Hemolytic*uremic syndrome Hemolytic-uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP) and malignant hypertension have overlapping but not identical clinical features' and similar ultrastructural histopathologic abnormalities.2 The most consistent pathologic finding is a microangiopathy with alteration and detachment of endothelial cells and the formation of a subendothelial space between the endothelium and basement membrane.2'3 Various substances including fibrin, fibrinogen-related products and lipid accumulate in this space. Hence HUS, TTP and malignant hypertension can be thought of as a group of syndromes with endothelial damage.4 HUS is defined by the sudden onset of hemolytic anemia, thrombocytopenia and renal failure. The anemia is characterized by fragmented erythrocytes in the peripheral circulation. Thrombocytopenia may not be found in every case. The severity of renal failure may range from slight elevation of the blood urea nitrogen concentration to prolonged anuria.5 There are similar findings in TTP of hemolytic anemia (with fragmented erythrocytes), thrombocytopenia and organ involvement, but TTP differs from HUS in several respects: it occurs in an older age group, it involves the central nervous system, renal disease is inconstant and it has a very poor prognosis. Malignant hypertension can be defined by the sudden increase in blood pressure with end-organ damage. Hemolytic anemia and renal failure are frequent sequelae and thrombocytopenia may . Systemic lupus erythematosus (SLE) by analogy belongs to a group of syndromes that includes scleroderma, dermatomyositis and rheumatoid arthritis - the collagen vascular diseases. However, patients who have SLE subsets can be defined by a number of clinical variables such as SLE and proteinuria, and SLE with hypertension.8 Therefore, in our view, HUS, TTP and malignant hypertension can be regarded as members of a group of syndromes with endothelial damage. HUS as a syndrome has several subsets including its well defined typical form, a genetic form, HUS with recurrent episodes and HUS in adults. This concept can be carried a step further by recognizing that features of the different syndromes may overlap. As in SLE and other types of collagen vascular disease, there is an overlap between HUS and TTP and between subsets of HUS such as the genetic and recurrent forms. The epidemiology of HUS provides further
evidence supporting the idea that it may not be a homogenous or homogeneous entity. HUS occurs infrequently in Canada; usually only a few cases are seen each year in pediatric hospitals. By contrast larger numbers of cases are seen in Argentina, Southern California, South Africa and the Netherlands. The mean age of children at the onset of HUS differs from one area to another, ranging from 8 to 12 months in South Africa and Argentina, to 4½ years in the Netherlands and 3½ years in Montreal. HUS occurs infrequently in black children in Africa and the United States. The typical form of HUS is a well recognized, discrete clinicopathologic entity characterized by the almost simultaneous onset of acute renal failure, hemolytic anemia with fragmented erythrocytes and thrombocytopenia. It occurs more frequently in temperate climates, usually in children under 4 years of age. With rare exceptions there is a prodromal illness of gastroenteritis or upper respiratory tract infection a few days to several weeks before the onset of the syndrome. Recurrences are uncommon, the prognosis is good and the mortality can be as low as 5% .. A familial, possibly genetic, form of HUS has been defined by the onset of the syndrome in two or more siblings more than a year apart. HUS has been reported in at least 50 families in which up to four siblings have been affected, and in one family in which the syndrome has occurred in more than one generation.5 Although the triad of features of HUS were present these patients differed from those with the typical form in that they were older at the onset of the syndrome, lived in nonendemic areas, often had a downward course and had a high mortality (70% ).5 Patients with recurrent episodes of HUS may be considered to form a subset because they share an important specific characteristic - they have more than 1 and as many as 14 recurring episodes. Such patients tend not to have a typical prodromal illness and they have rarely been from areas in which the syndrome is endemic. In contrast to the typical form of HUS more than 50% of the patients are over 4 years of age at onset (mean, 4½ years). The prognosis does not seem to be related to the number of recurrences and the mortality is about 30%. HUS is rare in adults, is usually associated with pregnancy or use of oral contraceptives and has a mortality of 60% to 70% 9,10 The renal histologic lesion that is 1246 CMA JOURNAL/DECEMBER 3, 1977/VOL. 117
characteristic in HUS is detected by electron microscopy; microangiopathy occurs not only in HUS but also in TTP and malignant hypertension. Although these endothelial changes may result in fragmentation of erythrocytes, thrombocytopenia, renal failure or damage to other viscera, or both, the sequence of events may differ. For example, endothelial injury could be the primary event in HUS and result in hypertension; however, in malignant hypertension it is possible that the endothelial abnormalities are a consequence of the hypertension. The sequence of events in TTP is poorly understood. To account for the features of HUS a hypothesis has been proposed that recognizes the endothelial damage as the primary and major event.2 The resulting disturbances in endothelial function with regard to local control of coagulation and fibrinolysis may lead to deposition of fibrin and, in some cases, thrombosis. A major problem in this approach to syndromes in which the etiology and pathogenesis are unknown is the pitfalls inherent in choosing one or more clinical features on which to base a classification. Therefore this method should be seen as an attempt to provide general groupings rather than as a definitive classification. There are advantages to be gained from surveying a scene from the highest peak. However, there are times when one must also look at the details. Both approaches to these syndromes are important, especially in those that are complex and poorly understood. By constructing groups of syndromes one may achieve better understanding of their pathogenesis, and by looking at subsets an attempt can be made to compare the results of treatment and offer a more accurate prognosis. BERNARD S. KAPLAN, MB, B CH, FCP (sA) Assistant director Department of nephrology JEAN-PIERRE DE CHADAREVIAN, MD, FRCP[C] Assistant pathologist Department of pathology Montreal Children's Hospital Montreal, PQ
References I. DACIE JV: The Haemolytic Anaemias. Congenital and Acquired. Part 111 - Secondary or Symptomatic Haemolytic Anaemias, 2nd ed, London, Churchill, 1967 2. DE CHADAR.VIAN J-P, KAPLAN BS: The hemolytic uremic syndrome of childhood, in Perspectives in Pediatric Pathology, vol 4, RosENBERG H, BOLANDE R (eds), Chicago, Year Bk Med, 1977 (in press) 3. FELDMAN JD, MAROINEY MR, UNANUE ER, et al: The vascular pathology of thrombotic thrombocytopenic purpura. An immunohistochemical and ultrastructural study. Lab Invest
15: 927, 1966 4. PINsKY L: A community of human malformation syndromes involving the Mullerian ducts, distal extremities, urinary tract, and ears. Teratology 9: 65, 1974
5. KAPLAN BS, THOMPSON PD, DE CHADAR.VIAN J-P: The hemolytic uremic syndrome. Pediatr Clin North Am 23: 761, 1976 6. BERMAN N, FINKLESTEIN JZ: Thrombotic thrombocytopenic purpura in childhood. Resuits of a survey and re-examination of the literature. Scand / HaematoL 14: 286, 1975
7. LINTON AL, GAVRAS H, GLEADLE RI, et al: Microangiopathic haemolytic anaemia and the pathogenesis of malignant hypertension. Lancet 1: 1277, 1969 8. FRIES JF, HOLMAN HR: Systemic Lupus
Ery:hema:osus. A Clinical Analysis, Philadelphia, Saunders, 1975, pp 8-20
9. BROWN CR, CLARKSON AR, ROBSON JS, Ct al:
Haemolytic uraemic syndrome in women taking oral contraceptives. Lancet 1: 1479, 1973 10. Haemolytic-uraemic syndrome of young women (E). Lancet 1: 943, 1977
Sex therapy The mention of sex counselling in the surgeons lounge usually raises an eyebrow or two and is followed by a round of the latest jokes. One conjures up an image of the physician-teacher singlehandedly correcting the technique of the eager young coital couple; so much for fantasy. In fact, sex counselling uncovers sex-related anxiety, provides useful information and helps the individual integrate this information into his or her .life. Sex therapy has these aims and also includes the direct treatment of specific sexual dysfunctions and the management of problematic sexual behaviour. As physicians we do sex counselling whether we want to or not. By showing embarrassment or sloughing off sexrelated questions, passing our own moral judgement and ignoring obvious clues to sexual problems, we convey negative or "put-down" messages. Unfortunately few practising physicians have received preparation in medical school to do sex counselling effectively. To update these skills physicians must uncover their own anxieties and misconceptions about sex and sexuality, then re-examine their attitudes in the light of new information. Only then can they deal more effectively with their patients' concerns, confident that they are not influenced by their own attitudes. By attending a seminar that provokes examination of one's own attitudes and feelings the physician will be in a better position to learn from the burgeoning sex-related literature. Sex therapy as a discipline has evolved since Masters and Johnson1 reported on a therapeutic approach to sexual dysfunction based on laboratory studies of the physiologic aspects of sexual function. Reports on continuing research by scientists and clinicians in many fields are available in periodicals such as the Journal of Sex Research, Archives of Sexual Behavior and the Journal of Sex & Marital Therapy. Other therapists have reported similar results using different modes of therapy, time frames and therapistpatient combinations,IA including such modifications as interim sessions2 rather than a 2-week acute treatment program
and couples' groups. Barbach3 reported Conference on Ethical Issues in Sex excellent results from group sex therapy Therapy and Research.5 As there is with preorgasmic women. In contrast to no licensing procedure for sex therthe techniques of Masters and Johnson1 apists anyone can legally present himand their cotherapy teams most sex or herself to the public as a qualified therapists work alone with couples, practitioner. In an attempt to establish though some use a cotherapy approach some standards of qualification the in special circumstances. While there Board of Examiners in Sexual Therapy may be no unaffected partner in a re- and Counselling in Ontario (BESTCO) lationship in which one partner has a was established in 1975 to offer volunsexual dysfunction, many people with- tary registration of sex therapists. For out a regular sexual partner also seek the past 2 years applicants have first therapy. One therapist working with had to be accepted as members of the one patient in such circumstances can Ontario Association of Marriage and achieve excellent results. These new Family Counsellors. Requirements for approaches emphasize flexibility and membership in this organization include the selection of a therapeutic technique an advanced academic degree in a clinmost appropriate to a given situation. ical field of medicine, or in social work Therapeutic aids such as erotica, fan- or another related field, special studies tasy, audiovisual resources and sur- in marital-relationship counselling and rogates are part of the expanding fron- a period of supervised clinical training tier of sex therapy. in such therapy. BESTCO then added Many opportunities were lost by the requirements of supervision in sex adherents to Freud's contention that therapy plus written and oral examinanothing must interfere with the relation- tions by the board. ship between therapist and patient. While the discipline of sex therapy These opportunities can now be grasped is still in its infancy much has been when conjoint marital or family ther- accomplished, especially in the basic apy is applied appropriately. Masters and clinical sciences. The ethics of new and Johnson1 advocated the use of a research and treatment must be estabmale-female cotherapy team for sex lished. Higher accreditation standards therapy because they believed that men for therapists and some regulation of cannot fully understand a woman's re- their practices must be attained. These sponses and vice versa. With adequate areas may be of primary interest to sex training in sensitivity, however, people therapists but, as sex counsellors, all can understand each other's feelings of us are interested in contributing to and responses. Kaplan,4 a renowned the increased sexual comfort of our psychiatrist, showed that female sex patients - and perhaps even of ourtherapists can work effectively with selves. The mention of a sexual probboth male and female patients. Male lem in the surgeon's lounge could then therapists can be trained to empathize be followed by comfortable discussion with both men and women and to un- rather than by embarrassed laughter. derstand their experiences. AB. CHERNICK, MD, FRcs[c], FACOG In Canada today most sex therapists B.A. CHERNICK, MD, PH D have first been trained in such fields 648 lIuron St. London, Ont. as medicine, social work, psychology, nursing and pastoral care. Th.y bring References a variety of backgrounds and thera1. MASTERS WH, JOHNSON VE: Human Sexual peutic skills to the treatment of sexual Inadequacy, Boston, Little, 1970 2. CHERNICK BA, CHERNICK AR: In Touch, problems. Toronto, Macmillan, 1977 Public protection from possible abuse 3. BARBACH LG: For Yourself: the Fulfillment of Female Sexuality, New York, Doubleday, and the ethics of sex therapy are major 1975 4. KAPLAN HS: The New Sex Therapy: Active concerns. Ongoing discussions take Treatment of Sexual Dysfunctions, New York, place at major meetings such as the Brunner-Mazel, 1974 5. MASTERS WH, JOHNSON VE, KOLODNY RC: International Congress of Sexology in Ethical Issues in Sex Therapy and Research, Montreal in November 1976 and the Boston, Little, 1977 CMA JOURNAL/DECEMBER 3, 1977/VOL. 117
1247
evidence supporting the idea that it may not be a homogenous or homogeneous entity. HUS occurs infrequently in Canada; usually only a few cases are seen each year in pediatric hospitals. By contrast larger numbers of cases are seen in Argentina, Southern California, South Africa and the Netherlands. The mean age of children at the onset of HUS differs from one area to another, ranging from 8 to 12 months in South Africa and Argentina, to 4½ years in the Netherlands and 3½ years in Montreal. HUS occurs infrequently in black children in Africa and the United States. The typical form of HUS is a well recognized, discrete clinicopathologic entity characterized by the almost simultaneous onset of acute renal failure, hemolytic anemia with fragmented erythrocytes and thrombocytopenia. It occurs more frequently in temperate climates, usually in children under 4 years of age. With rare exceptions there is a prodromal illness of gastroenteritis or upper respiratory tract infection a few days to several weeks before the onset of the syndrome. Recurrences are uncommon, the prognosis is good and the mortality can be as low as 5% .. A familial, possibly genetic, form of HUS has been defined by the onset of the syndrome in two or more siblings more than a year apart. HUS has been reported in at least 50 families in which up to four siblings have been affected, and in one family in which the syndrome has occurred in more than one generation.5 Although the triad of features of HUS were present these patients differed from those with the typical form in that they were older at the onset of the syndrome, lived in nonendemic areas, often had a downward course and had a high mortality (70% ).5 Patients with recurrent episodes of HUS may be considered to form a subset because they share an important specific characteristic - they have more than 1 and as many as 14 recurring episodes. Such patients tend not to have a typical prodromal illness and they have rarely been from areas in which the syndrome is endemic. In contrast to the typical form of HUS more than 50% of the patients are over 4 years of age at onset (mean, 4½ years). The prognosis does not seem to be related to the number of recurrences and the mortality is about 30%. HUS is rare in adults, is usually associated with pregnancy or use of oral contraceptives and has a mortality of 60% to 70% 9,10 The renal histologic lesion that is 1246 CMA JOURNAL/DECEMBER 3, 1977/VOL. 117
characteristic in HUS is detected by electron microscopy; microangiopathy occurs not only in HUS but also in TTP and malignant hypertension. Although these endothelial changes may result in fragmentation of erythrocytes, thrombocytopenia, renal failure or damage to other viscera, or both, the sequence of events may differ. For example, endothelial injury could be the primary event in HUS and result in hypertension; however, in malignant hypertension it is possible that the endothelial abnormalities are a consequence of the hypertension. The sequence of events in TTP is poorly understood. To account for the features of HUS a hypothesis has been proposed that recognizes the endothelial damage as the primary and major event.2 The resulting disturbances in endothelial function with regard to local control of coagulation and fibrinolysis may lead to deposition of fibrin and, in some cases, thrombosis. A major problem in this approach to syndromes in which the etiology and pathogenesis are unknown is the pitfalls inherent in choosing one or more clinical features on which to base a classification. Therefore this method should be seen as an attempt to provide general groupings rather than as a definitive classification. There are advantages to be gained from surveying a scene from the highest peak. However, there are times when one must also look at the details. Both approaches to these syndromes are important, especially in those that are complex and poorly understood. By constructing groups of syndromes one may achieve better understanding of their pathogenesis, and by looking at subsets an attempt can be made to compare the results of treatment and offer a more accurate prognosis. BERNARD S. KAPLAN, MB, B CH, FCP (sA) Assistant director Department of nephrology JEAN-PIERRE DE CHADAREVIAN, MD, FRCP[C] Assistant pathologist Department of pathology Montreal Children's Hospital Montreal, PQ
References I. DACIE JV: The Haemolytic Anaemias. Congenital and Acquired. Part 111 - Secondary or Symptomatic Haemolytic Anaemias, 2nd ed, London, Churchill, 1967 2. DE CHADAR.VIAN J-P, KAPLAN BS: The hemolytic uremic syndrome of childhood, in Perspectives in Pediatric Pathology, vol 4, RosENBERG H, BOLANDE R (eds), Chicago, Year Bk Med, 1977 (in press) 3. FELDMAN JD, MAROINEY MR, UNANUE ER, et al: The vascular pathology of thrombotic thrombocytopenic purpura. An immunohistochemical and ultrastructural study. Lab Invest
15: 927, 1966 4. PINsKY L: A community of human malformation syndromes involving the Mullerian ducts, distal extremities, urinary tract, and ears. Teratology 9: 65, 1974
5. KAPLAN BS, THOMPSON PD, DE CHADAR.VIAN J-P: The hemolytic uremic syndrome. Pediatr Clin North Am 23: 761, 1976 6. BERMAN N, FINKLESTEIN JZ: Thrombotic thrombocytopenic purpura in childhood. Resuits of a survey and re-examination of the literature. Scand / HaematoL 14: 286, 1975
7. LINTON AL, GAVRAS H, GLEADLE RI, et al: Microangiopathic haemolytic anaemia and the pathogenesis of malignant hypertension. Lancet 1: 1277, 1969 8. FRIES JF, HOLMAN HR: Systemic Lupus
Ery:hema:osus. A Clinical Analysis, Philadelphia, Saunders, 1975, pp 8-20
9. BROWN CR, CLARKSON AR, ROBSON JS, Ct al:
Haemolytic uraemic syndrome in women taking oral contraceptives. Lancet 1: 1479, 1973 10. Haemolytic-uraemic syndrome of young women (E). Lancet 1: 943, 1977
Sex therapy The mention of sex counselling in the surgeons lounge usually raises an eyebrow or two and is followed by a round of the latest jokes. One conjures up an image of the physician-teacher singlehandedly correcting the technique of the eager young coital couple; so much for fantasy. In fact, sex counselling uncovers sex-related anxiety, provides useful information and helps the individual integrate this information into his or her .life. Sex therapy has these aims and also includes the direct treatment of specific sexual dysfunctions and the management of problematic sexual behaviour. As physicians we do sex counselling whether we want to or not. By showing embarrassment or sloughing off sexrelated questions, passing our own moral judgement and ignoring obvious clues to sexual problems, we convey negative or "put-down" messages. Unfortunately few practising physicians have received preparation in medical school to do sex counselling effectively. To update these skills physicians must uncover their own anxieties and misconceptions about sex and sexuality, then re-examine their attitudes in the light of new information. Only then can they deal more effectively with their patients' concerns, confident that they are not influenced by their own attitudes. By attending a seminar that provokes examination of one's own attitudes and feelings the physician will be in a better position to learn from the burgeoning sex-related literature. Sex therapy as a discipline has evolved since Masters and Johnson1 reported on a therapeutic approach to sexual dysfunction based on laboratory studies of the physiologic aspects of sexual function. Reports on continuing research by scientists and clinicians in many fields are available in periodicals such as the Journal of Sex Research, Archives of Sexual Behavior and the Journal of Sex & Marital Therapy. Other therapists have reported similar results using different modes of therapy, time frames and therapistpatient combinations,IA including such modifications as interim sessions2 rather than a 2-week acute treatment program
and couples' groups. Barbach3 reported Conference on Ethical Issues in Sex excellent results from group sex therapy Therapy and Research.5 As there is with preorgasmic women. In contrast to no licensing procedure for sex therthe techniques of Masters and Johnson1 apists anyone can legally present himand their cotherapy teams most sex or herself to the public as a qualified therapists work alone with couples, practitioner. In an attempt to establish though some use a cotherapy approach some standards of qualification the in special circumstances. While there Board of Examiners in Sexual Therapy may be no unaffected partner in a re- and Counselling in Ontario (BESTCO) lationship in which one partner has a was established in 1975 to offer volunsexual dysfunction, many people with- tary registration of sex therapists. For out a regular sexual partner also seek the past 2 years applicants have first therapy. One therapist working with had to be accepted as members of the one patient in such circumstances can Ontario Association of Marriage and achieve excellent results. These new Family Counsellors. Requirements for approaches emphasize flexibility and membership in this organization include the selection of a therapeutic technique an advanced academic degree in a clinmost appropriate to a given situation. ical field of medicine, or in social work Therapeutic aids such as erotica, fan- or another related field, special studies tasy, audiovisual resources and sur- in marital-relationship counselling and rogates are part of the expanding fron- a period of supervised clinical training tier of sex therapy. in such therapy. BESTCO then added Many opportunities were lost by the requirements of supervision in sex adherents to Freud's contention that therapy plus written and oral examinanothing must interfere with the relation- tions by the board. ship between therapist and patient. While the discipline of sex therapy These opportunities can now be grasped is still in its infancy much has been when conjoint marital or family ther- accomplished, especially in the basic apy is applied appropriately. Masters and clinical sciences. The ethics of new and Johnson1 advocated the use of a research and treatment must be estabmale-female cotherapy team for sex lished. Higher accreditation standards therapy because they believed that men for therapists and some regulation of cannot fully understand a woman's re- their practices must be attained. These sponses and vice versa. With adequate areas may be of primary interest to sex training in sensitivity, however, people therapists but, as sex counsellors, all can understand each other's feelings of us are interested in contributing to and responses. Kaplan,4 a renowned the increased sexual comfort of our psychiatrist, showed that female sex patients - and perhaps even of ourtherapists can work effectively with selves. The mention of a sexual probboth male and female patients. Male lem in the surgeon's lounge could then therapists can be trained to empathize be followed by comfortable discussion with both men and women and to un- rather than by embarrassed laughter. derstand their experiences. AB. CHERNICK, MD, FRcs[c], FACOG In Canada today most sex therapists B.A. CHERNICK, MD, PH D have first been trained in such fields 648 lIuron St. London, Ont. as medicine, social work, psychology, nursing and pastoral care. Th.y bring References a variety of backgrounds and thera1. MASTERS WH, JOHNSON VE: Human Sexual peutic skills to the treatment of sexual Inadequacy, Boston, Little, 1970 2. CHERNICK BA, CHERNICK AR: In Touch, problems. Toronto, Macmillan, 1977 Public protection from possible abuse 3. BARBACH LG: For Yourself: the Fulfillment of Female Sexuality, New York, Doubleday, and the ethics of sex therapy are major 1975 4. KAPLAN HS: The New Sex Therapy: Active concerns. Ongoing discussions take Treatment of Sexual Dysfunctions, New York, place at major meetings such as the Brunner-Mazel, 1974 5. MASTERS WH, JOHNSON VE, KOLODNY RC: International Congress of Sexology in Ethical Issues in Sex Therapy and Research, Montreal in November 1976 and the Boston, Little, 1977 CMA JOURNAL/DECEMBER 3, 1977/VOL. 117
1247
