- Email: [email protected]
DIFFERENTIAL COUNTS AND SURVIVAL IN LUNG CANCER
1317
in-neutralising activity in plasma reflected by prostaglandin synthesis.
to
platelet function
as
CANCER
thrombotic disease an increase in P.F.410 and in the plasma has been reported. It will be of interest p-T.G." to see if an inverse relation between intra-platelet and extraplatelet levels of these molecules can be demonstrated. It will be of even greater interest if chronic disturbances of this kind reflect a predisposition to thrombosis. Indeed it has already been suggested that a raised plasma heparin-neutralising activity may, on occasions, indicate a prothrombotic state. 12 Portsmouth and South East Hampshire District Pathology Service, St. Mary’s Hospital, Portsmouth PO3 6AG J. R. O’BRIEN In
acute
PNEUMOCOCCAL INFECTION AFTER VACCINATION
SIR,-Although pneumococcal vaccine is effective in population groups, 12 its protective value in certain immunodeficient patients predisposed to pneumococcal infections may be limited.3 We have studied a 46-year-old male with chronic lymphocytic leukxmia diagnosed in 1968 who required intermittent therapy with cyclophosphamide, prednisone, and procarbazine. His serum-immunoglobulins are below normal, IgG 194 mg/dl (800-1800), IgA 110 mg/dl (90-450), and IgM 52 mg/dl (60-250), and he frequently has to be admitted to hospital for pulmonary and urinary-tract infections. On March 21, 1978, he received 0.5ml ’Pneumovax’ intramuscularly. He was readmitted on April 7, with a 24 h history of chills and fever. Admission white-cell count was 13 100/1 with 1% PNEUMOCOCCAL
TYPE*
DIFFERENTIAL COUNTS AND SURVIVAL IN LUNG
ANTIBODY LEVEL
SIR,-Methodological difficulties can lead to spurious associations between technically complex tests of immune function, such as erythrocyte rosette formation 1or mitogen responsiveness,3 and disease severity. Factors such as the standardisation of reagents, sampling error, and the variation in composition of cell suspensions prepared by gradient separation of blood can complicate the interpretation of these assays.4-6 Consequently, simpler tests which can be carried out with precision need to be re-evaluated or developed. We have found that accurate white-blood-cell and differential counts are valuable predictors of survival in patients with unresectable lung cancer. Differential counts were done as part of the initial clinical and immunological evaluation of all patients seen in the University of Chicago Hospitals for suspected lung cancer. A Technicon ’Hemalog D’ counter was used because it counts 30 000 cells and produces very accurate counts for cells, such as monocytes, which occur at low frequency. Cell-counts were unremarkable in patients with resectable lung cancer (stages 1, 2, and 3 MO) but were unexpectedly related to survival in unresectable lung cancer. (MEAN±S.D. pI) IN PATIENTS WITH UNRESECTABLE LUNG CANCER
TABLE I-TOTAL AND DIFFERENTIAL BLOOD COUNTS
PER
(ng/ml)tj-
TABLE II-SURVIVAL OF PATIENTS WITH UNRESECTABLE LUNG CANCER RELATIVE TO WHITE-BLOOD-CELL COUNT
*Danish nomenclature. tR.i.A. by Dr G. Schiffman.
bands, 11% polymorphs, 87% lymphocytes, and 1% monocytes. Chest X-ray revealed bilateral infiltrates. Blood and spucultures were positive for Streptococcus pneumoniae. The isolate was typed by counterimmunoelectrophoresis and was found to be one of the vaccine types, type 9. The patient retum
sponded to treatment. Serial serum specimens failed to demonstrate development of significant levels of type 9 antibody in response to either the antecedent vaccine or the current infection. Antibody titres to other penumococcal vaccine types were equally unim-
most
pressive. This case shows how patients with defective immunoglobulin synthesis secondary to underlying disease or chemotherapy may fail to develop protective levels of antipneumococcal antibody after natural infection or pneumococcal vaccine. While there is no apparent contraindication to administering the vaccine to such patients, the diagnosis of pneumococcal infection by vaccine or non-vaccine types must still be considered in this group of vaccine recipients. Section of Infectious Diseases, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, U.S.A.
Median survival,
as determined by life-table analysis, for 51 with unresectable lung cancer, excluding those with small-cell undifferentiated (oat cell) carcinoma, was 4.8 months. Cell-counts in relation to survival for more or less than 4 months are shown in table L There was a highly significant increase in white blood-cells in patients surviving less than 4 months, which seems to be a summation of increases in neutrophils, monocytes, and immature myeloid cells. Lymphocyte-counts did not differ between the two groups. However, as others have found in breast cancer, 17 lymphocyte numbers were lower in the unresectable cases as a group than in patients with less advanced disease. Table 11 shows survival of patients whose white-blood-cell counts were greater than or less than 10 800/1, the mean
patients
1.
LAUREL PREHEIM MICHAEL RYTEL
10. Handin, R. I., McDonough, M., Lesch, M. J. Lab. clin. Med. (in the press). 11. Ludlam, C. A., Bolton, A. E., Moore, S., Cash, J. D. Lancet, 1975, ii, 259. 12. O’Brien, J. R., Etherington, M. D., Jamieson, S., Lawford, P., Lincoln, S. V., Alkjaersig, N. J. Thromb.Diath. haemorrh. 1975, 34, 453. 1. Amman, A. J., and others. New Engl. J. Med. 1977, 297, 897. 2. Smit, P., and others. J. Am.med. Ass. 1977, 238, 2613. 3. Morbid. Mortal. wkly Rep. 1977, 26, 345.
Teasdale, C., Thatcher, J., Whitehead, R. H., Chare, M. J. B., Hughes, L.
E.
Lancet, 1977, i, 543. 2. Byrom, N. A., Campbell, M. A., Staughton, R. C. D., Timlin, D. M. ibid.
1977, ii, 1132. 3. Moore, D. L.,Heyworth, B., Brown, J. Clin. exp. Immun. 1974, 17, 647. 4. Winchester, R. J., Ross, G. in Manual of Clinical Immunology (edited by N. R. Rose and H. Fnedman); p. 64. Washington, 1976. 5. Oppenheim, J. J., Schechter, B. ibid. p. 81. 6. Check, I., Merker, R., Vardiman, J., DeMeester, T. R., Wolfman, H., Coley, T., Matutis, A., Hunter, R. in Proceedings of the Second American Society for Microbiology Conference on Diagnostic Immunology (edited by H. Friedman and N. R. Rose). Washington (in the press). 7. Bainbridge, E. T., Ford, C. H. J., Newman, C. E. Lancet, 1978, i, 1203.
1318 value for patients surviving less than 4 months. Survival was highly correlated with white cell number above or below 10 800/1 and with numbers of neutrophils, monocytes, and immature myeloid cells (P<0.001, 0.05, and 0-005, respect-
ively). The increased white-blood-cell number at time of staging is unlikely to reflect terminal infection since most patients (18 of 24) who died within 4 months lived longer than a month- Nor can differences be accounted for by histological type of cancer: there were approximately equal numbers of squamous-cell and
adenocarcinoma in each group. In 1970, Riesco8 found a similar- negative correlation between neutrophils and "curability" of 589 cases of different kinds of cancer. We cannot explain this difference in total white-blood-cell counts in patients surviving less than or more than 4 months. However, the blood count is accurate and easy to do. Since it seems to predict survival in unresectable lung cancer this finding is worth pursuing. This work
was
supported by grant
CA 14599 from the U.S. Public
Health Service.
Departments of Pathology and Surgery, University of Chicago, Chicago, Illinois 60637, U.S.A.
I. J. CHECK T. DEMEESTER J. VARDIMAN R. L. HUNTER
NITROUS OXIDE AND VITAMIN
B12
SiR,—The finding of Rosemary Deacon and her colleagues (Nov. 11, p. 1023) that selected inactivation of vitamin B12 may be produced by nitrous oxide may have important implications for a recently described neurological syndrome.’ In man this syndrome consists of the association of nitrous-oxide inhalation with symptoms of dysxsthesia and reduced vibration and proprioception, as well as weakness. While described as a neuropathy, two of three patients had band-like
both these react with the polyvalent antigen to the same titre as they do to the type 1 and 2 components separately. Hence it would seem that polyvalent antigen is a real possibility for initial screening of sera, and this view has been reinforced by examination of positive sera from cases which previously reacted with type 1 antigen both on examination in this laboratory and at the Center for Disease Control, Atlanta. We thank Dr R. Weaver of C.D.C. Atlanta for strains of L. pneumoand 4 and Dr H. Wilkinson also of C.D.C. for positive control serum for serotype 2. Papers on nomenclature and serology by C.D.C. workers are to appear in the Annals ofInternalMedicine.
phila, serotypes 3
Department of Laboratory Medicine, Ruchill Hospital, Glasgow G20 9NB
R. J. FALLON W. H. ABRAHAM
BETA-BLOCKADE AND MUSCLE FUNCTION
SIR,-Despite the widespread tissue distribution of adrenergic receptors beta-blockade produces remarkably few sideeffects. One common problem is a sensation of muscle fatigue. The reason for this is unclear although decreased blood-flow to the exercising muscles is one possibility. However, when blood-flow was measured over the leg before and during exercise beta-blockade had little effect.Another possibility is a metabolic change, such as reduced substrate supply (i.e., decreased muscle glycogenolysis combined with inhibited freetatty-acid mobilisation). During exercise up to the point of exhaustion this mechanism appears of importance.2 Carlsson et al.3 reported that beta-blockade influenced plasma potassium levels during and after exercise. Such an effect may influence the muscle-action potential and excitability and directly contribute to the muscle fatique. To characterise the effect of beta-blockade on muscle strength and we have studied six healthy volunteers (three males and
performance
TABLE I-RESULTS FROM BICYCLE TESTS
sensations about the waist, two a form of Lhermitte’s sign, one demonstrated brisk deep tendon reflexes, and none had the stocking-glove distribution of parsesthesias usually found in
(100 W)
polyneuropathy. As an alternative interpretation I propose that these patients exhibited both myelopathic and peripheral neuropathic features, in some ways reminiscent of vitamin B12 deficiency. These include the presumed dorsal column involvement, longtract signs in at least one of their patients, and evidence of "axonal" neuropathy. Although the rats studied by Deacon et al. did not increase their urinary excretion of methylmalonic acid, as is typically found in vitamin Blz deficiency, it would be of interest to pursue this measure in humans exposed to nitrous oxide, and, more importantly, to determine whether or not parenteral administration of vitamin B12 might improve their symptoms. Palo Alto Medical Clinic, 300 Homer Avenue, Palo Alto, California 94301, U.S.A.
BRUCE T. ADORNATO
DETECTING LEGIONNAIRES’ DISEASE
SIR,-In their interesting article Dr Edelstein and his colleagues (Dec. 2, p. 1172) suggest that various serotypes must be included in serological tests for greater diagnostic sensitivity of legionnaires’ disease. Using heat-killed Legionella pneumophila of serotypes 1, 2, 3, and 4 as antigen we have made a polyvalent antigen for the indirect fluorescent antibody test for the presence of antibodies to L. pneumophila. Although as yet we have known positive control sera only for types 1 and 2, 8. Riesco, A. Cancer, 1970, 25, 135. 1. Layzer, R. B., Fishman, R. A., Schafer,
28, 504.
J. A. Neurology, Minneapolis, 1978,
Means±s.E.M., n=6. three
females) aged 24-33. They were given in a randomised and doubcross-over study, placebo tablets, propranolol 80 mg (nonselective) or metoprolol 100 mg (beta, -selective), all twice a day for 3 days. The wash-out period was 1 week between the drugs. The last le-blind
tablet
was taken 2 h before the muscle-function tests. The volunteers asked whether they felt more tired and if they felt that their physical performance was reduced by the treatment. All volunteers felt well on placebo while two volunteers, not the same, felt more tired and experienced reduced physical performance ability while taking propranolol or metoprolol. Thus, the volunteers experiencing side-effects on propranolol felt well while taking metoprolol and vice versa. Before the muscle-strength tests, the volunteers exercised for 6 min on a mechanically braked ergometer bicycle at a work load of 100 W to warm up and for measurement of heart-rate and perceived exertion, on a scale from 6 to 20.4 Isometric and dynamic muscle strength was measured for the right quadriceps muscle on a ’Cybex 11’.5 Right handgrip strength was measured with a strain-gauge dynamometer. Static endurance was assessed from the decline in handgrip force at twelve repeated contractions during 2 min. The quadriceps dynamic endurance was assessed from fifty repeated contractions with maximal effort and an angular velocity of 180°/s. The perception of effort for the quadriceps (static contraction) and handgrip was studied by asking
were
1. Julin-Dannfelt, A., Aström, H. Scand. J. Lab. clin. Invest. (in the press). 2. Galbo, H., Christensen, N. J., Holst, J. J. J. appl. Physiol. 1977, 42, 525. 3. Carlsson, E., Fellenius, E., Lundberg, P. & Svensson, L. Lancet, 1978, ii, 424. 4. Borg, G. Scand. J. Rehab. Med. 1970, 2, 92. 5. Thorstensson, A., Grimby, G. & Karlsson, J. J. appl. Physiol. 1976, 40, 12.
in-neutralising activity in plasma reflected by prostaglandin synthesis.
to
platelet function
as
CANCER
thrombotic disease an increase in P.F.410 and in the plasma has been reported. It will be of interest p-T.G." to see if an inverse relation between intra-platelet and extraplatelet levels of these molecules can be demonstrated. It will be of even greater interest if chronic disturbances of this kind reflect a predisposition to thrombosis. Indeed it has already been suggested that a raised plasma heparin-neutralising activity may, on occasions, indicate a prothrombotic state. 12 Portsmouth and South East Hampshire District Pathology Service, St. Mary’s Hospital, Portsmouth PO3 6AG J. R. O’BRIEN In
acute
PNEUMOCOCCAL INFECTION AFTER VACCINATION
SIR,-Although pneumococcal vaccine is effective in population groups, 12 its protective value in certain immunodeficient patients predisposed to pneumococcal infections may be limited.3 We have studied a 46-year-old male with chronic lymphocytic leukxmia diagnosed in 1968 who required intermittent therapy with cyclophosphamide, prednisone, and procarbazine. His serum-immunoglobulins are below normal, IgG 194 mg/dl (800-1800), IgA 110 mg/dl (90-450), and IgM 52 mg/dl (60-250), and he frequently has to be admitted to hospital for pulmonary and urinary-tract infections. On March 21, 1978, he received 0.5ml ’Pneumovax’ intramuscularly. He was readmitted on April 7, with a 24 h history of chills and fever. Admission white-cell count was 13 100/1 with 1% PNEUMOCOCCAL
TYPE*
DIFFERENTIAL COUNTS AND SURVIVAL IN LUNG
ANTIBODY LEVEL
SIR,-Methodological difficulties can lead to spurious associations between technically complex tests of immune function, such as erythrocyte rosette formation 1or mitogen responsiveness,3 and disease severity. Factors such as the standardisation of reagents, sampling error, and the variation in composition of cell suspensions prepared by gradient separation of blood can complicate the interpretation of these assays.4-6 Consequently, simpler tests which can be carried out with precision need to be re-evaluated or developed. We have found that accurate white-blood-cell and differential counts are valuable predictors of survival in patients with unresectable lung cancer. Differential counts were done as part of the initial clinical and immunological evaluation of all patients seen in the University of Chicago Hospitals for suspected lung cancer. A Technicon ’Hemalog D’ counter was used because it counts 30 000 cells and produces very accurate counts for cells, such as monocytes, which occur at low frequency. Cell-counts were unremarkable in patients with resectable lung cancer (stages 1, 2, and 3 MO) but were unexpectedly related to survival in unresectable lung cancer. (MEAN±S.D. pI) IN PATIENTS WITH UNRESECTABLE LUNG CANCER
TABLE I-TOTAL AND DIFFERENTIAL BLOOD COUNTS
PER
(ng/ml)tj-
TABLE II-SURVIVAL OF PATIENTS WITH UNRESECTABLE LUNG CANCER RELATIVE TO WHITE-BLOOD-CELL COUNT
*Danish nomenclature. tR.i.A. by Dr G. Schiffman.
bands, 11% polymorphs, 87% lymphocytes, and 1% monocytes. Chest X-ray revealed bilateral infiltrates. Blood and spucultures were positive for Streptococcus pneumoniae. The isolate was typed by counterimmunoelectrophoresis and was found to be one of the vaccine types, type 9. The patient retum
sponded to treatment. Serial serum specimens failed to demonstrate development of significant levels of type 9 antibody in response to either the antecedent vaccine or the current infection. Antibody titres to other penumococcal vaccine types were equally unim-
most
pressive. This case shows how patients with defective immunoglobulin synthesis secondary to underlying disease or chemotherapy may fail to develop protective levels of antipneumococcal antibody after natural infection or pneumococcal vaccine. While there is no apparent contraindication to administering the vaccine to such patients, the diagnosis of pneumococcal infection by vaccine or non-vaccine types must still be considered in this group of vaccine recipients. Section of Infectious Diseases, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, U.S.A.
Median survival,
as determined by life-table analysis, for 51 with unresectable lung cancer, excluding those with small-cell undifferentiated (oat cell) carcinoma, was 4.8 months. Cell-counts in relation to survival for more or less than 4 months are shown in table L There was a highly significant increase in white blood-cells in patients surviving less than 4 months, which seems to be a summation of increases in neutrophils, monocytes, and immature myeloid cells. Lymphocyte-counts did not differ between the two groups. However, as others have found in breast cancer, 17 lymphocyte numbers were lower in the unresectable cases as a group than in patients with less advanced disease. Table 11 shows survival of patients whose white-blood-cell counts were greater than or less than 10 800/1, the mean
patients
1.
LAUREL PREHEIM MICHAEL RYTEL
10. Handin, R. I., McDonough, M., Lesch, M. J. Lab. clin. Med. (in the press). 11. Ludlam, C. A., Bolton, A. E., Moore, S., Cash, J. D. Lancet, 1975, ii, 259. 12. O’Brien, J. R., Etherington, M. D., Jamieson, S., Lawford, P., Lincoln, S. V., Alkjaersig, N. J. Thromb.Diath. haemorrh. 1975, 34, 453. 1. Amman, A. J., and others. New Engl. J. Med. 1977, 297, 897. 2. Smit, P., and others. J. Am.med. Ass. 1977, 238, 2613. 3. Morbid. Mortal. wkly Rep. 1977, 26, 345.
Teasdale, C., Thatcher, J., Whitehead, R. H., Chare, M. J. B., Hughes, L.
E.
Lancet, 1977, i, 543. 2. Byrom, N. A., Campbell, M. A., Staughton, R. C. D., Timlin, D. M. ibid.
1977, ii, 1132. 3. Moore, D. L.,Heyworth, B., Brown, J. Clin. exp. Immun. 1974, 17, 647. 4. Winchester, R. J., Ross, G. in Manual of Clinical Immunology (edited by N. R. Rose and H. Fnedman); p. 64. Washington, 1976. 5. Oppenheim, J. J., Schechter, B. ibid. p. 81. 6. Check, I., Merker, R., Vardiman, J., DeMeester, T. R., Wolfman, H., Coley, T., Matutis, A., Hunter, R. in Proceedings of the Second American Society for Microbiology Conference on Diagnostic Immunology (edited by H. Friedman and N. R. Rose). Washington (in the press). 7. Bainbridge, E. T., Ford, C. H. J., Newman, C. E. Lancet, 1978, i, 1203.
1318 value for patients surviving less than 4 months. Survival was highly correlated with white cell number above or below 10 800/1 and with numbers of neutrophils, monocytes, and immature myeloid cells (P<0.001, 0.05, and 0-005, respect-
ively). The increased white-blood-cell number at time of staging is unlikely to reflect terminal infection since most patients (18 of 24) who died within 4 months lived longer than a month- Nor can differences be accounted for by histological type of cancer: there were approximately equal numbers of squamous-cell and
adenocarcinoma in each group. In 1970, Riesco8 found a similar- negative correlation between neutrophils and "curability" of 589 cases of different kinds of cancer. We cannot explain this difference in total white-blood-cell counts in patients surviving less than or more than 4 months. However, the blood count is accurate and easy to do. Since it seems to predict survival in unresectable lung cancer this finding is worth pursuing. This work
was
supported by grant
CA 14599 from the U.S. Public
Health Service.
Departments of Pathology and Surgery, University of Chicago, Chicago, Illinois 60637, U.S.A.
I. J. CHECK T. DEMEESTER J. VARDIMAN R. L. HUNTER
NITROUS OXIDE AND VITAMIN
B12
SiR,—The finding of Rosemary Deacon and her colleagues (Nov. 11, p. 1023) that selected inactivation of vitamin B12 may be produced by nitrous oxide may have important implications for a recently described neurological syndrome.’ In man this syndrome consists of the association of nitrous-oxide inhalation with symptoms of dysxsthesia and reduced vibration and proprioception, as well as weakness. While described as a neuropathy, two of three patients had band-like
both these react with the polyvalent antigen to the same titre as they do to the type 1 and 2 components separately. Hence it would seem that polyvalent antigen is a real possibility for initial screening of sera, and this view has been reinforced by examination of positive sera from cases which previously reacted with type 1 antigen both on examination in this laboratory and at the Center for Disease Control, Atlanta. We thank Dr R. Weaver of C.D.C. Atlanta for strains of L. pneumoand 4 and Dr H. Wilkinson also of C.D.C. for positive control serum for serotype 2. Papers on nomenclature and serology by C.D.C. workers are to appear in the Annals ofInternalMedicine.
phila, serotypes 3
Department of Laboratory Medicine, Ruchill Hospital, Glasgow G20 9NB
R. J. FALLON W. H. ABRAHAM
BETA-BLOCKADE AND MUSCLE FUNCTION
SIR,-Despite the widespread tissue distribution of adrenergic receptors beta-blockade produces remarkably few sideeffects. One common problem is a sensation of muscle fatigue. The reason for this is unclear although decreased blood-flow to the exercising muscles is one possibility. However, when blood-flow was measured over the leg before and during exercise beta-blockade had little effect.Another possibility is a metabolic change, such as reduced substrate supply (i.e., decreased muscle glycogenolysis combined with inhibited freetatty-acid mobilisation). During exercise up to the point of exhaustion this mechanism appears of importance.2 Carlsson et al.3 reported that beta-blockade influenced plasma potassium levels during and after exercise. Such an effect may influence the muscle-action potential and excitability and directly contribute to the muscle fatique. To characterise the effect of beta-blockade on muscle strength and we have studied six healthy volunteers (three males and
performance
TABLE I-RESULTS FROM BICYCLE TESTS
sensations about the waist, two a form of Lhermitte’s sign, one demonstrated brisk deep tendon reflexes, and none had the stocking-glove distribution of parsesthesias usually found in
(100 W)
polyneuropathy. As an alternative interpretation I propose that these patients exhibited both myelopathic and peripheral neuropathic features, in some ways reminiscent of vitamin B12 deficiency. These include the presumed dorsal column involvement, longtract signs in at least one of their patients, and evidence of "axonal" neuropathy. Although the rats studied by Deacon et al. did not increase their urinary excretion of methylmalonic acid, as is typically found in vitamin Blz deficiency, it would be of interest to pursue this measure in humans exposed to nitrous oxide, and, more importantly, to determine whether or not parenteral administration of vitamin B12 might improve their symptoms. Palo Alto Medical Clinic, 300 Homer Avenue, Palo Alto, California 94301, U.S.A.
BRUCE T. ADORNATO
DETECTING LEGIONNAIRES’ DISEASE
SIR,-In their interesting article Dr Edelstein and his colleagues (Dec. 2, p. 1172) suggest that various serotypes must be included in serological tests for greater diagnostic sensitivity of legionnaires’ disease. Using heat-killed Legionella pneumophila of serotypes 1, 2, 3, and 4 as antigen we have made a polyvalent antigen for the indirect fluorescent antibody test for the presence of antibodies to L. pneumophila. Although as yet we have known positive control sera only for types 1 and 2, 8. Riesco, A. Cancer, 1970, 25, 135. 1. Layzer, R. B., Fishman, R. A., Schafer,
28, 504.
J. A. Neurology, Minneapolis, 1978,
Means±s.E.M., n=6. three
females) aged 24-33. They were given in a randomised and doubcross-over study, placebo tablets, propranolol 80 mg (nonselective) or metoprolol 100 mg (beta, -selective), all twice a day for 3 days. The wash-out period was 1 week between the drugs. The last le-blind
tablet
was taken 2 h before the muscle-function tests. The volunteers asked whether they felt more tired and if they felt that their physical performance was reduced by the treatment. All volunteers felt well on placebo while two volunteers, not the same, felt more tired and experienced reduced physical performance ability while taking propranolol or metoprolol. Thus, the volunteers experiencing side-effects on propranolol felt well while taking metoprolol and vice versa. Before the muscle-strength tests, the volunteers exercised for 6 min on a mechanically braked ergometer bicycle at a work load of 100 W to warm up and for measurement of heart-rate and perceived exertion, on a scale from 6 to 20.4 Isometric and dynamic muscle strength was measured for the right quadriceps muscle on a ’Cybex 11’.5 Right handgrip strength was measured with a strain-gauge dynamometer. Static endurance was assessed from the decline in handgrip force at twelve repeated contractions during 2 min. The quadriceps dynamic endurance was assessed from fifty repeated contractions with maximal effort and an angular velocity of 180°/s. The perception of effort for the quadriceps (static contraction) and handgrip was studied by asking
were
1. Julin-Dannfelt, A., Aström, H. Scand. J. Lab. clin. Invest. (in the press). 2. Galbo, H., Christensen, N. J., Holst, J. J. J. appl. Physiol. 1977, 42, 525. 3. Carlsson, E., Fellenius, E., Lundberg, P. & Svensson, L. Lancet, 1978, ii, 424. 4. Borg, G. Scand. J. Rehab. Med. 1970, 2, 92. 5. Thorstensson, A., Grimby, G. & Karlsson, J. J. appl. Physiol. 1976, 40, 12.