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RADIOACTIVE PHOSPHORUS TREATMENT OF BONE-METASTATIC CARCINOMA OF THE PROSTATE
882
three patients
also failed
to
show any association
(table in). These results suggest that a low l.v.A.p. level is an essential feature of H.H.T. Further evidence of a haemorrhagic diathesis not directly associated with the telangiectatic lesions can usually be demonstrated in cases with very low l.v.A.p. levels. In contrast to normal subjects, gently " milking " the capillary blood-sample from the finger will often produce bruising around the digital puncture in patients with H.H.T. Although the bleeding-time is almost always normal in these cases, the amount of blood lost from a superficial stab wound in their normal flesh is often excessive, especially during the first 60-120 seconds. Such observations indicate that, besides the focal telangiectasia, patients with H.H.T. may have a mild generalised III-PARALLEL ESTIMATIONS OF PACKED-CELL VOLUME AND IN-VIVO ADHESIVE-PLATELET COUNTS ON SEVERAL OCCASIONS FOR
TABLE
3 PATIENTS
WITH H.H.T.
defect of primary hsemostasis. This is presumably due to their low LV.A.P. levels and must contribute to the severity and facility of bleeding from the telangiectases characteristic of this disease. The haemostatic status and genetic linkage of these and other patients with H.H.T. is being investigated, as are the relations between i.v.A.P. levels and age, development of telangiectasia, severity and frequency of bleeding, and systemic haemostatic therapy.
Summary In-vivo adhesive-platelet levels were estimated in twenty-two patients with hereditary haemorrhagic telangiectasia, and were found to be unusually low in eighteen of the nineteen with hasmorrhagic manifestations. No correlation was apparent between these low values and age or severity of telangiectasia, but in some patients particularly severe bleeding was associated with very low in-vivo adhesive-platelet levels and with other evidence of a mild generalised defect of primary hxmostasis. I am indebted to Prof. A. G. Heppleston for advice and criticism in the preparation of this paper, and to my colleagues at the Royal Victoria Infirmary, Newcastle upon Tyne, for access to their patients. Mr. T. Sheridan rendered technical assistance, and Mr. A. E. Young assisted with the photography. REFERENCES C. F. (1960) Acta med. scand. 168, 157. (1961) ibid. 170, 231. Brecher, G., Cronkite, E. P. (1950) J. appl. Physiol. 3, 365. Harrison, D. F. N. (1964) Quart. J. Med. 33, 25. Hellem, A. J. (1960) The Adhesiveness of Human Blood Platelets in p. 22. Oslo. Borchgrevink, C. F., Ames, S. B. (1961) Brit. J. Hœmat. 7, 42. Hugues, J. (1953) Arch. int. Physiol. 61, 565. Macfarlane, R. G. (1941) Quart. J. Med. 10, 1. Salzmann, E. R. (1963) J. lab. clin. Med. 62, 724. Vainer, H., Caen, J. P. (1964) J. clin. Path. 17, 191. Zucker, M. B. (1947) Amer. J. Physiol. 148, 275. (1963) Nature, Lond. 197, 601.
Borchgrevink, -
—
—
Vitro;
RADIOACTIVE PHOSPHORUS TREATMENT OF BONE-METASTATIC CARCINOMA OF THE PROSTATE
J. GORDON SMART M.B.
Lond., F.R.C.S.
SENIOR SURGICAL REGISTRAR, ST. AND ST. PETER’S
THOMAS’S HOSPITAL, LONDON, S.E.1., HOSPITAL, CHERTSEY
MULTIPLE bone metastases, predominantly in the lumbar spine and pelvis, occur in most patients with advanced carcinoma of the prostate. Relief of pain poses a difficult clinical problem, particularly since many of the patients are old and in very poor general condition. A combination of radioactive phosphorus (32P) and testosterone has been used in the United States with striking symptomatic improvement, measured by relief or abolition of pain, in half to two-thirds of the cases. In some instances the osteolytic metastatic areas underwent osteoblastic changes with subsequent resumption of a normal bony architecture (Maxfield et al. 1958, Vermooten et al. 1959, Wildermuth et al. 1960, Parsons 1961). The rationale of the treatment is based on the greater uptake of radioactive phosphorus by embryonic and neoplastic tissues than by other tissues (Shahon 1959) and on the increased uptake of phosphorus in new bone after the administration of androgens (Hertz 1950). Autoradiography has confirmed that when 32P is given in conjunction with testosterone it becomes concentrated in the tumorous areas and not in the normal bone or bone-marrow (Vermooten et al. 1959). There are no reports of the use of this form of treatment in Britain, the following case-reports which are of a preliminary nature, may therefore be of interest.
Case-reports Both patients were taken off stilboestrol therapy for a week before treatment. Seventeen daily intramuscular injections of testosterone proprionate were then given, and for the middle 7 days of this period 1 ’43 ml. of 32P with an activity of 10 mC. on day 1 was injected intravenously. 32P having a half life of 14.3 days, the total dosage was 8-68 mC. At the conclusion of this course of treatment the patients resumed the taking of stilbaestrol. FIRST PATIENT
A man, aged 68 years, presented in 1959 with prostatism. He had a large hard, fixed prostate, bilateral lower-limb oedema and probable block of the inferior vena cava. Intravenous pyelography revealed poor excretion and bilateral backpressure. No bony metastases were seen and the blood-urea was 95 mg. per 100 ml. The serum-acid-phosphatase level was 4 King-Armstrong units. A transurethral biopsy specimen of the prostate gland showed a poorly differentiated adenocarcinoma. The patient was given stilboestrol 100 mg. t.d.s., and in March, 1960, chlorotrianisene (’ Tace ’) (2 tablets t.d.s.) was substituted. In April, 1962, severe low lumbar pain radiating to both legs began and made sleep almost impossible. The patient was unable to rest comfortably in any position. Pethidine 100 mg. was given 3-hourly. X-rays showed extensive osteosclerotic metastases in the pelvis, sacrum, lumbar spine, ribs, and right scapula. On May 26, 1962, oestrogens therapy was stopped, and on June 3 seventeen daily intramuscular injections of testosterone propionate were begun. The pain worsened in the next 48 hours. From June 10 the patient was given seven daily intravenous doses of 1-43 ml. of 12P . Two days later the patient had no pain, and on June 23 he was discharged home, walking and free from pain. Stilboestrol therapy was resumed.
883 On
Sept. 9 there degree, and on Nov.
was a
sudden
30 the
return of pain, nulder in died of bronchopneumonia
A BEDSIDE METHOD OF
patient after an exacerbation of chronic pyelonephritis. The patient had had complete relief of pain for 41/2 months.
BLOOD-GLUCOSE ESTIMATION SIMON L. COHEN Lond., M.R.C.P.
SUSAN LEGG
MEDICAL REGISTRAR
HOUSE-PHYSICIAN
M.B. Lond.
M.B. SECOND PATIENT
A man, aged 72 years, presented in 1959, had had prostatism and low back pain for a year. Clinical examination’ revealed a large hard carcinomatous prostate. Intravenous pyelography showed moderate hydronephrosis and hydroureter (left) with extensive osteosclerotic metastases in the pelvis, lumbar spine, and ribs. The blood-urea was 40 mg. per 100 ml.; serum-acidphosphatase 90 King-Armstrong units. A prostatic smear confirmed the diagnosis of carcinoma of the prostate. Stilboestrol 25 mg. t.d.s. was begun, and bone pain diminished. In June, 1963, the patient had severe neck, lower dorsal, and lumbar pain. All spinal movement was greatly limited. Omnopon gr. 1/3 was given 3-hourly. X-rays showed extensive osteosclerotic metastases in the pelvis and lumbar spine. On June 30 stilbcestrol was stopped, and on July 6 the first of seventeen daily intramuscular injections of testosterone proprionate was given. From July 11 the patient received seven daily intravenous injections of 1.43 ml. of 32P. On July 15 he was free from pain, except for a slight ache in the left groin. 3 days later he could climb in and out of bed without pain or assistance, and on July 24 he was discharged home taking stilboestrol 25 mg. t.d.s. The patient died from an attack of coronary thrombosis in January, 1964. He had had almost complete relief from pain for 6 months until his death. Two further patients were treated in this way. One had partial relief, but died, 2 weeks after a course of 32P
and testosterone, from congestive cardiac failure; the other was considerably relieved of pain for 51/2 months before his death from carcinomatosis.
R. BIRD B.Sc., Ph.D. Birm. A.R.I.C. BIOCHEMIST
ROYAL NORTHERN
HOSPITAL, LONDON, N.7
IN the past few years several clinically valuable blood and urine tests have been simplified by the introduction of impregnated paper strips. We have undertaken a preliminary study of a similar method for estimating the blood-sugar level. Method The test
strip,’Dextrostix’, made by the Ames Co., Stoke Poges, Slough, Bucks, consists of absorbent paper impregnated at one end with a buffered mixture of glucose oxidase, peroxidase, and a chromogen system, and coated with a semipermeable membrane. A drop of capillary or venous blood is placed on the test end of the strip, and washed off after 60 seconds with cold running tap water; the colour change is then compared with a graded colour chart. The colours vary from pale grey at 40 mg. of glucose per 100 ml. blood, through deepening shades of blue-grey at 65, 90, 130, 150, and 200 mg., to a dark blue at 250 mg. of glucose per 100 ml. blood. The test strip can usually be matched to two adjacent colours on the chart, and the blood-glucose level is said to be in the range between these two values. Samples of blood have been taken simultaneously for blood-sugar estimation by analytical methods.
Blood-sugar in the venous samples was measured by autoanalyser microglucose method (’Technicon’ ferricyanide method N9), using the 15 mm. tubular-flow cell, and in the capillary samples by the manual glucoseoxidase procedure described by Marks (1959). the
Summary and Conclusions of the prostate and bone combination of radioactive phosphorus and testosterone propionate. The first had complete relief of pain for 41/2 months, and died a further 2 months later from bronchopneumonia. The second remained free of pain for 6 months after treatment and then died suddenly of coronary thrombosis. Of two further patients, one had partial relief; and the other, in his own opinion, had his pain reduced to a fifth of what it had previously been. Most of these patients are within a year of their death. This treatment, which provides symptomatic relief for much of the remainder of the patient’s life, is worth further trial, particularly since it avoids the risk associated with surgical operations, such as adrenalectomy or
Two
patients with carcinoma
metastases were
treated with
a
pituitary implantation. My
thanks
are
due
to my
chief, Mr. T. W. Mimpriss, for his treat these patients.
encouragement and cooperation in allowing me to REFERENCES
Hertz, S. (1950) J. clin. Invest. 29, 821. Maxfield, J. R. Jr., Maxfield, J. G., Maxfield, W. S. (1958) Sth. med. J. 51, 320. Parsons, R. L. (1961) J. Urol. 85, 342. Shahon, D. B. (1959) Cancer, 12, 862. Vermooten, V., Maxfield, J. R. Jr., Maxfield, J. G. (1959) West. J. Surg.
67, 245 Wildermuth, O., Parker, D., Archambeau, J. O., Chahbazian, C. (1960) J. Amer. Med. Ass. 172, 1607.
"...4A Friend’ is much mistaken in supposing that we approve of the forgeries which have at times appeared in The Lancet. Our remarks bear no such interpretation; but we meant, and we repeat, that the avidity with which the pages of that journal are opened to the reception of scandal and trash of every kind, renders its readers liable to be imposed upon by any one whose inventive faculties are stronger than his principles." -Land. med. Gaz. 1830, 17, 736.
Fig. I-Comparison of dextrostix and laboratory results for the total series (mg. glucose per 100 ml. blood).
three patients
also failed
to
show any association
(table in). These results suggest that a low l.v.A.p. level is an essential feature of H.H.T. Further evidence of a haemorrhagic diathesis not directly associated with the telangiectatic lesions can usually be demonstrated in cases with very low l.v.A.p. levels. In contrast to normal subjects, gently " milking " the capillary blood-sample from the finger will often produce bruising around the digital puncture in patients with H.H.T. Although the bleeding-time is almost always normal in these cases, the amount of blood lost from a superficial stab wound in their normal flesh is often excessive, especially during the first 60-120 seconds. Such observations indicate that, besides the focal telangiectasia, patients with H.H.T. may have a mild generalised III-PARALLEL ESTIMATIONS OF PACKED-CELL VOLUME AND IN-VIVO ADHESIVE-PLATELET COUNTS ON SEVERAL OCCASIONS FOR
TABLE
3 PATIENTS
WITH H.H.T.
defect of primary hsemostasis. This is presumably due to their low LV.A.P. levels and must contribute to the severity and facility of bleeding from the telangiectases characteristic of this disease. The haemostatic status and genetic linkage of these and other patients with H.H.T. is being investigated, as are the relations between i.v.A.P. levels and age, development of telangiectasia, severity and frequency of bleeding, and systemic haemostatic therapy.
Summary In-vivo adhesive-platelet levels were estimated in twenty-two patients with hereditary haemorrhagic telangiectasia, and were found to be unusually low in eighteen of the nineteen with hasmorrhagic manifestations. No correlation was apparent between these low values and age or severity of telangiectasia, but in some patients particularly severe bleeding was associated with very low in-vivo adhesive-platelet levels and with other evidence of a mild generalised defect of primary hxmostasis. I am indebted to Prof. A. G. Heppleston for advice and criticism in the preparation of this paper, and to my colleagues at the Royal Victoria Infirmary, Newcastle upon Tyne, for access to their patients. Mr. T. Sheridan rendered technical assistance, and Mr. A. E. Young assisted with the photography. REFERENCES C. F. (1960) Acta med. scand. 168, 157. (1961) ibid. 170, 231. Brecher, G., Cronkite, E. P. (1950) J. appl. Physiol. 3, 365. Harrison, D. F. N. (1964) Quart. J. Med. 33, 25. Hellem, A. J. (1960) The Adhesiveness of Human Blood Platelets in p. 22. Oslo. Borchgrevink, C. F., Ames, S. B. (1961) Brit. J. Hœmat. 7, 42. Hugues, J. (1953) Arch. int. Physiol. 61, 565. Macfarlane, R. G. (1941) Quart. J. Med. 10, 1. Salzmann, E. R. (1963) J. lab. clin. Med. 62, 724. Vainer, H., Caen, J. P. (1964) J. clin. Path. 17, 191. Zucker, M. B. (1947) Amer. J. Physiol. 148, 275. (1963) Nature, Lond. 197, 601.
Borchgrevink, -
—
—
Vitro;
RADIOACTIVE PHOSPHORUS TREATMENT OF BONE-METASTATIC CARCINOMA OF THE PROSTATE
J. GORDON SMART M.B.
Lond., F.R.C.S.
SENIOR SURGICAL REGISTRAR, ST. AND ST. PETER’S
THOMAS’S HOSPITAL, LONDON, S.E.1., HOSPITAL, CHERTSEY
MULTIPLE bone metastases, predominantly in the lumbar spine and pelvis, occur in most patients with advanced carcinoma of the prostate. Relief of pain poses a difficult clinical problem, particularly since many of the patients are old and in very poor general condition. A combination of radioactive phosphorus (32P) and testosterone has been used in the United States with striking symptomatic improvement, measured by relief or abolition of pain, in half to two-thirds of the cases. In some instances the osteolytic metastatic areas underwent osteoblastic changes with subsequent resumption of a normal bony architecture (Maxfield et al. 1958, Vermooten et al. 1959, Wildermuth et al. 1960, Parsons 1961). The rationale of the treatment is based on the greater uptake of radioactive phosphorus by embryonic and neoplastic tissues than by other tissues (Shahon 1959) and on the increased uptake of phosphorus in new bone after the administration of androgens (Hertz 1950). Autoradiography has confirmed that when 32P is given in conjunction with testosterone it becomes concentrated in the tumorous areas and not in the normal bone or bone-marrow (Vermooten et al. 1959). There are no reports of the use of this form of treatment in Britain, the following case-reports which are of a preliminary nature, may therefore be of interest.
Case-reports Both patients were taken off stilboestrol therapy for a week before treatment. Seventeen daily intramuscular injections of testosterone proprionate were then given, and for the middle 7 days of this period 1 ’43 ml. of 32P with an activity of 10 mC. on day 1 was injected intravenously. 32P having a half life of 14.3 days, the total dosage was 8-68 mC. At the conclusion of this course of treatment the patients resumed the taking of stilbaestrol. FIRST PATIENT
A man, aged 68 years, presented in 1959 with prostatism. He had a large hard, fixed prostate, bilateral lower-limb oedema and probable block of the inferior vena cava. Intravenous pyelography revealed poor excretion and bilateral backpressure. No bony metastases were seen and the blood-urea was 95 mg. per 100 ml. The serum-acid-phosphatase level was 4 King-Armstrong units. A transurethral biopsy specimen of the prostate gland showed a poorly differentiated adenocarcinoma. The patient was given stilboestrol 100 mg. t.d.s., and in March, 1960, chlorotrianisene (’ Tace ’) (2 tablets t.d.s.) was substituted. In April, 1962, severe low lumbar pain radiating to both legs began and made sleep almost impossible. The patient was unable to rest comfortably in any position. Pethidine 100 mg. was given 3-hourly. X-rays showed extensive osteosclerotic metastases in the pelvis, sacrum, lumbar spine, ribs, and right scapula. On May 26, 1962, oestrogens therapy was stopped, and on June 3 seventeen daily intramuscular injections of testosterone propionate were begun. The pain worsened in the next 48 hours. From June 10 the patient was given seven daily intravenous doses of 1-43 ml. of 12P . Two days later the patient had no pain, and on June 23 he was discharged home, walking and free from pain. Stilboestrol therapy was resumed.
883 On
Sept. 9 there degree, and on Nov.
was a
sudden
30 the
return of pain, nulder in died of bronchopneumonia
A BEDSIDE METHOD OF
patient after an exacerbation of chronic pyelonephritis. The patient had had complete relief of pain for 41/2 months.
BLOOD-GLUCOSE ESTIMATION SIMON L. COHEN Lond., M.R.C.P.
SUSAN LEGG
MEDICAL REGISTRAR
HOUSE-PHYSICIAN
M.B. Lond.
M.B. SECOND PATIENT
A man, aged 72 years, presented in 1959, had had prostatism and low back pain for a year. Clinical examination’ revealed a large hard carcinomatous prostate. Intravenous pyelography showed moderate hydronephrosis and hydroureter (left) with extensive osteosclerotic metastases in the pelvis, lumbar spine, and ribs. The blood-urea was 40 mg. per 100 ml.; serum-acidphosphatase 90 King-Armstrong units. A prostatic smear confirmed the diagnosis of carcinoma of the prostate. Stilboestrol 25 mg. t.d.s. was begun, and bone pain diminished. In June, 1963, the patient had severe neck, lower dorsal, and lumbar pain. All spinal movement was greatly limited. Omnopon gr. 1/3 was given 3-hourly. X-rays showed extensive osteosclerotic metastases in the pelvis and lumbar spine. On June 30 stilbcestrol was stopped, and on July 6 the first of seventeen daily intramuscular injections of testosterone proprionate was given. From July 11 the patient received seven daily intravenous injections of 1.43 ml. of 32P. On July 15 he was free from pain, except for a slight ache in the left groin. 3 days later he could climb in and out of bed without pain or assistance, and on July 24 he was discharged home taking stilboestrol 25 mg. t.d.s. The patient died from an attack of coronary thrombosis in January, 1964. He had had almost complete relief from pain for 6 months until his death. Two further patients were treated in this way. One had partial relief, but died, 2 weeks after a course of 32P
and testosterone, from congestive cardiac failure; the other was considerably relieved of pain for 51/2 months before his death from carcinomatosis.
R. BIRD B.Sc., Ph.D. Birm. A.R.I.C. BIOCHEMIST
ROYAL NORTHERN
HOSPITAL, LONDON, N.7
IN the past few years several clinically valuable blood and urine tests have been simplified by the introduction of impregnated paper strips. We have undertaken a preliminary study of a similar method for estimating the blood-sugar level. Method The test
strip,’Dextrostix’, made by the Ames Co., Stoke Poges, Slough, Bucks, consists of absorbent paper impregnated at one end with a buffered mixture of glucose oxidase, peroxidase, and a chromogen system, and coated with a semipermeable membrane. A drop of capillary or venous blood is placed on the test end of the strip, and washed off after 60 seconds with cold running tap water; the colour change is then compared with a graded colour chart. The colours vary from pale grey at 40 mg. of glucose per 100 ml. blood, through deepening shades of blue-grey at 65, 90, 130, 150, and 200 mg., to a dark blue at 250 mg. of glucose per 100 ml. blood. The test strip can usually be matched to two adjacent colours on the chart, and the blood-glucose level is said to be in the range between these two values. Samples of blood have been taken simultaneously for blood-sugar estimation by analytical methods.
Blood-sugar in the venous samples was measured by autoanalyser microglucose method (’Technicon’ ferricyanide method N9), using the 15 mm. tubular-flow cell, and in the capillary samples by the manual glucoseoxidase procedure described by Marks (1959). the
Summary and Conclusions of the prostate and bone combination of radioactive phosphorus and testosterone propionate. The first had complete relief of pain for 41/2 months, and died a further 2 months later from bronchopneumonia. The second remained free of pain for 6 months after treatment and then died suddenly of coronary thrombosis. Of two further patients, one had partial relief; and the other, in his own opinion, had his pain reduced to a fifth of what it had previously been. Most of these patients are within a year of their death. This treatment, which provides symptomatic relief for much of the remainder of the patient’s life, is worth further trial, particularly since it avoids the risk associated with surgical operations, such as adrenalectomy or
Two
patients with carcinoma
metastases were
treated with
a
pituitary implantation. My
thanks
are
due
to my
chief, Mr. T. W. Mimpriss, for his treat these patients.
encouragement and cooperation in allowing me to REFERENCES
Hertz, S. (1950) J. clin. Invest. 29, 821. Maxfield, J. R. Jr., Maxfield, J. G., Maxfield, W. S. (1958) Sth. med. J. 51, 320. Parsons, R. L. (1961) J. Urol. 85, 342. Shahon, D. B. (1959) Cancer, 12, 862. Vermooten, V., Maxfield, J. R. Jr., Maxfield, J. G. (1959) West. J. Surg.
67, 245 Wildermuth, O., Parker, D., Archambeau, J. O., Chahbazian, C. (1960) J. Amer. Med. Ass. 172, 1607.
"...4A Friend’ is much mistaken in supposing that we approve of the forgeries which have at times appeared in The Lancet. Our remarks bear no such interpretation; but we meant, and we repeat, that the avidity with which the pages of that journal are opened to the reception of scandal and trash of every kind, renders its readers liable to be imposed upon by any one whose inventive faculties are stronger than his principles." -Land. med. Gaz. 1830, 17, 736.
Fig. I-Comparison of dextrostix and laboratory results for the total series (mg. glucose per 100 ml. blood).