosis and convulsions. (3) If there is doubt about whether isoniazid is the cause of the convulsions or coma, an early therapeutic trial of intravenous pyridoxine therapy should be considered, because of its relative safety and potential benefits. The optimal pyridoxine dose should be at least equal to the maximum amount of isoniazid allegedly ingested. Pyridoxine is mixed with water in a 5 or 10% solution and administered intravenously for a 5-minute period. It is repeated at intervals of 5 to 20 minutes as needed in comatose or convulsing patients. (3) If the ingested dose of isoniazid is unknown, 5 g of pyridoxine should be administered initially, followed every few minutes with the administration of an additional 5 g until seizures cease or consciousness is regained. No adverse effects were observed in one study of subjects receiving pyridoxine in doses ranging from 50 to 357 mg/kg.
Husnu Kursad, MD
Mehmet Kizilkaya, MD
Murat Sahin, MD
Nazim Dogan, MD
Asim Ilgaz, MD
Department of Anesthesiology and Reanimation
Ataturk University Medical Faculty Erzurum, Turkey
References
(1.) Temmerman w, Dhondt A, Vandewoude K. Acute isoniazid intoxication: seizures, acidosis and coma. Acta Clin Belg 1999;54:211-216.
(2.) Brent J, Vo N, Kulig K, Rumack BH. Reversal of prolonged isoniazid-induced coma by pyridoxine. Arch Intern Med 1990;150:1751-1753.
(3.) Yona A, Syama A, Baumal J, et al: Introduction, in Ellenhorn MJ (ed): Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. Baltimore, Williams & Wilkins, 1997, ed 2, pp 224-249.
(4.) Osborn H: Antituberculosis agents, in Goldfrank LR, Flomenbaum N, Lewin N, Howland MA, Hoffman R, Nelson L (eds): Goldfrank's Toxicologic Emergencies. Stamford, Appleton & Lange, 1998, ed 6, pp 727-737.
Ascaris Lumbricoides?
To the Editor: I am writing with regard to an article published in the Southern Medical Journal concerning the finding of an Ascaris lumbricoides adult worm that had supposedly exited from a man's urethra while he was urinating. (1) The article included a figure showing the 15-cm worm. As a reasonable expert in the diagnosis of human parasitic infections--I am coauthor of the Atlas of Human Parasitology, now in its Fourth Edition--I could not help being interested in this case report.
The worm in the photograph appears to be dark in color, instead of the off-white appearance typical of an adult Ascaris. It really does not look like an Ascaris; from its appearance, it would seem to be an earthworm. Since the patient brought the worm to the emergency department and no one witnessed the actual voiding of the worm, I wrote to the authors early in June 2001, questioning the validity of this case report. In my letter to Dr. Quick, I offered to look at the worm, because it would be appropriate to correct this report if the patient did not actually void a living Ascaris adult.
There has been no response to my letter, and I question...
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