101 were

adjusted

200 000/pLl. 289 tests

300 000

to

were

carried

platelets/.1

out.

at

or,

times,

to

The results showed that the

platelet aggregation and platelet-release reaction was much stronger in both heparinised P.R.P. and citrated heparinised P.R.P. when compared with citrated P.R.P. In noradrenaline and collagen induced platelet aggregation, when heparin P.R.P. was used the aggregation was weaker than when

A.D.P.-induced

citrated

P.R.P.

was

studied.

However,

when

citrated

heparinised P.R.P. was used, platelet aggregation and release ability were increased. These studies show that heparin intensifies platelet aggregation and release. As a result, besides Ur’s explanation for the thromboembolic complications sometimes seen during heparin treatment the effects of heparin on platelets should also be considered. Department of Hæmatology, Clinic of Internal Medicine, Istanbul Medical

Faculty,

Çapa, Istanbul, Turkey

YÜKSEL

PEKÇELEN

SEREF INCEMAN

FERTILITY-RATES AFTER ORAL CONTRACEPTIVES Fig. 2-Theoretical improvement in separation of P.A.B.A. values in patients and controls after 2 g dose of tripeptide.

An alternative approach is to consider their data in terms of enzyme kinetics. If an enzyme is reacting under conditions first order with respect to enzyme, a doubling of the enzyme concentration will result in a doubling of the rate of the reaction and therefore of products formed per unit time. This will

continue until the substrate or some other factor becomes ratelimiting when the reaction-rate will become independent of enzyme concentration (zero order with respect to enzyme). It is possible that substrate exhaustion caused the overlap in P.A.B.A. excretion between the normal and diseased populations (fig. 1). If the situation for chymotrypsin activity is analogous to that for trypsin, doubling the amount of substrate present by increasing the dose of tripeptide in adults from lg to 2g should, on theoretical grounds, give a clear discrimination between the two populations (fig. 2). Alternatively, substrate exhaustion might be avoided if P.A.B.A. excretion were measured over a shorter period than the 8 h described. Department of Chemical Pathology, St. James’s University Hospital, Leeds LS9 7TF

J. G. SALWAY R. B. PAYNE

HEPARIN AND EMBOLISM

SIR,-Url has suggested that the apparently paradoxical of heparin occasionally inducing thrombosis is due to the post-heparin state of hypercoagulability. However, there are also reports which suggest that heparin induces increased pla2

event

telet aggregation. We have done some studies on blood from healthy individuals, using the turbidimetric method to establish the effect of heparin on platelet aggregation. In the in-vitro studies (n=40) heparin concentrations ranging from 0.125 to 100 units/ml were used in heparin platelet-rich plasma (P.R.P.), while in the citrated heparinised P.R.P. studies the heparin concentrations varied from 0 - 000to 100 units/ml. In the in-vivo studies (n=12), the volunteers were injected intravenously with 5000 units of heparin. Both direct and citrated blood-samples were examined 15 min later. The A.D.P. doses used ranged between 0-25 and 5 fLmol;1; the noradrenaline concentration was 12.5 fLmol/1; while the collagen was used both as such or diluted by half. The P.R.P.s 1. Ur, A. Lancet, 1976, i, 959. Zucker, M. B. Thromb. Diath. hœmorrh. 1974, 33, 63.

2.

Sttt; Janerich et al. identified a fertility-rate after discontinuation of the use of oral contraceptives that consistently followed an oscillatory pattern approximately four menstrual cycles in length.’ They advanced three hypotheses to explain this pattern. The first mechanism was a synchronisation of a previously unrecognised natural oscillatory cycle. We agree, but suggest that the well-known seasonal patterns of "heat" and fertility in polyoestric mammals2should be considered, especially since seasonal fluctuations in fertility-rate have been recognised in non-human primates4and in man. b-9 The human monthof-birth distribution consistently shows a major and a minor birth peak in winter and summer, respectively, and as a mirror image 6 months removed in the southern hemisphere. This two-peaked birth curve has been associated with a "basic animal rhythm"2 being present in man or with an "internal seasonal biological rhythm".7 An increase in conceptions together with normalisation of the ovulatory pattern and, in contrast, a decrease of conceptions together with an increase of the incidence of endometrial hyperplasia (i.e., anovulation’O) have been proposed as a basis for the understanding the two-peaked birth curve.*’ 12 This oscillatory natural rhythm of alternating periods of ovulation and anovulation was also the basis for the seasonal pre-ovulatory overripeness hypothesis, explaining the characteristic month-of-birth distribution of patients with congenital malformations and psychopathology. 11- 14 A second hypothesis proposed by Janerich et al.concerns possible infertile periods associated with early intrauterine has been recogmortality. However, a seasonal distribution nised for spontaneous abortions," 17 as well as for births, and 1. Janerich, D. T., Lawrence, D. E., Jacobson, H. I. Lancet, 1976, i, 1051. 2. Huntington, E. Season of Birth. London, 1938. 3. Steinbach, J., Balogun, A. A. Int. J. Biometeor. 1971, 15, 71. 4. Hartman, C. G. Contrib. Embryol. Carnegie Inst. 1932, 23, 38. 5. Nomura, T., Ohsawa, N., Tajima, Y., Tanaka, T., Kotera, S., Ando, A., Nigi, H. Acta endocr., Copenh. 1972, suppl. 166, 473. 6. van Eyk, H. H. Ned. T. Geneesk. 1904, 40, 1304. 7. Fitt, A. B. N.Z. Coun. educ. Res. Ser. 1941, no. 17. 8. Cowgill, U. M. Man, 1966, 1, 232. 9. Parkes, A. S. Eugen. Soc. Symp. 1968, 4, 128. 10. Timonen, S., Franzas, B., Wichmann, K. Ann. chir. gynœc. fenn. 1964, 53, 165. 11. Jongbloet, P. H. Clin. Genet. 1971, 2, 315. 12. Jongbloet, P. H. in Aging Gametes (International Symposium held in Seat13. 14.

tle, 1973); p. 300. Basle, 1975. P. H., Zwets, J. H. J. Int. J. Gynœc. Obstet. (in the press). P. H., Zwets, J. H. J., Holleman, G. Proc. 4th int. Congr.

Jongbloet, Jongbloet,

I.A.S.S.M.D. (in the press). 15. Belavalgidad, M. I. J. Obstet. Gynœc., India, 1963, 13, 23. 16. McDonald, A. D. Br. J. prev. soc. Med. 1971, 25, 222. 17. Sandahl, B. Acta obstet. gynœc. scand. 1974, 53, 251.

102 the the

corresponding conceptions seem to coincide with those of highest birth-rate. Therefore peaks in the conception curve may be expected to be levelled out, and the troughs are difficult

to

explain by excessive pregnancy wastage.

Thirdly, spontaneous intrauterine mortality after pill use is said not necessarily to imply a harmful after-effect. We do not agree with this statement because intrauterine loss seems to be only a small part of the "continuum of reproductive menstrual cycles after disconcasualty"." In fact in the first tinuing oral contraceptives18 19 a protraction of the pre-ovulatory phase has been noted.111-20 Therefore in these situations, an increased risk of pre-ovulatory overripeness and ensuing ovopathy can, theoretically, be expected." These aspects, we suggest, might be included in the clinical and laboratory studies we and Janerich et al. plead for. Huize "Marie Roepaan", Centre of Observation and Treatment of Mental Retardates, Ottersum (L.), Netherlands Institute of Human Free University,

P.

H. JONGBLOET

Genetics,

These data confirm the association of colitis with S. enteritidis infection; small-bowel changes appear less prominent. The possible role of an enterotoxin similar to those excreted by Vibrio cholerce and enteropathogenic Escherichia coli strainsz3 requires elucidation. Departments of Microbiology, Pædiatrics and Pathology, Faculty of Medicine, University of Natal, South Africa

P. C. APPELBAUM

J. SCRAGG M. M. SCHONLAND

SIR,-We are grateful to Dr Thomas and Mrs Tillett23 for drawing our attention to their interesting work,24 showing the frequency of dysenteric features in Salmonella infections, because it provides good indirect evidence in support of our view that colonic involvement occurs commonly in human salmonellosis.2 We have not, however, noted any special propensity for S. typhimurium to cause colonic involvement; approximately half of our colitic cases (9 out of 21) had S. typhimurium infection, "other salmonellas" accounting for the rest.

J. H. J. ZWETS

Amsterdam

Regional Department

of Infectious Diseases,

Monsall Hospital, Manchester 10

B. K. MANDAL V. MANI

COLONIC INVOLVEMENT IN SALMONELLOSIS

ANÆSTHESIA FOR SHORT-STAY SURGERY

SIR,-We read with interest the article by Mandal and Mani,21 and wish to confirm their findings. We have reviewed case-histories of 68 children from whom Salmonella enteritidis serotypes had been isolated from stools during life and who subsequently died and were examined post mortem. Most patients (87%) were in the first year of life. At death, nutritional status varied: 18 children were well nourished, 16 had suboptimal nutritional status, 24 were marasmic, and 10 had kwashiorkor. Various disease processes were evident at necropsy and macroscopic gut lesions were present in 46 cases:

SIR,-Prescott et al.26 conclude that atropine/droperidol premedication is preferable to atropine alone or atropine/diazepam in anaesthesia for major day surgery because it causes less nausea, headache, and pain postoperatively. In my study comparing different types of general anaesthesia in short-stay surgery27 patients were premedicated with atropine 0.1 mg/10kg and pethidine 1 mg/kg. The anaathetic technique in my halothane group (47 patients) seems to be similar to that used by Prescott et al. except that induction was done with propanidid (’Epontol’) instead of thiopentone. All patients were women being operated on for varicose veins with stripping and Trendelenburg. The patients stayed in hospital overnight. On the morning after surgery 7% complained of nausea, 2% of vomiting, and 8% of headache, frequencies which are less than those in the atropine/droperidol group reported on by Prescott et al. who recorded nausea in 19% and headache in 17%. In my study 15% of patients complained of dizziness and 2% of drowsiness. These different results may be due to the different premedications or on the differences between Finnish and Scottish populations. Furthermore the same anaesthetic techniques in different hands can give different results. When the effect of premedications is studied in short-stay surgery the patient groups should be as homogeneous as possible with regard to sex, age, and operation performed. The evaluation of recovery should be based not only on the occurrence of nausea, headache, and pain but also on other indices such as motor coordination and ability to concentrate. Few drug combinations for premedication have been compared so far. Droperidol is long-acting, and it affects motor coordination for at .least 10 h.28 Several other drug combinations should be studied before firm recommendations on premedication for short-stay surgery are made. A study of this kind is under way in the department of anuesthesiology, University of Helsinki.

No. 10 9

Necropsy findings Enterocolitis (E.C.) only E.c. E.C.

with marantic thrombosis with marantic thrombosis and

2 17 4

bronchopneumonia with bronchopneumonia E.c. with systemic candidiasis E.c.

with meningtis/pyelonepktritis/hepatic necrosis

E.c.

4

The 22 cases without macroscopic evidence of gut lesions died of a miscellany of diseases including bronchopneumonia, meningitis, non-specific liver necrosis, cirrhosis, tuberculosis, and cerebral abscess. Macroscopic examination of the bowel at necropsy revealed lesions in small and large intestine in 30 (44%), colonic lesions only in 9 (13%), and small-intestinal lesions in 7 (10%) cases. A variety of macroscopic lesions was found, including mucosal hyperaemia and oedema, superficial haemorrhage and ulceration, and lymphoid hyperplasia. The small bowel was occasionally dilated, and 2 cases showed pneumatosis coli. Histological examination of the bowel was undertaken in 23 cases. Large-bowel sections were reviewed in 16, small bowel in 5, and in the remainder both were available. Superficial ulceration with a predominantly mononuclear-cell infiltration was a feature in 9 colonic sections. In 3 of these the ulceration extended deep into the muscularis mucosae, and in 1 signs of peritonitis were present. More commonly, changes were less specific, especially in the small bowel; these included hypersemia and oedema (7) and lymphoid hyperplasia (4); in 5 cases the histological picture was normal. 18. Larsson-Cohn, U. ibid. 1969, 48, 416. 19. Homesley, H. D., Goss, D. A. Obstet. Gynœc. 1970, 35, 734. 20. Girotti, M. Ovulationshemmer und Reproduktive Funktion. Bern, 1975. 21 Mandal, B. K., Mani, V. Lancet, 1976, i, 887. 22. Kantor, H. S. J. infect. Dis. 1975, 131, suppl.

S22.

Department of Anæsthesiology, Meilahti University Central Hospital, 00290 Helsinki 29, Finland

ULLA AROMAA

Thomas, M., Tillett, H. Lancet, 1976, i, 1129. Thomas, M., Mogford, H. E. J. Hyg, Camb. 1970, 68, 663. Mandal, B. K., Mani, V. Lancet, 1976, i, 887. Prescott, R. J., Espley, A. J., Davie, I. T., Slawson, K. B., Ruckley, C Lancet, 1976, i, 1148. 27. Aromaa, U. Ann. Chir. Gynœc. fenn. 1974, suppl. 187, p. 63. 28. Korttila, K., Linnoila, M. Br. J. Anœsth. 1974, 46, 961.

23. 24. 25. 26.

Letter: Fertility-rates after oral contraceptives.

101 were adjusted 200 000/pLl. 289 tests 300 000 to were carried platelets/.1 out. at or, times, to The results showed that the platelet...
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