- Email: [email protected]
Recombinant human erythropoietin and hypophosphatemia in patients with cirrhosis
503
partly account for the lack of understanding of breast cancer aetiology since the absolute effect of childbearing can usually no longer be estimated. As a consequence, epidemiologists search for other causes, such as diet and genetic predisposition. The likelihood of success will be small if the effect of the major risk factor childbearing cannot be fully measured. Perhaps the time has come for a reassessment of the relative impact of childbearing in breast cancer risk. In the Norwegian cohort study the same effect of high parity was shown for cancer of the ovary3 and uterus, and for all three cancers together.’
approach to the analysis of drug use in different prehistoric and historic cultures. This analysis can be extended to include cultures that had not mastered the process of mummification. The methods will allow reconstruction of socio-anthropological aspects of drug use (eg, to motivate the workforce), socio-political aspects (eg, use of drugs in selected classes, political heads, priests), and use of drugs for analgesia. Institute for Anthropology and Human Genetics, 8000 Munich 2, Germany
FRANZ PARSCHE
Institute of Community Medicine, University of Tromsø,
University of Ulm, Ulm, Germany
SVETLANA BALABANOVA WOLFGANG PIRSIG
Breivika, N-9037 Tromsø, Norway
EILIV LUND 1. Balabanova
1. Lund E.
Childbearing in marriage and mortality from breast cancer in Norway. Int J Epidenol 1990; 19: 527-31. 2. Lund E. Breast cancer mortality and the change in fertility nsk factors at menopause: a prospective study of 800 000 married Norwegian women. Epidemiology 1991; 2: 285-88. 3. Lund E. Mortality from ovarian cancer among women with many children. Int J Epidemiol 1992; 21: 872-76. 4. Lund E. Number of children and death from hormone-dependent cancers. Int J Cancer 1990; 46: 998-1000.
Drugs in ancient populations SIR,-Drugs such as morphine, cocaine, nicotine, hashish, and caffeine are found in tissues from addicts.l-6 The analysis of hair from mummies has also been described.7-9 Since hair is only rarely preserved in prehistoric remnants, which are usually skeletal tissue, we decided to analyse the concentrations of various drugs in soft tissues and bones from natural and artificial mummies and in earth-buried skeletal remnants to see whether drugs were present. We analysed hair, skin, muscle, brain, teeth, and bones from 72 Peruvian (200-1500 AD) and 11 Egyptian mummies (1070 BC to 395 AD) and skeletal tissue from Sudan (2 individuals, 5000-4000 BC and 400-1400 AD) and south Germany (10 individuals, 2500 BC, bell culture) for cocaine, nicotine, and hashish, and their metabolites. Tissue samples were pulverised with a steel-ball at - 180°C. 1 g was dissolved in 0-9% saline, homogenised ultrasonically, and centrifuged. 1 mL supernatant was extracted with chloroform (pH 9). The extracts were dried under nitrogen and re-dissolved in 1 ml phosphate buffer (pH 7-4) and analysed with radioimmunoassay and gas-chromatography/mass-spectrometry. The highest concentrations of drugs were found in hair and soft tissue (table). Bone tissue contained drug above the concentrations we regard as significant. A comparison with recently analysed data from hair of German drug addicts demonstrated values similar to the mummies’ hair (ng/g dry weight: cocaine, 3-15 000 [n== 130], nicotine, 3-20 000 [n= 190]; hashish, 2-1000 [n=70]). Neither bone material from the south German bell culture nor from the Sudan contained cocaine or hashish, although the sample size was small (table). Our data show that analytical methods can be used on earth-buried skeletal tissue. We present a new investigational CONCENTRATIONS (ng/g) OF ALKALOIDS AND METABOLITES
No of
samples in parentheses.
S, Homoki J. Determination of cocaine in human hair by
gaschromatography/mass spectrometry. Z Rechtsmed 1987; 98: 235-40. 2. Balabanova S, Schneider E. Nicotin im Kopf-, Achsel- und Schamhaar. Deut Apoth Z 1990: 40: 2200-01. 3. Balabanova S, Parsche F, Pirsig W. Drugs in cranial hair of pre-Columbian Peruvian mummies. Baessler Archiv NF 1992: 40. 4. Balabanova S, Parsche F, Pirsig W. First identification of drugs in Egyptian mummies. Naturwissenschaften 1992; 8: 358. 5. Baumgartner AM, Jones PF, Werner A, Black CH. Radioimmunoassay of hair for determining opiate-abusing histories. J Nucl Med 1979; 20: 748-52. 6. Cartmell L, Aufderheide AC, Springfield A, Weems C, Arriaza B. The frequency and antiquity of prehistoric coca-leaf-chewing practices in northern Chile: radioimmunoassay of a cocaine metabolite in human-mummy hair. Latin Am Antiquity 1991; 2: 260-68. 7. Haley NJ, Hoffmann B. Analysis for nicotine and cotinine in hair to determine cigarette smoker status. Clin Chem 1985; 31: 1598-600. 8. Klug E. Determination of morphine in human head hair. Z Rechtsmed 1980; 84: 189-93. 9. Valente D, Cassini M, Pigliapochi M, Vansetti G. Hair as the sample in assessing morphine and cocaine addiction. Clin Chem 1981; 27: 1952-53.
Recombinant human erythropoietin and in patients with cirrhosis
hypophosphatemia
SIR,-Although recombinant human erythropoietin (rh-EPO) has been administered preoperatively to enhance autologous blood donation for patients undergoing elective surgery, there are few reports on the use of this agent in patients with chronic disorders.2 We used preoperative autologous blood donation to prevent or reduce the need for intraoperative or postoperative homologous blood transfusion in patients with liver cancer and cirrhosis. We have done a randomised study to clarify the effect of rh-EPO on preoperative autologous blood donation. Between August, 1991, and November, 1992, 21 patients with hepatocellular carcinoma and post-necrotic cirrhosis donated autologous blood before hepatectomy. They were divided into two groups at random: 11patients (group A) received rh-EPO 3000 U per day subcutaneously during the preoperative period, while 10 patients were not treated (group B). Informed consent was obtained. 2-3 weeks before the operation, 400 mL autologous blood was collected from each patient once or twice a week (up to 1200 mL). Each patient received 80 mg iron sulphate intravenously on the day of blood collection followed by 100 mg orally once daily until operation. Groups A and B did not differ significantly in age or serum concentrations of aminotransferases and albumin. The mean (SD) reticulocyte count before blood donation was 72 (2-0) x 109/L in group A and 58 (2-3) x 109/L in group B, which was not significantly different. After donation, the reticulocyte count was 189 (2-1) x 109/L in group A and 124 (3-5) x 109/L in group B (p < 001, t-test). In all patients, serum phosphate concentrations before donation were normal (25-45 mg/dL). After donation, serum phosphate in group A fell below 2-5 mg/dL (minimum 0-7 mg/dL) in 6 patients (55%), whereas no patient in group B had this abnormality (p < 005, x2-test; figure). There were no significant alterations in serum concentrations of calcium, parathyroid hormone, calcitonin, or 25-hydroxyvitamin D in any patient preoperatively. Hypophosphataemia has been reported in patients with chronic liver disease, and has been attributed to poor nutrition,3 malabsorption,4 or vitamin D deficiency.s Clinically, significant hypophosphataemia has occurred on refeeding after starvation because of the sudden shift of phosphate into cells for phosphorylation of glucose and protein synthesis.6 Therefore, acute
504
0
before blood donation
immediately before operation !—! normal range .
Alterations of
serum
phosphate concentrations.
erythropoiesis due to blood donation and rh-EPO administration in patients with cirrhosis and preexisting low plasma inorganic phosphorous is believed to induce an acute shift of phosphate into erythroid cells, thus leading to hypophosphataemia. Hypophosphataemia itself causes liver damage7 and hypophosphataemia after major hepatic surgery is related to the development of serious postoperative complications.8 Accordingly, doctors should be aware that treatment of cirrhotic patients with rh-EPO for autologous blood collection can lead to hypophosphataemia.
Department of Surgery II, Nagoya University School of Medicine, Nagoya 466, Japan 1.
MASAKI KAJIKAWA TOSHIAKI NONAMI TSUYOSHI KUROKAWA AKIO HARADA AKIMASA NAKAO HIROSHI TAKAGI
Goodnough LT, Rudnick S, Price TH, et al. Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy. N Engl J Med
1989; 321: 1163-68. 2. Thompson FL, Powers JS, Graber SE, Krantz SB. Use of recombinant human
erythropoietin to enhance autologous blood donation in a patient with multiple red cell allo-antibodies and the anemia of chronic disease. Am J Med 1991; 90: 398-400. 3. Amatuzio DS, Stutzman F, Shrifter N, Nesbitt S. A study of serum electrolytes (Na, K, Ca, P) in patients with severely decompensated portal cirrhosis of the liver. Lab J Clin Med 1952; 39: 26-29. 4. Caniggia A, Gennari C. Intestinal absorption of radiophosphate after physiological doses of 25(OH)D3 in normals, liver cirrhosis and chronic renal failure patients. In: Norman AW, et al. Vitamin D: biochemical, chemical and clinical aspects related to calcium metabolism. Proceedings of the Third Workshop on Vitamin D, California, Jan 1977. Berlin: de Gruyter, 1977: 755-57. 5. Long RG, Skinner RK, Wills MR, Sherlock S. Serum-25-hydroxy-vitamin-D in untreated parenchymal and cholestatic liver disease. Lancet 1976; ii: 650-52. 6. Cummings AD, Farquhar JR, Bouchier IAD. Refeeding hypophosphataemia in anorexia nervosa and alcoholism. BMJ 1987; 295: 490-91. 7. Nanji AA, Anderson FH. Acute liver failure: a possible consequence of severe hypophosphataemia. J Clin Gastroenterol 1985; 7: 338-40. 8. George R, Shiu MH. Hypophosphateamia after major hepatic resection. Surgery 1992; 111: 281-86.
Can undescended testes be
acquired?
SIR,-Undescended testes remain a highly controversial topic in paediatric surgical practice. Cryptorchidism during childhood is related to poor sperm counts in adult life, presumably because of the adverse effects of the higher temperature of the non-scrotal testis. Despite recommendations for early surgery for congenital undescended testes to avoid secondary degeneration, many operations are still not done until 8-12 years ofage.1 Why is this so? One explanation is that the earlier attendants failed to diagnose cryptorchidism and therefore no intervention was suggested in infancy. Most surgeons (including ourselves), when faced with undiagnosed undescended testes in a pre-adolescent, would have hitherto assumed that earlier examiners must have got it wrong. A different view suggests that some undescended testes are acquired postnatally. Clinicians have begun to define these as pathological retractile testes2-4 and ascending testes School
medical officers are familiar with the 6-8-year-old boy with a flat, empty scrotum and inguinal testes that are hard to find and yet at birth were thought to be normal. How can this be? We propose that most children first presenting over the age of 5 years did not have undescended testes at birth but have an acquired anomaly. For the testes to be in the scrotum at 10-14 years of age,’ normal prenatal migration of the gubemaculum and testis, and normal growth and elongation of the spermatic cord with age, so that the testis stays level with the scrotum, are required. Acquired maldescent is caused by failure of the cord to elongate, which keeps the testis high as the pubis-scrotum distance increases with age. At birth the scrotum is lax and scrotal testes easily seen, so few parents need a doctor’s opinion about their presence. Furthermore, late "ascent" is now well-documented in the John Radcliffe Hospital long-term follow-up6,7and in other studies.1,4,s Not only should undescended testes be separated into congenital and acquired categories but we should also take seriously the risk of infertility2,3 and malignancy3,8,9 in the acquired group, in which the damaging effects of temperature will occur, albeit for a shorter time and to a lesser degree than in congenital cryptorchidism.lO Surgical Research Unit, Royal Children’s Hospital, Melbourne,
JOHN M. HUTSON
Victoria 3052, Australia
DAY WAY GOH
1. Fenton EJM, Woodward AA, Hudson IL, Marschner I. The ascending testis. Pediatr Surg Int 1990; 5: 6-9. 2. Goh DW, Hutson JM. Is the retractile testis a normal, physiological variant or an anomaly that requires active treatment? Pediatr Surg Int 1992; 7: 249-52. 3. Goh DW, Hutson JM. The retractile testis: time for a reappraisal. J Pediatr Child Health (in press). 4. Wyllie GG. The retractile testis. Med J Aust 1984; 140: 403-05. 5. Atwell JD. Ascent of the testis: fact or fiction. Br J Urol 1985; 57: 474-77. 6. John Radcliffe Hospital Cryptorchidism Study Group. Boys with late descending testes: the source of patients with "retractile" testes undergoing orchidopexy. BMJ 1986; 293: 789-90. 7. John Radcliffe Hospital Cryptorchidism Study Group. Cryptorchidism: a prospective study of 7500 consecutive male births, 1984-88. Arch Dis Child 1992; 67: 892-99. 8. Batata MA, Chu FCH, Hilaris BS, Whitemore WF, Golbey RB. Testicular cancer in cryptorchids. Cancer 1982; 49: 1023-30. 9. Chilvers C, Dudley NE, Gough MH, Jackson MB, Pike MC. Undescended testis: the effect of treatment on subsequent risk of subfertility and malignancy. J Pediatr Surg
1986; 21: 691-96. BT, Ingerslev HJ, Hostrup H. Bilateral spontaneous descent of the testis after the age of 10: subsequent effects on fertility. Br J Surg 1988; 75: 820
10. Rasmussen
Thrombin generation and myocardial infarction during infusion of tissue-plasminogen activator SIR,-The success of coronary artery thrombolysis depends on the balance between coagulant and fibrinolytic activity. The differential properties of specific plasminogen activators determine the degree of thrombin and plasmin generation, and hence the rate at which clots lyse and the extent to which recurrent thrombosis is inhibited. In-vivo thrombin and plasmin generation can now be measured by plasma concentrations of activation-dependent peptides and enzyme-inhibitor complexes. The concentration in plasma of the prothrombin cleavage peptide F1.2 and the enzyme-inhibitor complex thrombin-antithrombin III (TAT) reflect thrombin generation while the concentration ofD-dimer and fragment E reflect fibrin(ogen) proteolysis by plasmin. Monoclonal antibodies reactive with intact fragment-E/fibrinopeptide-A specifically identify plasmin proteolysis of fibrinogen that has not been exposed to thrombin. By contrast, plasmin proteolysis of thrombin crosslinked fibrin results in D-dimer formation. Therefore, it is now theoretically possible to distinguish relative degrees of systemic and local fibrinolysis. Furthermore, measurement of thrombin and plasmin activity may help to clarify mechanisms responsible for failure of coronary thrombolysis. Failure of coronary patency may occur during thrombolytic therapy because of delayed clot lysis or after recanalisation as a consequence of re-occlusion. Thrombin generation appears to be a major determinant of coronary patencyl and may result from direct activation of the coagulation system by plasmin2 or by positive feedback of the coagulation system by clot-bound thrombin.3 We report differential thrombin and plasmin activity during
partly account for the lack of understanding of breast cancer aetiology since the absolute effect of childbearing can usually no longer be estimated. As a consequence, epidemiologists search for other causes, such as diet and genetic predisposition. The likelihood of success will be small if the effect of the major risk factor childbearing cannot be fully measured. Perhaps the time has come for a reassessment of the relative impact of childbearing in breast cancer risk. In the Norwegian cohort study the same effect of high parity was shown for cancer of the ovary3 and uterus, and for all three cancers together.’
approach to the analysis of drug use in different prehistoric and historic cultures. This analysis can be extended to include cultures that had not mastered the process of mummification. The methods will allow reconstruction of socio-anthropological aspects of drug use (eg, to motivate the workforce), socio-political aspects (eg, use of drugs in selected classes, political heads, priests), and use of drugs for analgesia. Institute for Anthropology and Human Genetics, 8000 Munich 2, Germany
FRANZ PARSCHE
Institute of Community Medicine, University of Tromsø,
University of Ulm, Ulm, Germany
SVETLANA BALABANOVA WOLFGANG PIRSIG
Breivika, N-9037 Tromsø, Norway
EILIV LUND 1. Balabanova
1. Lund E.
Childbearing in marriage and mortality from breast cancer in Norway. Int J Epidenol 1990; 19: 527-31. 2. Lund E. Breast cancer mortality and the change in fertility nsk factors at menopause: a prospective study of 800 000 married Norwegian women. Epidemiology 1991; 2: 285-88. 3. Lund E. Mortality from ovarian cancer among women with many children. Int J Epidemiol 1992; 21: 872-76. 4. Lund E. Number of children and death from hormone-dependent cancers. Int J Cancer 1990; 46: 998-1000.
Drugs in ancient populations SIR,-Drugs such as morphine, cocaine, nicotine, hashish, and caffeine are found in tissues from addicts.l-6 The analysis of hair from mummies has also been described.7-9 Since hair is only rarely preserved in prehistoric remnants, which are usually skeletal tissue, we decided to analyse the concentrations of various drugs in soft tissues and bones from natural and artificial mummies and in earth-buried skeletal remnants to see whether drugs were present. We analysed hair, skin, muscle, brain, teeth, and bones from 72 Peruvian (200-1500 AD) and 11 Egyptian mummies (1070 BC to 395 AD) and skeletal tissue from Sudan (2 individuals, 5000-4000 BC and 400-1400 AD) and south Germany (10 individuals, 2500 BC, bell culture) for cocaine, nicotine, and hashish, and their metabolites. Tissue samples were pulverised with a steel-ball at - 180°C. 1 g was dissolved in 0-9% saline, homogenised ultrasonically, and centrifuged. 1 mL supernatant was extracted with chloroform (pH 9). The extracts were dried under nitrogen and re-dissolved in 1 ml phosphate buffer (pH 7-4) and analysed with radioimmunoassay and gas-chromatography/mass-spectrometry. The highest concentrations of drugs were found in hair and soft tissue (table). Bone tissue contained drug above the concentrations we regard as significant. A comparison with recently analysed data from hair of German drug addicts demonstrated values similar to the mummies’ hair (ng/g dry weight: cocaine, 3-15 000 [n== 130], nicotine, 3-20 000 [n= 190]; hashish, 2-1000 [n=70]). Neither bone material from the south German bell culture nor from the Sudan contained cocaine or hashish, although the sample size was small (table). Our data show that analytical methods can be used on earth-buried skeletal tissue. We present a new investigational CONCENTRATIONS (ng/g) OF ALKALOIDS AND METABOLITES
No of
samples in parentheses.
S, Homoki J. Determination of cocaine in human hair by
gaschromatography/mass spectrometry. Z Rechtsmed 1987; 98: 235-40. 2. Balabanova S, Schneider E. Nicotin im Kopf-, Achsel- und Schamhaar. Deut Apoth Z 1990: 40: 2200-01. 3. Balabanova S, Parsche F, Pirsig W. Drugs in cranial hair of pre-Columbian Peruvian mummies. Baessler Archiv NF 1992: 40. 4. Balabanova S, Parsche F, Pirsig W. First identification of drugs in Egyptian mummies. Naturwissenschaften 1992; 8: 358. 5. Baumgartner AM, Jones PF, Werner A, Black CH. Radioimmunoassay of hair for determining opiate-abusing histories. J Nucl Med 1979; 20: 748-52. 6. Cartmell L, Aufderheide AC, Springfield A, Weems C, Arriaza B. The frequency and antiquity of prehistoric coca-leaf-chewing practices in northern Chile: radioimmunoassay of a cocaine metabolite in human-mummy hair. Latin Am Antiquity 1991; 2: 260-68. 7. Haley NJ, Hoffmann B. Analysis for nicotine and cotinine in hair to determine cigarette smoker status. Clin Chem 1985; 31: 1598-600. 8. Klug E. Determination of morphine in human head hair. Z Rechtsmed 1980; 84: 189-93. 9. Valente D, Cassini M, Pigliapochi M, Vansetti G. Hair as the sample in assessing morphine and cocaine addiction. Clin Chem 1981; 27: 1952-53.
Recombinant human erythropoietin and in patients with cirrhosis
hypophosphatemia
SIR,-Although recombinant human erythropoietin (rh-EPO) has been administered preoperatively to enhance autologous blood donation for patients undergoing elective surgery, there are few reports on the use of this agent in patients with chronic disorders.2 We used preoperative autologous blood donation to prevent or reduce the need for intraoperative or postoperative homologous blood transfusion in patients with liver cancer and cirrhosis. We have done a randomised study to clarify the effect of rh-EPO on preoperative autologous blood donation. Between August, 1991, and November, 1992, 21 patients with hepatocellular carcinoma and post-necrotic cirrhosis donated autologous blood before hepatectomy. They were divided into two groups at random: 11patients (group A) received rh-EPO 3000 U per day subcutaneously during the preoperative period, while 10 patients were not treated (group B). Informed consent was obtained. 2-3 weeks before the operation, 400 mL autologous blood was collected from each patient once or twice a week (up to 1200 mL). Each patient received 80 mg iron sulphate intravenously on the day of blood collection followed by 100 mg orally once daily until operation. Groups A and B did not differ significantly in age or serum concentrations of aminotransferases and albumin. The mean (SD) reticulocyte count before blood donation was 72 (2-0) x 109/L in group A and 58 (2-3) x 109/L in group B, which was not significantly different. After donation, the reticulocyte count was 189 (2-1) x 109/L in group A and 124 (3-5) x 109/L in group B (p < 001, t-test). In all patients, serum phosphate concentrations before donation were normal (25-45 mg/dL). After donation, serum phosphate in group A fell below 2-5 mg/dL (minimum 0-7 mg/dL) in 6 patients (55%), whereas no patient in group B had this abnormality (p < 005, x2-test; figure). There were no significant alterations in serum concentrations of calcium, parathyroid hormone, calcitonin, or 25-hydroxyvitamin D in any patient preoperatively. Hypophosphataemia has been reported in patients with chronic liver disease, and has been attributed to poor nutrition,3 malabsorption,4 or vitamin D deficiency.s Clinically, significant hypophosphataemia has occurred on refeeding after starvation because of the sudden shift of phosphate into cells for phosphorylation of glucose and protein synthesis.6 Therefore, acute
504
0
before blood donation
immediately before operation !—! normal range .
Alterations of
serum
phosphate concentrations.
erythropoiesis due to blood donation and rh-EPO administration in patients with cirrhosis and preexisting low plasma inorganic phosphorous is believed to induce an acute shift of phosphate into erythroid cells, thus leading to hypophosphataemia. Hypophosphataemia itself causes liver damage7 and hypophosphataemia after major hepatic surgery is related to the development of serious postoperative complications.8 Accordingly, doctors should be aware that treatment of cirrhotic patients with rh-EPO for autologous blood collection can lead to hypophosphataemia.
Department of Surgery II, Nagoya University School of Medicine, Nagoya 466, Japan 1.
MASAKI KAJIKAWA TOSHIAKI NONAMI TSUYOSHI KUROKAWA AKIO HARADA AKIMASA NAKAO HIROSHI TAKAGI
Goodnough LT, Rudnick S, Price TH, et al. Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy. N Engl J Med
1989; 321: 1163-68. 2. Thompson FL, Powers JS, Graber SE, Krantz SB. Use of recombinant human
erythropoietin to enhance autologous blood donation in a patient with multiple red cell allo-antibodies and the anemia of chronic disease. Am J Med 1991; 90: 398-400. 3. Amatuzio DS, Stutzman F, Shrifter N, Nesbitt S. A study of serum electrolytes (Na, K, Ca, P) in patients with severely decompensated portal cirrhosis of the liver. Lab J Clin Med 1952; 39: 26-29. 4. Caniggia A, Gennari C. Intestinal absorption of radiophosphate after physiological doses of 25(OH)D3 in normals, liver cirrhosis and chronic renal failure patients. In: Norman AW, et al. Vitamin D: biochemical, chemical and clinical aspects related to calcium metabolism. Proceedings of the Third Workshop on Vitamin D, California, Jan 1977. Berlin: de Gruyter, 1977: 755-57. 5. Long RG, Skinner RK, Wills MR, Sherlock S. Serum-25-hydroxy-vitamin-D in untreated parenchymal and cholestatic liver disease. Lancet 1976; ii: 650-52. 6. Cummings AD, Farquhar JR, Bouchier IAD. Refeeding hypophosphataemia in anorexia nervosa and alcoholism. BMJ 1987; 295: 490-91. 7. Nanji AA, Anderson FH. Acute liver failure: a possible consequence of severe hypophosphataemia. J Clin Gastroenterol 1985; 7: 338-40. 8. George R, Shiu MH. Hypophosphateamia after major hepatic resection. Surgery 1992; 111: 281-86.
Can undescended testes be
acquired?
SIR,-Undescended testes remain a highly controversial topic in paediatric surgical practice. Cryptorchidism during childhood is related to poor sperm counts in adult life, presumably because of the adverse effects of the higher temperature of the non-scrotal testis. Despite recommendations for early surgery for congenital undescended testes to avoid secondary degeneration, many operations are still not done until 8-12 years ofage.1 Why is this so? One explanation is that the earlier attendants failed to diagnose cryptorchidism and therefore no intervention was suggested in infancy. Most surgeons (including ourselves), when faced with undiagnosed undescended testes in a pre-adolescent, would have hitherto assumed that earlier examiners must have got it wrong. A different view suggests that some undescended testes are acquired postnatally. Clinicians have begun to define these as pathological retractile testes2-4 and ascending testes School
medical officers are familiar with the 6-8-year-old boy with a flat, empty scrotum and inguinal testes that are hard to find and yet at birth were thought to be normal. How can this be? We propose that most children first presenting over the age of 5 years did not have undescended testes at birth but have an acquired anomaly. For the testes to be in the scrotum at 10-14 years of age,’ normal prenatal migration of the gubemaculum and testis, and normal growth and elongation of the spermatic cord with age, so that the testis stays level with the scrotum, are required. Acquired maldescent is caused by failure of the cord to elongate, which keeps the testis high as the pubis-scrotum distance increases with age. At birth the scrotum is lax and scrotal testes easily seen, so few parents need a doctor’s opinion about their presence. Furthermore, late "ascent" is now well-documented in the John Radcliffe Hospital long-term follow-up6,7and in other studies.1,4,s Not only should undescended testes be separated into congenital and acquired categories but we should also take seriously the risk of infertility2,3 and malignancy3,8,9 in the acquired group, in which the damaging effects of temperature will occur, albeit for a shorter time and to a lesser degree than in congenital cryptorchidism.lO Surgical Research Unit, Royal Children’s Hospital, Melbourne,
JOHN M. HUTSON
Victoria 3052, Australia
DAY WAY GOH
1. Fenton EJM, Woodward AA, Hudson IL, Marschner I. The ascending testis. Pediatr Surg Int 1990; 5: 6-9. 2. Goh DW, Hutson JM. Is the retractile testis a normal, physiological variant or an anomaly that requires active treatment? Pediatr Surg Int 1992; 7: 249-52. 3. Goh DW, Hutson JM. The retractile testis: time for a reappraisal. J Pediatr Child Health (in press). 4. Wyllie GG. The retractile testis. Med J Aust 1984; 140: 403-05. 5. Atwell JD. Ascent of the testis: fact or fiction. Br J Urol 1985; 57: 474-77. 6. John Radcliffe Hospital Cryptorchidism Study Group. Boys with late descending testes: the source of patients with "retractile" testes undergoing orchidopexy. BMJ 1986; 293: 789-90. 7. John Radcliffe Hospital Cryptorchidism Study Group. Cryptorchidism: a prospective study of 7500 consecutive male births, 1984-88. Arch Dis Child 1992; 67: 892-99. 8. Batata MA, Chu FCH, Hilaris BS, Whitemore WF, Golbey RB. Testicular cancer in cryptorchids. Cancer 1982; 49: 1023-30. 9. Chilvers C, Dudley NE, Gough MH, Jackson MB, Pike MC. Undescended testis: the effect of treatment on subsequent risk of subfertility and malignancy. J Pediatr Surg
1986; 21: 691-96. BT, Ingerslev HJ, Hostrup H. Bilateral spontaneous descent of the testis after the age of 10: subsequent effects on fertility. Br J Surg 1988; 75: 820
10. Rasmussen
Thrombin generation and myocardial infarction during infusion of tissue-plasminogen activator SIR,-The success of coronary artery thrombolysis depends on the balance between coagulant and fibrinolytic activity. The differential properties of specific plasminogen activators determine the degree of thrombin and plasmin generation, and hence the rate at which clots lyse and the extent to which recurrent thrombosis is inhibited. In-vivo thrombin and plasmin generation can now be measured by plasma concentrations of activation-dependent peptides and enzyme-inhibitor complexes. The concentration in plasma of the prothrombin cleavage peptide F1.2 and the enzyme-inhibitor complex thrombin-antithrombin III (TAT) reflect thrombin generation while the concentration ofD-dimer and fragment E reflect fibrin(ogen) proteolysis by plasmin. Monoclonal antibodies reactive with intact fragment-E/fibrinopeptide-A specifically identify plasmin proteolysis of fibrinogen that has not been exposed to thrombin. By contrast, plasmin proteolysis of thrombin crosslinked fibrin results in D-dimer formation. Therefore, it is now theoretically possible to distinguish relative degrees of systemic and local fibrinolysis. Furthermore, measurement of thrombin and plasmin activity may help to clarify mechanisms responsible for failure of coronary thrombolysis. Failure of coronary patency may occur during thrombolytic therapy because of delayed clot lysis or after recanalisation as a consequence of re-occlusion. Thrombin generation appears to be a major determinant of coronary patencyl and may result from direct activation of the coagulation system by plasmin2 or by positive feedback of the coagulation system by clot-bound thrombin.3 We report differential thrombin and plasmin activity during