1324 shown no formation of fibrin and nsures.
Department of Pædiatrics, Hokkaido University Hospital,
Sapporo, Hokkaido, Japan.
a
good spread of mitotic TADASHI KAJII TOSHIO IMAI TAKEMI HOMMA KIYOSHI OIKAWA.
CHROMOSOMES OF AMNIOTIC-FLUID CELLS
SIR,-Iread with great interest Dr. Steele and Dr. Breg’s article (Feb. 19). I have been doing sex-chromatin determinations on amniotic fluid from amniocenteses performed because of Rh-incompatibility, and have predicted the sex correctly in all 10 patients studied to date. In contrast to Dr. Steele and Dr. Breg I found 0% chromatin in male infants. I feel, with Patou, that no chromatin should be present in males. I have determined sex chromatin as early as 28 weeks. I should like to comment on the need for immediate fixation of amniocentesis cells. By suspending them for a whole week in their own media I have been able to determine with accuracy the sex chromatin. Once smears are made, however, they are placed immediately in 95% alcohol. The only precaution I advise if immediate fixation is impossible is to refrigerate the amniocentesis fluid. The practicality of this procedure is especially of interest for genetic counselling. Cytogenetics Laboratory, St. Albans Naval Hospital, St. Albans, New York. JAMES J. LA POLLA.
as Hartman’s, should be used: if the patient is normotensive, hypotonic half-strength Hartman’s solution
solution, such
should be used; if hypotensive, an initial 1-2 litres of fullstrength solution may be indicated. Each case must be treated on its merits however. If, for instance, the blood-sugar level after insulin therapy falls precipitately, the fluid which was osmotically held in the extracellular space can pass so rapidly into the intracellular space as to dehydrate the extracellular space and cause hypotension. In such instances, 5% dextrose solution is indicated to slow down the rate of fall of the bloodsugar and provide water for the intracellular compartment. Thus the article of Dr. Halmos and his colleagues contains a point, in that 5% dextrose solution has a role in the early treatment of diabetic coma, but it is unfortunate that they have taken uo such an extreme oosition. Pathology Department, Worthing Hospital,
J. E. TOVEY.
Sussex.
CARDIOGENIC SHOCK SIR,-I have read with interest the series of papers on this subject and on surgical shock,! but I am surprised that you and your contributors make no attempt to estimate the cardiac output and the effect on this of the therapeutic measures described. Dye-dilution techniques are now simplified to a point where they can be used at the bed-side, especially in an intensive care unit, but even simpler is measurement of the arterial-venous (A.v.) oxygen difference. This is done here by sampling from a vena-caval catheter introduced percutaneously via the subclavian vein. An arterial puncture is also done, and RADIATION AND MONGOLISM the blood is analysed for oxygen in a Van Slyke apparatus or a SiR,ŁYour annotation (Jan. 22) on radiation exposure of hxmo-reflector. The same caval catheter is used to read the parents of mongol children was most interesting. Chromosomal central venous pressure (c.v.p.) and for transfusion purposes. abnormalities can be caused by a number of other agents, such Wilson2 has reported a series of patients, with shock due to a as natural radiation, urethane, nitrogen mustards, radioactive variety of causes, who were intensively studied with the above isotopes, and colchicine. Of the therapeutic agents colchicine techniques. His paper repays careful study. Having classified has by far the most venerable history, having been used in shock according to the primary physiological derangement, therapeutics since at least the sixth century A.D., and specifically hypovolsmia, cardiac insufficiency, and vasomotor collapse, for gout since 1763.1 It could have been causing reduplication Wilson indicates how each can be diagnosed and treated, thus of chromosomes in man for all this time. providing a basis for rational therapy. He stresses that knowing Colchicine causes failure of mitosis at the metaphase by the aetiology is inadequate for making a physiological diagnosis. damage to the spindle. It is known to be effective in man, for Thus in cardiogenic shock there will usually be cardiac it is used in the technique for counting chromosomes. It is insufficiency-i.e., a low cardiac output as shown by a wide actually used in horticulture for this very purpose of reduplica- A.v. oxygen difference-but there may also be hypovolxmia tion of chromosomes to produce new cultivars from seeds such as Dr. Nixon and his colleagues (May 14) found in their grown from shoots on which colchicine has been painted.2 In three cases, as shown by response to rapid infusion of a volume medicine colchicine is used less now than formerly, but it still expander. But to conclude that this is always present and has a place in the treatment of gout, and less specifically of would be benefited by dextran infusion would be dangerous. rheumatism-Eade’s gout and rheumatic pill contains roughly In the two cases of myocardial infarction in Wilson’s series the 1 mg. of colchicine. Do gouty parents produce more mongol c.v.p., despite its low level, was raised by 4 cm. of water by and other offspring with reduplication of chromosomes than rapid infusion, while the cardiac output actually fell. In these the average parents ? Slugs are avid devourers of colchicum and other cases Wilson has observed a rise in blood-pressure bulbs and weakly colchicum leaves. Are slugs’ chromosomes (B.P.) after rapid infusion, with a fall in cardiac output, which affected ? also stresses the importance of measuring this index. St. Peter’s Hospital, The policy here at present therefore is to watch the general J. S. PHILLPOTTS. Chertsey, Surrey. condition of the patient, the pulse, and the urine output, but to rely mainly on measurement of B.P., c.v.P., and mixed venous oxygen-saturation, and then to observe the effect on these of a rapid infusion of 250 ml. 5% dextrose solution, and HYPEROSMOLAR COMA IN DIABETES of adrenaline or other cardiac stimulant, or of noradrenaline or SIR,-Many letters have appeared in your correspondence other vasoconstrictor, according to the type of shock which we columns criticising Dr. Halmos and his colleagues (March 26) think to be present. A recent case of cardiogenic shock for administering 5% dextrose solution to diabetics in hyperillustrates this. osmolar coma. The alternative suggested by most criticsA man of 55 years admitted on April 5, 1966, diagnosed as saline solution-also has its disadvantage. Saline is an unhad a myocardial infarct, sustained a second attack on a having excess of solution pronounced containing physiological chloride; unless this excess is counterbalanced with 1/6 M April 16, and collapsed with typical signs of cardiogenic shock. He was treated for 12 hours with noradrenaline infusion and sodium lactate or excreted by the kidneys, which is unlikely in a dehydrated diabetic, the risk of hyperchlorsemic acidosis is oxygen with no improvement, his B.P. dropping from 100/80 I of a instead more saline, high. May suggest that, physiological mm. Hg until it was unrecordable. He was anuric for this time. 1.
2.
Goodman, L. S., Gilman, A. G. Pharmacological Basis of Therapeutics; p. 339. London, 1965. Polunin, O., Huxley, A. Flowers of the Mediterranean; p. 208. London, 1965.
1.
McGowan, G. K., Walters, G. Lancet, March 19, 1966, p. 611; ibid. p. 645; Nixon, P. G. F., Ikram, H., Morton, S. ibid. May 14, 1966,
2.
Wilson, J.
p. 1077; ibid. p. 1085. N. Archs
Surg., Chicago, 1965, 91, 92.
1325 LEUCOCYTES IN RHEUMATOID ARTHRITIS SIR,-" Rheumatoid factor appears to be made in plasma cells in the rheumatoid synovial membrane. There is evidence that leucocytes in the synovial fluid phagocytize complexes of rheumatoid factor and 7S gamma-globulin that have formed in the fluid. Specific granules (lysosomes) in the leucocytes appear to coalesce around these intercellular aggregates, presumably to digest them." 1 The first descriptions of these inclusions have been published in the past two years. Delbarre et al. have called them ragocytes, and Hollander et al.3 R.A. cells. Vacuoles in synovial leucocytes have been described by one of 4 us in stained smears; these vacuoles could correspond, by
A caval catheter was then inserted and the c.v.p. was found tc be +19 cm. of water. Even on oxygen (nasal catheter) his peripheral shut-down was such that his lips and tongue appearec cyanosed, but a femoral-artery sample was found to be 100°c saturated with oxygen. Acidosis was suspected, and the patien1 was given 200 ml. 8-4% sodium bicarbonate solution rapidly; 3C minutes later the standard bicarbonate level was found to be still only 18 (normal 24) mEq. per litre, pH 7-30 units, and Pco, 36 mm. Hg. His condition improved slightly after correcting the acidosis, and c.v.p. fell to 15 cm. of water, but the B.P. remained unrecordable. The oxygen difference was found to be 7-5 (normal about 4) ml. per 100 ml., indicating a low cardiac output. Adrenaline was then given very slowly by adding 5 ml. 0-1% adrenaline to 500 ml. 5%dextrose solution (1 bottle in 6 hours). This rapidly resulted in improvement in his general condition in the next hour. He became less restless, the skin became dry, B.P. rose to 120/90, c.v.o. fell to 9 cm., and the central venous oxygen saturation rose. Attempts to stop the adrenaline at first resulted in rapid return to the previous condition with rise in c.v.p. and fall of B.P. and central venous oxygen saturation, but after 4 days it was possible to stop the drip. He made an uneventful recovery and was discharged on May 6. In this patient a cardiac stimulant with fluid restriction seemed to be the treatment of choice, but I wish to make the plea that at this stage rather than search for a single panacea for all cases of cardiogenic or any other variety of shock we should try to match the treatment to the individual patient’s need, as revealed by these fairly simple observations. Department of Thoracic Surgery, Christian Medical College and Hospital, Vellore, South India.
JAMES S. MILLEDGE.
PLASMA-AMINOACIDS IN KWASHIORKOR
SIR,-I have read with great interest the letter (May 21) from the workers in Professor Hansen’s department on their carefully carried-out investigations into plasma-aminoacid ratios. Reasons were suggested why South African children with kwashiorkor did not show the aminoacid pattern found in Uganda. This raises an important point-it is obvious that malnourished (or undernourished) children can be given the same clinical diagnosis, though they exhibit different metabolic abnormalities. This problem has been under investigation in the M.R.C. metabolic unit in Uganda. In uncomplicated kwashiorkor the aminoacid ratio is always above 4-0, the hydroxyproline index1 below 1-5, and the serum-protein below 5-5 g. per 100 ml. In marasmus the ratio is below 3-0, the index below 1-5, and the serum-protein above 5-5 g. per 100 ml. From a combination of these three tests a differential diagnosis between protein malnutrition and total-calorie undernutrition is possible. In protein-malnourished children in whom the clinical abnormalities seem to be of acute rather than chronic origin the biochemical picture is not the same-for example, the hydroxyproline index is only slightly reduced. Details of this and other biochemical differences will be published
shortly. Many malnourished children studied
their number and localisa-
tion,
to
granular inclusions
in unstained smears. In the study we report here, exudates from 28 joints of 26 patients with rheumatoid arthritis were investigated by unstained smears, and all contained leucocytes with inclusions (fig. 1). There was no case with inclusions among 3 other rheumatic patients with 5 ioints investigated. We have also found that our from patients contained inclusions similar to those in synovial leucocytes (fig. 2). Out of 54 patients with rheumatoid arthritis, 53 had inclusions in their urine leucocytes; these were found in only 6 of a control group of 68 normal persons or patients with other rheumatic conditions. It is clear that the source of leucocytes in urine can only be blood, in agreement with the findings of Astorga and Bollet5 of granular inclusions in blood-leucocytes from rheumatic patients, mainly with rheumatoid arthritis. It would be of great advantage to use such an accessible biological material as urine for diagnostic purposes, especially in patients without joint effusions. Further investigations, including serological studies,are in progress.
leucocytes
We thank Dr. M.
urine of
Chyle for preparing the figures.
Research Institute of Rheumatology, Na Slupi 4, Prague 2, Czechoslovakia.
O. VOJTÍŠEK S. HAVELKA P. VILÍMEK.
in metabolic wards
have additional abnormalities which can modify the typical biochemical pattern: these may be intercurrent infections,
infestations of
in the intestine, mineral and vitamin (as in the South African children) a period of acute starvation before admission. It seems probable that these and other superimposed factors are the cause of much of the controversy which confuses constructive thought in the nutri-
deficiencies,
worms
or
tional sciences. Professor Hansen and his colleagues are their objective approach to this problem. M.R.C. Infantile Malnutrition Research Unit, Mulago Hospital,
Kampala, Uganda. 1.
to
be thanked for
7S AND 19S DERMATOTOXIC GLOBULINS SIR,-By immunising rabbits to guineapig-skin-saline suspension we obtained antisera (dermatotoxic sera) which elicited skin reactions (dermatotoxic dermatitis) in other guineapigs. The rabbit antisera against guineapig kidney possessed similar 1. 2. 3.
R. G. WHITEHEAD.
Whitehead, R. G. Lancet, 1965, ii,
567.
4. 5. 6.
Hamerman, D., Barland, P. Bull. rheum. Dis. 1966, 16, 396. Delbarre, F., Kahan, A., Amor, B., Krassinine, G. Presse med. 1964, 72, 2129. Hollander, J. E., McCarty, D. J., Jr., Astorga, G., Castro-Murillo, E. Ann. intern. Med. 1965, 62, 271. Vojtí&sbreve;ek, O. Z. Rheumaforsch. 1963, 23, 23. Astorga, G., Bollet, A. J. Arthritis Rheum. 1965, 8, 511. Havelka, S., Kalvodová, D., Neuzil, A. Unpublished.