- Email: [email protected]
THE VULNERABLE ŒSOPHAGUS
571 It was not found possible to resolve individual microvilli in these whole specimens of intestine, due perhaps to the presence of the fuzzy coat of the intestinal microvilli.1 The three-dimensional study of the villous pattern, whether using binocular light microscopy or reconstruction techniques, has proved a valuable aid in the examination of human intestinal biopsies.2-6 It seems likely that the scanning electron microscope could extend the range of the binocular light microscope in this type of study. A preliminary investigation of human intestinal biopsies using this technique has confirmed that satisfactory results can readily be obtained and has shown that features can be distinguished in human specimens similar to those outlined above in the rat. The clarity and the threedimensional effect of the scanning micrograph make this technique of value also for teaching purposes. We are grateful to Prof. R. M. Kenedi, Bio-Engineering Unit University of Strathclyde, and Prof. J. R. Anderson, Department of Pathology, Western Infirmary, for the use of the facilities of their departments.
Bio-Engineering Unit, University of Strathclyde, Glasgow. Western Infirmary Department of Pathology Glasgow.
KATHARINE E. CARR.
PETER G. TONER.
HEATSTROKE the line from Homer (Iliad, xvi, 762) quoted by SIR,-In Dr. Marsh (Aug. 24, p. 455) there is no word of Patroclus nor of heatstroke. If one reads on in Book xvi, however, one sees that Patroclus was killed by Phcebus Apollo-that is, perhaps, by the effects of the sun. JOHN PENMAN.
PRADER-WILLI SYNDROME SIR,-Since Prader et al.’described in 1956 a syndrome of low birth-weight, hypotonia, mental retardation, early onset of obesity, acromicria, and often diabetes mellitus, developing during childhood or adolescence, more than 50 cases of the disorder have been reported. The finding of 3 patients with this condition, among 1000 patients in 3 hospitals for the mentally retarded serving a population of 840,000, suggests that the syndrome may not be uncommon. All men, aged 18, 19 and 23, these 3 patients have the characteristic dwarfed stature, small external genitalia,
obesity (average weight 14 stones [88 kg.]), almond-shaped eyes with slightly overhanging eyelids, high cranial vault above the eyes, and open fish-like mouths. Their hands and feet are small and their dermatoglyphics show no significant abnormality. On standard intelligence testing, their intelligence quotients fall within the 50-60 (subnormal) range. Their buccal smears and karyotypes are of the normal male type. Electroencephalography, skull X-ray, serum proteins, electrolytes, urea, and cholesterol, and excretion of ketosteroids and 17-hydroxycorticosteroids are all within normal limits. The 23-year-old patient has had diabetes mellitus since the age of 12. The mental state of patients with this syndrome has received less attention than the physical features. These 3 patients had histories of aggressive conduct before their admission, but they have shown no disturbance of behaviour in hospital, where they are placid and friendly. They exhibit hyperphagia and a tendency to somnolence, perhaps associated with the 1. Ito, S. J. Cell Biol. 1965, 27, 475. 2. Rubin, C. E., Brandborg, L. L., Phelps, P. C., Taylor, H. C. Gastroenterology, 1960, 38, 28. 3. Holmes, R., Hourihane, O’B. D., Booth, C. C. Lancet, 1961, i, 81. 4. Booth, C. C., Stewart, J. S., Holmes, R., Brackenbury, W. in Intestinal Biopsy (edited by G. E. W. Wolstenholm and M. P. Cameron). Boston, 1962. 5. McCarthy, C. F., Borland, J. L., Kurtz, S. M., Ruffin, J. M. Am. J. Path. 1964, 44 585. 6. Cocco, A. E., Dohrmann, M. J., Hendrix, T. R. Gastroenterology, 1966, 51, 24. 7. Prader, A., Labhart, A., Willi, H. Schweiz. med. Wschr. 1956, 86, 1260.
obesity/hypoventilation phenomenon. Their general ance is reminiscent of the Fat Boy of Pickwick. Westwood Hospital, Bradford 6, Yorkshire.
appear-
D. A. SPENCER.
ERYTHROID-CELL ENZYME ACTIVITY IN CHRONIC RENAL FAILURE Wardle in his letter (Aug. 24, p. 457) points out SIR,-Dr. that our observation of a normal lactate-dehydrogenase content in erythroid cells in patients with chronic renal failure does not exclude abnormalities of other enzymes in the preceding stages of the Embden-Meyerhof pathway. We agree with this; our study was devised merely to determine whether the inhibitor of lactate dehydrogenase reported in ursemic plasma1 has a demonstrable effect on that enzyme in erythroid cells in vivo. Enzymes from the pentose-phosphate shunt and tricarboxylicacid cycle were included only as a basis for comparison in the event of an increased enzyme content in erythroid cells in the urxmic patients due to a young cell population. No assumption can be made from our results of the activity of other enzymes in these pathways nor of the rate-controlling mechanisms which operate in them. J. STUART P. N. SKOWRON Department of Hæmatology, J. J. KRAMER Institute of Child Health, G. A. NELSTROP. London W.C.1.
THE VULNERABLE ŒSOPHAGUS
SIR,-Your leading article expounding the views of Palmer2 (Aug. 3, p. 267) is bound to provoke some comments. Reflux of gastric juice must be the cause of the oesophagitis of most patients with hiatal hernia. In our department aesophageal-pressure readings, pH-determinations by glass electrode, and the hydrochloric-acid provocation test of Bernstein,34 are all applied in order to define this reflux. It can also be demonstrated by keeping the tip of the oesophagoscope just above the hiatal plane when the patient is beginning to wake up after general anaesthesia for oesophagoscopy, straining will cause reflux, and the uppermost part of the stomach may be seen to pass up, too, if the hiatus is incompetent. When reflux has been proved to take place, a clearcut indication for operative repair has, in our opinion, been established. If at all possible, an augmented histamine-stimulation test is performed in order to decide whether a vagotomy and pyloroplasty should be added to the hernia repair. On the other hand, reflux of bile or alkaline duodenal juice may provoke pain in patients after gastrectomy, because of hiatal incompetence. And we have clinical proof, in several instances, that operative repair affords a cure of this condition. As to medical versus surgical treatment of hiatus hernia and crsophagitis, Palmer’s recent views are not in accordance with the recommendations put forward in his textbook.5 In this connection, a thoracic surgeon cannot help citing the views of Flavell 6: "When the presence of a hernia has, in fact, been diagnosed, some physicians (especially those who pride themselves upon their sober conservatism) are inclined to treat this anatomical mishap by’medical means ’. The regime consists first of alkaline draughts, ineffective when they are not actually injurious; and secondly, of weight reduction; but it is yesterday’s fat which has contributed to the hernia, and to reduce it now is to close the stable door after the horse has kicked a hole through the roof. Thirdly, of admonishments to sleep propped upright; but anyone who has tried this knows it to be impossible, and in any case it is as sensible a form of therapy as standing a 1. 2. 3. 4.
5. 6.
Emerson, P. M., Withycome, W. A., Wilkinson, J. H. Lancet, 1965, ii, 571. Palmer, E. D. Am. J. Med. 1968, 44, 566. Bernstein, L. M., Baker, L. A. Gastroenterology, 1958, 34, 760. Bernstein, L. M., Fruin, R. C., Pacini, R. Medicine, Baltimore, 1962, 41, 143. Palmer, E. D. Clinical Gastroenterology; p. 77. New York, 1963. Flavell, G. The Œsophagus; p. 98. London, 1963.
572
patient with an inguinal hernia on his head for the rest of his life. Many patients come to accept (and some are told to accept) chronic dyspepsia as an ineluctable accompaniment of existence." The final stage of hiatal hernia with oesophagitis is the fixed hernia with oesophageal stricture, a condition very often calling for major surgery in elderly people (not without risk). As we have to treat a fair number of such cases in our department, this is in our opinion another strong reason for operative repair of symptomatic hiatal hernia with proven reflux oeso-
phagitis. Copenhagen City Clinic for Thoracic Surgery, Bispebjerg Hospital, Denmark.
ERIK CHRISTENSEN.
SYNOVECTOMY FOR HÆMOPHILIC HÆMARTHROSIS SIR,-Repeated haemarthrosis of the knee, with consequent chronic arthropathy, is one of the more frequent and disabling manifestations of haemophilia. Hxmophilic arthropathy shows many clinical and histological features akin to those of nodular villous pigmented arthrosynovitis, a condition which benefits considerably from synovectomy. Accordingly we have tried synovectomy in patients with haemophilic arthropathy, particularly since so far both orthopaedic and medical treatment, even in specialised centres, has generally been unable to prevent haemophilic arthropathy from evolving towards permanent
day), in later operations we adopted a standard therapeutic scheme; using small quantities of fresh frozen plasma (8-10 ml. per kg. per day for 8-10 days) and antifibrinolytic compounds (parotid inhibitor 100,000/500,000 units intra-articularly during operation, and aminocaproic acid 0-3 to 1 g. per kg. per day for 4 weeks), which yielded excellent results. According to their parents, all these children now lead a much less troublesome life, being able to attend school more regularly and undertake some physical exertion. The X-ray picture also seemed to improve, but further confirmation of this is still required. Some interesting effects of these operations (e.g., the efficacy of antifibrinolytic treatment, especially in one patient who became immunised against factor vni 30 hours after operation) suggest the two following hypotheses: (1) hyperactivity of the enzymatic fibrinogen-fibrinolysin system should lead to persistence of intra-articular bleeding and occurrence of haemorrhage in other sites; (2) synovectomy, by removing a considerable amount of synovial tissue, which histologically resembles an angioma, would eliminate a very active source of fibrinolytic tissue activators, as indicated by Astrup’s studies on normal synovial tissue.1
per
Istituto di Patologia Speciale Medica e Metodologia Clinica, University of Modena, Italy.
E. A. E. P.
STORTI TRALDI TOSATTI G. DAVOLI.
ankylosis. So far, in twelve patients with severe haemophilia, we have carried out fourteen synovectomies; in nine cases the operative procedure was confined to one knee; in one case (no. 4) synovectomy was performed on both knees, but at different times; in another case (no. 9) synovectomy was performed, in the course of the same operation, on both knees, and later on the tibiotarsal joint. The considerable length of time which has elapsed since the operation was carried out in most of the patients enables us to assess its effects with some confidence. The results of the operation are summarised below: 1. In all cases there was no recurrence of bleeding in the knees subjected to synovectomy, pain and functional disability disappeared, and joint function was regained (see accompanying
table). 2. So far in each case the bleeding episodes affecting sites other than the joint subjected to synovectomy have ceased completely, or have become much rarer and of shorter duration than in the preoperative period, suggesting that removal of the synovial tissue might have benefited the patient as a whole. 3. None of the fourteen surgical procedures was marred by any complication, although in the first two patients the post-
TWO FORMS OF HÆMOPHILIA ? SIR,-Iwas interested to read the letter by Mr. Denson (July 27, p. 222) and Dr. Hoyer and Dr. Breckenridge (Aug. 24, p. 457), since these seem to confirm my results.2 These showed that deficiency of blood-factor vni could be caused either by actual lack of this factor or by impairment of its evolvement (activation). Furthermore, my diagrammatic model for the behaviour of blood-factors vni and ix and their evolvers in health and disease predicted and offered an explanation for the possible types of factors vin and ix defects. It now seems that in the rare variety of haemophilia (so-called haemophilia A+) the evolver is lacking, but the concentration of factor vin is normal.3 Final proof can be provided only by cross-transfusions between the two types of patients. Meanwhile, it would be more correct to say that there are two types (or more) of factor-viii and factorix defects,4 rather than two types of haemophilia and Christmas disease. Department of Pathology, Shenley Hospital, near
RESULTS OF SYNOVECTOMY FOR H&MOPHILIC
Postoperative period
less than
one
F. NOUR-ELDIN.
1. Astrup, T., Sjolin, R. E. Proc. Soc. exp. Biol. Med. 1958, 97, 852. 2. Nour-Eldin, F. Ann. N.Y. Acad. Sci. 1966, 136, 219. 3. Nour-Eldin, F. Blood Coagulation Simplified; p. 91. London, 1967. 4. Nour-Eldin, F. Lancet, 1967, i, 783.
operative period was unduly prolonged. Since bleeding in the first two cases was incompletely controlled by the infusion of fresh frozen plasma (18-20 ml. per kg.
*
St. Albans, Herts.
year.
HPEMARTHROSIS
Flex. =flexion.
Ext. =extension.
Bio-Engineering Unit, University of Strathclyde, Glasgow. Western Infirmary Department of Pathology Glasgow.
KATHARINE E. CARR.
PETER G. TONER.
HEATSTROKE the line from Homer (Iliad, xvi, 762) quoted by SIR,-In Dr. Marsh (Aug. 24, p. 455) there is no word of Patroclus nor of heatstroke. If one reads on in Book xvi, however, one sees that Patroclus was killed by Phcebus Apollo-that is, perhaps, by the effects of the sun. JOHN PENMAN.
PRADER-WILLI SYNDROME SIR,-Since Prader et al.’described in 1956 a syndrome of low birth-weight, hypotonia, mental retardation, early onset of obesity, acromicria, and often diabetes mellitus, developing during childhood or adolescence, more than 50 cases of the disorder have been reported. The finding of 3 patients with this condition, among 1000 patients in 3 hospitals for the mentally retarded serving a population of 840,000, suggests that the syndrome may not be uncommon. All men, aged 18, 19 and 23, these 3 patients have the characteristic dwarfed stature, small external genitalia,
obesity (average weight 14 stones [88 kg.]), almond-shaped eyes with slightly overhanging eyelids, high cranial vault above the eyes, and open fish-like mouths. Their hands and feet are small and their dermatoglyphics show no significant abnormality. On standard intelligence testing, their intelligence quotients fall within the 50-60 (subnormal) range. Their buccal smears and karyotypes are of the normal male type. Electroencephalography, skull X-ray, serum proteins, electrolytes, urea, and cholesterol, and excretion of ketosteroids and 17-hydroxycorticosteroids are all within normal limits. The 23-year-old patient has had diabetes mellitus since the age of 12. The mental state of patients with this syndrome has received less attention than the physical features. These 3 patients had histories of aggressive conduct before their admission, but they have shown no disturbance of behaviour in hospital, where they are placid and friendly. They exhibit hyperphagia and a tendency to somnolence, perhaps associated with the 1. Ito, S. J. Cell Biol. 1965, 27, 475. 2. Rubin, C. E., Brandborg, L. L., Phelps, P. C., Taylor, H. C. Gastroenterology, 1960, 38, 28. 3. Holmes, R., Hourihane, O’B. D., Booth, C. C. Lancet, 1961, i, 81. 4. Booth, C. C., Stewart, J. S., Holmes, R., Brackenbury, W. in Intestinal Biopsy (edited by G. E. W. Wolstenholm and M. P. Cameron). Boston, 1962. 5. McCarthy, C. F., Borland, J. L., Kurtz, S. M., Ruffin, J. M. Am. J. Path. 1964, 44 585. 6. Cocco, A. E., Dohrmann, M. J., Hendrix, T. R. Gastroenterology, 1966, 51, 24. 7. Prader, A., Labhart, A., Willi, H. Schweiz. med. Wschr. 1956, 86, 1260.
obesity/hypoventilation phenomenon. Their general ance is reminiscent of the Fat Boy of Pickwick. Westwood Hospital, Bradford 6, Yorkshire.
appear-
D. A. SPENCER.
ERYTHROID-CELL ENZYME ACTIVITY IN CHRONIC RENAL FAILURE Wardle in his letter (Aug. 24, p. 457) points out SIR,-Dr. that our observation of a normal lactate-dehydrogenase content in erythroid cells in patients with chronic renal failure does not exclude abnormalities of other enzymes in the preceding stages of the Embden-Meyerhof pathway. We agree with this; our study was devised merely to determine whether the inhibitor of lactate dehydrogenase reported in ursemic plasma1 has a demonstrable effect on that enzyme in erythroid cells in vivo. Enzymes from the pentose-phosphate shunt and tricarboxylicacid cycle were included only as a basis for comparison in the event of an increased enzyme content in erythroid cells in the urxmic patients due to a young cell population. No assumption can be made from our results of the activity of other enzymes in these pathways nor of the rate-controlling mechanisms which operate in them. J. STUART P. N. SKOWRON Department of Hæmatology, J. J. KRAMER Institute of Child Health, G. A. NELSTROP. London W.C.1.
THE VULNERABLE ŒSOPHAGUS
SIR,-Your leading article expounding the views of Palmer2 (Aug. 3, p. 267) is bound to provoke some comments. Reflux of gastric juice must be the cause of the oesophagitis of most patients with hiatal hernia. In our department aesophageal-pressure readings, pH-determinations by glass electrode, and the hydrochloric-acid provocation test of Bernstein,34 are all applied in order to define this reflux. It can also be demonstrated by keeping the tip of the oesophagoscope just above the hiatal plane when the patient is beginning to wake up after general anaesthesia for oesophagoscopy, straining will cause reflux, and the uppermost part of the stomach may be seen to pass up, too, if the hiatus is incompetent. When reflux has been proved to take place, a clearcut indication for operative repair has, in our opinion, been established. If at all possible, an augmented histamine-stimulation test is performed in order to decide whether a vagotomy and pyloroplasty should be added to the hernia repair. On the other hand, reflux of bile or alkaline duodenal juice may provoke pain in patients after gastrectomy, because of hiatal incompetence. And we have clinical proof, in several instances, that operative repair affords a cure of this condition. As to medical versus surgical treatment of hiatus hernia and crsophagitis, Palmer’s recent views are not in accordance with the recommendations put forward in his textbook.5 In this connection, a thoracic surgeon cannot help citing the views of Flavell 6: "When the presence of a hernia has, in fact, been diagnosed, some physicians (especially those who pride themselves upon their sober conservatism) are inclined to treat this anatomical mishap by’medical means ’. The regime consists first of alkaline draughts, ineffective when they are not actually injurious; and secondly, of weight reduction; but it is yesterday’s fat which has contributed to the hernia, and to reduce it now is to close the stable door after the horse has kicked a hole through the roof. Thirdly, of admonishments to sleep propped upright; but anyone who has tried this knows it to be impossible, and in any case it is as sensible a form of therapy as standing a 1. 2. 3. 4.
5. 6.
Emerson, P. M., Withycome, W. A., Wilkinson, J. H. Lancet, 1965, ii, 571. Palmer, E. D. Am. J. Med. 1968, 44, 566. Bernstein, L. M., Baker, L. A. Gastroenterology, 1958, 34, 760. Bernstein, L. M., Fruin, R. C., Pacini, R. Medicine, Baltimore, 1962, 41, 143. Palmer, E. D. Clinical Gastroenterology; p. 77. New York, 1963. Flavell, G. The Œsophagus; p. 98. London, 1963.
572
patient with an inguinal hernia on his head for the rest of his life. Many patients come to accept (and some are told to accept) chronic dyspepsia as an ineluctable accompaniment of existence." The final stage of hiatal hernia with oesophagitis is the fixed hernia with oesophageal stricture, a condition very often calling for major surgery in elderly people (not without risk). As we have to treat a fair number of such cases in our department, this is in our opinion another strong reason for operative repair of symptomatic hiatal hernia with proven reflux oeso-
phagitis. Copenhagen City Clinic for Thoracic Surgery, Bispebjerg Hospital, Denmark.
ERIK CHRISTENSEN.
SYNOVECTOMY FOR HÆMOPHILIC HÆMARTHROSIS SIR,-Repeated haemarthrosis of the knee, with consequent chronic arthropathy, is one of the more frequent and disabling manifestations of haemophilia. Hxmophilic arthropathy shows many clinical and histological features akin to those of nodular villous pigmented arthrosynovitis, a condition which benefits considerably from synovectomy. Accordingly we have tried synovectomy in patients with haemophilic arthropathy, particularly since so far both orthopaedic and medical treatment, even in specialised centres, has generally been unable to prevent haemophilic arthropathy from evolving towards permanent
day), in later operations we adopted a standard therapeutic scheme; using small quantities of fresh frozen plasma (8-10 ml. per kg. per day for 8-10 days) and antifibrinolytic compounds (parotid inhibitor 100,000/500,000 units intra-articularly during operation, and aminocaproic acid 0-3 to 1 g. per kg. per day for 4 weeks), which yielded excellent results. According to their parents, all these children now lead a much less troublesome life, being able to attend school more regularly and undertake some physical exertion. The X-ray picture also seemed to improve, but further confirmation of this is still required. Some interesting effects of these operations (e.g., the efficacy of antifibrinolytic treatment, especially in one patient who became immunised against factor vni 30 hours after operation) suggest the two following hypotheses: (1) hyperactivity of the enzymatic fibrinogen-fibrinolysin system should lead to persistence of intra-articular bleeding and occurrence of haemorrhage in other sites; (2) synovectomy, by removing a considerable amount of synovial tissue, which histologically resembles an angioma, would eliminate a very active source of fibrinolytic tissue activators, as indicated by Astrup’s studies on normal synovial tissue.1
per
Istituto di Patologia Speciale Medica e Metodologia Clinica, University of Modena, Italy.
E. A. E. P.
STORTI TRALDI TOSATTI G. DAVOLI.
ankylosis. So far, in twelve patients with severe haemophilia, we have carried out fourteen synovectomies; in nine cases the operative procedure was confined to one knee; in one case (no. 4) synovectomy was performed on both knees, but at different times; in another case (no. 9) synovectomy was performed, in the course of the same operation, on both knees, and later on the tibiotarsal joint. The considerable length of time which has elapsed since the operation was carried out in most of the patients enables us to assess its effects with some confidence. The results of the operation are summarised below: 1. In all cases there was no recurrence of bleeding in the knees subjected to synovectomy, pain and functional disability disappeared, and joint function was regained (see accompanying
table). 2. So far in each case the bleeding episodes affecting sites other than the joint subjected to synovectomy have ceased completely, or have become much rarer and of shorter duration than in the preoperative period, suggesting that removal of the synovial tissue might have benefited the patient as a whole. 3. None of the fourteen surgical procedures was marred by any complication, although in the first two patients the post-
TWO FORMS OF HÆMOPHILIA ? SIR,-Iwas interested to read the letter by Mr. Denson (July 27, p. 222) and Dr. Hoyer and Dr. Breckenridge (Aug. 24, p. 457), since these seem to confirm my results.2 These showed that deficiency of blood-factor vni could be caused either by actual lack of this factor or by impairment of its evolvement (activation). Furthermore, my diagrammatic model for the behaviour of blood-factors vni and ix and their evolvers in health and disease predicted and offered an explanation for the possible types of factors vin and ix defects. It now seems that in the rare variety of haemophilia (so-called haemophilia A+) the evolver is lacking, but the concentration of factor vin is normal.3 Final proof can be provided only by cross-transfusions between the two types of patients. Meanwhile, it would be more correct to say that there are two types (or more) of factor-viii and factorix defects,4 rather than two types of haemophilia and Christmas disease. Department of Pathology, Shenley Hospital, near
RESULTS OF SYNOVECTOMY FOR H&MOPHILIC
Postoperative period
less than
one
F. NOUR-ELDIN.
1. Astrup, T., Sjolin, R. E. Proc. Soc. exp. Biol. Med. 1958, 97, 852. 2. Nour-Eldin, F. Ann. N.Y. Acad. Sci. 1966, 136, 219. 3. Nour-Eldin, F. Blood Coagulation Simplified; p. 91. London, 1967. 4. Nour-Eldin, F. Lancet, 1967, i, 783.
operative period was unduly prolonged. Since bleeding in the first two cases was incompletely controlled by the infusion of fresh frozen plasma (18-20 ml. per kg.
*
St. Albans, Herts.
year.
HPEMARTHROSIS
Flex. =flexion.
Ext. =extension.