- Email: [email protected]
VINBLASTINE
1390 late sexual consequences. From this viewpoint Dr. Trowell’s letter makes good sense. Professor Hubble’s and Dr. Comfort’s generalisation may be appropriate for the majority, but to what extent will they be preaching to the converted ?
relatively
Maudsley Hospital,
P. D. SCOTT.
London, S.E.5.
NÆVUS SEBACEUS AND BASAL-CELL CARCINOMA IN A NIGERIAN SiR,-Much I know has already been written on the association between exposure to sunlight, particularly in
fair-skinned people, and the causation of basal-cell carcinoma of the face. None the less I believe the following will interest some of your readers. A male albino Nigerian, aged about 40, had an ulcer of the cheek below the right eye, 3/4 in. in diameter. He said it had been present for about six months and was steadily increasing. It looked typical of a rodent ulcer. A biopsy was taken from the edge, and the report read: "Sections show masses of mature sebaceous glands below an ulcerated epidermis, with abortive hair follicles and apocrine glands. This is typical nasvus sebaceus. In one area there is definite carcinomatous change, which seems to be of basal-cell origin (although in parts there case
ing its absorption, although Armstrong et al. indicated clearly that a leucopenia was effected on the doses they employed. A patient with Hodgkin’s disease was found in the fifth month of pregnancy to have large densities in the right lung field, in the left hilum, and in the left lung field. The patient had a persistent cough, tachypncea, tachycardia, and bodytemperature as high as 103°F. When X-ray therapy to the right lower lung field (872r tumour dose) failed to control the patient’s symptoms she was given v.L.B. intravenously 0.1 mg. per kg. weekly. She received 47-8 mg. intravenously in nine divided doses and her clinical condition improved remarkably. She could undertake vigorous physical activity without cough or shortness of breath. She became afebrile and gained 24 1/2 lb. in two months up to the point of delivery. The white-bloodcell count never fell below 5000 per c.mm. a week after the v.L.B.
injection.
A healthy boy weighing 6 lb. 11 oz. was delivered after normal labour of seven hours. The child is three months old and is thriving. Maintenance V.L.B. therapy is being continued. Memorial Hospital for Cancer and Allied Diseases, and the James Ewing Hospital, MORTIMER J. LACHER. New York, N.Y. 10021, U.S.A.
CENTRAL VENOUS PRESSURE IN OLIGÆMIC SHOCK
is a mixed basi- quamo s ap e rance)."
General
Hospital, Makurdi,
SIR,-In your leading article on this subjectyou EDWIN
Northern Nigeria.
J. WRIGLEY.
"
VINBLASTINE
report evidence of a teratogenic of the anti-tumour agent, vinblastine.
SIR,-We wish effect
on rats
This
to
an alkaloid of Vinca rosea Linn., arrests mitosis in metaphase rapidly proliferating cells, and has been shown to be effective in generalised Hodgkin’s disease and choriocarcinoma2 when these neoplasms fail to respond to conventional therapy. Its effectiveness in other malignant conditions is still being evaluated. Vinblastine was given to rats and mice in the last trimester of pregnancy, and the foetuses were examined for mitotic figures at intervals thereafter. Preliminary data revealed a significant increase in mitotic figures in vinblastine-treated foetuses as compared to those in controls. We administered vinblastine (0-12-0-30 mg. per kg. in a concentration of 1 mg. to 8 ml. saline solution) intraperitoneally to pregnant rats from the 7th to the 12th day of gestation. Of 94 pregnant rats treated, total litter resorption occurred in 56 (60%). The 38 litters that came to term yielded 304 young with gross anomalies in 24 (8%). The deformed young were stunted and exhibited varying degrees of exencephaly, hydrocephalus, iniencephaly, rachischis, gastroschisis, and malformations of the lower
drug,
at
extremity. Since we first wrote this letter, Fermhas shown that vinblastine and vincristine are teratogenic in the pregnant hamster. Department of Pediatrics, New York
University School of Medicine, 500, First Avenue, New York 16, N.Y.
SIDNEY Q. COHLAN JOSEPH DANCIS DAVID KITAY.
SiR,-Ferm3 reported embryocidal and teratogenic effects in pregnant golden hamsters after treatment with vinblastine sulphate (v.L.B.) or vincristine sulphate (v.c.R.). Armstrong et al. reported that a patient became pregnant, and was carried to term and delivered a normal child, while being maintained on 5 mg. tablets of oral V.L.B. taken as often as five consecutive days each week. The patient spontaneously delivered a normal full-term male infant without any obvious abnormalities. Because the V.L.B. was given orally there could be some doubt concern1. 2. 3 4.
Hodes, M. E., Rohn, R. J., Bond, W. H. Cancer Res. 1960, 20, 1041. Hertz, R., Lipsett, M. D., Moy, R. H. ibid. p. 1050. Ferm, V. H. Science, 1963, 141, 426. Armstrong, J. G., Dyke, R. W., Fouts, P. J. ibid. 1964, 143, 703.
state
that
although the
test can help in determining when the circulavolume has been restored, it cannot assist in calculating tory the extent of the deficit when it is reduced. Other methods are needed for estimating blood or plasma loss and the amount of fluid to be transfused."
logic of this is not clear, for, if the central venous (c.v.P.) indicates when the circulatory volume has been restored, it is only necessary to transfuse until this state has been achieved, and it is unnecessary to know The
pressure
the
extent
of the deficit in advance.
Furthermore, in
cases where loss continues during treatment, calculation of the initial deficit is not a reliable guide to the amount required. In any event it is difficult to determine the deficit accurately from blood-volume estimations because of uncertainty of the normal value for a given patient, especially if obese or emaciated. We have found that, when c.v.P. measurements can be made, determinations of blood-volume are of no additional value.2 We feel we should disclaim any credit implied by your " statement that we invented " a gauge to measure c.v.P. Ours is a modification of that described by Allenand subsequently modified by Borst and Molhuysen,4whose work was acknowledged in our paper.2 Dr. Furlerclaims that " warm hypotension " is a dangerous state in which the tissues are inadequately perfused, and cites a case with an unrecordable blood-pressure and anuria. We would suggest that this term ought to be used only for the syndrome in which a good pulse-volume accompanies the low blood-pressure and the warm extremities. In such cases the blood-pressure is easy to record, the urine secretion is usually well maintained, and the peripheral circulation appears to be good. If the circulation deteriorates, the first sign is a diminution of the pulse-volume which heralds the onset of " cold hypotension "-a much more dangerous condition in which the pulse-volume is small. It may, however, be some time before the extremities actually become cold, since this depends on environmental temperature and the exposure of the limbs; we presume that Dr. Furler’s patient falls into this category. We suggest that the pulse is much more reliable than the skin temperature for distinguishing relatively benign forms of hvootension from the severe forms.
1. 2. 3. 4. 5.
Lancet, May 23, 1964, p. 1143. McGowan, G. K., Walters, G. Brit. J. Surg. 1963, 50, 821. Allen, P. Canad. med. Ass. J. 1948, 59, 960. Borst, J. G. G., Molhuysen, J. A Lancet, 1952, ii, 304. Furler, I. K. ibid. April 18, 1964, p. 878.
relatively
Maudsley Hospital,
P. D. SCOTT.
London, S.E.5.
NÆVUS SEBACEUS AND BASAL-CELL CARCINOMA IN A NIGERIAN SiR,-Much I know has already been written on the association between exposure to sunlight, particularly in
fair-skinned people, and the causation of basal-cell carcinoma of the face. None the less I believe the following will interest some of your readers. A male albino Nigerian, aged about 40, had an ulcer of the cheek below the right eye, 3/4 in. in diameter. He said it had been present for about six months and was steadily increasing. It looked typical of a rodent ulcer. A biopsy was taken from the edge, and the report read: "Sections show masses of mature sebaceous glands below an ulcerated epidermis, with abortive hair follicles and apocrine glands. This is typical nasvus sebaceus. In one area there is definite carcinomatous change, which seems to be of basal-cell origin (although in parts there case
ing its absorption, although Armstrong et al. indicated clearly that a leucopenia was effected on the doses they employed. A patient with Hodgkin’s disease was found in the fifth month of pregnancy to have large densities in the right lung field, in the left hilum, and in the left lung field. The patient had a persistent cough, tachypncea, tachycardia, and bodytemperature as high as 103°F. When X-ray therapy to the right lower lung field (872r tumour dose) failed to control the patient’s symptoms she was given v.L.B. intravenously 0.1 mg. per kg. weekly. She received 47-8 mg. intravenously in nine divided doses and her clinical condition improved remarkably. She could undertake vigorous physical activity without cough or shortness of breath. She became afebrile and gained 24 1/2 lb. in two months up to the point of delivery. The white-bloodcell count never fell below 5000 per c.mm. a week after the v.L.B.
injection.
A healthy boy weighing 6 lb. 11 oz. was delivered after normal labour of seven hours. The child is three months old and is thriving. Maintenance V.L.B. therapy is being continued. Memorial Hospital for Cancer and Allied Diseases, and the James Ewing Hospital, MORTIMER J. LACHER. New York, N.Y. 10021, U.S.A.
CENTRAL VENOUS PRESSURE IN OLIGÆMIC SHOCK
is a mixed basi- quamo s ap e rance)."
General
Hospital, Makurdi,
SIR,-In your leading article on this subjectyou EDWIN
Northern Nigeria.
J. WRIGLEY.
"
VINBLASTINE
report evidence of a teratogenic of the anti-tumour agent, vinblastine.
SIR,-We wish effect
on rats
This
to
an alkaloid of Vinca rosea Linn., arrests mitosis in metaphase rapidly proliferating cells, and has been shown to be effective in generalised Hodgkin’s disease and choriocarcinoma2 when these neoplasms fail to respond to conventional therapy. Its effectiveness in other malignant conditions is still being evaluated. Vinblastine was given to rats and mice in the last trimester of pregnancy, and the foetuses were examined for mitotic figures at intervals thereafter. Preliminary data revealed a significant increase in mitotic figures in vinblastine-treated foetuses as compared to those in controls. We administered vinblastine (0-12-0-30 mg. per kg. in a concentration of 1 mg. to 8 ml. saline solution) intraperitoneally to pregnant rats from the 7th to the 12th day of gestation. Of 94 pregnant rats treated, total litter resorption occurred in 56 (60%). The 38 litters that came to term yielded 304 young with gross anomalies in 24 (8%). The deformed young were stunted and exhibited varying degrees of exencephaly, hydrocephalus, iniencephaly, rachischis, gastroschisis, and malformations of the lower
drug,
at
extremity. Since we first wrote this letter, Fermhas shown that vinblastine and vincristine are teratogenic in the pregnant hamster. Department of Pediatrics, New York
University School of Medicine, 500, First Avenue, New York 16, N.Y.
SIDNEY Q. COHLAN JOSEPH DANCIS DAVID KITAY.
SiR,-Ferm3 reported embryocidal and teratogenic effects in pregnant golden hamsters after treatment with vinblastine sulphate (v.L.B.) or vincristine sulphate (v.c.R.). Armstrong et al. reported that a patient became pregnant, and was carried to term and delivered a normal child, while being maintained on 5 mg. tablets of oral V.L.B. taken as often as five consecutive days each week. The patient spontaneously delivered a normal full-term male infant without any obvious abnormalities. Because the V.L.B. was given orally there could be some doubt concern1. 2. 3 4.
Hodes, M. E., Rohn, R. J., Bond, W. H. Cancer Res. 1960, 20, 1041. Hertz, R., Lipsett, M. D., Moy, R. H. ibid. p. 1050. Ferm, V. H. Science, 1963, 141, 426. Armstrong, J. G., Dyke, R. W., Fouts, P. J. ibid. 1964, 143, 703.
state
that
although the
test can help in determining when the circulavolume has been restored, it cannot assist in calculating tory the extent of the deficit when it is reduced. Other methods are needed for estimating blood or plasma loss and the amount of fluid to be transfused."
logic of this is not clear, for, if the central venous (c.v.P.) indicates when the circulatory volume has been restored, it is only necessary to transfuse until this state has been achieved, and it is unnecessary to know The
pressure
the
extent
of the deficit in advance.
Furthermore, in
cases where loss continues during treatment, calculation of the initial deficit is not a reliable guide to the amount required. In any event it is difficult to determine the deficit accurately from blood-volume estimations because of uncertainty of the normal value for a given patient, especially if obese or emaciated. We have found that, when c.v.P. measurements can be made, determinations of blood-volume are of no additional value.2 We feel we should disclaim any credit implied by your " statement that we invented " a gauge to measure c.v.P. Ours is a modification of that described by Allenand subsequently modified by Borst and Molhuysen,4whose work was acknowledged in our paper.2 Dr. Furlerclaims that " warm hypotension " is a dangerous state in which the tissues are inadequately perfused, and cites a case with an unrecordable blood-pressure and anuria. We would suggest that this term ought to be used only for the syndrome in which a good pulse-volume accompanies the low blood-pressure and the warm extremities. In such cases the blood-pressure is easy to record, the urine secretion is usually well maintained, and the peripheral circulation appears to be good. If the circulation deteriorates, the first sign is a diminution of the pulse-volume which heralds the onset of " cold hypotension "-a much more dangerous condition in which the pulse-volume is small. It may, however, be some time before the extremities actually become cold, since this depends on environmental temperature and the exposure of the limbs; we presume that Dr. Furler’s patient falls into this category. We suggest that the pulse is much more reliable than the skin temperature for distinguishing relatively benign forms of hvootension from the severe forms.
1. 2. 3. 4. 5.
Lancet, May 23, 1964, p. 1143. McGowan, G. K., Walters, G. Brit. J. Surg. 1963, 50, 821. Allen, P. Canad. med. Ass. J. 1948, 59, 960. Borst, J. G. G., Molhuysen, J. A Lancet, 1952, ii, 304. Furler, I. K. ibid. April 18, 1964, p. 878.