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IN-VITRO PRODUCTION OF HUMAN PLATELETS
400 IN-VITRO PRODUCTION OF HUMAN PLATELETS
SiR,—Dr Tange and colleagues (July 23,
p
218) claim
to
have
observed platelet production from megakaryocytes cultured from the peripheral blood of a patient with chronic myelogenous leukaemia. Unfortunately, it is not possible to say from their description whether true platelet production has occurred, or whether the ageing megakaryocytes have simply disintegrated in culture. Thiery and Bessis1 attributed similar observations on in vitro to cell degeneration. The fact that the culture of Tange et al was composed of dividing cells also makes platelet production unlikely. Platelets arise from polyploid megakaryocytes, which do not divide. The process of the production of anucleate platelets from polyploid megakaryocytes remains unsolved. The four contending mechanisms2 proposed are pulmonary fragmentation of megakaryocytes, predetermination of platelet territories by the demarcation membrane system, production of filamentous processes from megakaryocytes, and the budding of platelets from the surface of megakaryocytes. We propose megakaryocyte fragments should only be accepted as platelets if they are granular,3 contain a peripheral bundle of microtubules,4 have an asymmetrical volume distribution with a positive skew,56 and are similar in functional characteristics to
megakaryocytes
circulating platelets. J. F. MARTIN
Wellcome Research Laboratories, Beckenham, Kent BR3 3BS 1. 2.
A. M. GLADWIN
Thiery JP, Bessis M. La genèse des plaquettes sanguines à partir des mégacaryocytes observée sur la cellule vivante. CR Acad Sci 1956; 242: 290-92. Martin JF, Slater DN, Trowbridge EA. Evidence that platelets are produced m the pulmonary circulation by a physical process. In: Levine RF, Williams N, Levin J, Evatt BL, eds. Megakaryocyte development and function. New York: Alan Liss,
1986: 405-16. 3. White JG. Platelet morphology. In: Johnson SA, ed. The circulating platelet. New York: Academic Press, 1971: 45-121. 4. Behnke O. Microtubules in disc shaped blood platelets. Int Rev Exp Pathol 1970; 9: 1-92. 5. Paulus JM. Platelet size in man. Blood 1971; 46: 321-36. 6. Trowbridge EA, Warren CW, Martin JF. Platelet volume heterogeneity in acute thrombocytopenia. Clin Phys Physiol Meas 1986; 7: 203-10.
showed that the mucosa was coated with sucralfate and that the bleeding points had healed. Treatment was continued for another week and then discontinued. She was symptom-free more than six weeks later. Case 3 (F, 42; stage II).-She received two sessions of intracavitary irradiation (total dose 75 Gy), followed by 35 Gy external radiation over 3 weeks. She remained well for -14 months when she began to bleed per rectum, losing 50-100 ml daily. She was pale and had postural hypotension; her haemoglobin was 63 g/dl. She was given three units of blood. The results in the other two patients encouraged us to try sucralfate enemas (20 g twice a day). She felt better by day 7 and the bleeding had stopped by day 16. Sucralfate enemas were administered for a further week. 4 weeks later, she remains well and symptom-free with a haemoglobin of 105 g/dl. Sucralfate is a locally acting non-systemic anti-ulcer agent’ that shields the base of peptic ulcers by the formation of a viscous coagulum ;4 it also has a cytoprotective role.5 It has been used to control bleeding after colonic polypectomy.6 In our patients sucralfate enemas controlled bleeding secondary to radiation proctitis and repeat proctoscopy in two patients revealed a white suspension adhering to bleeding points. Our experience suggests that sucralfate may be of benefit in mucosal ulceration of the rectosigmoid. Henrikson et all have used oral sucralfate to prevent radiation-associated small-bowel diarrhoea in one patient but do not state the dose. We used 2-0 g empirically. A prospective study to define the dose and duration of therapy is underway.
proctosigmoidoscopy
Departments of Gastroenterology and Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
R. KOCHHAR S. C. SHARMA B. B. GUPTA S. K. MEHTA
M, Romney S, Dayen H. Gastrointestinal tract complications following radiotherapy of uterine cervical cancer: Past and present. J Surg Oncol 1981; 18:
1. Yoonessi
135-42. 2. 3.
Gilinsky NH, Burns DG, Barzebat GO, et al. The natural history of radiation-induced proctosigmoiditis: an analysis of 88 patients. Quart J Med 1983; 205: 40-53. Goldstein F, Khoury J, Thomton JJ. Treatment of chronic radiation enteritis and colitis with salicylazosulfapyridine and systemic corticosteroids. Am J Gastroenterol 1976; 65: 201-08.
Nagashima R. Development and characteristics of sucralfate. J Clin Gastroenterol 1981; 3: 103-10. 5. Tesler MA, Lim ES. Protection of gastric mucosa by sucralfate from aspirin-induced erosions. J Clin Gastroenterol 1981; 3: 175-79. 6. Bronner MH, Yantis PL. Intracolonic sucralfate suspension for postpolypectomy hemorrhage. Gastrointest Endosc 1986; 32: 362-63. 7. Henriksson R, Franzen L, Littbrand B. Does sucralfate reduce radiation-induced 4.
RECTAL SUCRALFATE IN RADIATION PROCTITIS
SIR,-Proctitis accounts for more than 75% of radiation injuries the gut1 and often develops after radiotherapy for gynaecological malignancies.1,2 Sulphasalazine and oral or rectal steroids are the mainstay of medical therapy of radiation proctitiS.2,3 However, the symptoms sometimes persist, and surgery has to be resorted to.zWe have treated three patients with sucralfate enemas with encouraging results. Case 1 (F, 48 carcinoma of cervix stage II).-She was given external radiation (45 Gy over 4 weeks) followed by intracavitary irradiation delivering 35 Gy. 6 months later diarrhoea developed, with 4-6 stools per day, with tenesmus, mucus, and blood. In March, 1988, she was anaemic (haemoglobin 8-2 g/dl) and proctosigmoidoscopy revealed erythema, telangiectasia, friability, and ulceration in the rectal mucosa. Microbiological studies of stool were negative. She did not respond to oral sulphasalazine 3 g daily and rectal prednisolone 40 mg daily for 2 weeks and sucralfate was then tried, in the form of twice daily enemas with 2 0 g suspended in 20 ml tap water. On the fourth day of treatment the diarrhoea and bleeding had improved and by day 7 she was symptom-free. Proctoscopy revealed pale, friable mucosa covered with cheesy white material. The treatment was continued for another week. 2 months later she remains free of any symptoms. Case 2 (F, 37; carcinoma of cervix stage IIIb).—She was given 45 Gy external radiation over 4 weeks followed by 35 Gy intracavitary irradiation. 8 months after the completion of radiotherapy she started bleeding per rectum, with tenesmus. When seen by us in April, 1988, she was pale. Proctosigmoidoscopy revealed diffuse hyperaemia, loss of vascular pattern, friability, and ulceration of the rectal mucosa. Microbiological studies of stool were negative. A 2 week course of oral sulphasalazine 3-0 g daily and prednisolone enemas 40 mg per day was unhelpful and sucralfate enemas were to
tried
(2
g twice
daily). By day
10 she
was
symptom-free
and
diarrhoea. Acta Radiol Oncol 1987; 26: 76-77.
SYNCOPE WHILE VOMITING DURING MIGRAINE ATTACK
SiR,—We describe a patient who fainted while vomiting during a
migraine attack. A 41-year-old man was found unconscious at the roadside, was admitted, and spontaneously recovered. While driving, he had noted worsening right frontal headache and nausea; he stopped, vomited, and lost consciousness. His electrocardiogram (ECG) on admission showed atrial fibrillation with a ventricular rate of60/min and frequent ventricular ectopic beats. A further episode of vomiting and syncope was associated with complete atrioventricular (AV) block and ventricular standstill without slowing of the sinus rate (figure, top). He recovered without treatment. He had experienced similar attacks once or twice a year for 15 years, always characterised by unilateral headache (on either side) without preceding aura, and followed by nausea, vomiting, and syncope with spontaneous recovery. Routine examination and tests and a prolonged ambulatory ECG were normal, as was a treadmill exercise test during which his heart rate increased to 175/min with normal AV conduction. The cardiovascular responses to carotid sinus massage and to the Valsalva manoeuvre were normal. 250 mg carbachol given subcutaneously had no effect on AV conduction. A dual-chamber permanent pacemaker was implanted and further studies were done with the patient’s consent. The pacemaker was reprogrammed to a demand rate of 30/min and AV interval of 200 ms. 7 mg apomorphine was given subcutaneously to
SiR,—Dr Tange and colleagues (July 23,
p
218) claim
to
have
observed platelet production from megakaryocytes cultured from the peripheral blood of a patient with chronic myelogenous leukaemia. Unfortunately, it is not possible to say from their description whether true platelet production has occurred, or whether the ageing megakaryocytes have simply disintegrated in culture. Thiery and Bessis1 attributed similar observations on in vitro to cell degeneration. The fact that the culture of Tange et al was composed of dividing cells also makes platelet production unlikely. Platelets arise from polyploid megakaryocytes, which do not divide. The process of the production of anucleate platelets from polyploid megakaryocytes remains unsolved. The four contending mechanisms2 proposed are pulmonary fragmentation of megakaryocytes, predetermination of platelet territories by the demarcation membrane system, production of filamentous processes from megakaryocytes, and the budding of platelets from the surface of megakaryocytes. We propose megakaryocyte fragments should only be accepted as platelets if they are granular,3 contain a peripheral bundle of microtubules,4 have an asymmetrical volume distribution with a positive skew,56 and are similar in functional characteristics to
megakaryocytes
circulating platelets. J. F. MARTIN
Wellcome Research Laboratories, Beckenham, Kent BR3 3BS 1. 2.
A. M. GLADWIN
Thiery JP, Bessis M. La genèse des plaquettes sanguines à partir des mégacaryocytes observée sur la cellule vivante. CR Acad Sci 1956; 242: 290-92. Martin JF, Slater DN, Trowbridge EA. Evidence that platelets are produced m the pulmonary circulation by a physical process. In: Levine RF, Williams N, Levin J, Evatt BL, eds. Megakaryocyte development and function. New York: Alan Liss,
1986: 405-16. 3. White JG. Platelet morphology. In: Johnson SA, ed. The circulating platelet. New York: Academic Press, 1971: 45-121. 4. Behnke O. Microtubules in disc shaped blood platelets. Int Rev Exp Pathol 1970; 9: 1-92. 5. Paulus JM. Platelet size in man. Blood 1971; 46: 321-36. 6. Trowbridge EA, Warren CW, Martin JF. Platelet volume heterogeneity in acute thrombocytopenia. Clin Phys Physiol Meas 1986; 7: 203-10.
showed that the mucosa was coated with sucralfate and that the bleeding points had healed. Treatment was continued for another week and then discontinued. She was symptom-free more than six weeks later. Case 3 (F, 42; stage II).-She received two sessions of intracavitary irradiation (total dose 75 Gy), followed by 35 Gy external radiation over 3 weeks. She remained well for -14 months when she began to bleed per rectum, losing 50-100 ml daily. She was pale and had postural hypotension; her haemoglobin was 63 g/dl. She was given three units of blood. The results in the other two patients encouraged us to try sucralfate enemas (20 g twice a day). She felt better by day 7 and the bleeding had stopped by day 16. Sucralfate enemas were administered for a further week. 4 weeks later, she remains well and symptom-free with a haemoglobin of 105 g/dl. Sucralfate is a locally acting non-systemic anti-ulcer agent’ that shields the base of peptic ulcers by the formation of a viscous coagulum ;4 it also has a cytoprotective role.5 It has been used to control bleeding after colonic polypectomy.6 In our patients sucralfate enemas controlled bleeding secondary to radiation proctitis and repeat proctoscopy in two patients revealed a white suspension adhering to bleeding points. Our experience suggests that sucralfate may be of benefit in mucosal ulceration of the rectosigmoid. Henrikson et all have used oral sucralfate to prevent radiation-associated small-bowel diarrhoea in one patient but do not state the dose. We used 2-0 g empirically. A prospective study to define the dose and duration of therapy is underway.
proctosigmoidoscopy
Departments of Gastroenterology and Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
R. KOCHHAR S. C. SHARMA B. B. GUPTA S. K. MEHTA
M, Romney S, Dayen H. Gastrointestinal tract complications following radiotherapy of uterine cervical cancer: Past and present. J Surg Oncol 1981; 18:
1. Yoonessi
135-42. 2. 3.
Gilinsky NH, Burns DG, Barzebat GO, et al. The natural history of radiation-induced proctosigmoiditis: an analysis of 88 patients. Quart J Med 1983; 205: 40-53. Goldstein F, Khoury J, Thomton JJ. Treatment of chronic radiation enteritis and colitis with salicylazosulfapyridine and systemic corticosteroids. Am J Gastroenterol 1976; 65: 201-08.
Nagashima R. Development and characteristics of sucralfate. J Clin Gastroenterol 1981; 3: 103-10. 5. Tesler MA, Lim ES. Protection of gastric mucosa by sucralfate from aspirin-induced erosions. J Clin Gastroenterol 1981; 3: 175-79. 6. Bronner MH, Yantis PL. Intracolonic sucralfate suspension for postpolypectomy hemorrhage. Gastrointest Endosc 1986; 32: 362-63. 7. Henriksson R, Franzen L, Littbrand B. Does sucralfate reduce radiation-induced 4.
RECTAL SUCRALFATE IN RADIATION PROCTITIS
SIR,-Proctitis accounts for more than 75% of radiation injuries the gut1 and often develops after radiotherapy for gynaecological malignancies.1,2 Sulphasalazine and oral or rectal steroids are the mainstay of medical therapy of radiation proctitiS.2,3 However, the symptoms sometimes persist, and surgery has to be resorted to.zWe have treated three patients with sucralfate enemas with encouraging results. Case 1 (F, 48 carcinoma of cervix stage II).-She was given external radiation (45 Gy over 4 weeks) followed by intracavitary irradiation delivering 35 Gy. 6 months later diarrhoea developed, with 4-6 stools per day, with tenesmus, mucus, and blood. In March, 1988, she was anaemic (haemoglobin 8-2 g/dl) and proctosigmoidoscopy revealed erythema, telangiectasia, friability, and ulceration in the rectal mucosa. Microbiological studies of stool were negative. She did not respond to oral sulphasalazine 3 g daily and rectal prednisolone 40 mg daily for 2 weeks and sucralfate was then tried, in the form of twice daily enemas with 2 0 g suspended in 20 ml tap water. On the fourth day of treatment the diarrhoea and bleeding had improved and by day 7 she was symptom-free. Proctoscopy revealed pale, friable mucosa covered with cheesy white material. The treatment was continued for another week. 2 months later she remains free of any symptoms. Case 2 (F, 37; carcinoma of cervix stage IIIb).—She was given 45 Gy external radiation over 4 weeks followed by 35 Gy intracavitary irradiation. 8 months after the completion of radiotherapy she started bleeding per rectum, with tenesmus. When seen by us in April, 1988, she was pale. Proctosigmoidoscopy revealed diffuse hyperaemia, loss of vascular pattern, friability, and ulceration of the rectal mucosa. Microbiological studies of stool were negative. A 2 week course of oral sulphasalazine 3-0 g daily and prednisolone enemas 40 mg per day was unhelpful and sucralfate enemas were to
tried
(2
g twice
daily). By day
10 she
was
symptom-free
and
diarrhoea. Acta Radiol Oncol 1987; 26: 76-77.
SYNCOPE WHILE VOMITING DURING MIGRAINE ATTACK
SiR,—We describe a patient who fainted while vomiting during a
migraine attack. A 41-year-old man was found unconscious at the roadside, was admitted, and spontaneously recovered. While driving, he had noted worsening right frontal headache and nausea; he stopped, vomited, and lost consciousness. His electrocardiogram (ECG) on admission showed atrial fibrillation with a ventricular rate of60/min and frequent ventricular ectopic beats. A further episode of vomiting and syncope was associated with complete atrioventricular (AV) block and ventricular standstill without slowing of the sinus rate (figure, top). He recovered without treatment. He had experienced similar attacks once or twice a year for 15 years, always characterised by unilateral headache (on either side) without preceding aura, and followed by nausea, vomiting, and syncope with spontaneous recovery. Routine examination and tests and a prolonged ambulatory ECG were normal, as was a treadmill exercise test during which his heart rate increased to 175/min with normal AV conduction. The cardiovascular responses to carotid sinus massage and to the Valsalva manoeuvre were normal. 250 mg carbachol given subcutaneously had no effect on AV conduction. A dual-chamber permanent pacemaker was implanted and further studies were done with the patient’s consent. The pacemaker was reprogrammed to a demand rate of 30/min and AV interval of 200 ms. 7 mg apomorphine was given subcutaneously to