- Email: [email protected]
Human brain natriuretic peptide, a novel cardiac hormone
801
under-reported.’,’ Patients with renal failure are especially prone4 to colchicine-induced rhabdomyolysis, since the drug and its metabolites are partly excreted by the kidneys and may accumulate if correct dose adjustments are not made. Gout is a known side-effect of cyclosporin therapy, and renal transplant patients on this drug often show moderate degrees of renal failure that would favour the accumulation of colchicine during the treatment of gout. This patient group should therefore be at high risk for colchicine rhabdomyolysis and doctors should be aware of this potential problem. Some "cyclosporin myopathies" in these patients could be colchicine rhabdomyolysis. That the myotoxic effects of both cyclosporin and colchicine might potentiate each other should also be considered. This is suggested by experience in patients with familial Mediterranean fever.8 It would therefore be of interest to know whether or not some patients hitherto described as having cyclosporin-induced myopathy had concomitant colchicine therapy. Cases such as that reported by Grezard and colleagues highlight the importance of a complete listing of drugs-even of those not suspected as being causally related-when reporting
supposed drug toxicity. The list of myotoxic drugs is growing longer-for example, clofibrate, bezafibrate, neuroleptics, narcotics and muscle relaxants, colchicine, cyclosporin, cocaine, amphetamine, theophylline, phenytoin, lovastatin--and one asks, which drug will be next? The fact that we know so little about the mechanisms of drug-induced myopathy syndromes underlines the need for basic clinical research in this area. Department of Nephrology and Rheumatology, University Hospital, D-3400 Goettingen, FRG
K. WOLFGANG RUMPF HANS V. HENNING
1. Goy JJ, Stauffer JC, Deruaz JP, et al. Myopathy as a possible side-effect of cyclosporin. Lancet 1989; i: 1446-17. 2. Chassagne P, Mejjad O, Moore N, Leloet X, Deshayes P. Myopathy as a possible side-effect of cyclosporin. Lancet 1989; ii: 1104. 3. Riggs JE, Schochet SS, Gutmann L, Crosby TW, DiBartolomeo AG. Chronic human colchicine neuropathy and myopathy. Arch Neurol 1986; 43: 521-23. 4. Kuncl RW, Duncan G, Watson D, Alderson K, Rogawski MA, Peper M. Colchicine myopathy and neuropathy. N Engl J Med 1987; 316: 1562-68. 5. Besana C, Comi G, Baldini V, Ciboddo G, Bianchi R. Colchicine myoneuropathy. Lancet 1977; ii: 1271-72. 6. Gendron Y, Bronstein JA, Gras C, Boz P. Neuromuscular toxicity of colchicine: case. Nouv Presse Med 1989; 18: 1256. 7. Editorial. Colchicine myoneuropathy. Lancet 1987; ii: 668. 8. Cohen SL, Boner G, Shmueli D, Yusim A, Rosenfeld J, Shapira Z. Cyclosporin: poorly tolerated in familial Mediterranean fever. Nephrol Dial Transplant 1989; 4: 201-04.
Human brain natriuretic peptide, cardiac hormone
a
novel
SIR,-Brain natriuretic peptide (BNP), a natriuretic peptide with 26 aminoacids isolated from the porcine brain,l has a striking homology to atrial natriuretic peptide (ANP) both in aminoacid sequence and in peripheral and central actions.1-4 BNP is also synthesised in and secreted from the porcine hearth We have isolated and sequenced BNP with 45 aminoacids from the rat heart .6However, antisera against porcine or rat BNP failed to detect BNP-like immunoreacivity (BNP-LI) in human tissues, indicating a diversity of the BNP sequence among species. Recently, we have isolated human BNP (hBNP) from the atrium and found it to have 32 aminoacid residues with an intramolecular disulphide bridge, similar to that found in ANP.8 We have developed a monoclonal antibody to hBNP and with a specific radioimmunoassay (RIA) have measured hBNP-LI in the plasma of 11 healthy controls and 86 patients, and compared them with plasma ANP measured simultaneously.9 39 patients had heart disease with various degrees of congestive heart failure, 14 had chronic renal failure, 21 had essential hypertension, 2 had primary aldosteronism, 3 had Cushing’s syndrome, and 2 had phaeochromocytoma. In 6 patients with heart failure samples were obtained from various sites, including the coronary sinus during catheterisation.
Plasma BNP (8) and ANP (0) levels in healthy controls and
patients. Plasma hBNP-LI levels in the coronary sinus ranged from 38 to 813 fmol/ml (mean 293-2 [113°5 SEM]) and were comparable with ANP-LI levels; there was a significant (2-3 fold) increase compared with levels in the aortic root in all 6 cases. This shows that hBNP is secreted into the circulation through the coronary sinus from the
heart.
peripheral hBNP-LI levels were 0 90 (0’07) which was only 16% of ANP-LI. In contrast, plasma hBNP-LI levels were high in congestive heart failure and often surpassed the concentration of ANP-LI (figure). Plasma hBNP-LI levels (182-0 [35-9] finol/ml) in 21 patients with severe heart failure (class III or IV) were significantly higher than those in patients of less severe failure (44’6 [21 °6] fmol/ml) (p < 001). hBNP-LI levels were also significantly increased in renal failure (24 [6-0]), hypertension (104 [1’2]), and primary aldosteronism (120 [2°5] finol/ml) compared with control values (p < 0-01), and tended to increase in Cushing’s syndrome and phaeochromocytoma also. These increases in hBNP in patients were much more prominent than the increases in ANP (eg, a 200-fold increase of hBNP vs a In healthy controls
finol/m1,
20-fold increase of ANP in severe congestive heart failure). These findings in patients, together with the presence of a receptor more specific for BNP10 and the equivalent biological action of hBNP and ANP, indicate the significance of hBNP as a novel cardiac hormone in the dual natriuretic peptide system.
Second Division, Department of Medicine, Kyoto University School of Medicine,
Kyoto 606, Japan
MASASHI MUKOYAMA KAZUWA NAKAO YOSHIHIKO SAITO YOSHIHIRO OGAWA KIMINORI HOSODA SHIN-ICHI SUGA GOTARO SHIRAKAMI MICHIHISA JOUGASAKI HIROO IMURA
1. Sudoh T, Kangawa K, Minamino N, Matsuo H. A new natriuretic peptide in porcine brain. Nature 1988; 332: 78-81.
802
2. Itoh H, Nakao K, Yamada T, et al. Antidipsogenic action of a novel peptide "brain natriuretic peptide" in rats. Eur J Pharmacol 1988; 150: 193-96. 3. Shirakami G, Nakao K, Yamada T, et al. Inhibitory effect of brain natriuretic peptide on central angiotensin II-stimulated pressor response in conscious rats. Neurosci Lett 1988; 91: 77-83. 4. Yamada T, Nakao K, Itoh H, et al. Intracerebroventricular injection of brain natriuretic peptide inhibits vasopressin secretion in conscious rats. Neurosci Lett 1988; 95: 223-28. 5. Saito Y, Nakao K, Itoh H, et al. Brain natriuretic peptide is a novel cardiac hormone. Biochem Biophys Res Commun 1989; 158: 360-68. 6. Itoh H, Nakao K, Kambayashi Y, et al. Occurrence of a novel cardiac natriuretic peptide in rats. Biochem Biophys Res Commun 1989; 161: 732-39. 7. Kambayashi Y, Nakao K, Itoh H, et al. Isolation and sequence determination of rat cardiac natriuretic peptide. Biochem Biophys Res Commun 1989; 163: 233-40. 8. Kambayashi Y, Nakao K, Mukoyama M, et al. Isolation and sequence determination of human brain natriuretic peptide in human atrium. FEBS Lett 1990; 259: 341-45. 9. Itoh H, Nakao K, Sugawara A, et al. &ggr;-Atrial natriureric polypepride (&ggr;-ANP)-derived peptides in human plasma: cosecretion of N-terminal &ggr;-ANP fragment and &agr;-ANP. J Clin Endocrinol Metab 1988; 67: 429-37. 10. Chang MS, Lowe DG, Lewis M, et al. Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases. Nature 1989; 341: 68-72.
Chronic high-dose pamidronate in
refractory malignant hypercalcaemia in the
SiR,—The role of the biphosphonate pamidronate (APD) treatment of hypercalcaemia due to malignancy is well established, and the efficacy of single infusions has been demonstrated in several centres.1,2 Dose recommendations have been made for calcium concentration and there is thought to be a dose-response relation with respect to duration of response.3,4 Treatment is usually repeated every three weeks, which maintains control of hypercalcaemia in most patients. Lower doses tend to be associated with more rapid relapse. Clearly the ability to control hypercalcaemia quickly may be lifesaving, but the role of biphosphonates in the long-term prevention of recurrent hypercalcaemia is still being investigated. We report our experience with this drug in chronic high-dose. A 52-year-old man with an 18-month history of multiple myeloma who became refractory to chemotherapy began receiving regular treatment with pamidronate in August, 1988. He had previously been treated by combination chemotherapy with vincristine, doxorubicin hydrochloride, and methylprednisolone (VAMP), followed by high-dose melphalan. Following disease recurrence in August, 1988, he was again given chemotherapy but failed to respond and persistent thrombocytopenia and hypercalcaemia developed. Large doses of pamidronate were needed to control the calcium, which only stabilised after doses as high as 90 mg. Chemotherapy was discontinued in November and he was given supportive care alone. A dose of 60 mg intravenous pamidronate every week was needed to maintain plasma calcium concentration under 26 mmol/l. Attempts to lengthen the interval between treatments to two weeks were invariably accompanied by the return of symptoms and a rise in plasma calcium to over 3-0 mmol/1. He remained in bone marrow failure but despite anaemia and thrombocytopenia necessitating frequent blood and platelet transfusions he remained active, with a reasonable quality of life for 9 months. This patient’s life was probably substantially prolonged by this treatment. In view of the apparent dose-response relation for pamidronate, patients with hypercalcaemia due to malignant disease should not be regarded as refractory to this treatment until frequent high doses have been tested. Long-term control of malignant hypercalcemia may be achieved even in end-stage patients. CRC Section of Medicine, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey SM2 5PX, UK
IAN JUDSON
Pathology Department, Royal Berkshire Hospital, Reading
FRANK BOOTH
CRC Section of Medicine, Institute of Cancer Research and Royal Marsden Hospital
MARTIN GORE TIM MCELWAIN
1. Cantwell
BMJ,
Harris
AL.
Effect
of
ammohydroxypropylidene biphosphonate Br Med J 1987; 294: 467-69.
single high dose infusions of hypercalcaemia caused by cancer.
on
2. Morton AR, Cantrill JA,
Craig AE, Howell A, Davies M, Anderson DC. Single dose daily intravenous aminohydroxypropylidene biphosphonate (APD) for the hypercalcaemia of malignancy. Br MedJ 1988; 296: 811-14. 3. Body J-J, Pot M, Borkowski A, Sculier JP, Klastersky J. Dose/response study of aminohydroxypropylidene biphosphonate in tumor-associated hypercalcemia. Am J Med 1987, 82: 957-63. 4. Thiébaud D, Jaeger Ph, Jaquet AF, Burckhardt P. Dose-response in the treatment of hypercalcemia of malignancy by a single infusion of the biphosphonate AHPrBP. J Clin Oncol 1988; 6: 762-68. 5. Gore ME, Selby PJ, Viner C, et al. Intensive treatment of multiple myeloma and criteria for complete remission. Lancet 1989; i: 879-82. versus
Reading and inclined surfaces SIR,-In your Nov 11 note (p 1171), Are you sitting comfortably? ask, "would use of inclined surfaces for both writing and reading further reduce stresses on the head and neck?". The eyes (in combination with the work of the hands) generally determine body posture. When held for a long time the direction of sight can only deviate a few degrees from the axis of the eye socket. Therefore, the position of the head and the body must be adapted to the direction of you
sight/ When bending the head forward the load on muscles and vertebrae increases according to a sinus function-ie, the change in length of the lever arms of the weight force of the head with respect to the joint axes in the cervical spine.2 Reading and writing at a horizontal desk always forces the head in forward bend position, putting a high load on the cervical spine. Improvement would be expected if an inclined desk is used. To prevent items sliding, a desk (’Erasmus Office Desk’ European patent no 6442800) with an incline of only 10° was developed. We have shown that such a modest inclination improved head position by a mean of 7° creating a 15% (in some individuals up to 35%) decrease in load on the cervical spine (unpublished results). The load on the thoracolumbar spine decreased by a mean of 22 %, and one individual showed 95%
improvement. In general a neutral or unconstrained position of the head is defined by a line of sight 10-150 below horizontal. This corresponds with the recommendation in most US human engineering guidelines, including design standards used by the US military. However, the German safety regulation 2H 1/618 identifies 35’ below horizontal as optimum, and the Swedish TCO, 1984, recommends "about 200".3 For reading it is generally advisable to position the face of computer screens or sheets of paper perpendicular to the direction of sight to avoid perspective deformation of letters. This, together with a proper reading distance, results in recommendations for the height of computer screens.
Recently a computer model was developed to study the complicated loadings of the cervical spine arising in highperformance aircraft: improvement in loading was identified when the direction of sight was horizontal." This posture was called "the F-16 posture", which we now advise for visual display units (unpublished). This advice is strikingly different from existing regulations.4 Advice for Lancet readers might be: never read with the journal on a horizontal desk but use a surface inclined by at least 10°. When The Lancet becomes available on floppy disc, adopt the F-16 fighter pilot posture. Department of Biomedical Physics and Technology, Erasmus University, 3000 DR, Rotterdam, Netherlands
C. J. SNIJDERS M. P. J. M. VAN RIEL
Occupational Health and Safety, Hoogovens IJmuiden BV
J. C. F. M. AGHINA
Department of Anatomy, Erasmus University
R. STOECKART
1. Hofling G. Schlechte Haltung beim schreiben. Stuttgart: Hippokrates Verlag, 1972.
Urasche und ihre
Beseitigung.
2. Le Veau B. Williams and Lissner: biomechanics of human modon. Philadelphia: WB Saunders Company, 1976. 3. Kroemer KHE, Hill SG. Preferred line of sight. Proceedings: work with display units, Stockholm, 1986: 415-18. 4. Snijders CJ, Roosch ER. The cervical spine under high G-load. symposium: neck injury in advanced military aircraft environments, Munich, 1989.
under-reported.’,’ Patients with renal failure are especially prone4 to colchicine-induced rhabdomyolysis, since the drug and its metabolites are partly excreted by the kidneys and may accumulate if correct dose adjustments are not made. Gout is a known side-effect of cyclosporin therapy, and renal transplant patients on this drug often show moderate degrees of renal failure that would favour the accumulation of colchicine during the treatment of gout. This patient group should therefore be at high risk for colchicine rhabdomyolysis and doctors should be aware of this potential problem. Some "cyclosporin myopathies" in these patients could be colchicine rhabdomyolysis. That the myotoxic effects of both cyclosporin and colchicine might potentiate each other should also be considered. This is suggested by experience in patients with familial Mediterranean fever.8 It would therefore be of interest to know whether or not some patients hitherto described as having cyclosporin-induced myopathy had concomitant colchicine therapy. Cases such as that reported by Grezard and colleagues highlight the importance of a complete listing of drugs-even of those not suspected as being causally related-when reporting
supposed drug toxicity. The list of myotoxic drugs is growing longer-for example, clofibrate, bezafibrate, neuroleptics, narcotics and muscle relaxants, colchicine, cyclosporin, cocaine, amphetamine, theophylline, phenytoin, lovastatin--and one asks, which drug will be next? The fact that we know so little about the mechanisms of drug-induced myopathy syndromes underlines the need for basic clinical research in this area. Department of Nephrology and Rheumatology, University Hospital, D-3400 Goettingen, FRG
K. WOLFGANG RUMPF HANS V. HENNING
1. Goy JJ, Stauffer JC, Deruaz JP, et al. Myopathy as a possible side-effect of cyclosporin. Lancet 1989; i: 1446-17. 2. Chassagne P, Mejjad O, Moore N, Leloet X, Deshayes P. Myopathy as a possible side-effect of cyclosporin. Lancet 1989; ii: 1104. 3. Riggs JE, Schochet SS, Gutmann L, Crosby TW, DiBartolomeo AG. Chronic human colchicine neuropathy and myopathy. Arch Neurol 1986; 43: 521-23. 4. Kuncl RW, Duncan G, Watson D, Alderson K, Rogawski MA, Peper M. Colchicine myopathy and neuropathy. N Engl J Med 1987; 316: 1562-68. 5. Besana C, Comi G, Baldini V, Ciboddo G, Bianchi R. Colchicine myoneuropathy. Lancet 1977; ii: 1271-72. 6. Gendron Y, Bronstein JA, Gras C, Boz P. Neuromuscular toxicity of colchicine: case. Nouv Presse Med 1989; 18: 1256. 7. Editorial. Colchicine myoneuropathy. Lancet 1987; ii: 668. 8. Cohen SL, Boner G, Shmueli D, Yusim A, Rosenfeld J, Shapira Z. Cyclosporin: poorly tolerated in familial Mediterranean fever. Nephrol Dial Transplant 1989; 4: 201-04.
Human brain natriuretic peptide, cardiac hormone
a
novel
SIR,-Brain natriuretic peptide (BNP), a natriuretic peptide with 26 aminoacids isolated from the porcine brain,l has a striking homology to atrial natriuretic peptide (ANP) both in aminoacid sequence and in peripheral and central actions.1-4 BNP is also synthesised in and secreted from the porcine hearth We have isolated and sequenced BNP with 45 aminoacids from the rat heart .6However, antisera against porcine or rat BNP failed to detect BNP-like immunoreacivity (BNP-LI) in human tissues, indicating a diversity of the BNP sequence among species. Recently, we have isolated human BNP (hBNP) from the atrium and found it to have 32 aminoacid residues with an intramolecular disulphide bridge, similar to that found in ANP.8 We have developed a monoclonal antibody to hBNP and with a specific radioimmunoassay (RIA) have measured hBNP-LI in the plasma of 11 healthy controls and 86 patients, and compared them with plasma ANP measured simultaneously.9 39 patients had heart disease with various degrees of congestive heart failure, 14 had chronic renal failure, 21 had essential hypertension, 2 had primary aldosteronism, 3 had Cushing’s syndrome, and 2 had phaeochromocytoma. In 6 patients with heart failure samples were obtained from various sites, including the coronary sinus during catheterisation.
Plasma BNP (8) and ANP (0) levels in healthy controls and
patients. Plasma hBNP-LI levels in the coronary sinus ranged from 38 to 813 fmol/ml (mean 293-2 [113°5 SEM]) and were comparable with ANP-LI levels; there was a significant (2-3 fold) increase compared with levels in the aortic root in all 6 cases. This shows that hBNP is secreted into the circulation through the coronary sinus from the
heart.
peripheral hBNP-LI levels were 0 90 (0’07) which was only 16% of ANP-LI. In contrast, plasma hBNP-LI levels were high in congestive heart failure and often surpassed the concentration of ANP-LI (figure). Plasma hBNP-LI levels (182-0 [35-9] finol/ml) in 21 patients with severe heart failure (class III or IV) were significantly higher than those in patients of less severe failure (44’6 [21 °6] fmol/ml) (p < 001). hBNP-LI levels were also significantly increased in renal failure (24 [6-0]), hypertension (104 [1’2]), and primary aldosteronism (120 [2°5] finol/ml) compared with control values (p < 0-01), and tended to increase in Cushing’s syndrome and phaeochromocytoma also. These increases in hBNP in patients were much more prominent than the increases in ANP (eg, a 200-fold increase of hBNP vs a In healthy controls
finol/m1,
20-fold increase of ANP in severe congestive heart failure). These findings in patients, together with the presence of a receptor more specific for BNP10 and the equivalent biological action of hBNP and ANP, indicate the significance of hBNP as a novel cardiac hormone in the dual natriuretic peptide system.
Second Division, Department of Medicine, Kyoto University School of Medicine,
Kyoto 606, Japan
MASASHI MUKOYAMA KAZUWA NAKAO YOSHIHIKO SAITO YOSHIHIRO OGAWA KIMINORI HOSODA SHIN-ICHI SUGA GOTARO SHIRAKAMI MICHIHISA JOUGASAKI HIROO IMURA
1. Sudoh T, Kangawa K, Minamino N, Matsuo H. A new natriuretic peptide in porcine brain. Nature 1988; 332: 78-81.
802
2. Itoh H, Nakao K, Yamada T, et al. Antidipsogenic action of a novel peptide "brain natriuretic peptide" in rats. Eur J Pharmacol 1988; 150: 193-96. 3. Shirakami G, Nakao K, Yamada T, et al. Inhibitory effect of brain natriuretic peptide on central angiotensin II-stimulated pressor response in conscious rats. Neurosci Lett 1988; 91: 77-83. 4. Yamada T, Nakao K, Itoh H, et al. Intracerebroventricular injection of brain natriuretic peptide inhibits vasopressin secretion in conscious rats. Neurosci Lett 1988; 95: 223-28. 5. Saito Y, Nakao K, Itoh H, et al. Brain natriuretic peptide is a novel cardiac hormone. Biochem Biophys Res Commun 1989; 158: 360-68. 6. Itoh H, Nakao K, Kambayashi Y, et al. Occurrence of a novel cardiac natriuretic peptide in rats. Biochem Biophys Res Commun 1989; 161: 732-39. 7. Kambayashi Y, Nakao K, Itoh H, et al. Isolation and sequence determination of rat cardiac natriuretic peptide. Biochem Biophys Res Commun 1989; 163: 233-40. 8. Kambayashi Y, Nakao K, Mukoyama M, et al. Isolation and sequence determination of human brain natriuretic peptide in human atrium. FEBS Lett 1990; 259: 341-45. 9. Itoh H, Nakao K, Sugawara A, et al. &ggr;-Atrial natriureric polypepride (&ggr;-ANP)-derived peptides in human plasma: cosecretion of N-terminal &ggr;-ANP fragment and &agr;-ANP. J Clin Endocrinol Metab 1988; 67: 429-37. 10. Chang MS, Lowe DG, Lewis M, et al. Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases. Nature 1989; 341: 68-72.
Chronic high-dose pamidronate in
refractory malignant hypercalcaemia in the
SiR,—The role of the biphosphonate pamidronate (APD) treatment of hypercalcaemia due to malignancy is well established, and the efficacy of single infusions has been demonstrated in several centres.1,2 Dose recommendations have been made for calcium concentration and there is thought to be a dose-response relation with respect to duration of response.3,4 Treatment is usually repeated every three weeks, which maintains control of hypercalcaemia in most patients. Lower doses tend to be associated with more rapid relapse. Clearly the ability to control hypercalcaemia quickly may be lifesaving, but the role of biphosphonates in the long-term prevention of recurrent hypercalcaemia is still being investigated. We report our experience with this drug in chronic high-dose. A 52-year-old man with an 18-month history of multiple myeloma who became refractory to chemotherapy began receiving regular treatment with pamidronate in August, 1988. He had previously been treated by combination chemotherapy with vincristine, doxorubicin hydrochloride, and methylprednisolone (VAMP), followed by high-dose melphalan. Following disease recurrence in August, 1988, he was again given chemotherapy but failed to respond and persistent thrombocytopenia and hypercalcaemia developed. Large doses of pamidronate were needed to control the calcium, which only stabilised after doses as high as 90 mg. Chemotherapy was discontinued in November and he was given supportive care alone. A dose of 60 mg intravenous pamidronate every week was needed to maintain plasma calcium concentration under 26 mmol/l. Attempts to lengthen the interval between treatments to two weeks were invariably accompanied by the return of symptoms and a rise in plasma calcium to over 3-0 mmol/1. He remained in bone marrow failure but despite anaemia and thrombocytopenia necessitating frequent blood and platelet transfusions he remained active, with a reasonable quality of life for 9 months. This patient’s life was probably substantially prolonged by this treatment. In view of the apparent dose-response relation for pamidronate, patients with hypercalcaemia due to malignant disease should not be regarded as refractory to this treatment until frequent high doses have been tested. Long-term control of malignant hypercalcemia may be achieved even in end-stage patients. CRC Section of Medicine, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey SM2 5PX, UK
IAN JUDSON
Pathology Department, Royal Berkshire Hospital, Reading
FRANK BOOTH
CRC Section of Medicine, Institute of Cancer Research and Royal Marsden Hospital
MARTIN GORE TIM MCELWAIN
1. Cantwell
BMJ,
Harris
AL.
Effect
of
ammohydroxypropylidene biphosphonate Br Med J 1987; 294: 467-69.
single high dose infusions of hypercalcaemia caused by cancer.
on
2. Morton AR, Cantrill JA,
Craig AE, Howell A, Davies M, Anderson DC. Single dose daily intravenous aminohydroxypropylidene biphosphonate (APD) for the hypercalcaemia of malignancy. Br MedJ 1988; 296: 811-14. 3. Body J-J, Pot M, Borkowski A, Sculier JP, Klastersky J. Dose/response study of aminohydroxypropylidene biphosphonate in tumor-associated hypercalcemia. Am J Med 1987, 82: 957-63. 4. Thiébaud D, Jaeger Ph, Jaquet AF, Burckhardt P. Dose-response in the treatment of hypercalcemia of malignancy by a single infusion of the biphosphonate AHPrBP. J Clin Oncol 1988; 6: 762-68. 5. Gore ME, Selby PJ, Viner C, et al. Intensive treatment of multiple myeloma and criteria for complete remission. Lancet 1989; i: 879-82. versus
Reading and inclined surfaces SIR,-In your Nov 11 note (p 1171), Are you sitting comfortably? ask, "would use of inclined surfaces for both writing and reading further reduce stresses on the head and neck?". The eyes (in combination with the work of the hands) generally determine body posture. When held for a long time the direction of sight can only deviate a few degrees from the axis of the eye socket. Therefore, the position of the head and the body must be adapted to the direction of you
sight/ When bending the head forward the load on muscles and vertebrae increases according to a sinus function-ie, the change in length of the lever arms of the weight force of the head with respect to the joint axes in the cervical spine.2 Reading and writing at a horizontal desk always forces the head in forward bend position, putting a high load on the cervical spine. Improvement would be expected if an inclined desk is used. To prevent items sliding, a desk (’Erasmus Office Desk’ European patent no 6442800) with an incline of only 10° was developed. We have shown that such a modest inclination improved head position by a mean of 7° creating a 15% (in some individuals up to 35%) decrease in load on the cervical spine (unpublished results). The load on the thoracolumbar spine decreased by a mean of 22 %, and one individual showed 95%
improvement. In general a neutral or unconstrained position of the head is defined by a line of sight 10-150 below horizontal. This corresponds with the recommendation in most US human engineering guidelines, including design standards used by the US military. However, the German safety regulation 2H 1/618 identifies 35’ below horizontal as optimum, and the Swedish TCO, 1984, recommends "about 200".3 For reading it is generally advisable to position the face of computer screens or sheets of paper perpendicular to the direction of sight to avoid perspective deformation of letters. This, together with a proper reading distance, results in recommendations for the height of computer screens.
Recently a computer model was developed to study the complicated loadings of the cervical spine arising in highperformance aircraft: improvement in loading was identified when the direction of sight was horizontal." This posture was called "the F-16 posture", which we now advise for visual display units (unpublished). This advice is strikingly different from existing regulations.4 Advice for Lancet readers might be: never read with the journal on a horizontal desk but use a surface inclined by at least 10°. When The Lancet becomes available on floppy disc, adopt the F-16 fighter pilot posture. Department of Biomedical Physics and Technology, Erasmus University, 3000 DR, Rotterdam, Netherlands
C. J. SNIJDERS M. P. J. M. VAN RIEL
Occupational Health and Safety, Hoogovens IJmuiden BV
J. C. F. M. AGHINA
Department of Anatomy, Erasmus University
R. STOECKART
1. Hofling G. Schlechte Haltung beim schreiben. Stuttgart: Hippokrates Verlag, 1972.
Urasche und ihre
Beseitigung.
2. Le Veau B. Williams and Lissner: biomechanics of human modon. Philadelphia: WB Saunders Company, 1976. 3. Kroemer KHE, Hill SG. Preferred line of sight. Proceedings: work with display units, Stockholm, 1986: 415-18. 4. Snijders CJ, Roosch ER. The cervical spine under high G-load. symposium: neck injury in advanced military aircraft environments, Munich, 1989.