59
peak
in
some.
NAA is
thought
to
be located
primarily
within
neurons.4 The very low level of NAA in the chronic plaque described here is consistent with a major degree of axonal loss, as occasionally reported pathologically.5 The milder reduction in the acute plaque could indicate less severe axonal loss, axonal shrinkage
secondary to demyelination,6inflammatory oedema,7 or perhaps axonal dysfunction. The origin of the choline peak on proton MRS is less clear, although there is probably a major contribution from phosphorylcholine and glycerophosphorylcholine, which are involved in membrane synthesis and breakdown. Both oedema and vasculitis have been described in new plaques,’ and it is conceivable that such changes might reduce oxygen delivery to cells and so explain the Lac peak we and others have found. Although one might have expected mobile lipid due to recent myelin breakdown in our acute lesion, none was observed on MRS. Although the basis for the abnormalities is not completely understood, the striking differences between an acute and a chronic MS plaque suggest a role for MRS in monitoring MS.
Institute of Neurology, National Hospital, London WC1 N 3BG, UK, and Institute of Child Health, London WC1
D. H. MILLER S. J. AUSTIN A. CONNELLY B. D. YOUL D. G. GADIAN W. I. MCDONALD
south-east England. 66 patients with recurrent chest-wall disease and 10 with advanced primary carcinomas of the breast have so far been randomised to radiotherapy or to radiotherapy and hyperthermia. This trial is planned to continue for another two years and to recruit 280 patients. MRC
Hyperthermia Clinic, Cyclotron Unit, Hammersmith Hospital, London W12 0HS, UK
C. C. VERNON
Department of Radiotherapy and Oncology, Hammersmith Hospital
M. HARRISON
Dunlop PR, Hand JW, Dickinson RJ, Field SB. An assessment of local hyperthermia in clinical practice. Int J Hyperthermia 1986; 2: 39-50. 2. Egawa S, Tsukiyama I, Watanabe S, et al. J Jpn Soc Ther Radiol Oncol 1989; 1: 1
135-40. 3. Gonzalez Gonzalez E, van Dijk JDP, Blank LECM. Chestwall recurrences of breast cancer results of combined treatment with radiation and hyperthermia Radiother Oncol 1988, 12: 95-103. 4. Lindholm CE, Kjellen E, Nilsson P, Hertzman S. Microwave induced hyperthermia and radiotherapy in human superficial tumours. clinical results with a comparative study of combined treatment versus radiotherapy alone Int Hyperthermia 1987, J 3: 393-411. 5. Perez CA, Pajak T, Emami B, Homback NB, Tupchong L, Rubin P Randomised phase III study comparing irradiation and hyperthermia with irradiation alone in superficial measurable tumours. Am JClin Oncol (in press). 6 van der Zee J, Truerniet-Donker AD, The SK, et al. Low dose re-irradiation in combination with hyperthermia: a palliative treatment for patients with breast cancer recurring in previously irradiated areas Int J Radiation Oncol Biol Phys
1988; 15: 1407-13
Rudge P, Johnson G, et al Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis Brain 1988; 111: 927-39. 2. Hawkins CP, Munro PMG, Mackenzie F, et al Duration and selectivity of blood-brain barrier breakdown in chronic experimental allergic encephalomyelitis studies using gadolinium-DTPA and protein markers. Brain 1990; 113: 365-78. 3. Ordidge RJ, Bendall MR, Gordon RE, Connelly A. Volume selection for in-vivo biological spectroscopy. In: Govind, Khetrapal, Saran, eds Magnetic resonance in biology and medicine. New Delhi Tata McGraw-Hill, 1985: 387-97. 4. Birken DL, Oldendorf WH. N-acetyl aspartate: a literature review of a compound prominent in 1H-NMR spectroscopic studies Neurosci Behav Rev 1989; 13: 23-31 5. Adams CWM. A colour atlas of multiple sclerosis and other myelin disorders. Ipswich. 1 Miller DH,
Wolfe, 1989. 6. Prineas JW, Connel F. The fine structure of the chronically active plaque m multiple sclerosis. Neurology 1978, 28: 68-75. 7. Adams CWM Inflammatory vasculitis in multiple sclerosis J Neurol Sci 1985; 69: 269-83
Hyperthermia with low-dose radiotherapy for recurrent breast carcinoma SIR,-We read with interest Mr Novell and colleagues’ letter p 1383) describing a ’Lipiodol’/epirubicin infusion
(Dec 1,
of two patients with advanced local carcinoma of the breast. We agree that local failure in this disease, after surgery, radiotherapy, hormones, and chemotherapy, can be a major problem. We describe here a less invasive and well-tolerated treatment that has promise. Hyperthermia with low-dose radiotherapy is becoming well accepted’-’----indeed in the USA randomised studies are difficult because of patients’ and clinicians’ preferences. Via microwaves, and also by ultrasound and radiofrequency, the temperature is raised in a careful, controlled way to 42-44°C. Treatments last 1-2 h, usually once a week, and only three or four are needed. Hyperthermia probably works at the cellular membrane level by direct cell kill and also by radiosensitisation of radioresistant S-phase cells and nutrient deprived, low pH hypoxic cells. It can also prevent recovery from sublethal and potentially lethal radiation damage. Abnormal blood flow kinetics in tumours may allow the induction of higher temperatures than in normal tissues, which are relatively protected by heat dissipation through the microcirculation. A review of well-controlled studies with good hyperthermia quality, and comparing similar doses of radiotherapy with and without hyperthermia, in patients with chest-wall recurrences points to a 29% improvement: with radiotherapy alone the complete remission rate was 33% and with radiotherapy plus hyperthermia it was 67%. (The low response to radiotherapy alone is due to the advanced state of the disease in these trials.) A randomised trial is being conducted by the Medical Research Council/Hammersmith Hospital, patients being recruited from treatment
Prothrombin fragments and thrombotic occlusion of coronary stents SIR,-Coronary stents are successfully implanted to avoid acute vessel occlusion after balloon angioplasty.’ Despite an aggressive anticoagulation regimen with high-dose heparin, phenprocoumon, aspirin, dipyridamole, and infusion of dextran, a high percentage of patients treated by coronary stent implantation have a subacute thrombotic occlusion of the stented segment within the first few days.’1 We have therefore monitored daily in eight patients indices of the coagulation system: prothrombin ratio (PR), activated partial thromboplastin time (APTT), prothrombin fragment Fl and F2 (PTF, normal range 0.5-1.0 nmol/1), and thrombin-antithrombin III complex (TAT, 0.8-5.0 ng/1) (table). Although patients on oral anticoagulant therapy have normal TAT values, PTF concentrations (range 0.2-0.5 nmol/1) are substantially decreased .2 During the first few days after implantation, six of eight patients had PTF concentrations not higher than 0-5 nmol/l, which did not exceed the normal range after changing from heparin to phenprocoumon. However, in two patients PTF concentrations were higher than 0-5 nmol/1 immediately from implantation. In these two patients an additional rise was seen after reduction of heparin, which finally resulted in a subacute thrombotic occlusion four or five days later despite phenprocoumon and heparin therapy. In contrast to PTF, TAT concentrations were normal (below 5 ltg/1) until occlusion occurred. The biocompatibility of a stenting device is dependent on its surface chemistry, surface energy, and surface texture. Because endothelium cannot be grown on bare metal surfaces and requires COAGULATION INDICES AFTER INTRACORONARY STENTING
n= 8 patients, - occlusion (2 patients), - = no occlusion (6 patients) Therapeutic ranges PR, 2 8-4 8, APTT, 60-120, PTF, 0 2-0 5, TAT, 0 8-5 0
peak
in
some.
NAA is
thought
to
be located
primarily
within
neurons.4 The very low level of NAA in the chronic plaque described here is consistent with a major degree of axonal loss, as occasionally reported pathologically.5 The milder reduction in the acute plaque could indicate less severe axonal loss, axonal shrinkage
secondary to demyelination,6inflammatory oedema,7 or perhaps axonal dysfunction. The origin of the choline peak on proton MRS is less clear, although there is probably a major contribution from phosphorylcholine and glycerophosphorylcholine, which are involved in membrane synthesis and breakdown. Both oedema and vasculitis have been described in new plaques,’ and it is conceivable that such changes might reduce oxygen delivery to cells and so explain the Lac peak we and others have found. Although one might have expected mobile lipid due to recent myelin breakdown in our acute lesion, none was observed on MRS. Although the basis for the abnormalities is not completely understood, the striking differences between an acute and a chronic MS plaque suggest a role for MRS in monitoring MS.
Institute of Neurology, National Hospital, London WC1 N 3BG, UK, and Institute of Child Health, London WC1
D. H. MILLER S. J. AUSTIN A. CONNELLY B. D. YOUL D. G. GADIAN W. I. MCDONALD
south-east England. 66 patients with recurrent chest-wall disease and 10 with advanced primary carcinomas of the breast have so far been randomised to radiotherapy or to radiotherapy and hyperthermia. This trial is planned to continue for another two years and to recruit 280 patients. MRC
Hyperthermia Clinic, Cyclotron Unit, Hammersmith Hospital, London W12 0HS, UK
C. C. VERNON
Department of Radiotherapy and Oncology, Hammersmith Hospital
M. HARRISON
Dunlop PR, Hand JW, Dickinson RJ, Field SB. An assessment of local hyperthermia in clinical practice. Int J Hyperthermia 1986; 2: 39-50. 2. Egawa S, Tsukiyama I, Watanabe S, et al. J Jpn Soc Ther Radiol Oncol 1989; 1: 1
135-40. 3. Gonzalez Gonzalez E, van Dijk JDP, Blank LECM. Chestwall recurrences of breast cancer results of combined treatment with radiation and hyperthermia Radiother Oncol 1988, 12: 95-103. 4. Lindholm CE, Kjellen E, Nilsson P, Hertzman S. Microwave induced hyperthermia and radiotherapy in human superficial tumours. clinical results with a comparative study of combined treatment versus radiotherapy alone Int Hyperthermia 1987, J 3: 393-411. 5. Perez CA, Pajak T, Emami B, Homback NB, Tupchong L, Rubin P Randomised phase III study comparing irradiation and hyperthermia with irradiation alone in superficial measurable tumours. Am JClin Oncol (in press). 6 van der Zee J, Truerniet-Donker AD, The SK, et al. Low dose re-irradiation in combination with hyperthermia: a palliative treatment for patients with breast cancer recurring in previously irradiated areas Int J Radiation Oncol Biol Phys
1988; 15: 1407-13
Rudge P, Johnson G, et al Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis Brain 1988; 111: 927-39. 2. Hawkins CP, Munro PMG, Mackenzie F, et al Duration and selectivity of blood-brain barrier breakdown in chronic experimental allergic encephalomyelitis studies using gadolinium-DTPA and protein markers. Brain 1990; 113: 365-78. 3. Ordidge RJ, Bendall MR, Gordon RE, Connelly A. Volume selection for in-vivo biological spectroscopy. In: Govind, Khetrapal, Saran, eds Magnetic resonance in biology and medicine. New Delhi Tata McGraw-Hill, 1985: 387-97. 4. Birken DL, Oldendorf WH. N-acetyl aspartate: a literature review of a compound prominent in 1H-NMR spectroscopic studies Neurosci Behav Rev 1989; 13: 23-31 5. Adams CWM. A colour atlas of multiple sclerosis and other myelin disorders. Ipswich. 1 Miller DH,
Wolfe, 1989. 6. Prineas JW, Connel F. The fine structure of the chronically active plaque m multiple sclerosis. Neurology 1978, 28: 68-75. 7. Adams CWM Inflammatory vasculitis in multiple sclerosis J Neurol Sci 1985; 69: 269-83
Hyperthermia with low-dose radiotherapy for recurrent breast carcinoma SIR,-We read with interest Mr Novell and colleagues’ letter p 1383) describing a ’Lipiodol’/epirubicin infusion
(Dec 1,
of two patients with advanced local carcinoma of the breast. We agree that local failure in this disease, after surgery, radiotherapy, hormones, and chemotherapy, can be a major problem. We describe here a less invasive and well-tolerated treatment that has promise. Hyperthermia with low-dose radiotherapy is becoming well accepted’-’----indeed in the USA randomised studies are difficult because of patients’ and clinicians’ preferences. Via microwaves, and also by ultrasound and radiofrequency, the temperature is raised in a careful, controlled way to 42-44°C. Treatments last 1-2 h, usually once a week, and only three or four are needed. Hyperthermia probably works at the cellular membrane level by direct cell kill and also by radiosensitisation of radioresistant S-phase cells and nutrient deprived, low pH hypoxic cells. It can also prevent recovery from sublethal and potentially lethal radiation damage. Abnormal blood flow kinetics in tumours may allow the induction of higher temperatures than in normal tissues, which are relatively protected by heat dissipation through the microcirculation. A review of well-controlled studies with good hyperthermia quality, and comparing similar doses of radiotherapy with and without hyperthermia, in patients with chest-wall recurrences points to a 29% improvement: with radiotherapy alone the complete remission rate was 33% and with radiotherapy plus hyperthermia it was 67%. (The low response to radiotherapy alone is due to the advanced state of the disease in these trials.) A randomised trial is being conducted by the Medical Research Council/Hammersmith Hospital, patients being recruited from treatment
Prothrombin fragments and thrombotic occlusion of coronary stents SIR,-Coronary stents are successfully implanted to avoid acute vessel occlusion after balloon angioplasty.’ Despite an aggressive anticoagulation regimen with high-dose heparin, phenprocoumon, aspirin, dipyridamole, and infusion of dextran, a high percentage of patients treated by coronary stent implantation have a subacute thrombotic occlusion of the stented segment within the first few days.’1 We have therefore monitored daily in eight patients indices of the coagulation system: prothrombin ratio (PR), activated partial thromboplastin time (APTT), prothrombin fragment Fl and F2 (PTF, normal range 0.5-1.0 nmol/1), and thrombin-antithrombin III complex (TAT, 0.8-5.0 ng/1) (table). Although patients on oral anticoagulant therapy have normal TAT values, PTF concentrations (range 0.2-0.5 nmol/1) are substantially decreased .2 During the first few days after implantation, six of eight patients had PTF concentrations not higher than 0-5 nmol/l, which did not exceed the normal range after changing from heparin to phenprocoumon. However, in two patients PTF concentrations were higher than 0-5 nmol/1 immediately from implantation. In these two patients an additional rise was seen after reduction of heparin, which finally resulted in a subacute thrombotic occlusion four or five days later despite phenprocoumon and heparin therapy. In contrast to PTF, TAT concentrations were normal (below 5 ltg/1) until occlusion occurred. The biocompatibility of a stenting device is dependent on its surface chemistry, surface energy, and surface texture. Because endothelium cannot be grown on bare metal surfaces and requires COAGULATION INDICES AFTER INTRACORONARY STENTING
n= 8 patients, - occlusion (2 patients), - = no occlusion (6 patients) Therapeutic ranges PR, 2 8-4 8, APTT, 60-120, PTF, 0 2-0 5, TAT, 0 8-5 0
