393 determined regularly throughout the course of treatment and data for these two patients are shown in the accompanying table. In both cases the onset of neutropenia was accompanied by As soon as a severe a sore throat, general malaise, and fever. neutropenia was confirmed, the patients were admitted to hospital and treatment stopped. Within 7-10 days of stopping metiamide, the neutropenia had been completely reversed and both patients made an uneventful recovery. The bone-marrow in case 1 taken on day 35, 4 days after stopping metiamide, showed active normoblastic erythropoiesis. Myelopoiesis was relatively depressed, M/E ratio being lower than normal, and there was an absence of metamyelocytes and segmented neutrophils. Eosinophils and their precursors were increased. Lymphocytes and plasma cells were prominent but not increased. Megakaryocytes were normal. Stainable iron The appearances were consistent with those seen was normal. in some forms of agranulocytosis, the left shift in myelopoiesis indicating early recovery from the disease process, or reflecting hyperutilisation of cells with a relative depletion of the myeloid storage compartment. The biopsy in case 2 taken on day 103, again 4 days after stopping metiamide, showed megakaryocytes in normal numbers, and the erythrocyte series was active and normal in appearance. The myeloid series was plentiful but there was marked reduction in metamyelocytes and segmented neutrophils. No abnormal cells were seen. The picture was compatible with the recovery phase following agranulocytosis. Both bone-marrow films were submitted to Prof. David Mollin, who confirmed the reports detailed above.
Metiamide has been shown, both by us and by many other investigators, to be effective in controlling gastricacid secretion. In a double-blind trial30 patients with symptoms of duodenal ulceration were treated for 5-8 weeks with either metiamide 1 g. daily by mouth or with placebo. The 15 patients receiving metiamide had a striking and significant improvement of daytime pain after 2 weeks of therapy and a significant improvement of nocturnal pain throughout the period of study. Antacid consumption by the metiamide group was significantly reduced. The results suggest that histamine H2-receptor antagonists are likely to be useful in the medical management of duodenal ulceration. In the 2 patients reported here metiamide controlled the symptoms of duodenal ulcer. Metiamide would appear to be a potentially useful drug and, therefore, merits further careful and extensive evaluation with particular attention to the detection of what, in our patients, was a readily reversible neutropenia. University Department of Therapeutics, Royal Infirmary, Edinburgh.
J. A. H. FORREST D. J. C. SHEARMAN.
Department of Gastroenterology, Frenchay Hospital, Bristol.
R. SPENCE L. R. CELESTIN.
LEUKÆMIA AND LYMPHOMA LINKED BY PRIOR SOCIAL CONTACT their article on leuksemia and lymphoma patients SiR,—In interlinked by prior social contact (Jan. 18, p. 124), Dr Schimpff and others state that " the earliest detailed investigation suggesting that A.L.L. might be due to an infectious agent was done by Heath and Hasterlik " and cite a 1963 reference. However, in 1937, C. E. Kellett described35 cases of acute leukaemia (4 myelocytic and 1 lymphocytic) in Ashington, a mining village north of Newcastle upon Tyne, during a 3-year period. The patient with acute lymphocytic leukaemia came from the same street and at the same time as a patient with acute myelocytic leukaemia. He suggested that this concentration of cases supported the contention that the disease was due to an infection, widespread but of low infectivity. Dr Kellett 2. 3.
now
lives in retirement
at
Shotley Bridge, County
Pounder, R. E., et al. (in the press). Kellett, C. E. Archs Dis. Childh. 1937, 70,
239.
Durham, and I castle upon
am
Tyne,
indebted
for
to
placing
Dr Ronald
me
Thompson, of Newin communication with him.
Milwaukee Children’s Hospital,
Milwaukee, Wisconsin 53233, U.S.A.
DONALD PINKEL.
SIR,-It is time we put an end to the epidemic of articles uncontrolled studies of clusters of Hodgkin’s disease/ One cannot seriously consider lymphoma/leukaemia. randomly selected patients with Hodgkin’s disease as a on
proper control for other
Hodgkin’s cases. Dr Schimpff and his colleagues promise that they will use as a comparison group non-cases matched for age, sex, race, and home location. I hope that they are aware of the need for a more rigorous standard definition of a social interaction or " close personal association ". Also needed would be data showing that the cases and controls did indeed have the same number of such associations (persons at risk or denominator). Alternatively, they might compare the case rate per associate for cases and controls. Even then, the patient’s biased recall of associates with the disease is difficult to get around . in a retrospective study, particularly because this kind of article is causing the disease to be emotionally laden. Patients may be afraid they are infecting their associates when in fact to date there are no substantial data to support the infectious-disease model. Without a forbiddingly expensive prospective study, however, this issue is not easily resolved. Department of Community Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19174 U.S.A.
ANITA K. BAHN.
WHITE CELLS IN ALCOHOLISM SIR,--Dr Goedert and his colleaguesreport raised white-cell counts in nearly half of 124 untreated alcoholics and stated that the reason was unclear. However, the number of blood leucocytes is regulated by mobilisation from the bone-marrow and by diapedesis through the venule walls, the normal half-time disappearance being less than 7 hours. Before leaving the bloodstream leucocytes must adhere to the epithelium of venules.3 MacGregor et al. have shown the in-vitro adhesiveness of leucocytes to be significantly reduced in patients who have ingested alcohol.4 It is therefore to be expected that diapedesis of leucocytes will decrease in the presence of alcohol. Alcohol-dependent reduction in extravascular mobilisation of leucocytes was demonstrated by Brayton et al. by the use of a skinwindow technique. High white-cell counts in untreated alcoholics can be explained by a reduction in leucocyte adhesiveness resulting in delayed turnover. Conceivably alcohol ingestion and consequent reduction in leucocyte adhesiveness will also result in a shift from the marginated to the circulating pool of leucocytes, as is the the case for corticosteroids.6 Medical Department, Haukeland Hospital, University of Bergen Medical School, N-5016 Bergen, Norway.
GUNNAR HOPEN AKSEL SCHREINER.
1. Goedert, M., Schaeffer, F., Neuberg, P. Lancet, Jan. 4, 1975, p. 52. Cartwright, G. E., Athens, J. W., Wintrobe, M. M. Blood, 1964, 24, 780. 3. Grant, L. in The Inflammatory Process (edited by B. W. Zweifach, L. Grant, and R. J. McClusky); vol. I, p. 197. New York, 1965. 4. MacGregor, R. R., Spagnuolo, P. J., Lentnek, A. L. New Engl. J. Med. 1974, 291, 642. 5. Brayton, R. G., Stokes, P. E., Schwartz, M. S., Louria, D. B. ibid. 1970, 282, 123. 6. Dale, D. C., Fauci, A. S., Wolff, S. M. ibid. 1974, 291, 1154.
2.
Metiamide has been shown, both by us and by many other investigators, to be effective in controlling gastricacid secretion. In a double-blind trial30 patients with symptoms of duodenal ulceration were treated for 5-8 weeks with either metiamide 1 g. daily by mouth or with placebo. The 15 patients receiving metiamide had a striking and significant improvement of daytime pain after 2 weeks of therapy and a significant improvement of nocturnal pain throughout the period of study. Antacid consumption by the metiamide group was significantly reduced. The results suggest that histamine H2-receptor antagonists are likely to be useful in the medical management of duodenal ulceration. In the 2 patients reported here metiamide controlled the symptoms of duodenal ulcer. Metiamide would appear to be a potentially useful drug and, therefore, merits further careful and extensive evaluation with particular attention to the detection of what, in our patients, was a readily reversible neutropenia. University Department of Therapeutics, Royal Infirmary, Edinburgh.
J. A. H. FORREST D. J. C. SHEARMAN.
Department of Gastroenterology, Frenchay Hospital, Bristol.
R. SPENCE L. R. CELESTIN.
LEUKÆMIA AND LYMPHOMA LINKED BY PRIOR SOCIAL CONTACT their article on leuksemia and lymphoma patients SiR,—In interlinked by prior social contact (Jan. 18, p. 124), Dr Schimpff and others state that " the earliest detailed investigation suggesting that A.L.L. might be due to an infectious agent was done by Heath and Hasterlik " and cite a 1963 reference. However, in 1937, C. E. Kellett described35 cases of acute leukaemia (4 myelocytic and 1 lymphocytic) in Ashington, a mining village north of Newcastle upon Tyne, during a 3-year period. The patient with acute lymphocytic leukaemia came from the same street and at the same time as a patient with acute myelocytic leukaemia. He suggested that this concentration of cases supported the contention that the disease was due to an infection, widespread but of low infectivity. Dr Kellett 2. 3.
now
lives in retirement
at
Shotley Bridge, County
Pounder, R. E., et al. (in the press). Kellett, C. E. Archs Dis. Childh. 1937, 70,
239.
Durham, and I castle upon
am
Tyne,
indebted
for
to
placing
Dr Ronald
me
Thompson, of Newin communication with him.
Milwaukee Children’s Hospital,
Milwaukee, Wisconsin 53233, U.S.A.
DONALD PINKEL.
SIR,-It is time we put an end to the epidemic of articles uncontrolled studies of clusters of Hodgkin’s disease/ One cannot seriously consider lymphoma/leukaemia. randomly selected patients with Hodgkin’s disease as a on
proper control for other
Hodgkin’s cases. Dr Schimpff and his colleagues promise that they will use as a comparison group non-cases matched for age, sex, race, and home location. I hope that they are aware of the need for a more rigorous standard definition of a social interaction or " close personal association ". Also needed would be data showing that the cases and controls did indeed have the same number of such associations (persons at risk or denominator). Alternatively, they might compare the case rate per associate for cases and controls. Even then, the patient’s biased recall of associates with the disease is difficult to get around . in a retrospective study, particularly because this kind of article is causing the disease to be emotionally laden. Patients may be afraid they are infecting their associates when in fact to date there are no substantial data to support the infectious-disease model. Without a forbiddingly expensive prospective study, however, this issue is not easily resolved. Department of Community Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19174 U.S.A.
ANITA K. BAHN.
WHITE CELLS IN ALCOHOLISM SIR,--Dr Goedert and his colleaguesreport raised white-cell counts in nearly half of 124 untreated alcoholics and stated that the reason was unclear. However, the number of blood leucocytes is regulated by mobilisation from the bone-marrow and by diapedesis through the venule walls, the normal half-time disappearance being less than 7 hours. Before leaving the bloodstream leucocytes must adhere to the epithelium of venules.3 MacGregor et al. have shown the in-vitro adhesiveness of leucocytes to be significantly reduced in patients who have ingested alcohol.4 It is therefore to be expected that diapedesis of leucocytes will decrease in the presence of alcohol. Alcohol-dependent reduction in extravascular mobilisation of leucocytes was demonstrated by Brayton et al. by the use of a skinwindow technique. High white-cell counts in untreated alcoholics can be explained by a reduction in leucocyte adhesiveness resulting in delayed turnover. Conceivably alcohol ingestion and consequent reduction in leucocyte adhesiveness will also result in a shift from the marginated to the circulating pool of leucocytes, as is the the case for corticosteroids.6 Medical Department, Haukeland Hospital, University of Bergen Medical School, N-5016 Bergen, Norway.
GUNNAR HOPEN AKSEL SCHREINER.
1. Goedert, M., Schaeffer, F., Neuberg, P. Lancet, Jan. 4, 1975, p. 52. Cartwright, G. E., Athens, J. W., Wintrobe, M. M. Blood, 1964, 24, 780. 3. Grant, L. in The Inflammatory Process (edited by B. W. Zweifach, L. Grant, and R. J. McClusky); vol. I, p. 197. New York, 1965. 4. MacGregor, R. R., Spagnuolo, P. J., Lentnek, A. L. New Engl. J. Med. 1974, 291, 642. 5. Brayton, R. G., Stokes, P. E., Schwartz, M. S., Louria, D. B. ibid. 1970, 282, 123. 6. Dale, D. C., Fauci, A. S., Wolff, S. M. ibid. 1974, 291, 1154.
2.
