1267 GAMMA SCANNING OF ATHEROSCLEROTIC PLAQUES IN CAROTID ARTERIES
SIR,,-It was encouraging to have the positive comment from Dr Jonkheer (March 25, p. 657) on our preliminary report (Feb. 4, p. 242). The Brussels group are using 99mTc-fibrinogen, a technique we considered as an alternative when we started our project two years ago. However, Jonkheer misunderstands one aspect of our method for evaluation of accumulated radiolabelled fibrinogen in cervical arteries. We are well aware of the venous blood pool which is the major contribution to the total blood pool of the cervical vessels. However, the venous as well as the arterial blood pool is of minor interest in this study as its volume does not change with time, and so could be eliminated from the total picture. Ours was a temporal study where we observed an increase of activity after 3 h in the region of verified atherosclerotic plaques. We evaluate the blood pool not only by looking at the activity at various times after administration of the isotope but also by using the contralateral, non-atherosclerotic bifurcation region as a reference. Thus a unilateral hot spot appearing in the expected affected vessel segment at one stage of a temporal study is more likely to represent accumulation of fibrinogen in an active plaque than the blood pool of venous junctions. Department of Neurology, Karolinsha Sjukhuset,
K. L. METTINGER
S-104 01 Stockholm 60, Sweden
S. LARSSON
MITHRAMYCIN IN PAGET’S DISEASE
SIR,-In your editorial on the treatment of Paget’s disease of the bone (April 29, p. 914) you state that "Mithramycin is selectively toxic to osteoclasts"; Minkin’s 1973 paper is given as a reference. Your statement and Minkin’s conclusions are in conflict. Minkin stated: "The mechanism is not specific in that it appears to be of a general cytotoxic nature and inhibits bone formation as well". Mithramycin is an antibiotic with cytotoxic activity which blocks D.N.A.-directed R.N.A. synthesis2 and has no selective toxic action on osteoclasts. Mithramycin would interfere with the metabolism of the most active cells, which happen to be the osteoclasts in the destructive phase of Paget’s disease; but this does not mean that mithramycin is selectively toxic to osteoclasts. It has also been proposed that mithramycin may inhibit bone resorption by blocking the differentiation of osteoclasts from the osteoprogenitor pool. This is further supported by the fact that mithramycin takes about 24 h effectively to inhibit bone resorption, and this process is not easily reversed.’ Calcitonin, however, acts much more rapidly since it specifically inhibits the osteoclasts. Mithramycin therapy is usually accompanied by serious sideeffects since it is toxic to the liver, kidneys, and platelets. Whereas hepatocellular damage lasts only 2-3 days after mithramycin is withdrawn, as evidenced by the return of circulat-
ing hepatocellular enzymes to normal levels, the nephrotoxicity tends to last 1-2 weeks and is reflected by an increase in serum-creatinine, blood-urea, and proteinuria.1 Red and white blood-cells have also been identified in the urine of about 5% of patients receiving mithramycin. Thrombocytopenia and bleeding diatheses have been reported.5 These toxic effects are dose-related; however "The most effective resorption inhibition is found at levels of antibiotic which appear to be toxic".’ The main aim of prescribing calcitonin, mithramycin, or other therapy specific against Paget’s disease should be to pre-
complications (fractures, cranial-nerve compression, inhydrocephalus, brain failure, neurological deficits) and to relieve the pain. Besides, in most cases, pain in patients
Paget’s disease is due to an associated arthritis usually resulting from the altered lines of mechanical stress as a result of the bone deformities. The pain usually responds to ordinary analgesic compounds. The use of specific antipagetic drugs as a first therapeutic line solely to control pain is an expensive luxury fraught with many side-effects, especially if mithramycin or diphosphonates are used. One should always suspect an osteosarcoma if the onset of pain in a patient with Paget’s disease is sudden and the pain is resistant to analgesics; in this situation biopsy should be done because the prognosis is usually very poor. with
Department of Clinical Gerontology, Roehampton Health District, St. John’s Hospital, London SW11 1SP
PULMONARY TUBERCULOSIS AND BRONCHIAL CARCINOMA
SiR,—As Dr Howie (April 22, p. 881) states, tuberculosis and bronchial carcinoma commonly coexist. In one series’ the frequency of mycobacterial infection in patients with all types of malignancy was 6.4 times that in the general hospital population. 13 of the 40 patients studied had carcinoma of the lung. In two other much larger series2·3 the frequency of tuberculosis per 1000 cases of bronchial carcinoma was 7 and 9, respectively. In Peamount Hospital (Newcastle, County Dublin), a hospital for all types of respiratory disease, there have been in the past ten years 19 cases of coexisting pulmonary tuberculosis and carcinoma of the lung. This is a frequency for tuberculosis of 32 per 1000 cases of bronchial carcinoma. In all patients there was bacteriological and histological proof of the diagnoses. In all but 4 the tuberculosis was diagnosed first, and the average delay in the diagnosis of the carcinoma was 7 months. Tuberculosis is a common opportunistic infection in patients with carcinoma of the lung, and their coexistence causes diagnostic and therapeutic difficulties. Department of Pathology, University College, Dublin
2, Ireland
SIR,-Professor Langman and Dr Wormsley (April 29, p. 932), reporting the disappointing recurrence-rates when maintenance treatment with cimetidine ceased, ask how long cimetidine maintenance has to be maintained before we can be sure that surgery will never be required. I am afraid that clinicians keep neglecting the notion that ulcers cannot always be equated with acid secretion.4 I and my colleagues have reported alterations in gastric mucin after cimetidine treatment,5 suggesting that relapses of healed ulcers are due to an impaired protective function of mucous barrier. If this is so then in prolonging cimetidine treatment we are not preventing relapse but merely deferring it. To prevent recurrence of ulceration after healing by cimetidine, I suggest that maintenance treatment with drugs enhancing defensive factors (such as carbenoxolone or sulphoglycopeptide) may be better. Clinica Medica III,
ternal
University of Milan, Milan, Italy
1. Minkin, C. Calc. Tiss. Res. 1973, 13, 249. 2. Northrup, G., Taylor, S. C., Northrup, R. L. Cancer Res. 3. Owen, M. R. Int. Rev. Cytol. 1970, 28, 213 4. Ryan, W. G. Clin. Orthop. rel. Res. 1977, 127, 106. 5. Kennedy, B. J. Am. J. Med. 1970, 48, 494.
1969, 29, 1916.
T. M. HEALY
IMPORTANCE OF GASTRIC MUCUS
vent
not
RONNIE HAMDY
MARIO GUSLANDI
1. Ortbals, D. W., Marr, J. J. Am. Rev. resp. Dis. 1978, 117, 39. 2. Feld, R., Bodey, G. P., Groschel, D. Archs intern. Med. 1976, 136, 3. Kaplan, M. H., Armstrong, D., Rosen, P. Cancer, 1974, 33, 850. 4. Menguy, R., Masters, Y. F. Surgery, 1963, 54, 19 5. Guslandi, M., and others Br. med. J. 1978, i, 718.
67.
SIR,,-It was encouraging to have the positive comment from Dr Jonkheer (March 25, p. 657) on our preliminary report (Feb. 4, p. 242). The Brussels group are using 99mTc-fibrinogen, a technique we considered as an alternative when we started our project two years ago. However, Jonkheer misunderstands one aspect of our method for evaluation of accumulated radiolabelled fibrinogen in cervical arteries. We are well aware of the venous blood pool which is the major contribution to the total blood pool of the cervical vessels. However, the venous as well as the arterial blood pool is of minor interest in this study as its volume does not change with time, and so could be eliminated from the total picture. Ours was a temporal study where we observed an increase of activity after 3 h in the region of verified atherosclerotic plaques. We evaluate the blood pool not only by looking at the activity at various times after administration of the isotope but also by using the contralateral, non-atherosclerotic bifurcation region as a reference. Thus a unilateral hot spot appearing in the expected affected vessel segment at one stage of a temporal study is more likely to represent accumulation of fibrinogen in an active plaque than the blood pool of venous junctions. Department of Neurology, Karolinsha Sjukhuset,
K. L. METTINGER
S-104 01 Stockholm 60, Sweden
S. LARSSON
MITHRAMYCIN IN PAGET’S DISEASE
SIR,-In your editorial on the treatment of Paget’s disease of the bone (April 29, p. 914) you state that "Mithramycin is selectively toxic to osteoclasts"; Minkin’s 1973 paper is given as a reference. Your statement and Minkin’s conclusions are in conflict. Minkin stated: "The mechanism is not specific in that it appears to be of a general cytotoxic nature and inhibits bone formation as well". Mithramycin is an antibiotic with cytotoxic activity which blocks D.N.A.-directed R.N.A. synthesis2 and has no selective toxic action on osteoclasts. Mithramycin would interfere with the metabolism of the most active cells, which happen to be the osteoclasts in the destructive phase of Paget’s disease; but this does not mean that mithramycin is selectively toxic to osteoclasts. It has also been proposed that mithramycin may inhibit bone resorption by blocking the differentiation of osteoclasts from the osteoprogenitor pool. This is further supported by the fact that mithramycin takes about 24 h effectively to inhibit bone resorption, and this process is not easily reversed.’ Calcitonin, however, acts much more rapidly since it specifically inhibits the osteoclasts. Mithramycin therapy is usually accompanied by serious sideeffects since it is toxic to the liver, kidneys, and platelets. Whereas hepatocellular damage lasts only 2-3 days after mithramycin is withdrawn, as evidenced by the return of circulat-
ing hepatocellular enzymes to normal levels, the nephrotoxicity tends to last 1-2 weeks and is reflected by an increase in serum-creatinine, blood-urea, and proteinuria.1 Red and white blood-cells have also been identified in the urine of about 5% of patients receiving mithramycin. Thrombocytopenia and bleeding diatheses have been reported.5 These toxic effects are dose-related; however "The most effective resorption inhibition is found at levels of antibiotic which appear to be toxic".’ The main aim of prescribing calcitonin, mithramycin, or other therapy specific against Paget’s disease should be to pre-
complications (fractures, cranial-nerve compression, inhydrocephalus, brain failure, neurological deficits) and to relieve the pain. Besides, in most cases, pain in patients
Paget’s disease is due to an associated arthritis usually resulting from the altered lines of mechanical stress as a result of the bone deformities. The pain usually responds to ordinary analgesic compounds. The use of specific antipagetic drugs as a first therapeutic line solely to control pain is an expensive luxury fraught with many side-effects, especially if mithramycin or diphosphonates are used. One should always suspect an osteosarcoma if the onset of pain in a patient with Paget’s disease is sudden and the pain is resistant to analgesics; in this situation biopsy should be done because the prognosis is usually very poor. with
Department of Clinical Gerontology, Roehampton Health District, St. John’s Hospital, London SW11 1SP
PULMONARY TUBERCULOSIS AND BRONCHIAL CARCINOMA
SiR,—As Dr Howie (April 22, p. 881) states, tuberculosis and bronchial carcinoma commonly coexist. In one series’ the frequency of mycobacterial infection in patients with all types of malignancy was 6.4 times that in the general hospital population. 13 of the 40 patients studied had carcinoma of the lung. In two other much larger series2·3 the frequency of tuberculosis per 1000 cases of bronchial carcinoma was 7 and 9, respectively. In Peamount Hospital (Newcastle, County Dublin), a hospital for all types of respiratory disease, there have been in the past ten years 19 cases of coexisting pulmonary tuberculosis and carcinoma of the lung. This is a frequency for tuberculosis of 32 per 1000 cases of bronchial carcinoma. In all patients there was bacteriological and histological proof of the diagnoses. In all but 4 the tuberculosis was diagnosed first, and the average delay in the diagnosis of the carcinoma was 7 months. Tuberculosis is a common opportunistic infection in patients with carcinoma of the lung, and their coexistence causes diagnostic and therapeutic difficulties. Department of Pathology, University College, Dublin
2, Ireland
SIR,-Professor Langman and Dr Wormsley (April 29, p. 932), reporting the disappointing recurrence-rates when maintenance treatment with cimetidine ceased, ask how long cimetidine maintenance has to be maintained before we can be sure that surgery will never be required. I am afraid that clinicians keep neglecting the notion that ulcers cannot always be equated with acid secretion.4 I and my colleagues have reported alterations in gastric mucin after cimetidine treatment,5 suggesting that relapses of healed ulcers are due to an impaired protective function of mucous barrier. If this is so then in prolonging cimetidine treatment we are not preventing relapse but merely deferring it. To prevent recurrence of ulceration after healing by cimetidine, I suggest that maintenance treatment with drugs enhancing defensive factors (such as carbenoxolone or sulphoglycopeptide) may be better. Clinica Medica III,
ternal
University of Milan, Milan, Italy
1. Minkin, C. Calc. Tiss. Res. 1973, 13, 249. 2. Northrup, G., Taylor, S. C., Northrup, R. L. Cancer Res. 3. Owen, M. R. Int. Rev. Cytol. 1970, 28, 213 4. Ryan, W. G. Clin. Orthop. rel. Res. 1977, 127, 106. 5. Kennedy, B. J. Am. J. Med. 1970, 48, 494.
1969, 29, 1916.
T. M. HEALY
IMPORTANCE OF GASTRIC MUCUS
vent
not
RONNIE HAMDY
MARIO GUSLANDI
1. Ortbals, D. W., Marr, J. J. Am. Rev. resp. Dis. 1978, 117, 39. 2. Feld, R., Bodey, G. P., Groschel, D. Archs intern. Med. 1976, 136, 3. Kaplan, M. H., Armstrong, D., Rosen, P. Cancer, 1974, 33, 850. 4. Menguy, R., Masters, Y. F. Surgery, 1963, 54, 19 5. Guslandi, M., and others Br. med. J. 1978, i, 718.
67.
