1218

petitive protein-binding assays for cortisol, it is possible to startimmediately with treatment while awaiting the results of

laboratory diagnosis, which is usually performed within a fewhours. If human or rabbit diluted plasma is used as a sourceof transcortin it is possible to administer intravenously injec-table salts of some potent synthetic glucocorticoids-i.e., dexa-methasone, betamethasone, or 6-methylprednisolone; unlikeprednisolone, these steroids do not interfere with the cortisolassay, since they do not show appreciable affinity for the bind-ing protein.2 8 9

Clinica Medica II,Università degli Studi,Via Genova 3,10126 Torino,Italy,

ALBERTO ANGELIROBERTO FRAJRIA

SEPTICÆMIA DUE TO PORCINE STREPTOCOCCI

SIR Attention has lately been drawn to the pathogenicityof the porcine streptococcus, Strep. subacidus (Lancefieldgroup R) in man.’ 15 cases of human infection have beenrecorded, and it is remarkable that all well-documented reportshave come from the Netherlandsl 2and Denmark3 4 and that

nearly all patients had a purulent meningitis. However, wehave observed a patient with a clinical picture of severe sep-ticaemia without signs of meningitis.The patient was a 24-year-old woman, who was working in a

butcher’s shop. 3 days after injuring her right forefinger with the boneof a pork chop, she suddenly felt ill with chills, vomiting, anddiarrhoea. About 12 hours later she became hypotensive, and largeconfluent haemorrhagic areas developed on upper and lower limbs. Shecomplained of extreme pain in both feet. On arrival in our hospital shewas in shock. Body-temperature was 38.5°C. Her feet were painfuland showed acrocyanosis. The injury of the right forefinger was in-fected. Leucocytosis of 24 OOO/mm3 with 34% bandforms was present.Although the clinical picture resembled the Waterhouse-Friedrichsensyndrome, the neurologist did not find any symptom of meningitis.Strep. subacidus (Lancefield group R) was cultured from the bloodand the infected injury. She recovered after treatment with high dosesof penicillin and corticosteroids. Unfortunately necrosis of the distalphalanges of all toes developed during the first week of observation,and signs of demarcation were visible on discharge.

As mentioned by Zanen and Engel,’ it seems unlikey thatsuch infections with porcine streptococci are confined to Den-mark and Holland. We wish to call attention again to this in-fection emphasising, in particular, that meningitis is not

always present.University Hospital,Groningen, The Netherlands.

M. KLOPPENBURGN. H. MULDER

J. HOUWERZIJL

TYPE-IV HYPERLIPIDÆMIA

SIR,-In the article by Professor Blacket and others (Sept.20, p. 517) I find the statistical analysis both inadequate andfallacious. The authors show the reduction in weight of the 20men in their sample to be statistically significant (p<0.001).Likewise, the reduction in the serum-triglyceride level for thesemen is also statistically significant (p<0.001). Ergo, theydeduce that the way to reduce hypertriglyceridsemia for menwith type-iv hyperlipidaemia is to reduce their weight. How-ever, from their evidence, weight reduction will work only inan incidental way, provided that the conditions of theirexperiment, such as the reduction in sugar consumption, arealso taking place. Weight reduction is only incidental because

8. Peets, E. A., Staub, M., Symchowitz, S. Biochem. Pharmac. 1969, 18, 1655.9. Sandberg, A. A., Slaunwhite, W. R., Jr. in Human Adrenal Cortex (edited

by N. P. Christy); p. 69. New York and London, 1971.

1. Zanen, H. C., Engel, H. W. B. Lancet, 1975, i, 1286.2. Zanen, H. C. Ned. Tijdschr. Geneesk. 1970, 114, 1660.3 Perch, B., Kristjansen, P., Skadhauge, Kn. Acta path. microbiol scand

1968, 74, 69.4 Koldjaer, O., Nielsen, G Br. med. J. 1972, ii, 765.

the coefficient of determination (R2) between change in body-weight and change in serum-triglyceride level is less than 0.04.

Blacket et al. suggest that a larger sample size may producea statistically significant relationship between these two vari-ables. However, given their earlier cited evidence of a signifi-cant reduction in weight and an equally significant reductionin triglyceride level, a sample size of 20 is certainly sufficientfor statistical inference. Thus, the probability of obtaining astatistically significant relationship by increasing the samplesize is virtually nil. In effect, what this means is that the trigly-ceride level went down significantly, not because weight alsowent down significantly, but for one or more other reasons.These reasons cannot be deduced from the published data, butprobably could be determined from a proper multivariateanalysis of the underlying data on individual patients.68 Princeton Arms South,Cranbury,New Jersey 08512, U.S.A. ELLIOT WETZLER

TREATMENT OF WILSON’S DISEASE

SIR,-Following reports that triethylene tetramine dihyd-rochloride (T.E.T.A.) is a useful, orally active chelating agent inWilson’s disease, 1 2 we had occasion to study this drug in acase of Wilson’s disease. We used a modified method forT.E.T.A. preparation which we believe has some advantages.

100 g of triethylene tetramine (practical grade ’Fluka’ wasdissolved in 200 ml of 95% ethanol and cooled in an ice/salt-bath. To this was added 135 g of concentrated hydrochloricacid (lOmol/1, 37%), 120 drops/min, with continuous stirring.The solvent was evaporated and 500 ml of absolute ethanolwas added to the residual thick syrup. The suspension was re-fluxed for 15 min and filtered leaving 16 g of a crystalline resi-due, the main component of which had the same melting pointas 2,2’, 2"-triaminotriethylene trihydrochloride.3 We added500 ml of absolute ethanol to the filtrate and stood the result-

ing solution in the refrigerator for 48 hours. The crystalsformed were filtered and dried at 50&deg;C. Thin-layer chromato-graphy of the product showed two spots, but after two recrys-tallisations from 95% ethanol only one could be detected. Theproduct had a melting point of 120-122C (when impure thiswas 115-118&deg;C 4) and the yield was 64 g. This material wasmade into 100 mg capsules. T.E.T.A. is a white crystalline sulrstance with a characteristic odour. It is soluble in water (60%w/v at 20&deg;C) and 1% w/v aqueous solution has a pH of about7. T.E.T.A. has been reported to be extremely hygroscopic,requiring a desiccator for storage,4 however, the method ofpreparation reported here gives a non-hygroscopic, pure pro-duct which is stable at room temperature if kept in the dark.Our limited experience confirms reports that T.E.T.A. is an activecopper-chelating agent, which can, as far as we know, be safelyadministered orally in and may be used for patients with Wil-son’s disease who are intolerant of D-penicillamine.Department of Internal Medicine,Hospital Pharmacy, University Hospital,Lund, Sweden.

IONEL BUCURKARL HENRIK HASSELGREN

SEX OF HUMAN ZYGOTES

Dr W. H. JAMFS (Galton Laboratory, University College, LondonWC1) writes: "Information is required on a hypothesis concerning thesex of human zygotes. For this purpose, will anyone with data on thesex of any monoamniotic twin pairs please communicate with me."

1. Walshe, J. M. Lancet, 1969, ii, 1401.2. Dubois, R. S., Rodgerson, D. O., Slovis, T. L., Hambidge, K M., Bianchi,

T. A. ibid. 1970, ii, 7753. Mann, F. G., Pope, W. J. Proc. R. Soc. A, 1925, 444, 109.4. Dixon, H. B. F., Gibbs, K., Walshe, J. M. Lancet, 1972, i, 853