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Diagnostic value of zinc levels in pleural effusions
LETTERS TO THE
ASYMPTOMATtC
BACTERIURIA
IN THE ELDERLY
To the Editor: I have read with great interest the recent article by Nicolle et al (Am J Med 1987; 83: 27-33) on asymptomatic bacteriuria in elderly women, as it is a problem frequently encountered in the management of the elderly, both as outpatients and as inpatients. In an earlier study involving geriatric ward male patients with asymptomatic bacteriuria, Nicolle et al [l] concluded that the treatment of the bacteriuria was neither necessary nor effective. In their study of bacteriuria in the elderly, Boscia et al [2] suggested that the transient nature of the bacteriuria argued against active treatment. Nordenstam et al [3] have shown that when other diseases (i.e., cancers) were considered, the relation between bacteriuria and mortality was not significant. However, what was disappointing in these earlier studies was the lack of data on the presence of pyuria in the urine samples of the patients. In the most recent study, however, Nicolle et al did include data on pyuria (Table I of the article). At my institution, the presence of pyuria is used as a parameter of the extent of inflammation associated with the bacteriuria and often as an important determinant of whether an initial attempt is made to eradicate the bacteriuria. Although Nicolle et al conclude that treatment for asymptomatic bacteriuria in this population is not necessary, I would be curious to see if a comparison of the results on outcome of bacteriuria, morbidity, and mortality in the patients with pyuria in the two treatment groups would yield significant differences. DAVID
BASKIN,
M.D.
St. Luke’sRoosevelt Medical Center New York, New York 10019 1.
2.
3.
Nicolle L, Bjornson J, Harding G, Mactlonell J: Bacteriuria in elderly institutionalized men. N Engl J Med 1983; 309: 14201425. Boscia J, Kobasa W, Knight R, Abrutyn E, Levison M, Kaye D: Epidemiology of bacteriuria in an elderly ambulatory population. Am J Med 1986; 80: 208-214. Nordenstam G, Brandberg C, Oden A. Svanborg C, Svanborg A: Bacteriuria and mortality in an elderly population. N Engl J Med 1986; 314: 1152-1156. Submitted
August
11, 1987, and accepted
TREATMENT OF CALCINOSIS LOW-DOSE WARFARIN
August
UNIVERSALIS
26, 1987
WITH
To the Editor: I read with interest the study of Berger et al (Am J Med 1987; 83: 72-76) concerning treatment of calcinosis universalis with low-dose warfarin. Although data from the few patients presented would suggest that low-dose warfarin could inhibit the development of calcinosis in dermatomyositis or systemic sclero-
sis, two major problems must temper the widespread clinical use of this treatment. The authors correctly pointed out that they studied a low number of patients, and the difficulty in making clinical decisions from such studies. Several previous studies have suggested the success of various treatments for calcinosis, but each has presented few number of patients and has often not followed up with additional patients in double-blind controlled studies [ 1,2]. The authors neglected to point out that other reports have shown up to a 55 percent spontaneous resolution rate for calcinosis without treatment directed specifically at the calcific manifestations of the underlying muscle disease ]31* Although this study was theoretically interesting, further double-blind trials with large numbers of patients from several different centers would better define the treatment of calcinosis universalis. Such controlled studies will need to take into account the large percentage of patients with spontaneous resolution of calcinosis in childhood dermatomyositis before making recommendations for widespread clinical treatment. NICHOLAS
A. PATRONE,
M.D.
East Carolina University School of Medicine Greenville, North Carolina 27858-4354 1.
2.
3.
Tabron J, Bole G, Thompson G: Colchicine suppression of local and systemic inflammation due to calcinosis universalis in chronic dermatomyositis. Ann Intern Med 1978; 89: 648-649. Steiner RM, Glassman L, Schwartz M, Vanace P: Radiological findings in dermatomyositis of children. Radiology 1974; ill: 385-393. Fink CW, Cook JD: Spontaneous resolution of calcinosis in childhood dermatomyositis. Arthritis Rheum 1986; 29(suppl): S91. Submitted
DIAGNOSTIC EFFUSIONS
August
VALUE
10, 1987, and accepted
OF ZINC LEVELS
August
26, 1987
IN PLEURAL
To the Editor: Pleural effusions that remain undiagnosed after initial thoracentesis and pleural needle biopsy are an important and relatively frequent clinical problem [I]. Because these effusions may be due to a wide variety of malignant and nonmalignant causes, numerous substances (e.g., carcinoembryonic antigen and lysozyme) [z] have been assayed in pleural fluid in an attempt to make the distinction between the possible causes. Unfortunately, due to poor sensitivity and/or specificity of these tests [2], clinicians are, at present, left without a relatively inexpensive, noninvasive diagnostic test to help with the decision concerning what course to follow (e.g., close observation or thoracotomy) when the results of initial thoracentesis and pleural needle biopsy are nondiagnostic.
November 1987
The American Journal of Medicine
Volume 83
1003
LETTERS TO THE EDITOR
cancer. Am J Med 1985; 79: 209-215. Minkel DT, Dolhun PJ, Calhoun BL, Saryan LA, Petering DH: Zinc deficiency and growth of Ehrlich ascites tumor. Cancer Res 1979; 39: 2451-2456. Ryan CJ, Rodgers RF, Unni KK, Hepper NGG: The outcome of patients with pleural effusion of indeterminate cause at thoracotomy. May Clin Proc 1981; 56: 145-149.
4.
5.
Submitted
Figure 1. Zinc concentrations (ng/dl) 13 malignant, malignant, and indeterminate pleural effusions.
July 28, 1987, and accepted
Zinc is a trace element with many important functions in humans and may improve T lymphocyte function and host immunity in patients with cancer 131. Additionally, It is important in the growth of proliferating malignant tissues. The demonstration that mouse serosal tumors concentrate zinc [4] and the fact that tumor cells are shed, in varying amounts, into the pleural space in malignant pleural effusions suggest that pleural fluid zinc levels may be a useful diagnostic test that can be used to distinguish malignant from benign effusions. The present study was designed to examine this. After the approval of the human investigations committee was obtained, zinc concentrations of unconcentrated pleural fluid specimens sent consecutively to the cytology laboratory were determined using the atomic absorber. The charts were then examined to ascertain whether the cause of the effusion was malignant or nonmalignant. Those effusions in which no diagnosis became apparent within 30 days after the thoracentesis by additional diagnostic procedures or autopsy findings were classified as indeterminate. The results of this analysis are shown in Figure 1. As can be seen from Figure 1, there is considerable overlap in zinc concentrations in pleural effusions due to malignant and nonmalignant processes. The determination of the zinc level in pleural fluid is, therefore, of no diagnostic value as an isolated parameter in distinguishing malignant from nonmalignant effusions. Consequently, physicians must continue to rely on clinical judgment in deciding what course to follow in patients in whom diagnostic thoracentesis, pleural needle biopsy [I], and occasionally even thoracotomy [8] fail to establish a cause. KENNETH E. SHEPHERD, M.D. Massachusetts General Hospital Boston, Massachusetts 02114
2. 3.
1004
Story DD, Dines DE, Coles DT: Pleural effusion: a diagnostic dilemma. JAMA 1976; 236: 2163-2166. Light RW: Pleural diseases. Philadelphia: Lea and Febiger, 1983; 33-60. Allen JI, Bell E, Boosalis MG, et al: Association between urinary zinc excretion and lymphocyte dysfunction in patients with lung
November
1987
The American
Journal
26, 1987
norb
CRYPTOCOCCAL MEDlASTlNlTlS LYMPHOMA IN THE ACQUIRED DEFICIENCY SYNDROME
1.
August
of Medicine
MIMICKING IMMUNE
To the Editor: Disseminated cryptococcosis is an often fatal manifestation of the acquired immune deficiency syndrome (AIDS). I recently cared for a patient with AIDS with an unusual presentation of disseminated disease and an initial paradoxic response to antifungal chemotherapy. A 38-year-old homosexual man who had successfully recovered from Pneumocystis carinii pneumonia presented with fevers, cough, headaches, photophobia, and disorganized speech. Examination of the cerebrospinal fluid by India ink preparation revealed budding yeasts, and cultures of blood and cerebrospinal fluid revealed Cryptococcus neoformans. Cerebrospinal fluid cryptococcal antigen titer was 1~2,048 and serum cryptococcal antigen titer was 1:18,384 upon initiation of therapy with intravenous amphotericin B and oral 5-flucytosine. The patient had improvement of symptoms within two weeks, and repeat cultures of the cerebrospinal fluid and blood showed no growth. Repeat cerebrospinal fluid cryptococcal antigen titer was 1:258, yet serum antigen titer rose to 1:2,097,592. A rapidly enlarging mass was noted in the right supraclavicular fossa extending to the anterior cervical triangle, measuring 7 by 5 by 8 cm. Chest radiography revealed a mediastinal mass; thus, a high-grade lymphoma was highly suspect. Computed tomography of the chest revealed a lymphomatous process involving the mediastinum, compressing the trachea and esophagus, and encircling the great vessels at the base of the neck (see figure 1). True cut biopsy of the neck mass revealed inflamed granulation tissue, innumerable cryptococci, and no evidence of lymphoma. Superior vena caval obstruction developed and the patient died on the 23rd hospital day. This case illustrates the protean manifestation of cryptococcal disease in patients with AIDS. Kovacs and associates [I] have reported the unreliability of the cerebrospinal fluid cryptococcal antigen titer as a prognostic factor in patients with AIDS. In this patient, a three-fold decline in cerebrospinal fluid antigen titer did not correlate with progression of disseminated disease. Cryptococal antigen clearance is defective in patients with AIDS [2] and accounts for persistently elevated serum antigen titers, which often have no relation to the antigen level in the cerebrospi-
Volume
83
ASYMPTOMATtC
BACTERIURIA
IN THE ELDERLY
To the Editor: I have read with great interest the recent article by Nicolle et al (Am J Med 1987; 83: 27-33) on asymptomatic bacteriuria in elderly women, as it is a problem frequently encountered in the management of the elderly, both as outpatients and as inpatients. In an earlier study involving geriatric ward male patients with asymptomatic bacteriuria, Nicolle et al [l] concluded that the treatment of the bacteriuria was neither necessary nor effective. In their study of bacteriuria in the elderly, Boscia et al [2] suggested that the transient nature of the bacteriuria argued against active treatment. Nordenstam et al [3] have shown that when other diseases (i.e., cancers) were considered, the relation between bacteriuria and mortality was not significant. However, what was disappointing in these earlier studies was the lack of data on the presence of pyuria in the urine samples of the patients. In the most recent study, however, Nicolle et al did include data on pyuria (Table I of the article). At my institution, the presence of pyuria is used as a parameter of the extent of inflammation associated with the bacteriuria and often as an important determinant of whether an initial attempt is made to eradicate the bacteriuria. Although Nicolle et al conclude that treatment for asymptomatic bacteriuria in this population is not necessary, I would be curious to see if a comparison of the results on outcome of bacteriuria, morbidity, and mortality in the patients with pyuria in the two treatment groups would yield significant differences. DAVID
BASKIN,
M.D.
St. Luke’sRoosevelt Medical Center New York, New York 10019 1.
2.
3.
Nicolle L, Bjornson J, Harding G, Mactlonell J: Bacteriuria in elderly institutionalized men. N Engl J Med 1983; 309: 14201425. Boscia J, Kobasa W, Knight R, Abrutyn E, Levison M, Kaye D: Epidemiology of bacteriuria in an elderly ambulatory population. Am J Med 1986; 80: 208-214. Nordenstam G, Brandberg C, Oden A. Svanborg C, Svanborg A: Bacteriuria and mortality in an elderly population. N Engl J Med 1986; 314: 1152-1156. Submitted
August
11, 1987, and accepted
TREATMENT OF CALCINOSIS LOW-DOSE WARFARIN
August
UNIVERSALIS
26, 1987
WITH
To the Editor: I read with interest the study of Berger et al (Am J Med 1987; 83: 72-76) concerning treatment of calcinosis universalis with low-dose warfarin. Although data from the few patients presented would suggest that low-dose warfarin could inhibit the development of calcinosis in dermatomyositis or systemic sclero-
sis, two major problems must temper the widespread clinical use of this treatment. The authors correctly pointed out that they studied a low number of patients, and the difficulty in making clinical decisions from such studies. Several previous studies have suggested the success of various treatments for calcinosis, but each has presented few number of patients and has often not followed up with additional patients in double-blind controlled studies [ 1,2]. The authors neglected to point out that other reports have shown up to a 55 percent spontaneous resolution rate for calcinosis without treatment directed specifically at the calcific manifestations of the underlying muscle disease ]31* Although this study was theoretically interesting, further double-blind trials with large numbers of patients from several different centers would better define the treatment of calcinosis universalis. Such controlled studies will need to take into account the large percentage of patients with spontaneous resolution of calcinosis in childhood dermatomyositis before making recommendations for widespread clinical treatment. NICHOLAS
A. PATRONE,
M.D.
East Carolina University School of Medicine Greenville, North Carolina 27858-4354 1.
2.
3.
Tabron J, Bole G, Thompson G: Colchicine suppression of local and systemic inflammation due to calcinosis universalis in chronic dermatomyositis. Ann Intern Med 1978; 89: 648-649. Steiner RM, Glassman L, Schwartz M, Vanace P: Radiological findings in dermatomyositis of children. Radiology 1974; ill: 385-393. Fink CW, Cook JD: Spontaneous resolution of calcinosis in childhood dermatomyositis. Arthritis Rheum 1986; 29(suppl): S91. Submitted
DIAGNOSTIC EFFUSIONS
August
VALUE
10, 1987, and accepted
OF ZINC LEVELS
August
26, 1987
IN PLEURAL
To the Editor: Pleural effusions that remain undiagnosed after initial thoracentesis and pleural needle biopsy are an important and relatively frequent clinical problem [I]. Because these effusions may be due to a wide variety of malignant and nonmalignant causes, numerous substances (e.g., carcinoembryonic antigen and lysozyme) [z] have been assayed in pleural fluid in an attempt to make the distinction between the possible causes. Unfortunately, due to poor sensitivity and/or specificity of these tests [2], clinicians are, at present, left without a relatively inexpensive, noninvasive diagnostic test to help with the decision concerning what course to follow (e.g., close observation or thoracotomy) when the results of initial thoracentesis and pleural needle biopsy are nondiagnostic.
November 1987
The American Journal of Medicine
Volume 83
1003
LETTERS TO THE EDITOR
cancer. Am J Med 1985; 79: 209-215. Minkel DT, Dolhun PJ, Calhoun BL, Saryan LA, Petering DH: Zinc deficiency and growth of Ehrlich ascites tumor. Cancer Res 1979; 39: 2451-2456. Ryan CJ, Rodgers RF, Unni KK, Hepper NGG: The outcome of patients with pleural effusion of indeterminate cause at thoracotomy. May Clin Proc 1981; 56: 145-149.
4.
5.
Submitted
Figure 1. Zinc concentrations (ng/dl) 13 malignant, malignant, and indeterminate pleural effusions.
July 28, 1987, and accepted
Zinc is a trace element with many important functions in humans and may improve T lymphocyte function and host immunity in patients with cancer 131. Additionally, It is important in the growth of proliferating malignant tissues. The demonstration that mouse serosal tumors concentrate zinc [4] and the fact that tumor cells are shed, in varying amounts, into the pleural space in malignant pleural effusions suggest that pleural fluid zinc levels may be a useful diagnostic test that can be used to distinguish malignant from benign effusions. The present study was designed to examine this. After the approval of the human investigations committee was obtained, zinc concentrations of unconcentrated pleural fluid specimens sent consecutively to the cytology laboratory were determined using the atomic absorber. The charts were then examined to ascertain whether the cause of the effusion was malignant or nonmalignant. Those effusions in which no diagnosis became apparent within 30 days after the thoracentesis by additional diagnostic procedures or autopsy findings were classified as indeterminate. The results of this analysis are shown in Figure 1. As can be seen from Figure 1, there is considerable overlap in zinc concentrations in pleural effusions due to malignant and nonmalignant processes. The determination of the zinc level in pleural fluid is, therefore, of no diagnostic value as an isolated parameter in distinguishing malignant from nonmalignant effusions. Consequently, physicians must continue to rely on clinical judgment in deciding what course to follow in patients in whom diagnostic thoracentesis, pleural needle biopsy [I], and occasionally even thoracotomy [8] fail to establish a cause. KENNETH E. SHEPHERD, M.D. Massachusetts General Hospital Boston, Massachusetts 02114
2. 3.
1004
Story DD, Dines DE, Coles DT: Pleural effusion: a diagnostic dilemma. JAMA 1976; 236: 2163-2166. Light RW: Pleural diseases. Philadelphia: Lea and Febiger, 1983; 33-60. Allen JI, Bell E, Boosalis MG, et al: Association between urinary zinc excretion and lymphocyte dysfunction in patients with lung
November
1987
The American
Journal
26, 1987
norb
CRYPTOCOCCAL MEDlASTlNlTlS LYMPHOMA IN THE ACQUIRED DEFICIENCY SYNDROME
1.
August
of Medicine
MIMICKING IMMUNE
To the Editor: Disseminated cryptococcosis is an often fatal manifestation of the acquired immune deficiency syndrome (AIDS). I recently cared for a patient with AIDS with an unusual presentation of disseminated disease and an initial paradoxic response to antifungal chemotherapy. A 38-year-old homosexual man who had successfully recovered from Pneumocystis carinii pneumonia presented with fevers, cough, headaches, photophobia, and disorganized speech. Examination of the cerebrospinal fluid by India ink preparation revealed budding yeasts, and cultures of blood and cerebrospinal fluid revealed Cryptococcus neoformans. Cerebrospinal fluid cryptococcal antigen titer was 1~2,048 and serum cryptococcal antigen titer was 1:18,384 upon initiation of therapy with intravenous amphotericin B and oral 5-flucytosine. The patient had improvement of symptoms within two weeks, and repeat cultures of the cerebrospinal fluid and blood showed no growth. Repeat cerebrospinal fluid cryptococcal antigen titer was 1:258, yet serum antigen titer rose to 1:2,097,592. A rapidly enlarging mass was noted in the right supraclavicular fossa extending to the anterior cervical triangle, measuring 7 by 5 by 8 cm. Chest radiography revealed a mediastinal mass; thus, a high-grade lymphoma was highly suspect. Computed tomography of the chest revealed a lymphomatous process involving the mediastinum, compressing the trachea and esophagus, and encircling the great vessels at the base of the neck (see figure 1). True cut biopsy of the neck mass revealed inflamed granulation tissue, innumerable cryptococci, and no evidence of lymphoma. Superior vena caval obstruction developed and the patient died on the 23rd hospital day. This case illustrates the protean manifestation of cryptococcal disease in patients with AIDS. Kovacs and associates [I] have reported the unreliability of the cerebrospinal fluid cryptococcal antigen titer as a prognostic factor in patients with AIDS. In this patient, a three-fold decline in cerebrospinal fluid antigen titer did not correlate with progression of disseminated disease. Cryptococal antigen clearance is defective in patients with AIDS [2] and accounts for persistently elevated serum antigen titers, which often have no relation to the antigen level in the cerebrospi-
Volume
83