- Email: [email protected]
WHOLE BODY HYPERTHERMIA AND NATURAL KILLER CELL ACTIVITY
1079 the cellular membrane. The reaction with NADH might be an alternative or parallel mode of action, because the oxidation of NADH by phenothiazine free radicals has also been reported.44 Lithium chloride, diazepam, and medazepam in concentrations of 1 mmol/l did not convert V5 ions to V4 + ions (F and G). This does not, however, mean that lithium itself cannot displace V5 from the NA-K-ATPase2,4 moiety and thus make it available for reduction within the cell. on
We thank Dr P. Hnik for
reviewing the manuscript. F. VYSKOIL
Institute of Physiology, Czechoslovak Academy of Sciences, 142 20 Prague 4, Czechoslovakia, and Institute of Macromolecular Chemistry,
J. PILA
Prague
J. TEISINGER
H. ZEMKOVÁ
WHOLE BODY HYPERTHERMIA AND NATURAL KILLER CELL ACTIVITY
SIR,-Azocar,Nurmi,7
and their
colleagues have studied the
effect of hyperthermia on natural killer (NK) cell activity, and their in vitro results contrast with the beneficial effect of artificial
hyperthermia on the immune response.8Whole body hyperthermia is an established clinical treatment in our hospital, and, in patients
-
who gave their informed consent and who were treated with an extracorporeal device, NK cell activity was measured: A human malignant glioma cell line, similar in susceptibility to NK cell attack to the K562 cell line, was used for target cells with effector-target cell ratios of 10:1and 30:1. The results in a 17-yearold boy who had had Ewing’s sarcoma for 4 years and whose tumour was resistant to chemotherapy and radiology are summarised in the figure. The boy was scheduled for hyperthermia 5 weeks after the last cyclophosphamide regimen and his performance status on’the Karnofsky scale was 70%. On admission to hospital he had an NK activity of nearly zero. Peripheral blood lymphocytes, from a sample 2 h after the end of 6 h of whole body hyperthermia (41’8°C bladder temperature) exhibited a cytotoxicity of 30%, which steadily decreased to 10% within a week. 96 h after a second hyperthermic treatment, NK activity rose to over 60%, again followed by a remarkable drop to 20% over the next week. 2 days after the second hyperthermic session, the boy was discharged and went back to school. The restoration ofNK activity that we noted in this cancer patient was probably caused by the hyperthermic treatment. It is puzzling why human NK activity in vitro should be inversely related to increases in temperature over 37°C while activity is enhanced by hyperthermia in vivo. Temperature cannot be the sole determining factor-perhaps some latent infections, such as viral infections, are 4
ESR spectra.
(B) vanadate (V5+); and vanadate plus (C) methylene(A) vanadyl blue, (D) chlorpromazine; (E) imipramine; (F) diazepam; (G) lithium. Calibration in millitesla (mT). Amplification is two times higher in B, C, F,
(V4+);
and G than in
Løvstad RA. Interaction of phenothiazine
derivatives with human ceruloplasmin. Biochem Pharmacol 1974, 23: 1045-52 5. Naylor GJ, Dick DAT, Johnston BB, Hopwood SE, Dick EG, Smith AHW, Kay D. Possible explanation for therapeutic action of lithium, and a possible substitute (methylene-blue). Lancet 1981, ii 1145-46 6 Azocar J, Yunis EJ, Essex M Sensitivity of human natural killer cells to hyperthermia. Lancet 1982; i: 16-17. 7. Nurmi T, Uhari M, Konvalainen K. Temperature and natural killer cell activity. Lancet 1982; i: 516-17 8. Dickson JA, Shah SA. Hyperthermia and the immune response in cancer therapy. Cancer Immunol Immunother 1980; 9: 1-10.
A, D, and E.
reduced vanadium. This was surprising because methylene-blue active in promoting the vanadate-NADH-FAD reaction in the experiment of Naylor and Smith.2 On the other hand, in spectrophotometric experiments with 1 mmol/l NADH (in sodium phosphate buffer, no FAD, 25°C, A365nm) 50 mot/1 methyleneblue (but not 500 pmol/1 imipramine or chlorpromazine) reduced 0-33 NADH jÄmol/l/min by itself and promoted the "background" reduction of NADH1 in the presence of vanadate (molar ratio 1:1’) by 85%. Because both chlorpromazine and imipramine can reduce vanadate to vanadyl in equimolar concentrations, the claimed benefit of these drugs in manic-depressive syndromes, acting via vanadium, does not require the presence ofNADH and it may occur was most
Modulation of NK activity during two whole body hyperthermia treatments in a patient with Ewing’s sarcoma.
Effector-target cell columns).
ratios were
1 10
(open columns) and 1:30 (hatched
,
1080 activated by hyperthermia, which induces interferon and thus augments NK activity.9
production
Institute for Experimental Surgery, Technical University of Munich, 8000 Munich 80, West Germany
KURT S. ZÄNKER
Superficial parotidectomy, done by a surgeon skilled at and experienced in the technique, is the treatment of choice for pleomorphic adenomas of the parotid gland. Fine needle aspiration of parotid lumps will allow accurate diagnosis of these sometimes testing lesions so that unwarranted enucleation may be avoided.
Surgical Clinic and Polyclinic, Technical University of Munich
JOCHEN LANGE
Department of Surgery, Bristol Royal Infirmary,
PAROTID TUMOURS
SIR,-Your April 10 editorial on parotid tumours raises many interesting points. We have studied a series of 58 pleomorphic adenomas of the parotid gland treated at the Bristol Royal Infirmary year period. 40 superficial parotidectomies were done and 18 enucleations, with recurrence rates of 5% and 25%, respectively. Complications, however, were notably more common in those having the radical operation, and, when paraesthesiae and numbness in the distribution of the auriculotemporal nerve, facial palsy, and Frey’s syndrome were taken into account, only 30% of parotidectomy patients were judged normal, compared with 60% of those whose tumour had been enucleated. These results reflect two aspects of our survey: sequelae of the operation were asked about at personal follow-up by independent observers; and the patients had been under the care of ten different surgeons, thus restricting the experience that could be accumulated by any individual. Whatever the policy adopted, enucleation will from time to time be done when the diagnosis is wrong. A third of the tumours enucleated in this series were not recognised as parotid tumours preoperatively. Fine needle aspiration biopsy was performed on 26 patients and gave a precise diagnosis in 20. In the remaining 6 the lump was defined as a parotid tumour but the histology could not be more precise. Follow-up of these cases now ranges from 5 to 15 years, and there has been no evidence of local recurrence following fine needle aspiration biopsy and adequate operative treatment. over a ten
9. Herberman R, Ortaldo J, Bonnard G. Augmentation by interferon of human natural and antibody-dependent cell-mediated cytotoxicity. Nature 1979; 227: 221-23
Commentary from Westminster Labour Plans for the N.H.S. A WAR against private medicine is likely to be one of the main commitments of the next Labour Government, if there is to be one. Labour’s next General Election manifesto is almost certain to contain a wide range of proposals intended to "ensure that private practice is no longer allowed to flourish". A draft of the Health and Social Services chapter of the next manifesto has just been approved by the party’s social policy subcommittee. It has some way to go before final adoption. The manifesto will not be written until shortly before the next General Election. But the draft represents the consensus prevailing now between the "experts", the trade unionists, and the politicians whom the party has charged with suggesting policies. The subcommittee believes that the private health sector can profit only as a parasite on the N.H.S., using N.H.S. resources, staff, and back-up services. "Its continued growth would seriously hinder the objectives we have set for the N.H.S." Private practice, under Labour, would therefore be separated from the N.H.S., by removing all pay beds within the first two years of Government. "We shall also take into the N.H.S. those parts of the profit-making private sector which can be used to meet local health needs and reduce waiting lists. For the rest of the private sector we shall withdraw the considerable public subsidies enjoyed by way of tax concessions on private health insurance, the charitable status of certain hospitals, and access to specialised N.H.S. facilities." No new private hospital developments would be
R. G. HUGHES T. J. LYONS
Bristol BS2 8HW
FLUORESCEIN DILAURATE TEST OF PANCREATIC FUNCTION
SiR,—We read with interest your March 27 editorial on the diagnosis of chronic pancreatitis and agree with the value of screening patients with possible pancreatic insufficiency. You favour the use of the 14C-PABA (p-aminobenzoic acid) test but this has the disadvantages of requiring dietary and drug restriction and a complex assay and of being invalidated by drug or isotope interference (16/140, 11%). Radioisotope use makes the test unsuitable in pregnancy and in children. The sensitivity of the 14C-PABA test in the reference cited’ was 74%
frequently
(32/43). In a prospective study (to be published elsewhere) we found that the fluorescein dilaurate test identified 93% (14/15) of patients with proven chronic pancreatitis. The test is suitable for all patients and does not require a complex laboratory assay. In our opinion, the fluorescein dilaurate test is worth considering as the investigation of choice for screening patients with suspected pancreatic
insufficiency. E. J. S. BOYD J. G. R. CUMMING R. A. B. WOOD A. CUSCHIERI K. G. WORMSLEY
Department of Surgery, Ninewells Hospital, Dundee DD1 9SY 1. Tetlow
VA,
excretion
Herman K, Kay index (using
GH, Braganza JM. Diagnostic accuracy of the PABA
14C-PABA). Gut
1981, 22: A441.
part of a system of strict controls. Consultants’ would have to be renegotiated "so that full recognition is given to those who make a full-time commitment to the N.H.S." The draft does not mention compensation for expropriated private medical companies. We know Mr Benn is against paying up, and that nearly half the Labour Party wants Mr Benn to be leader. The otlicial leadership has steered clear of the compensation question. Career structure for doctors would have to be generally redirected, the draft continues, so it is "more geared to the needs of the N.H.S." If the N.H.S. is given increased
allowed,
as
contracts
resources, the authors
believe, there is nothing it cannot which the private sector can. It will be re-established provide as a free service, funded out of general taxation, in which "priority is given on the basis of medical need and not ability to pay". Naturally the draft promises that a Labour Government would give greater priority to the elderly, the physically and mentally handicapped, and the socially deprived. Higher pay awards for N.H.S. workers are virtually promised. A substantial number of N.H.S. employees are low-paid and their position must be improved. Greater democratic influence int he N.H.S. is also owed to N.H.S. trade-union members, the draft declares. Labour would introduce legislation to ensure that water authorities add fluoride to their supplies if necessary. Where that is not practical, alternative measures will be used. The abortion laws would be amended by a future Labour Government to ensure that all women have a right of choice in the termination of pregnancy, so that the choice can be effective wherever the woman lives. The drug companies will find life a little less comfortable under Labour. The party has drawn back from a policy of
We thank Dr P. Hnik for
reviewing the manuscript. F. VYSKOIL
Institute of Physiology, Czechoslovak Academy of Sciences, 142 20 Prague 4, Czechoslovakia, and Institute of Macromolecular Chemistry,
J. PILA
Prague
J. TEISINGER
H. ZEMKOVÁ
WHOLE BODY HYPERTHERMIA AND NATURAL KILLER CELL ACTIVITY
SIR,-Azocar,Nurmi,7
and their
colleagues have studied the
effect of hyperthermia on natural killer (NK) cell activity, and their in vitro results contrast with the beneficial effect of artificial
hyperthermia on the immune response.8Whole body hyperthermia is an established clinical treatment in our hospital, and, in patients
-
who gave their informed consent and who were treated with an extracorporeal device, NK cell activity was measured: A human malignant glioma cell line, similar in susceptibility to NK cell attack to the K562 cell line, was used for target cells with effector-target cell ratios of 10:1and 30:1. The results in a 17-yearold boy who had had Ewing’s sarcoma for 4 years and whose tumour was resistant to chemotherapy and radiology are summarised in the figure. The boy was scheduled for hyperthermia 5 weeks after the last cyclophosphamide regimen and his performance status on’the Karnofsky scale was 70%. On admission to hospital he had an NK activity of nearly zero. Peripheral blood lymphocytes, from a sample 2 h after the end of 6 h of whole body hyperthermia (41’8°C bladder temperature) exhibited a cytotoxicity of 30%, which steadily decreased to 10% within a week. 96 h after a second hyperthermic treatment, NK activity rose to over 60%, again followed by a remarkable drop to 20% over the next week. 2 days after the second hyperthermic session, the boy was discharged and went back to school. The restoration ofNK activity that we noted in this cancer patient was probably caused by the hyperthermic treatment. It is puzzling why human NK activity in vitro should be inversely related to increases in temperature over 37°C while activity is enhanced by hyperthermia in vivo. Temperature cannot be the sole determining factor-perhaps some latent infections, such as viral infections, are 4
ESR spectra.
(B) vanadate (V5+); and vanadate plus (C) methylene(A) vanadyl blue, (D) chlorpromazine; (E) imipramine; (F) diazepam; (G) lithium. Calibration in millitesla (mT). Amplification is two times higher in B, C, F,
(V4+);
and G than in
Løvstad RA. Interaction of phenothiazine
derivatives with human ceruloplasmin. Biochem Pharmacol 1974, 23: 1045-52 5. Naylor GJ, Dick DAT, Johnston BB, Hopwood SE, Dick EG, Smith AHW, Kay D. Possible explanation for therapeutic action of lithium, and a possible substitute (methylene-blue). Lancet 1981, ii 1145-46 6 Azocar J, Yunis EJ, Essex M Sensitivity of human natural killer cells to hyperthermia. Lancet 1982; i: 16-17. 7. Nurmi T, Uhari M, Konvalainen K. Temperature and natural killer cell activity. Lancet 1982; i: 516-17 8. Dickson JA, Shah SA. Hyperthermia and the immune response in cancer therapy. Cancer Immunol Immunother 1980; 9: 1-10.
A, D, and E.
reduced vanadium. This was surprising because methylene-blue active in promoting the vanadate-NADH-FAD reaction in the experiment of Naylor and Smith.2 On the other hand, in spectrophotometric experiments with 1 mmol/l NADH (in sodium phosphate buffer, no FAD, 25°C, A365nm) 50 mot/1 methyleneblue (but not 500 pmol/1 imipramine or chlorpromazine) reduced 0-33 NADH jÄmol/l/min by itself and promoted the "background" reduction of NADH1 in the presence of vanadate (molar ratio 1:1’) by 85%. Because both chlorpromazine and imipramine can reduce vanadate to vanadyl in equimolar concentrations, the claimed benefit of these drugs in manic-depressive syndromes, acting via vanadium, does not require the presence ofNADH and it may occur was most
Modulation of NK activity during two whole body hyperthermia treatments in a patient with Ewing’s sarcoma.
Effector-target cell columns).
ratios were
1 10
(open columns) and 1:30 (hatched
,
1080 activated by hyperthermia, which induces interferon and thus augments NK activity.9
production
Institute for Experimental Surgery, Technical University of Munich, 8000 Munich 80, West Germany
KURT S. ZÄNKER
Superficial parotidectomy, done by a surgeon skilled at and experienced in the technique, is the treatment of choice for pleomorphic adenomas of the parotid gland. Fine needle aspiration of parotid lumps will allow accurate diagnosis of these sometimes testing lesions so that unwarranted enucleation may be avoided.
Surgical Clinic and Polyclinic, Technical University of Munich
JOCHEN LANGE
Department of Surgery, Bristol Royal Infirmary,
PAROTID TUMOURS
SIR,-Your April 10 editorial on parotid tumours raises many interesting points. We have studied a series of 58 pleomorphic adenomas of the parotid gland treated at the Bristol Royal Infirmary year period. 40 superficial parotidectomies were done and 18 enucleations, with recurrence rates of 5% and 25%, respectively. Complications, however, were notably more common in those having the radical operation, and, when paraesthesiae and numbness in the distribution of the auriculotemporal nerve, facial palsy, and Frey’s syndrome were taken into account, only 30% of parotidectomy patients were judged normal, compared with 60% of those whose tumour had been enucleated. These results reflect two aspects of our survey: sequelae of the operation were asked about at personal follow-up by independent observers; and the patients had been under the care of ten different surgeons, thus restricting the experience that could be accumulated by any individual. Whatever the policy adopted, enucleation will from time to time be done when the diagnosis is wrong. A third of the tumours enucleated in this series were not recognised as parotid tumours preoperatively. Fine needle aspiration biopsy was performed on 26 patients and gave a precise diagnosis in 20. In the remaining 6 the lump was defined as a parotid tumour but the histology could not be more precise. Follow-up of these cases now ranges from 5 to 15 years, and there has been no evidence of local recurrence following fine needle aspiration biopsy and adequate operative treatment. over a ten
9. Herberman R, Ortaldo J, Bonnard G. Augmentation by interferon of human natural and antibody-dependent cell-mediated cytotoxicity. Nature 1979; 227: 221-23
Commentary from Westminster Labour Plans for the N.H.S. A WAR against private medicine is likely to be one of the main commitments of the next Labour Government, if there is to be one. Labour’s next General Election manifesto is almost certain to contain a wide range of proposals intended to "ensure that private practice is no longer allowed to flourish". A draft of the Health and Social Services chapter of the next manifesto has just been approved by the party’s social policy subcommittee. It has some way to go before final adoption. The manifesto will not be written until shortly before the next General Election. But the draft represents the consensus prevailing now between the "experts", the trade unionists, and the politicians whom the party has charged with suggesting policies. The subcommittee believes that the private health sector can profit only as a parasite on the N.H.S., using N.H.S. resources, staff, and back-up services. "Its continued growth would seriously hinder the objectives we have set for the N.H.S." Private practice, under Labour, would therefore be separated from the N.H.S., by removing all pay beds within the first two years of Government. "We shall also take into the N.H.S. those parts of the profit-making private sector which can be used to meet local health needs and reduce waiting lists. For the rest of the private sector we shall withdraw the considerable public subsidies enjoyed by way of tax concessions on private health insurance, the charitable status of certain hospitals, and access to specialised N.H.S. facilities." No new private hospital developments would be
R. G. HUGHES T. J. LYONS
Bristol BS2 8HW
FLUORESCEIN DILAURATE TEST OF PANCREATIC FUNCTION
SiR,—We read with interest your March 27 editorial on the diagnosis of chronic pancreatitis and agree with the value of screening patients with possible pancreatic insufficiency. You favour the use of the 14C-PABA (p-aminobenzoic acid) test but this has the disadvantages of requiring dietary and drug restriction and a complex assay and of being invalidated by drug or isotope interference (16/140, 11%). Radioisotope use makes the test unsuitable in pregnancy and in children. The sensitivity of the 14C-PABA test in the reference cited’ was 74%
frequently
(32/43). In a prospective study (to be published elsewhere) we found that the fluorescein dilaurate test identified 93% (14/15) of patients with proven chronic pancreatitis. The test is suitable for all patients and does not require a complex laboratory assay. In our opinion, the fluorescein dilaurate test is worth considering as the investigation of choice for screening patients with suspected pancreatic
insufficiency. E. J. S. BOYD J. G. R. CUMMING R. A. B. WOOD A. CUSCHIERI K. G. WORMSLEY
Department of Surgery, Ninewells Hospital, Dundee DD1 9SY 1. Tetlow
VA,
excretion
Herman K, Kay index (using
GH, Braganza JM. Diagnostic accuracy of the PABA
14C-PABA). Gut
1981, 22: A441.
part of a system of strict controls. Consultants’ would have to be renegotiated "so that full recognition is given to those who make a full-time commitment to the N.H.S." The draft does not mention compensation for expropriated private medical companies. We know Mr Benn is against paying up, and that nearly half the Labour Party wants Mr Benn to be leader. The otlicial leadership has steered clear of the compensation question. Career structure for doctors would have to be generally redirected, the draft continues, so it is "more geared to the needs of the N.H.S." If the N.H.S. is given increased
allowed,
as
contracts
resources, the authors
believe, there is nothing it cannot which the private sector can. It will be re-established provide as a free service, funded out of general taxation, in which "priority is given on the basis of medical need and not ability to pay". Naturally the draft promises that a Labour Government would give greater priority to the elderly, the physically and mentally handicapped, and the socially deprived. Higher pay awards for N.H.S. workers are virtually promised. A substantial number of N.H.S. employees are low-paid and their position must be improved. Greater democratic influence int he N.H.S. is also owed to N.H.S. trade-union members, the draft declares. Labour would introduce legislation to ensure that water authorities add fluoride to their supplies if necessary. Where that is not practical, alternative measures will be used. The abortion laws would be amended by a future Labour Government to ensure that all women have a right of choice in the termination of pregnancy, so that the choice can be effective wherever the woman lives. The drug companies will find life a little less comfortable under Labour. The party has drawn back from a policy of