SCANNING ELECTRON MICROSCOPY OF RAT INTESTINAL VILLI

570 and has returned to non-pregnant levels some three to five days after delivery. This return to normal is presumably associated with the removal of the oestrogen effect, and the further rise in platelet-count seen after normal delivery, caesarean section, or gynaecological operations,5 is presumably due to the effects of tissue damage and represents a separate but overlapping mechanism. The work of this unit is supported by W.H.O., the Medical Research Council, the British Heart Foundation, and the Rockefeller Foundation. Cardiovascular Research Unit, Department of Medicine, Makerere University College Medical School,

A. G. SHAPER JILL KEAR.

Kampala, Uganda.

PROGESTERONE LEVEL AND RESPONSE TO OXYTOCIN AT TERM role of endogenous progesterone in the initiation SIR9 The of human labour is incompletely understood. In order to obtain information to

on

why women

at term

respond differently

oxytocin infusion, peripheral-plasma levels of progesterone

measured at the start of the infusion using the competitive protein-binding technique. 6-8 5 units of oxytocin (’ Syntocinon ’) in 500 ml. of 5-5% glucose solution was slowly

were

Since the difference in progesterone concentrations between the two groups is highly significant, it seems safe to conclude that patients at term with a low progesterone level in plasma can more rapidly be brought into labour with oxytocin infusion than those with a higher level of progesterone. Thus measurement of plasma-progesterone may be a valuable tool in selecting patients for the induction of labour with oxytocin. Department of Obstetrics and Gynæcology, University of Uppsala,

Uppsala, Sweden.

ELOF D. B.

JOHANSSON.

SCANNING ELECTRON MICROSCOPY OF RAT INTESTINAL VILLI SIR,-We have used the scanning electron microscope with success to study the villous pattern of the rat intestine and the surface of the individual villi. The aim of this investigation was to establish satisfactory methods of specimen preparation for use in subsequent studies of the human intestine. Short lengths of rat intestine were removed and opened longitudinally. The full thickness of the intestine was pinned out on stout cork sheet, the mucosal surface upwards. The specimens were pinned out under appropriate tension to overcome the distorting effect of smooth muscular contraction on excision. A brief wash in isotonic saline solution helped to

infused, starting with 4 drops per minute. So far sixty-one patients, 37-43 weeks pregnant, have been investigated. The progesterone level ranged between 68 and

Low-magnification scanning electron micrograph of

rat

intestinal

villi.

Strands of mucus remain in places. Irregular creases cobblestone pattern over the surface of each villus.

225 ng. per ml. which agrees well with that found

by other investigators.99 10 Twenty-two patients responded rapidly-i.e., regular contractions within 3 hours from the start of the oxytocin infusion. If the membranes were ruptured as well contractions started within 1 hour. Thirty-nine patients had a slow or no response. The results are shown in the figure. The mean progesterone concentration in the rapid-response group was 96 ng. per ml. (s.E. ±36) and in the slow-or-no-response group 140 ng. per ml. (s.E. ±4-6). 5. Shaper, A. G., Kear, J., Macintosh, D. M., Patel, I. J. Obstet. Gynœc. Br. Commonw. 1968, 75, 442. 6. Murphy, B. E. P. J. clin. Endocr. Metab. 1967, 27, 973. 7. Neill, J. D., Johansson, E.D.B., Datta, J. K., Knobil, E. ibid. p. 1167. 8. Johansson, E. D. B., Neill, J. D., Knobil, E. Endocrinology, 1968, 82, 143. 9. Short, R. V., Eton, B. J. Endocr. 1959, 18, 418. 10. Greig, M., Coyle, M. G., Copper, W., Walker, J. J. Obstet. Gynæc. Br. Commonw. 1962, 69, 772.

a

food debris and mucus. The specimens were then immersed in 2% glutaraldehyde in phosphate buffer for two to four hours. After a wash in buffer solution, the tissues were fixed for one hour in 0-5% aqueous osmium tetroxide and then washed in water. The specimens were dehydrated in a vacuum desiccator. In order to prevent distortion, the tissue was kept pinned on the original cork sheet during these procedures. Pieces of tissue about 5 mm. square were then cut and mounted with adhesive on specimen carriers. The surface of the tissue was coated with a conducting layer of carbonplatinum in a vacuum evaporating unit, using carbon-platinum pellets and a rotating stage set at an angle of 45°. The specimens were examined in the Cambridge Stereoscan’ scanning electron microscope at 2-10 kV. It was found that this technique for the examination of the intestinal mucosa produced satisfactory and reliable results. The pattern of leaf-shaped villi which is typical of the rat intestine was clearly demonstrated at low magnifications (see accompanying figure), and it was also possible to show surface features of individual villi. An irregular pattern of surface creases forming a cobblestone appearance could be seen covering the surface of each villus. At higher resolution the rough hexagonal pattern of cell-surface outlines could just be distinguished and the mouths of goblet cells could be observed. remove

Response (o rapid, 0 slow or none) of sixty-one patients, 37-43 weeks pregnant, to oxytocin infusion.

produce

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.