1084
1.
Fitzgerald DE, Drumm JE. Non-invasive measurement of human fetal circulation using ultrasound: a new technique. Br Med J 1977; ii:
1450-51. 2. Eik-Nes SH, Brubakk AO, Ulstein MK. Measurement of human fetal blood flow. Br Med J 1980; i: 283-84. 3. Griffin D, Cohen-Overbeek T, Campbell S. Fetal and utero-placental blood flow. Clin Obstet Gynaecol 1983; 10: 565-602. 4. Ng A, Trudinger BJ. The application of umbilical artery studies to complicated pregnancies. In: Pearce JMF, eds. Doppler ultrasound in perinatal medicine. Oxford: Oxford University Press, 1992: 143-58. 5. Burke G, Stuart B, Crowley P, Scanaill SN, Drumm JE. Is intrauterine growth retardation with normal umbilical artery blood flow a benign condition? Br Med J 1990; 300: 1044-45. 6. Nicolaides KH, Bilardo CM, Soothill PW, Campbell S. Absence of end-diastolic frequencies in the umbilical artery: a sign of fetal hypoxia and acidosis. Br Med J 1988; 297: 1026-27. 7. McParland P, Steel SA, Pearce JMF. The clinical implications of absent or reversed end-diastolic frequencies in umbilical artery flow velocity waveforms. Eur J Obstet Gynecol Repro Biol 1990 37: 15-23. 8. Dornan J, Beattie B. Umbilical artery doppler ultrasonography as a screening tool. In: Pearce JMF, ed. Doppler ultrasound in perinatal medicine. Oxford: Oxford University Press, 1992: 95-111. 9. Campbell S, Diaz-Recasens J, Griffin DR, et al. New doppler technique for assessing uteroplacental blood flow. Lancet 1983; i: 675-77. 10. Ducey J, Schulman H, Farmakides G. A classification of hypertension based on doppler velocimetry. Am J Obstet Gynecol 1987; 157: 680-85. 11. Robertson WB, Brosens I, Dixon HG. The pathological response of the vessels of the placenta to hypertensive pregnancies. J Pathol Bacteriol 1967; 93: 581-92. 12. Morrow R, Adamson L, Ritchie K, Pearce JMF. The pathophysiological basis of Doppler waveforms. In: Pearce JMF, ed. Doppler ultrasound in perinatal medicine. Oxford: Oxford University Press, 1992: 196-220. 13. Vyas S, Campbell S. Doppler studies of the cerebral and renal circulations in small-for gestational age fetuses. In: Pearce JMF, ed. Doppler ultrasound in perinatal medicine. Oxford: Oxford University Press, 1992: 268-78. 14. Trudinger BJ, Cook CM, Giles WB, Connelly A, Thompson RS. Umbilical artery flow velocity waveforms in high-risk pregnancy. Lancet 1987; i: 188-90. 15. Tyrell SN, Lilford RJ, MacDonald HN, Nelson EJ, Porter J, Gupta JK. Randomised comparison of routine versus highly selective use of Doppler ultrasound and biophysical scoring to investigate high risk pregnancies. Br J Obstet Gynaecol 1990; 97: 909-16. 16. Newnham JP, O’Dea MR-A, Reid KP, Diepeveen DA. Doppler flow velocity waveform analysis in high risk pregnancies: a randomised controlled trial. Br J Obstet Gynaecol 1991; 98: 956-63. 17. Pearce JMF. The application of uteroplacental waveforms to complicated pregnancies. In: Pearce JMF, ed. Doppler ultrasound in pennatal medicine. Oxford: Oxford University Press, 1992: 159-77. 18. Trudinger BJ, Cook CM, Thompson RS, Giles WB, Connelly A. Low dose aspirin therapy improves fetal weight in umbilical placental insufficiency. Am J Obstet Gynecol 1988; 159: 681-85. 19. McParland P, Pearce JM, Chamberlain GVP. Doppler ultrasound and aspirin in recognition and prevention of pregnancy-induced hypertension. Lancet 1990; 335: 1552-55.
Lymphoma classification—where now? Management of patients with malignant lymphoma is largely determined by interpretation of histological features and, especially for non-Hodgkin lymphomas, by an allocation of subtype and grade. Most lymphomas represent a clonal expansion of B or T lymphocytes whose normal maturation has been arrested or disregulated. The histological appearance represents, to a variable degree, infiltration of normal structures with these malignant cells, the host (immune) response to the tumour, and reactive changes that may result from secretion of cytokines. These appearances may vary within and between tumour sites and from host to host and tumour to tumour.
Pathologists commonly examine lymphoma tissue (haematoxylin and eosin, Giemsa, periodic-acid-Schiff) and with immunohistochemical techniques, for which they use antibodies directed against leucocyte-specific, lineage-specific, and activation antigens. In difficult cases, cytogenetic analysis can help (eg, by revealing the 11;14 translocation of mantle cell lymphomas or the 14;18 translocation of follicle centre cell lymphomaS2) , as can analysis of DNA for clonal rearrangement of the T-cell receptor or immunoglobulin genes. Sometimes these studies produce conflicting results. Thus, cases with morphological and immunophenotypic characteristics of a T-cell lymphoma may not show clonal T-cell receptor gene rearrangements,3 which suggests that they may be reactive rather than malignant processes. Clinical classification of the lymphomas has been debated for decades. A major advance in the classification of the non-Hodgkin lymphomas was Rappaport’s appreciation in the 1950s that the presence of a follicular growth pattern was a feature associated with a more indolent natural history, and that large lymphocytes (then incorrectly described as histiocytes) were associated with a rapidly progressive 4 course and poor outcome. Rappaport’s classification4 proved clinically more relevant than earlier attempts, and its widespread acceptance coincided with the first descriptions of long-term remission for advanced diffuse large cell (histiocytic) lymphomas by combination chemotherapy.5 During the late 1970s this classification became outdated as the biology of lymphocyte maturation became better defmed, and the B-cell and T-cell lymphomas were recognised as separate entities. Classifications such as those described by the Kiel group in Europe6or Lukes and Collins in the USA’ were devised, leading to nosological chaos with multiple classifications in use around the world. A temporary respite, for clinicians at least, was provided by the introduction of the Working Formulation sponsored by National Cancer Institute.8 This compromise categorisation was based on the clinical behaviour (updated in 19889) of over a thousand well-documented cases of non-Hodgkin lymphoma from the USA and Europe. Only routine, stained sections were used in the study, and the non-Hodgkin lymphomas were divided into low, intermediate, and high grade types. For most cases of non-Hodgkin lymphoma, especially low-grade and high-grade varieties, this classification achieved international acceptance and served clinicians well. However, the Working Formulation has now become outdated, partly because of increased recognition of the peripheral T-cell lymphomas, but also because newer diagnostic techniques have led to characterisation of many new entities within the lymphoma spectrum. Peripheral T-cell lymphomas are difficult to classify, differ widely in their clinical presentation, and behave unpredictably. 11 Attempts to grade and with routine stains
1085
categorise these tumours histologically have not been of clonal absence The gene of these that some rearrangement suggests proliferations may not be neoplastic even though the clinical behaviour is that of a malignant process. In the absence of a satisfactory classification, many doctors base their treatment of T-cell lymphomas on clinical interpretation of tumour behaviour and are often extremely uncertain about prognosis. Advances in immunological molecular diagnosis and use of special techniques have led to numerous reports of new forms of non-Hodgkin lymphoma. In some cases well-recognised entities have been characterised (eg, enteropathy-associated T-cell lymphoma12 and mantle-cell-derived lymphoma1) but others are of more uncertain significance (eg, T-cellrich B-cell non-Hodgkin lymphoma13 and anaplastic Ki-1 positive large cell lymphoma 14 ) and require joint clinical and pathological analysis of large numbers of patients to determine the relevance of their separate classification. Meanwhile, the difficulties of histological interpretation of lymphoma cases and the large subjective element in their categorisation have become apparent. Although follicular lymphomas can be recognised easily by most pathologists, for many other categories of lymphoma there is poor agreement between pathologists and poor reproducibility when biopsy specimens are seen by the same pathologists on different occasions. 11,15,16 These difficulties come to the attention of clinicians when cases referred between institutions are reviewed or when old specimens are reviewed and reinterpreted. The diagnosis of Hodgkin’s disease has proved especially troublesome lately. This diagnosis is based on the finding of Reed Sternberg cells in an appropriate cellular background, with subdivision of cases into four groups according to the Rye classification. Despite intense research efforts, the histogenesis of the Reed Stemberg-cell remains an enigma, and immunohistochemistry and other techniques have shown that Hodgkin’s disease is a heterogeneous condition. Nodular lymphocyte predominant Hodgkin’s disease is now regarded as a B-cell proliferation that may progress to high-grade B-cell non-Hodgkin lymphoma,17 and many cases of lymphocyte-depleted Hodgkin’s disease have been reclassified as T-cell non-Hodgkin lymphoma. The interface between other cases of Hodgkin’s disease and non-Hodgkin lymphomas such as large cell anaplastic lymphoma has likewise become increasingly blurred. Clinical practice has also shifted: it is now widely accepted that doxorubicin-containing chemotherapy, the treatment of choice for and intermediate high-grade non-Hodgkin is also indicated for most patients with lymphoma, advanced Hodgkin’s disease.19 Where do we go from here? All too often clinicians and pathologists work separately and with different goals. The Working Formulation project showed that
successful."
large clinicopathological projects
are
possible.
Although increasing understanding of these tumours at a molecular level will increase the complexity of classification, clinicians and pathologists can surely collaborate in well-constructed clinical studies to verify the clinical validity of any new subgroups that may emerge. 1. Raffeld M, Jaffe ES. bcl-1, t(11;14), and mantle cell-derived lymphomas. Blood 1991, 78: 259-63. 2. Rowley JD. Chromosome studies in the non-Hodgkin’s lymphomas: the role of the 14:18 translocation. J Clin Oncol 1988; 6: 919-25. 3. Smith JL, Lane AC, Hodges E, et al. T-cell receptor variable (v) gene usage by lymphoid populations in T-cell lymphoma. J Pathol 1992; 166: 109-12. 4. Rappaport H. Tumors of the hematopoietic system. In: Atlas of tumor pathology, section 3, fascicle 8. Washington, DC: US Armed Forces Institute of Pathology, 1966: 270. 5. Berd D, Cornog J, DeConti RC, Levitt M, Bertino JR. Long term remission in diffuse histiocytic lymphoma treated with combination sequential chemotherapy. Cancer 1975; 35: 1050-54. 6. Lennert K, Mohri N. Histopathology and diagnosis of non-Hodgkin’s lymphomas. In: Lennert K, ed. Malignant lymphomas other than Hodgkin’s disease: histology, cytology, ultrastructure, immunology. Berlin: Springer-Verlag, 1978: 111-469. 7. Lukes RJ, Collins RD. Immunologic characterization of human malignant lymphomas. Cancer 1974; 34: 1488-503. 8. The Non-Hodgkin’s Lymphoma Pathologic Classification Project: National Cancer Institute sponsored study of classifications of
non-Hodgkin’s lymphomas. Summary and descriptions of a working formulation for clinical usage. Cancer 1982; 49: 2112-35. R, Durrleman S, Hoppe RT, et al. The Non-Hodgkin Lymphoma Pathologic Classification Project. Ann Intern Med 1988; 109: 939-45. 10. Nakamura S, Suchi T. Clinicopathologic study of node-based, lowgrade, peripheral T-cell lymphoma. Cancer 1991; 67: 2565-78. 11. Hastrup N, Hamilton-Dutoit S, Ralfkiaer E, Pallesen G. Peripheral T-cell lymphomas: an evaluation of reproducibility of the updated Kiel classification. Histopathology 1991; 18: 99-105. 12. Isaacson PG, Spencer J, Connolly CE, et al. Malignant histiocytosis of the intestine: a T-cell lymphoma. Lancet 1985; ii: 688-91. 13. Ramsay AD, Smith WJ, Isaacson PG. T-cell-rich B-cell lymphomas. Am J Surg Pathol 1988; 12: 433-43. 14. Greer JP, Kinney MC, Collins RD, et al. Clinical features of 31 patients with Ki-1 anaplastic large-cell lymphoma. J Clin Oncol 1991; 9: 539-47. 15. NCI Non-Hodgkin’s Classification Project Writing Committee. Classification of non-Hodgkin’s lymphomas. Cancer 1985; 55: 91-95. 16. Dick F, VanLier S, Banks P, et al. Use of the Working Formulation for non-Hodgkin’s lymphoma in epidemiological studies: agreement between reported diagnoses and a panel of experienced pathologists. J Natl Cancer Inst 1987; 78: 1137-44. 17. Miettinen M, Franssila KO, Saxen E. Hodgkin’s disease, lymphocytic predominant nodular: increased risk for subsequent non-Hodgkin’s lymphomas. Cancer 1983; 51: 2293-300. 18. Kant JA, Hubbard SM, Longo DL, et al. The pathologic and clinical heterogeneity of lymphocyte-depleted Hodgkin’s disease. J Clin Oncol 1986; 4: 284-94. 19. Bonadonna G, Valagussa P, Santoro A. Alternating non-cross-resistant combination chemotherapy of MOPP in stage IV Hodgkin’s disease: a report of 8-year results. Ann Intern Med 1986; 104: 739-46. 9. Simon
Proportional assist ventilation ventilatory support
for
require mechanical ventilation when they adequate gas exchange while breathing spontaneously, when they cannot protect their airway and mobilise secretions, or when, despite acceptable gas exchange, excessive respiratory work leads to exhaustion and clinical respiratory failure. For many Patients
cannot achieve
years, mechanical ventilators have been able to assume
full control of patient ventilatory requirements (controlled mechanical ventilation). Recent advances have concentrated on modes of partial ventilatory support, specifically for weaning from ventilation, and
1.
Fitzgerald DE, Drumm JE. Non-invasive measurement of human fetal circulation using ultrasound: a new technique. Br Med J 1977; ii:
1450-51. 2. Eik-Nes SH, Brubakk AO, Ulstein MK. Measurement of human fetal blood flow. Br Med J 1980; i: 283-84. 3. Griffin D, Cohen-Overbeek T, Campbell S. Fetal and utero-placental blood flow. Clin Obstet Gynaecol 1983; 10: 565-602. 4. Ng A, Trudinger BJ. The application of umbilical artery studies to complicated pregnancies. In: Pearce JMF, eds. Doppler ultrasound in perinatal medicine. Oxford: Oxford University Press, 1992: 143-58. 5. Burke G, Stuart B, Crowley P, Scanaill SN, Drumm JE. Is intrauterine growth retardation with normal umbilical artery blood flow a benign condition? Br Med J 1990; 300: 1044-45. 6. Nicolaides KH, Bilardo CM, Soothill PW, Campbell S. Absence of end-diastolic frequencies in the umbilical artery: a sign of fetal hypoxia and acidosis. Br Med J 1988; 297: 1026-27. 7. McParland P, Steel SA, Pearce JMF. The clinical implications of absent or reversed end-diastolic frequencies in umbilical artery flow velocity waveforms. Eur J Obstet Gynecol Repro Biol 1990 37: 15-23. 8. Dornan J, Beattie B. Umbilical artery doppler ultrasonography as a screening tool. In: Pearce JMF, ed. Doppler ultrasound in perinatal medicine. Oxford: Oxford University Press, 1992: 95-111. 9. Campbell S, Diaz-Recasens J, Griffin DR, et al. New doppler technique for assessing uteroplacental blood flow. Lancet 1983; i: 675-77. 10. Ducey J, Schulman H, Farmakides G. A classification of hypertension based on doppler velocimetry. Am J Obstet Gynecol 1987; 157: 680-85. 11. Robertson WB, Brosens I, Dixon HG. The pathological response of the vessels of the placenta to hypertensive pregnancies. J Pathol Bacteriol 1967; 93: 581-92. 12. Morrow R, Adamson L, Ritchie K, Pearce JMF. The pathophysiological basis of Doppler waveforms. In: Pearce JMF, ed. Doppler ultrasound in perinatal medicine. Oxford: Oxford University Press, 1992: 196-220. 13. Vyas S, Campbell S. Doppler studies of the cerebral and renal circulations in small-for gestational age fetuses. In: Pearce JMF, ed. Doppler ultrasound in perinatal medicine. Oxford: Oxford University Press, 1992: 268-78. 14. Trudinger BJ, Cook CM, Giles WB, Connelly A, Thompson RS. Umbilical artery flow velocity waveforms in high-risk pregnancy. Lancet 1987; i: 188-90. 15. Tyrell SN, Lilford RJ, MacDonald HN, Nelson EJ, Porter J, Gupta JK. Randomised comparison of routine versus highly selective use of Doppler ultrasound and biophysical scoring to investigate high risk pregnancies. Br J Obstet Gynaecol 1990; 97: 909-16. 16. Newnham JP, O’Dea MR-A, Reid KP, Diepeveen DA. Doppler flow velocity waveform analysis in high risk pregnancies: a randomised controlled trial. Br J Obstet Gynaecol 1991; 98: 956-63. 17. Pearce JMF. The application of uteroplacental waveforms to complicated pregnancies. In: Pearce JMF, ed. Doppler ultrasound in pennatal medicine. Oxford: Oxford University Press, 1992: 159-77. 18. Trudinger BJ, Cook CM, Thompson RS, Giles WB, Connelly A. Low dose aspirin therapy improves fetal weight in umbilical placental insufficiency. Am J Obstet Gynecol 1988; 159: 681-85. 19. McParland P, Pearce JM, Chamberlain GVP. Doppler ultrasound and aspirin in recognition and prevention of pregnancy-induced hypertension. Lancet 1990; 335: 1552-55.
Lymphoma classification—where now? Management of patients with malignant lymphoma is largely determined by interpretation of histological features and, especially for non-Hodgkin lymphomas, by an allocation of subtype and grade. Most lymphomas represent a clonal expansion of B or T lymphocytes whose normal maturation has been arrested or disregulated. The histological appearance represents, to a variable degree, infiltration of normal structures with these malignant cells, the host (immune) response to the tumour, and reactive changes that may result from secretion of cytokines. These appearances may vary within and between tumour sites and from host to host and tumour to tumour.
Pathologists commonly examine lymphoma tissue (haematoxylin and eosin, Giemsa, periodic-acid-Schiff) and with immunohistochemical techniques, for which they use antibodies directed against leucocyte-specific, lineage-specific, and activation antigens. In difficult cases, cytogenetic analysis can help (eg, by revealing the 11;14 translocation of mantle cell lymphomas or the 14;18 translocation of follicle centre cell lymphomaS2) , as can analysis of DNA for clonal rearrangement of the T-cell receptor or immunoglobulin genes. Sometimes these studies produce conflicting results. Thus, cases with morphological and immunophenotypic characteristics of a T-cell lymphoma may not show clonal T-cell receptor gene rearrangements,3 which suggests that they may be reactive rather than malignant processes. Clinical classification of the lymphomas has been debated for decades. A major advance in the classification of the non-Hodgkin lymphomas was Rappaport’s appreciation in the 1950s that the presence of a follicular growth pattern was a feature associated with a more indolent natural history, and that large lymphocytes (then incorrectly described as histiocytes) were associated with a rapidly progressive 4 course and poor outcome. Rappaport’s classification4 proved clinically more relevant than earlier attempts, and its widespread acceptance coincided with the first descriptions of long-term remission for advanced diffuse large cell (histiocytic) lymphomas by combination chemotherapy.5 During the late 1970s this classification became outdated as the biology of lymphocyte maturation became better defmed, and the B-cell and T-cell lymphomas were recognised as separate entities. Classifications such as those described by the Kiel group in Europe6or Lukes and Collins in the USA’ were devised, leading to nosological chaos with multiple classifications in use around the world. A temporary respite, for clinicians at least, was provided by the introduction of the Working Formulation sponsored by National Cancer Institute.8 This compromise categorisation was based on the clinical behaviour (updated in 19889) of over a thousand well-documented cases of non-Hodgkin lymphoma from the USA and Europe. Only routine, stained sections were used in the study, and the non-Hodgkin lymphomas were divided into low, intermediate, and high grade types. For most cases of non-Hodgkin lymphoma, especially low-grade and high-grade varieties, this classification achieved international acceptance and served clinicians well. However, the Working Formulation has now become outdated, partly because of increased recognition of the peripheral T-cell lymphomas, but also because newer diagnostic techniques have led to characterisation of many new entities within the lymphoma spectrum. Peripheral T-cell lymphomas are difficult to classify, differ widely in their clinical presentation, and behave unpredictably. 11 Attempts to grade and with routine stains
1085
categorise these tumours histologically have not been of clonal absence The gene of these that some rearrangement suggests proliferations may not be neoplastic even though the clinical behaviour is that of a malignant process. In the absence of a satisfactory classification, many doctors base their treatment of T-cell lymphomas on clinical interpretation of tumour behaviour and are often extremely uncertain about prognosis. Advances in immunological molecular diagnosis and use of special techniques have led to numerous reports of new forms of non-Hodgkin lymphoma. In some cases well-recognised entities have been characterised (eg, enteropathy-associated T-cell lymphoma12 and mantle-cell-derived lymphoma1) but others are of more uncertain significance (eg, T-cellrich B-cell non-Hodgkin lymphoma13 and anaplastic Ki-1 positive large cell lymphoma 14 ) and require joint clinical and pathological analysis of large numbers of patients to determine the relevance of their separate classification. Meanwhile, the difficulties of histological interpretation of lymphoma cases and the large subjective element in their categorisation have become apparent. Although follicular lymphomas can be recognised easily by most pathologists, for many other categories of lymphoma there is poor agreement between pathologists and poor reproducibility when biopsy specimens are seen by the same pathologists on different occasions. 11,15,16 These difficulties come to the attention of clinicians when cases referred between institutions are reviewed or when old specimens are reviewed and reinterpreted. The diagnosis of Hodgkin’s disease has proved especially troublesome lately. This diagnosis is based on the finding of Reed Sternberg cells in an appropriate cellular background, with subdivision of cases into four groups according to the Rye classification. Despite intense research efforts, the histogenesis of the Reed Stemberg-cell remains an enigma, and immunohistochemistry and other techniques have shown that Hodgkin’s disease is a heterogeneous condition. Nodular lymphocyte predominant Hodgkin’s disease is now regarded as a B-cell proliferation that may progress to high-grade B-cell non-Hodgkin lymphoma,17 and many cases of lymphocyte-depleted Hodgkin’s disease have been reclassified as T-cell non-Hodgkin lymphoma. The interface between other cases of Hodgkin’s disease and non-Hodgkin lymphomas such as large cell anaplastic lymphoma has likewise become increasingly blurred. Clinical practice has also shifted: it is now widely accepted that doxorubicin-containing chemotherapy, the treatment of choice for and intermediate high-grade non-Hodgkin is also indicated for most patients with lymphoma, advanced Hodgkin’s disease.19 Where do we go from here? All too often clinicians and pathologists work separately and with different goals. The Working Formulation project showed that
successful."
large clinicopathological projects
are
possible.
Although increasing understanding of these tumours at a molecular level will increase the complexity of classification, clinicians and pathologists can surely collaborate in well-constructed clinical studies to verify the clinical validity of any new subgroups that may emerge. 1. Raffeld M, Jaffe ES. bcl-1, t(11;14), and mantle cell-derived lymphomas. Blood 1991, 78: 259-63. 2. Rowley JD. Chromosome studies in the non-Hodgkin’s lymphomas: the role of the 14:18 translocation. J Clin Oncol 1988; 6: 919-25. 3. Smith JL, Lane AC, Hodges E, et al. T-cell receptor variable (v) gene usage by lymphoid populations in T-cell lymphoma. J Pathol 1992; 166: 109-12. 4. Rappaport H. Tumors of the hematopoietic system. In: Atlas of tumor pathology, section 3, fascicle 8. Washington, DC: US Armed Forces Institute of Pathology, 1966: 270. 5. Berd D, Cornog J, DeConti RC, Levitt M, Bertino JR. Long term remission in diffuse histiocytic lymphoma treated with combination sequential chemotherapy. Cancer 1975; 35: 1050-54. 6. Lennert K, Mohri N. Histopathology and diagnosis of non-Hodgkin’s lymphomas. In: Lennert K, ed. Malignant lymphomas other than Hodgkin’s disease: histology, cytology, ultrastructure, immunology. Berlin: Springer-Verlag, 1978: 111-469. 7. Lukes RJ, Collins RD. Immunologic characterization of human malignant lymphomas. Cancer 1974; 34: 1488-503. 8. The Non-Hodgkin’s Lymphoma Pathologic Classification Project: National Cancer Institute sponsored study of classifications of
non-Hodgkin’s lymphomas. Summary and descriptions of a working formulation for clinical usage. Cancer 1982; 49: 2112-35. R, Durrleman S, Hoppe RT, et al. The Non-Hodgkin Lymphoma Pathologic Classification Project. Ann Intern Med 1988; 109: 939-45. 10. Nakamura S, Suchi T. Clinicopathologic study of node-based, lowgrade, peripheral T-cell lymphoma. Cancer 1991; 67: 2565-78. 11. Hastrup N, Hamilton-Dutoit S, Ralfkiaer E, Pallesen G. Peripheral T-cell lymphomas: an evaluation of reproducibility of the updated Kiel classification. Histopathology 1991; 18: 99-105. 12. Isaacson PG, Spencer J, Connolly CE, et al. Malignant histiocytosis of the intestine: a T-cell lymphoma. Lancet 1985; ii: 688-91. 13. Ramsay AD, Smith WJ, Isaacson PG. T-cell-rich B-cell lymphomas. Am J Surg Pathol 1988; 12: 433-43. 14. Greer JP, Kinney MC, Collins RD, et al. Clinical features of 31 patients with Ki-1 anaplastic large-cell lymphoma. J Clin Oncol 1991; 9: 539-47. 15. NCI Non-Hodgkin’s Classification Project Writing Committee. Classification of non-Hodgkin’s lymphomas. Cancer 1985; 55: 91-95. 16. Dick F, VanLier S, Banks P, et al. Use of the Working Formulation for non-Hodgkin’s lymphoma in epidemiological studies: agreement between reported diagnoses and a panel of experienced pathologists. J Natl Cancer Inst 1987; 78: 1137-44. 17. Miettinen M, Franssila KO, Saxen E. Hodgkin’s disease, lymphocytic predominant nodular: increased risk for subsequent non-Hodgkin’s lymphomas. Cancer 1983; 51: 2293-300. 18. Kant JA, Hubbard SM, Longo DL, et al. The pathologic and clinical heterogeneity of lymphocyte-depleted Hodgkin’s disease. J Clin Oncol 1986; 4: 284-94. 19. Bonadonna G, Valagussa P, Santoro A. Alternating non-cross-resistant combination chemotherapy of MOPP in stage IV Hodgkin’s disease: a report of 8-year results. Ann Intern Med 1986; 104: 739-46. 9. Simon
Proportional assist ventilation ventilatory support
for
require mechanical ventilation when they adequate gas exchange while breathing spontaneously, when they cannot protect their airway and mobilise secretions, or when, despite acceptable gas exchange, excessive respiratory work leads to exhaustion and clinical respiratory failure. For many Patients
cannot achieve
years, mechanical ventilators have been able to assume
full control of patient ventilatory requirements (controlled mechanical ventilation). Recent advances have concentrated on modes of partial ventilatory support, specifically for weaning from ventilation, and
