potential forms of bundle-branch block
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Pyrophosphatase activity of human leucocyte and rat bone at pHvalues between 75 and 105.
phosphomonoesterase activity at pH 8-5. The exception is ahighly purified HeLa (Ch)-cell-line enzyme which, at this pH,is much more active as a pyrophosphatase than as a phospho-monoesterase. Omitting magnesium ions from the substratereduced the pyrophosphatase activity by 20 to 25%. Underthe same conditions phosphomonoesterase activity is decreasedby over 50%. The accompanying figure shows the pyro-phosphatase activity of human leucocyte and rat bone at
different pH values. These enzymes have a wide optimum pHwith a peak at about pH 85.These results indicate that several partially purified, and two
highly purified, mammalian alkaline phosphatase preparationsare also pyrophosphatases. Furthermore, the pyrophosphataseactivity has an optimum pH between 8 and 9 which ismuch closer to physiological pH than the optimum of 10-5for phosphomonoesterase activity. These findings supportMr. Russell’s suggestions that human alkaline phosphatase is apyrophosphatase and that PPi may be a natural substrate for thisenzyme. Fleisch and his collaborators have found that PPj isan inhibitor of calcium precipitation in vitro and that it alsoprevents mineralisation of chick-embryo femurs grown in tissueculture.9 10 The excretion of pyrophosphate is increased indiseases in which bone resorption is accelerated.ll Since PPj isable to combine with calcium, its hydrolysis by alkaline
phosphatase may be required for mineralisation of bone.This work was supported by research contract U-1296 of the
Health Research Council of the City of New York, and geneticstraining grant no. 5 Tl HE 5307 of the United States Public HealthService. M. J. G.’s present address is the Department of CancerResearch, University of Oklahoma School of Medicine, OklahomaCitv. Oklahoma.
BODY P. COXMARTIN J. GRIFFIN.
Department of Medicine,New York University Medical Center,
New York, New York 10016.
"DRAINAGE OPERATIONS "
SIR,-What does the fashionable phrase, " drainage opera-tion ", mean ? Those who use it appear to think of the stomachas though it were suspended in air. In fact it is contained in a
cavity which behaves as though filled with water.If a stomach be immersed in a bucket of water, and then
itself filled with water until the levels inside and outside are thesame, there is no tendency for water to escape through the openpylorus. Only pressure on the gastric side of the pylorus higherthan that on the duodenal side can cause material to passthrough, however wide open the pylorus may be.As might be expected, in the intact animal holding open the
pylorus delays emptying,i2for the pylorus normally acts as a non-return valve during duodenal cap " systole ". I do not denythat the gastric retention which is apt to follow division of the9. Fleisch, H., Newman, W. L. Am. J. Physiol. 1961, 200, 1296.
10. Fleisch, H., Schibler, D., Maerki, J., Fossard, I. Helv. physiol. pharmac.Acta, 1964, 22, C119.
11. Avioli, L. V., MacDonald, J. E., Singer, R. A. J. clin. Endocr. Metab.1965, 25, 912.
12. Crider, J. O., Thomas, J. E. Am. J. dig. Dis. 1937, 4, 295.
vagi is often relieved by pyloroplasty, but I suggest that this ismost probably because the circular muscle of the duodenumhas also been divided. The level of pressure here, whichpreviously prevented material from leaving the stomach, isthus decreased. It should be no surprise to find that pyloro-plasty does not always work, or that the stomach does notalways empty properly after gastroenterostomy. But it mustbe a great surprise to one who thinks in terms of
" drainageoperations ".
H. DAINTREE JOHNSON.
Department ofExperimental Surgery,
Postgraduate Medical School,London, W.12.
CRAMP
SIR,-For many years I have prescribed 10-20 minims
(0-6-1-2 ml.) of tincture of chloroform and morphine B.P.C.(double the pharmacopoeial dose) in a mixture to be taken atbedtime, and I am satisfied that an entirely cramp-free night hasinvariably followed. Elderly folk and expectant mothers alikehave testified to the efficacy of this remedy.
P. R. BOUCHER.
Winfrith,near Dochester,
Dorset.
POTENTIAL FORMS OF BUNDLE-BRANCH BLOCK
SIR, The electrocardiographic (E.C.G.) aspects of bundle-branch block (B.B.B.) have a double interest: (1) from the staticpoint of view, in their relation to heart-pathology 1 in general,and to specific heart-diseases in particular 2; and (2) from thepotential point of view, in their evolution and fate. With
regard to (2), there is conflicting evidence that partial orcomplete regression, with or without treatment, is possible,3as is exacerbation to more severe B.B.B. or to complete atrio-ventricular (A.v.) block.2-4 Are there, in fact, two differentkinds of block, one regressing, and the other exacerbating ?And from the practical point of view, is there any possibility offoreseeing those blocks which progress to the complete A.v.block, with its serious prognostic and therapeutic implications ?5From a large series of heart patients 2 we found 94 E.c.G.s,
half of which showed the new appearance of B.B.B. (fromprevious normal tracings), and the other half of which showedthe evolution of pre-existing B.B.B.s (18 regressions and 29exacerbations). Thus the overall exacerbation-rate (76/94) wassignificantly dominant (p < 00001) to the observed regression-rate (18/94). Among pre-existing cases of B.B.B., exacerbationwas significantly greater (P < 0-002) for incomplete (19/20) thanfor complete (10/27) B.B.B.s. Final analysis of the above casesshows that in complete forms of B.B.B. regression was morefrequent for left B.B.B. (10/13) than for right B.B.B. (7/14),though the difference does not attain the significance level(p > 0-2)-probably because of the smallness of these numbers.But grouping the microscopic findings of Lenegre,i we can
construct a contingency table of the likelihood of completeB.B.B., as shown by E.C.G., involving the contralateral bundlemicroscopically, as follows:
This shows that right B.B.B., as shown by E.C.G., is at least 3times more frequently associated with bilateral branch lesionsthan is left B.B.B., a finding which is extremely significant(P< 00001), and which is corroborated by clinical evidenceelsewhere.4Thus we can draw the following conclusions: (a) B.B.B.s
nearly always have some underlying microscopic evolutionaryprocess, and the observed E.C.G. regressions can well be
1. Lenègre, J. Archs Mal. Cœur, 1957, suppl. 1.2. Papazoglou, N., Maurice, P., Lenègre, J. ibid. 1965, 58, 56.3. Bauer, G. E. Br. Heart J. 1964, 26, 167.4. Blondeau, M., Lenèrge, J. Archs Mal. Cœur, 1964, 57, 1.5. Bluestone, R., Davies, G., Harris, A., Leatham, A., Siddons, H. Lancet,
Aug. 14, 1965, p. 307.
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explained as the temporary facilitation of conduction in acritical healthy zone of the bundles, as a result of variousfactors 2; (b) complete right B.B.B. is significantly more liablethan is left B.B.B. to progress to complete A.v. block, whichnearly always means bilateral blockade.6A prospective study on this subject would help to form a
more precise judgment of these problems.NICHOLAS M. PAPAZOGLOU.
Hippocrateion Hospital,Athens 139, Greece.
SILVER-SHADOWING AND SATELLITED
CHROMOSOMES
SIR,-Cooper and Hirschhorn pointed out that techniquesfor displaying the tiniest satellites were barely adequate, andthat " non-satellited " acrocentric chromosomes might actuallybear satellites whose size was below the power of resolution.Since that time little or no advance has been made in increasingthe resolving power with regard to the smaller satellites. Withregard to larger satellites it is desirable to demonstrate, as faras possible, the exact structure of these bodies. Giant satellitesare important as a marker to distinguish one member of achromosome pair from its homologous partner in order todetermine the parental source of a chromosome.8 Further, inthe study of a condition such as Marfan’s syndrome where the
Portion of metaphase plate shadowed with silver.Satellites are indicated by the arrow.
exact relation between syndrome and giant satellites is not yetclear, more exact details of the appearances of giant satellitesmay be of value.
It has been found that normal chromosome satellites cansometimes be better visualised by silver-shadowing 9 than byconventional techniques alone (see accompanying figure). Therehas not yet been an opportunity for examining giant satellites,but it is hoped that silver-shadowing may be of value in
providing more exact details of their structure.Silver-shadowing can be performed after routine chromo-
somal examination of slides provided that the chromosomes arespread by air-drying, and that they are not overlaid by a cover-slip. It is essential that all traces of immersion oil be removedwith xylol before silver-shadowing. Structural definition ofsatellites is dependent on a number of factors, including theconfiguration of the chromosomes, position of chromosomes inrelation to the source of silver, and the amount and angle ofsilver deposited.
I should like to thank Mr. D. L. Allinson and Mr. R. J. Caveneyfor silver-shadowing the slide from which the photograph wasmade. This study was supported by a Witwatersrand UniversityCouncil research grant.
C. WALLACE.
Department of Pathology and Microbiology,Division of Chemical Pathology,
Medical School,Witwatersrand University,Johannesburg, South Africa.
6. Lenègre, J. Malatt. cardiovasc. 1962, 3, 311.7. Cooper, H. L., Hirschhorn, K. Am. J. hum. Genet. 1962, 14, 107.8. Handmaker, S. D. ibid. 1963, 15, 11.9. Wallace, C., Allinson, D. L. S. Afr. J. med. Sci. 1964, 29, 53.
CYTOGENETIC FINDINGS IN
BLACKFAN-DIAMOND SYNDROME
SIR,-A 14-year-old boy in our clinical research centre
underwent complete hasmatological investigation, includingbone-marrow examinations, "Cr-labelled red-cell survivalstudies, and ferrokinetic studies. The findings were diagnosticof a pure red-cell aplasia (chronic erythroid hypoplasia). Thepatient, in addition, has hypocalcoemia. At present we cannotdetermine whether this is idiopathic hypoparathyroidism orpseudo-hypoparathyroidism.
Cytogenetic studies of 5 spaced peripheral-blood cultures and1 direct bone-marrow culture revealed a persistent distalchromatid lesion on the short arm of one member in chromo-some pair A-1. At least fifty intact metaphase plates werescored from each culture. The frequency in each peripheral-blood culture was 16%, and the bone-marrow culture displayedthe same lesion in 30% of the cells scored. Control cultureshad no quantitative or qualitative chromosomal aberrations.The patient’s past history rules out irradiation as a contributorycause of the achromatic area.There are no published reports of this kind of chromosomal
abnormality in patients with this disorder. Since this is thefirst report of such a finding, it is impossible to link the chromo-somal abnormality with the clinical syndrome. We should begrateful for any information about similar cases from otherworkers.
Haematological, cytogenetic, and endocrine details of thiscase will be published elsewhere.Department of Obstetrics and
ANTHONY P. AMAROSE.Gynecology, ANTHONY P. AMAROSE.
Department of Medicine, ANTHONY P. TARTAGLIA.
Sub-department of Hæmatology, SIMON PROPP.
Albany Medical College,Albany, New York 12208.
EFFECT OF HEAT AND DIMETHYL SULPHOXIDE
ON NORMAL AND LEUKÆMIC LYMPHOCYTES
SIR,—I have found that both heat and dimethyl sulphoxide(D.M.S.O.) are more toxic to leukaemic than to normal lympho-cytes.
Purified suspensions of lymphocytes were prepared from theblood of patients with chronic lymphocytic leukaemia and ofnormal individuals. After addition of D.M.S.O. or after exposureto 45°, 47°, or 50°C, the suspensions were incubated at 37°C.The number of viable lymphocytes in the treated and untreatedsuspensions were counted and the % effect was calculated.The methods have already been described in detail.l
Exposure to 45°C for 20 minutes or to 50°C for 1½ minutesand incubation at 37°C for 7 days produced a slight to moderatetoxic effect on normal lymphocytes and a greater effect onleukæmic lymphocytes (see accompanying table).
SENSITIVITY OF LYMPHOCYTES TO HEAT AND D.M.S.O.
* Number of persons tested in parentheses.
After 7 days’ incubation, D.M.S.O. (2%) had killed 26% ofthe normal lymphocytes but almost all the leukasmic lympho-cytes. The table shows that there is little or no overlap in thefrequency distributions of the ’?:, effects produced by D.M.s.O.on normal and leukæmic lymphocytes.
In contrast to these two reagents, X-irradiation and nitrogenmustard produced, on average, approximately the same cyto-toxic effect on normal and leukæmic lymphocytes.2
1. Schrek, R. J. natn. Cancer Inst. 1964, 33, 837.2. Schrek, R., Friedman, I. A., Leithold, S. L. ibid. 1958, 20, 1037.