- Email: [email protected]
COMBINED ORTHOPAEDIC-GERIATRIC CARE
349 ’Velosulin’ is diluted in normal saline and infused into a forearm vein through an indwelling venous cannula, with a Graseby MS 16 syringe driver. An initial rate of 1 U/h during the day and 0’ 5 U/h during the night is used. A pre-meal intravenous bolus of 12 units is given just before each meal, and the basal rate is increased to 2 U/h for 1 h postprandially. Hourly blood glucose is determined using Boehringer strips (’BM-Test-Glycemie 20-800’) and individual adjustments are made until euglycaemia (4-7 mmol/1) is achieved throughout 24 h. Using this method wehave treated thirteen males and four females, aged 41-73 (mean 54) with severe painful diabetic neuropathy. The duration of diabetes ranged from 0 to 23 years (mean 7 years) and symptoms from 1-12 months (mean 5 months). Glycosylated haemoglobin ranged from 5 - 5% to 17% (mean 10’1%; normal 4 -5-8’5%). Basal infusion rates to achieve 24 h euglycaemia were 1-4 U/h during the day and 0 5-2 U/h at night with a postprandial boost ofup to 12 U/h for 1 h. Patients were asked to record graphically any subjective improvement on a pain analogue scale with 100 as maximum pain before treatment and 0 as no pain. Euglycaemia was attained within 1-3 days, and relief of symptoms was dramatic and almost simultaneous with the euglycaemia; in 2-5 days pain scores had fallen by 50-90. Improvement continued for about 72 h and then pain scores levelled off. Patients were discharged home on four injections of subcutaneous insulin (three short plus one intermediate) to maintain preprandial blood sugars at 4 mmol/1 or less, as assessed by home monitoring with Boehringer strips at least four times a day. Of twelve patients followed up for 6 months, eleven have continued to experience symptomatic relief with tight control of diabetes, glycosylated haemoglobin ranging from 6 - 07o to 8-5% (mean
ROBERT J. YOUNG DAVID J. EWING BASIL F. CLARKE
Department of Medicine, Royal Infirmary, Edinburgh EH3 9YW
Young RJ, Ewing DJ, Clarke BF. A controlled trial of sorbinol, an aldose reductase inhibitor, in chronic painful neuropathy. Diabetes 1983; 32: 938-42. 2. Lewin IG, O’Brien IAD, Morgan MH, Corrall RJM. Clinical and electrophysiological studies with the aldose reductase inhibitor, sorbinol, in symptomatic diabetic neuropathy. Diabetologia 1984; 26: 445-48. 3. Young RJ, Prescott RJ, Ewing DJ, Clarke BF. Variations in neurophysiology and type of diabetic peripheral neuropathy. Presented to the Peripheral Neuropathy Association of America meeting on diabetic neuropathy (Keystone, Colorado, June, 1984). 4. Morley GK, Mooradian AD, Levine AL, Morley JE. Mechanisms of pain in diabetic peripheral neuropathy: Effect of glucose on pain perception in humans. Am J Med 1.
1984; 77: 79-82.
COMBINED ORTHOPAEDIC-GERIATRIC CARE
SIR,-Mr Bendall and colleagues (Jan 12, p 113) suggest the need more combined orthopaedic-geriatric beds to cope with increasing numbers of elderly trauma patients. From our two years’ experience of an orthogeriatric service based at Gartnavel General Hospital, Glasgow, we conclude that existing orthopaedic beds can adequately be used to provide this type of care with little change in staffing levels and, possibly, a net saving in the geriatricians’ time. for
7-4%). In this series painful symptoms were relieved within 2-5 days of and almost coincided with the attainment of 24 h
therapy
euglycaemia. Previous work with tight glucose control achieved by continuous
subcutaneous
insulin
infusion
demonstrated
improvement in 1-5 weeks (median 3 weeks).6 Rapid changes in blood glucose may alter nerve membrane ionic flux or modulate opioid receptors7 thus exacerbating painful symptoms, and we think that the maintenance of blood glucose levels within the physiological range (4-7 mmol/1) throughout 24 h period is vitally important in ameliorating such symptoms. Further, insulin itself may have some beneficial effect. We hope that our experience will encourage other physicians to try this method for symptoms that may be very distressing for the patient. Diabetic Unit, Leicester General Hospital, Leicester LE5 4PW
A. SAMANTA A. C. BURDEN
MJ, Martin JR, Asbury AK. Painful diabetic neuropathy: A morphometric study. Arch Neurol 1976; 33: 164-71. 2 Said G, Slama G, Selva J. Progressive centripetal degeneration of axons in small fibre diabetic polyneuropathy. Brain 1983; 106: 791-807. 3 Samanta A, Burden AC. Rapid improvement in diabetic neuropathic pain using an open-loop intravenous insulin infusion system. Practical Diabetes (in press). 4 Raskin P. Open and closed insulin infusion systems: Newer methods of insulin delivery In: Ellenberg M, Rifkin H, eds. Diabetes mellitus: Theory and practice, 3rd ed. New York: Medical Examination Publishing, 1983: 941-57. 5 Scott J. Hoskinsson EC. Graphic representation of pain. Pain 1976; 2: 175-84. 6. Boulton AJM, Drury J, Clarke B, Ward JD. Continuous subcutaneous insulin infusion in the management of painful diabetic neuropathy Diabetes Care 1982; 5: 386-90. 7. Morley GK, Mooradian AD, Levine AL, Morley JE. Mechanisms of pain in diabetic peripheral neuropathy: Effect of glucose on pain perception in humans. Am J Med 1 Brown
1984; 77: 79-82. DA, De Jesus PV, Winegrad AI. Effects of insulin and dietary myoinositol on impaired peripheral motor conduction velocity in acute streptozotocin rats. J Clin Invest 1975; 55: 1326-36.
8. Greene
SIR,-Your editorial
on pain in diabetic neuropathy draws neglected problem. However, the acute role of hyperglycaemia in pain generation should not be overemphasised at the expense of attention to its longer-term effect in causing structural neuropathy. While diabetics with painful neuropathy as a group have poorer blood glucose control than comparable diabetics without neuropathy, no relation between blood glucose concentration and severity or persistence of pain has been identified. Indeed pain is chronic in many who have apparently good control. In a prospective study of diabetics presenting with painful neuropathy of recent onset we found complete remission of pain in
attention
patients; this was associated with improved nerve function, despite progressive deterioration of blood glucose control. Your editorial also suggested that differences in glycaemic control might explain the contrasting results of two studies of sorbinil on chronic painful neuropathy. 1,2 In both glycaemic control was monitored carefully ,and remained stable, the mean glycosylated haemoglobin being the same (1I-6±2’5%). We did not find1 any relation between glycaemic control and response to sorbinol. We feel that structural neuropathy is primarily responsible for pain generation. As your editorial points out, damage to small fibres is a characteristic of such neuropathies.3 However, changes in blood glucose levels may affect pain perception.4 16 of 29
to a
Like other
units,2,3 we have observed a reduction in the average
length of stay of elderly patients since the opening of our unit, but we do not think that this type of care is yet of proven efficacy. Preselection of patients, the use of retrospective controls, and reliance on unsatisfactory performance indicators, such as length of stay in hospital, cast doubt on the conclusions drawn by all studies so far reported. Until the result of a controlled study on combined care of elderly trauma patients is published, we must temper our enthusiasm for this potentially effective approach. W. J. GILCHRIST Gartnavel General
R. J. NEWMAN D. L. HAMBLEN B. O. WILLIAMS
Hospital,
Glasgow G12 0YN 1.
Boyce WJ, Vessey
MP.
Rising incidence of fracture of the proximal femur. Lancet
1985; i: 150-51. 2.
Burley LE, et al. The joint geriatric orthopaedic service in south Edinburgh: November
3.
Boyd RE, et al. The Nottingham orthogeriatric unit after 1000 admissions. Injury 1983;
1979- October 1980. Health Bull 1984; 42: 133-40. 15: 193-96.
SIR,-Dr Donaldson and Mr Robbins (Nov 3, p 1028) conclude prolonged stay of fractured neck of femur cases in the orthopaedic wards is not due to surgical or medical problems but to continued occupancy of beds by patients who require rehabilitative measures or suitable alternative placement. They suggest that this delay could be reduced by greater involvement of geriatricians and social workers in orthopaedic wards from the day of hospital that the
admission. We would like to report our experience of joint management of these cases in a new district general hospital where "bed blockage" was an acute problem in orthopaedic wards. In January, 1982, ten beds were reserved in a newly opened rehabilitation ward for patients with fractured neck of femur who, despite successful surgery, had no immediate prospect of discharge. The orthopaedic surgeons identified these patients and the geriatricians assessed and
.
350
arranged transfer within three days wherever possible. The patient then jointly managed by both specialists, the geriatricians being in charge of day-to-day medical management and integrating them
was
in their case conferences. From January, 1982, to September, 1984, 134 patients were transferred to the rehabilitation ward. The mean age was 79 years. 55% lived alone. 102 patients had associated medical neurological or skeletal conditions necessitating prolonged rehabilitation. In many cases social problems contributed to a delayed discharge. This joint approach had an impressive effect on orthopaedic services. A total of 7091 hospital days were saved and, as a consequence, more beds
available for acute emergencies and waiting list cases. The following improvements were achieved in orthopaedic turnover (a detailed report including 1984 figures is in preparation): were
-
(1) Discharges and deaths (2) Average length of stay (3) Discharges and deaths per available bed
(4) Percentage occupancy (5) Hip replacements (6) Inpatient waiting list
1981 954 18-25
1983
Improvement
1652 12 - 80 days
73% 30%
14-91 88-36 55 290
22-23 78-06 107 20
50% 11-507o 94% 93%
Mr Bendall and colleagues (Jan 12, p 113) state that where geriatric and orthopaedic specialties cooperate and jointly manage
elderly patients, the experience is interesting and rewarding. Our study shows that such collaboration, based on goodwill and better understanding of each others’ roles, has a very positive effect on orthopaedic through-put and is of considerable benefit to the community. We find it surprising that, despite the recommendations in the Duthie report! and other evidence,2,3 this approach is not widely practised. Our findings have important implications for health authorities who "subcontract" total hip-replacements to the private sector.4 Departments of Geriatric Medicine and Orthopaedic Surgery, Sandwell District General Hospital,
H. N. DESAI M. H. SHAKEEL M. E. EL SAFTY
West Bromwich B71 4HJ
G-PCC with characteristic single-stranded chromatids from breast cancer.
G-banding. In a pseudodiploid breast carcinoma PCC was observed in 3, 3% of the cells studied, in a papillary bladder cancer PCC was found in 7-1% of metaphases. The percentage of PCC in an acute myelofibrosis and in an acute myeloid leukaemia was 8-6% and 1’ 4%, respectively. Lastly, PCC was found in 4% of metaphases in a malignant pleural effusion of a breast cancer. We found not only S-PCC but also G1-PCC in every case (figure) and G2-PCC in the two
Department of Health and Social Security. Orthopaedic services. Report of Working Party to the Secretary of State. London: HMSO, 1981. 2. Devas M. Geriatric orthopaedics. London: Academic Press, 1977. 3. Boyd RV, Compton E, Hawthorne J, Kenan JR. Orthogeriatric rehabilitation ward in Nottingham: a preliminary report. Br Med J 1982; 285: 937-38. 4. Anon. Private solution to hip-op waiting list chaos. Hosp Doctor 1985 (Jan 17): 20. 1.
SPONTANEOUS CELL FUSION IN HUMAN MALIGNANCIES: POSSIBLE MECHANISM LEADING TO HETEROGENEITY
SIR,-Most human tumours are heterogeneous in their metastatic potential, response to chemotherapy, growth rate, cell surface antigens, karyotype, and so on. This heterogeneity is not completely understood, but its cause may involve genetic instability and selective advantagesSome investigators believe that epigenetic factors are responsible.3 Somatic cell hybrid studies suggest that cell fusion can also lead to a heterogeneous cell population.4-7 Hybrid cells in experimental systems can be easily studied by cytogenetic and/or biochemical gene marker methods. However, in naturally occurring human tumours cell fusion in vivo could not normally be detected. We have seen premature chromosome condensation (PCC) in human malignancies and suggest that PCC provides evidence of cell fusion in such cases. PCC is induced when two cells are fused while one of them is in mitosis and the other in interphase. The morphology of PCC depends on the interphase cell: the PCC of a G1 cell consists of single chromatids, the S-PCC "pulverised", and the G2-PCC consists of two chromatids. The S-PCC can be simulated by pulverisation of chromosomes by virus infection, so an S-PCC can be interpreted in terms of cell fusion only if accompanied by Gl and/or G2 PCC. There is only one previous report, of a bladder 9 carcinoma, which meets this criterion.9 We have found PCC in 5 out of 166 human malignancies (128 haematological disorders, 35 carcinomas, and 3 malignant effusions) analysed in direct chromosome preparations with
appears
haematological cases.
Our observations suggest that cell fusion does occur in some human malignancies. Where it occurs, this process may affect the malignant phenotype. Cell fusion between two malignant cells or one malignant and one normal somatic cell followed by selective loss and retention of specific chromosomes carrying regulatory genes or reactivated one-genes could influence the phenotypic character of tumours. 10 This mechanism, along with other pathways, may help to explain the heterogeneity of tumour cell populations. Laboratory of Cytogenetics, Institute of Pathology, Hanover Medical School, D-3000 Hanover 61, West Germany
G. KOVACS A. GEORGII
1. Dexter DL, Calabresi P. Intraneoplastic diversity. Biochim Phys Acta 1982; 695: 97-112. 2. Nowell PC. The clonal evolution of tumor cell populations. Science 1976; 195: 23-28. 3. Rubin H. Is somatic mutation the major mechanism of malignant transformation? J Natl Cancer Inst 1980; 64: 995-1000. 4. Croce CM. Cancer genes in cell hybrids. Biochim Biophys Acta 1980; 605: 411-30. 5. Goldenberg DM, Pavia RA. In vivo horizontal oncogenesis by a human tumor in nude mice. Proc Natl Acad Sci USA 1982; 79: 2389-92. 6. Sabin AB. Suppression of malignancy m human cancer cells: Issues and challenges. Proc Natl Acad Sci USA 1981; 78: 7129-33. 7. Stanbridge EJ, Der CJ, Doersen CJ, et al. Human cell hybrids: Analysis of transformation and tumorigenicity. Science 1982; 215: 252-59. 8. Johnson RT, Rao PN. Mammalian cell fusion. II Induction of premature chromosome condensation in interphase nuclei. Nature 1970; 226: 717-22. 9. Atkin NB. Premature chromosome condensation in a carcinoma of the bladder presumptive evidence for fusion of normal and malignant cells. Cytogenet Cell Genet
1979; 23: 217-19. 10.
Shows TB. Suppression of tumorigenicity in somatic cell hybrids, II Human chromosomes implicated as suppressors of tumorigenicity in hybrids with Chinese hamster. J Natl Cancer Inst 1983; 71: 559-69.
Klinger HP,
OPHTHALMIA NEONATORUM TODAY
SIR,-Your editorial on ophthalmia neonatorum (Dec 15, p 1375) dealt mainly with conjunctivitis due to gonococcal and chlamydial infection. In our experience gonococcal ophthalmia neonatorum is
ROBERT J. YOUNG DAVID J. EWING BASIL F. CLARKE
Department of Medicine, Royal Infirmary, Edinburgh EH3 9YW
Young RJ, Ewing DJ, Clarke BF. A controlled trial of sorbinol, an aldose reductase inhibitor, in chronic painful neuropathy. Diabetes 1983; 32: 938-42. 2. Lewin IG, O’Brien IAD, Morgan MH, Corrall RJM. Clinical and electrophysiological studies with the aldose reductase inhibitor, sorbinol, in symptomatic diabetic neuropathy. Diabetologia 1984; 26: 445-48. 3. Young RJ, Prescott RJ, Ewing DJ, Clarke BF. Variations in neurophysiology and type of diabetic peripheral neuropathy. Presented to the Peripheral Neuropathy Association of America meeting on diabetic neuropathy (Keystone, Colorado, June, 1984). 4. Morley GK, Mooradian AD, Levine AL, Morley JE. Mechanisms of pain in diabetic peripheral neuropathy: Effect of glucose on pain perception in humans. Am J Med 1.
1984; 77: 79-82.
COMBINED ORTHOPAEDIC-GERIATRIC CARE
SIR,-Mr Bendall and colleagues (Jan 12, p 113) suggest the need more combined orthopaedic-geriatric beds to cope with increasing numbers of elderly trauma patients. From our two years’ experience of an orthogeriatric service based at Gartnavel General Hospital, Glasgow, we conclude that existing orthopaedic beds can adequately be used to provide this type of care with little change in staffing levels and, possibly, a net saving in the geriatricians’ time. for
7-4%). In this series painful symptoms were relieved within 2-5 days of and almost coincided with the attainment of 24 h
therapy
euglycaemia. Previous work with tight glucose control achieved by continuous
subcutaneous
insulin
infusion
demonstrated
improvement in 1-5 weeks (median 3 weeks).6 Rapid changes in blood glucose may alter nerve membrane ionic flux or modulate opioid receptors7 thus exacerbating painful symptoms, and we think that the maintenance of blood glucose levels within the physiological range (4-7 mmol/1) throughout 24 h period is vitally important in ameliorating such symptoms. Further, insulin itself may have some beneficial effect. We hope that our experience will encourage other physicians to try this method for symptoms that may be very distressing for the patient. Diabetic Unit, Leicester General Hospital, Leicester LE5 4PW
A. SAMANTA A. C. BURDEN
MJ, Martin JR, Asbury AK. Painful diabetic neuropathy: A morphometric study. Arch Neurol 1976; 33: 164-71. 2 Said G, Slama G, Selva J. Progressive centripetal degeneration of axons in small fibre diabetic polyneuropathy. Brain 1983; 106: 791-807. 3 Samanta A, Burden AC. Rapid improvement in diabetic neuropathic pain using an open-loop intravenous insulin infusion system. Practical Diabetes (in press). 4 Raskin P. Open and closed insulin infusion systems: Newer methods of insulin delivery In: Ellenberg M, Rifkin H, eds. Diabetes mellitus: Theory and practice, 3rd ed. New York: Medical Examination Publishing, 1983: 941-57. 5 Scott J. Hoskinsson EC. Graphic representation of pain. Pain 1976; 2: 175-84. 6. Boulton AJM, Drury J, Clarke B, Ward JD. Continuous subcutaneous insulin infusion in the management of painful diabetic neuropathy Diabetes Care 1982; 5: 386-90. 7. Morley GK, Mooradian AD, Levine AL, Morley JE. Mechanisms of pain in diabetic peripheral neuropathy: Effect of glucose on pain perception in humans. Am J Med 1 Brown
1984; 77: 79-82. DA, De Jesus PV, Winegrad AI. Effects of insulin and dietary myoinositol on impaired peripheral motor conduction velocity in acute streptozotocin rats. J Clin Invest 1975; 55: 1326-36.
8. Greene
SIR,-Your editorial
on pain in diabetic neuropathy draws neglected problem. However, the acute role of hyperglycaemia in pain generation should not be overemphasised at the expense of attention to its longer-term effect in causing structural neuropathy. While diabetics with painful neuropathy as a group have poorer blood glucose control than comparable diabetics without neuropathy, no relation between blood glucose concentration and severity or persistence of pain has been identified. Indeed pain is chronic in many who have apparently good control. In a prospective study of diabetics presenting with painful neuropathy of recent onset we found complete remission of pain in
attention
patients; this was associated with improved nerve function, despite progressive deterioration of blood glucose control. Your editorial also suggested that differences in glycaemic control might explain the contrasting results of two studies of sorbinil on chronic painful neuropathy. 1,2 In both glycaemic control was monitored carefully ,and remained stable, the mean glycosylated haemoglobin being the same (1I-6±2’5%). We did not find1 any relation between glycaemic control and response to sorbinol. We feel that structural neuropathy is primarily responsible for pain generation. As your editorial points out, damage to small fibres is a characteristic of such neuropathies.3 However, changes in blood glucose levels may affect pain perception.4 16 of 29
to a
Like other
units,2,3 we have observed a reduction in the average
length of stay of elderly patients since the opening of our unit, but we do not think that this type of care is yet of proven efficacy. Preselection of patients, the use of retrospective controls, and reliance on unsatisfactory performance indicators, such as length of stay in hospital, cast doubt on the conclusions drawn by all studies so far reported. Until the result of a controlled study on combined care of elderly trauma patients is published, we must temper our enthusiasm for this potentially effective approach. W. J. GILCHRIST Gartnavel General
R. J. NEWMAN D. L. HAMBLEN B. O. WILLIAMS
Hospital,
Glasgow G12 0YN 1.
Boyce WJ, Vessey
MP.
Rising incidence of fracture of the proximal femur. Lancet
1985; i: 150-51. 2.
Burley LE, et al. The joint geriatric orthopaedic service in south Edinburgh: November
3.
Boyd RE, et al. The Nottingham orthogeriatric unit after 1000 admissions. Injury 1983;
1979- October 1980. Health Bull 1984; 42: 133-40. 15: 193-96.
SIR,-Dr Donaldson and Mr Robbins (Nov 3, p 1028) conclude prolonged stay of fractured neck of femur cases in the orthopaedic wards is not due to surgical or medical problems but to continued occupancy of beds by patients who require rehabilitative measures or suitable alternative placement. They suggest that this delay could be reduced by greater involvement of geriatricians and social workers in orthopaedic wards from the day of hospital that the
admission. We would like to report our experience of joint management of these cases in a new district general hospital where "bed blockage" was an acute problem in orthopaedic wards. In January, 1982, ten beds were reserved in a newly opened rehabilitation ward for patients with fractured neck of femur who, despite successful surgery, had no immediate prospect of discharge. The orthopaedic surgeons identified these patients and the geriatricians assessed and
.
350
arranged transfer within three days wherever possible. The patient then jointly managed by both specialists, the geriatricians being in charge of day-to-day medical management and integrating them
was
in their case conferences. From January, 1982, to September, 1984, 134 patients were transferred to the rehabilitation ward. The mean age was 79 years. 55% lived alone. 102 patients had associated medical neurological or skeletal conditions necessitating prolonged rehabilitation. In many cases social problems contributed to a delayed discharge. This joint approach had an impressive effect on orthopaedic services. A total of 7091 hospital days were saved and, as a consequence, more beds
available for acute emergencies and waiting list cases. The following improvements were achieved in orthopaedic turnover (a detailed report including 1984 figures is in preparation): were
-
(1) Discharges and deaths (2) Average length of stay (3) Discharges and deaths per available bed
(4) Percentage occupancy (5) Hip replacements (6) Inpatient waiting list
1981 954 18-25
1983
Improvement
1652 12 - 80 days
73% 30%
14-91 88-36 55 290
22-23 78-06 107 20
50% 11-507o 94% 93%
Mr Bendall and colleagues (Jan 12, p 113) state that where geriatric and orthopaedic specialties cooperate and jointly manage
elderly patients, the experience is interesting and rewarding. Our study shows that such collaboration, based on goodwill and better understanding of each others’ roles, has a very positive effect on orthopaedic through-put and is of considerable benefit to the community. We find it surprising that, despite the recommendations in the Duthie report! and other evidence,2,3 this approach is not widely practised. Our findings have important implications for health authorities who "subcontract" total hip-replacements to the private sector.4 Departments of Geriatric Medicine and Orthopaedic Surgery, Sandwell District General Hospital,
H. N. DESAI M. H. SHAKEEL M. E. EL SAFTY
West Bromwich B71 4HJ
G-PCC with characteristic single-stranded chromatids from breast cancer.
G-banding. In a pseudodiploid breast carcinoma PCC was observed in 3, 3% of the cells studied, in a papillary bladder cancer PCC was found in 7-1% of metaphases. The percentage of PCC in an acute myelofibrosis and in an acute myeloid leukaemia was 8-6% and 1’ 4%, respectively. Lastly, PCC was found in 4% of metaphases in a malignant pleural effusion of a breast cancer. We found not only S-PCC but also G1-PCC in every case (figure) and G2-PCC in the two
Department of Health and Social Security. Orthopaedic services. Report of Working Party to the Secretary of State. London: HMSO, 1981. 2. Devas M. Geriatric orthopaedics. London: Academic Press, 1977. 3. Boyd RV, Compton E, Hawthorne J, Kenan JR. Orthogeriatric rehabilitation ward in Nottingham: a preliminary report. Br Med J 1982; 285: 937-38. 4. Anon. Private solution to hip-op waiting list chaos. Hosp Doctor 1985 (Jan 17): 20. 1.
SPONTANEOUS CELL FUSION IN HUMAN MALIGNANCIES: POSSIBLE MECHANISM LEADING TO HETEROGENEITY
SIR,-Most human tumours are heterogeneous in their metastatic potential, response to chemotherapy, growth rate, cell surface antigens, karyotype, and so on. This heterogeneity is not completely understood, but its cause may involve genetic instability and selective advantagesSome investigators believe that epigenetic factors are responsible.3 Somatic cell hybrid studies suggest that cell fusion can also lead to a heterogeneous cell population.4-7 Hybrid cells in experimental systems can be easily studied by cytogenetic and/or biochemical gene marker methods. However, in naturally occurring human tumours cell fusion in vivo could not normally be detected. We have seen premature chromosome condensation (PCC) in human malignancies and suggest that PCC provides evidence of cell fusion in such cases. PCC is induced when two cells are fused while one of them is in mitosis and the other in interphase. The morphology of PCC depends on the interphase cell: the PCC of a G1 cell consists of single chromatids, the S-PCC "pulverised", and the G2-PCC consists of two chromatids. The S-PCC can be simulated by pulverisation of chromosomes by virus infection, so an S-PCC can be interpreted in terms of cell fusion only if accompanied by Gl and/or G2 PCC. There is only one previous report, of a bladder 9 carcinoma, which meets this criterion.9 We have found PCC in 5 out of 166 human malignancies (128 haematological disorders, 35 carcinomas, and 3 malignant effusions) analysed in direct chromosome preparations with
appears
haematological cases.
Our observations suggest that cell fusion does occur in some human malignancies. Where it occurs, this process may affect the malignant phenotype. Cell fusion between two malignant cells or one malignant and one normal somatic cell followed by selective loss and retention of specific chromosomes carrying regulatory genes or reactivated one-genes could influence the phenotypic character of tumours. 10 This mechanism, along with other pathways, may help to explain the heterogeneity of tumour cell populations. Laboratory of Cytogenetics, Institute of Pathology, Hanover Medical School, D-3000 Hanover 61, West Germany
G. KOVACS A. GEORGII
1. Dexter DL, Calabresi P. Intraneoplastic diversity. Biochim Phys Acta 1982; 695: 97-112. 2. Nowell PC. The clonal evolution of tumor cell populations. Science 1976; 195: 23-28. 3. Rubin H. Is somatic mutation the major mechanism of malignant transformation? J Natl Cancer Inst 1980; 64: 995-1000. 4. Croce CM. Cancer genes in cell hybrids. Biochim Biophys Acta 1980; 605: 411-30. 5. Goldenberg DM, Pavia RA. In vivo horizontal oncogenesis by a human tumor in nude mice. Proc Natl Acad Sci USA 1982; 79: 2389-92. 6. Sabin AB. Suppression of malignancy m human cancer cells: Issues and challenges. Proc Natl Acad Sci USA 1981; 78: 7129-33. 7. Stanbridge EJ, Der CJ, Doersen CJ, et al. Human cell hybrids: Analysis of transformation and tumorigenicity. Science 1982; 215: 252-59. 8. Johnson RT, Rao PN. Mammalian cell fusion. II Induction of premature chromosome condensation in interphase nuclei. Nature 1970; 226: 717-22. 9. Atkin NB. Premature chromosome condensation in a carcinoma of the bladder presumptive evidence for fusion of normal and malignant cells. Cytogenet Cell Genet
1979; 23: 217-19. 10.
Shows TB. Suppression of tumorigenicity in somatic cell hybrids, II Human chromosomes implicated as suppressors of tumorigenicity in hybrids with Chinese hamster. J Natl Cancer Inst 1983; 71: 559-69.
Klinger HP,
OPHTHALMIA NEONATORUM TODAY
SIR,-Your editorial on ophthalmia neonatorum (Dec 15, p 1375) dealt mainly with conjunctivitis due to gonococcal and chlamydial infection. In our experience gonococcal ophthalmia neonatorum is