190

euphemism for strike. Without waiting to see the effects of last fall’s State legislation which, among other things, sharply restricted the rights of patient-claimants in medical malpractice

once to the steep rise in malpractice insurance premiums. It was up to the State government, they asserted, to rescue them--and, of course, their patients-from the new burdens.

Letters

to

the Editor

cases, the doctors decided to react at

(400%)

Before January was ten days old, the young Governor of California, a former Jesuit seminarian and no admirer of riders on the gravy train, responded. He charged that: "The doctors are the ones committing malpractice. It isn’t anybody else. Under our system of government, juries of 12 men and women are saying that patients have been injured and they are giving awards. The costs of those awards are represented by the insurance premiums, and now the doctors don’t want to pay those premiums." If doctors wanted the State to give them a subsidy to lower premium rates, he went on, they should be willing to engage in overall reform. In return for the establishment of a State-operated insurance plan with relatively small premiums, the doctors should obligate themselves to accept all Medicaid patients. Fees for reimbursement under this plan are set by the authorities. If a physician’s practice included fewer than 10% of such patients, he should give 20 days a year of free service in areas where medical services are found officially wanting or inadequate. To this suggestion the practitioners responded, at least for the time being, with a vigorous "No". Some said that they are already giving free service, but this, on examination, turns out to be the writing-off of uncollectable

NOMENCLATURE OF PEPTIDE HORMONES

SiR,—International Nonproprietary Names (I.N.N.) estab-

lished by W.H.O. already exist for some substances covered by the proposals of a subcommittee of the IUPAC/IUB Commission on Biochemical Nomenclature for naming peptide hormones (Dec. 27, p. 1318). I wish to draw attention to the legal status of I.N.N. and national nonproprietary names, to alen clinicians to the danger of dual nomenclature of therapeutically important substances and the reference materials by which some of them are standardised, and to caution researchworkers and editors against precipitate adoption of proposals which remain open to comment. I.N.N.’ and/or national nonproprietary names (e.g., British approved names2 and U.S. adopted names3) are, or will be, required by law to be used for labelling and regulatory purposes in the European Economic Community,4 America, Japan, Australia, Argentina, Sweden and other Nordic countries, and Poland and other Eastern European countries, and in practice they are used for the purpose in many others. In the U.K., the Licencing Authority normally requires an approved name for any new drug before a product licence can be issued. I.N.N. are taken as monograph titles in the European and other pharmacopoeias. They are also used for intercharges, not voluntary philanthropy. national standards and reference preparations of biological substances distributed to clinical, academic, and national conMeanwhile, the pressure on governmental hospitals and trol laboratories throughout the world. clinics slowly increases. One good thing has resulted. Patients The most serious divergence between the IUPAC/IUB proare being sent home earlier than usual. Loss of revenue from and established I.N.N. concerns hypothalamic releasing posals "prolongation" of hospital stays is made up, of course, by fillProtirelin was published as the I.N.N. for thyrotrofactors. ing the beds with the new admissions. Another unexpected phin-releasing factor in March, 1974, after nearly two years’ result has been reported. With the increased publicity that has discussion, during which the stem -relin was devised and been given to the doctors resentment of medical malpractice agreed internationally for "hypophyseal hormone releaselitigation, fewer and fewer awards by juries are being made in stimulating peptides", a definition designed to embrace both favour of the plaintiffs. In the present climate, some attorneys the natural products and their synthetic modifications which maintain, a litigant has little chance of a truly fair hearing are under clinical evaluation. In the following September, from a jury, and petitions have been made to the courts to gonadorelin was adopted as the I.N.N. for the decapeptide postpone, sine die, scheduled trials. Even in personal injury releasing luteinising and follicle-stimulating hormones. The (non-malpractice) cases, doctors are making themselves unIUPAC/IUB proposals, published subsequently, consider only available to the plaintiffs who depend on them to serve as natural products and take -liberin as an ending with a prefix expert witnesses in trials now in progress or soon to be heard. for the pituitary hormone released. The stem -statin, taken by Since many malpractice suits have their bases in the unIUPAC/IUB for release-inhibiting factors, has been used pm toward results of surgery, any efforts to regulate the often too viously to denote inhibition of many kinds (e.g., nystatin, a polyene antifungal antibiotic) and may be considered insuffiready employment of such therapy should tend to reduce risks to the patient, and costs to insurers of both patient and surciently distinctive. The principles and procedures for the selection and estab geon. Several years ago, two labour unions in the New York members for of I.N.N. (of which 3500 have been published) are set area secured the of some of their lishment cooperation City whom surgeons had recommended elective operations. Consulout in a report’ of the W.H.O. Expert Committee on Nonprotations with and examinations by faculty of a medical school prietary Names for Pharmaceutical Substances. The names are indicated that, on the average, 18-30% of the procedures were adopted after exhaustive evaluation, discussion, and comment inadvisable. A for dollar of of almost$8 saving every by interested parties, including national nomenclature authorithought ties and individual experts, and are chosen to avoid anatom panel-costs was the result. The saving of life and limb, of course, is incalculable. cal, physiological, pathological, or therapeutic suggestions toa patient and to avoid conflict with trade names. The system Late last year the New York Times reported that this prowhich has evolved is sufficiently flexible in the case of peptide cedure was being introduced by Blue Shield and Blue Cross hormones to permit assignment of related names not only to (the insurance plans paying for hospital and physician the natural products but also to synthetic analogues of there’ charges) working together. They were starting with volunteers peutic importance-e.g., tetracosactide (1-24 A.C.T.H.), desfrom a group of 150 000 workers in the banking and stock mopressin (l-deamino-{D-Arg8] vasopressin), pentagastrin (an exchange industries. Of 6000 certified surgeons in the New York area, 1500 agreed to accept a fee of$50 for the consul1. International Nonproprietary Names for Pharmaceutical Substances, cumutation as full payment for the "second opinion", and also lative list no. 3. World Health Organisation, 1971; and supplementary not to operate or treat the patient for the condition callagreed lists, the latest being supplement to W.H.O. Chron. 1975, 29, no. 9. for consultation. Blue Cross Blue Shield for the and pay ing 2. British Pharmacopœia Commission. Approved Names 1973. H.M. Stationery Office; and supplements. any tests requested, and all findings are to be furnished to the 3. Griffiths, M. C. (editor). USAN and the USP Dictionary of Drug Names patient who, after all, has to make the decision about what is U.S. Pharmacopeial Convention, Inc., Rockville, Maryland, 1975. to be done with his body. If the second opinion does not agree 4. Council Directives 75/318, 75/319. Off. J. Eur. Commun. 1975, 18, 1. 13. with that of the original surgeon, the patient may ask for con5. Nonproprietary Names for Pharmaceutical Substances (Tech. Rep.Ser. Wld. Hlth. Org. 1975, no. 581). sultation with a third doctor.

191

analogue of the active sequence of gastrin), salcatonin (the synthetic major component of salmon calcitonin). A list ofI.N.N. for peptide hormones and related substances is available on request. National Institute for Biological Standards and Control, Holly Hill, Hampstead, D. H. CALAM London NW3 6RB.

TOXICITY OF PARACETAMOL p. 35) regarding the of death in cases of acute paracetamol overdosage are greatly at variance with those of other workers. 1-3 We agree that some series’are biased towards the inclusion of cases with severe liver damage, but as workers in a regional centre of primary referral, to which all patients with known or suspected acute paracetamol poisoning are admitted, we believe that we are in a position to comment on Dr Dixon’s letter. Over the past 2 years we have seen 280 patients with acute paracetamol overdose confirmed by plasma-paracetamol estimation; admission did not depend upon the severity of the padent’s illness, and there were only 5 deaths. Dr Dixon purports to show that a high proportion of fatalities (8 out of 20) occur within 24 hours of ingestion, with sudden death caused by "acute toxicity" or by asphyxia resulting from inhalation of vomit, presumably in the unconscious patient. Such a rapid onset of unconsciousness has been seen in our series only in patients who had concomitantly taken other coma-producing drugs (hypnotics, sedatives, or alcohol), and we wonder whether this possibility has been excluded in Dr Dixon’s cases. Inhalation bronchopneumonia and cardiac arrest were other important causes of death in the Leeds study, and only 3 patients were thought to have died from acute hepatic failure, though 12 out of 17 did show hepatic necrosis of unspecified severity. We have never seen or heard of cardiac arrest after paracetamol overdose except in the presence of liver failure. Electrocardiograms and serial cardiac isoenzyme studies were performed on 200 of our patients; only minor cardiographic changes and transient enzyme rises were seen, in only 10 patients. None of our patients died in acute renal failure in the absence of significant liver damage; and, furthermore, daily plasma urea and electrolyte estimations and urihalysis failed to disclose any instances of isolated severe renal impairment. All5 of our fatal cases died in acute hepatic failure with associated severe disturbance of the clotting mechanism. The shortest interval between ingestion of paracetamol and death was 43 h, and the others died on the 4th, 5th, 6th, and 7th days. In all instances necropsy revealed subtotal lobular hepatic necrosis, although we considered that massive hamorrhage from acute gastric erosions was the immediate cause of death in one. This is in agreement with the view expressed in your recent editorial.5 If substantiated, Dr Dixon’s findings are so important that they must lead to a reappraisal of the best management of acute paracetamol poisoning. We realise that in the confines of a letter the credentials of his cases could not be fully documented ("twenty unselected fatal cases of paracetamol overdosage confirmed by toxicology"), and we look forward to early publication of the detailed evidence.

SIR,-Dr Dixon’s conclusions (Jan. 3,

causes

University Departments of Pathology and Medicine, Royal Victoria Infirmary,

Newcastle upon Tyne NE1 4LP

MILENA LESNA A. J. WATSON ADRIAN P. DOUGLAS A. N. HAMLYN OLIVER JAMES

1 Clark, R., Thompson, R. P. H., Borkrakchanyurat, V., Widdop, B., Davidson, A. R., Williams, R. Lancet, 1973, i, 66. 2 James, O., Lesna, M., Roberts, S. H., Pulman, L., Douglas, A. P., Smith, P. A., Watson, A. J. ibid. 1975, ii, 579. 3 Portmann, B., Talbot, I. C., Day, D. W., Davidson, A. R., Murray-Lyon, I M., Williams, R. J. Path. 1975, 117, 169. 4 Prescott, L. F., Newton, R. W., Swainson, C. P., Wright, N., Forrest, A. R. W., Matthew, H. Lancet, 1974, i, 588.

5 Lancet, 1975, ii, 1189.

SiR,—The article by Dr Douglas and his colleagues (Jan. 17, p. 111) on the use of cysteamine for acute paracetamol poia curious reasoning; having shown that patients treated with cysteamine show less severe histological change, lower transaminase levels, and lower serum ferritin values, these workers devote much of the discussion to minimising the significance of these findings. Instead they prefer to emphasise the serum-bilirubin and prothrombin-time. I have suggested that death or acute renal failure in this syndrome is often due to endotoxaemia.1 In that case an equal mortality or morbidity in treatment or placebo groups would be anticipated in a trial of the effect of cysteamine. However, disseminated intravascular coagulation, which is inevitable in this setting,2 whether it be simply due to release of thromboplastin from necrosed liver cells or due to endotoxin from the bowel, not only will itself lower the prothrombin-time (and perhaps equally in the two groups) but also, in causing some haemolysis, might invalidate the serum-bilirubin. I think that Dr Douglas and his colleagues have chosen to emphasise the wrong indices. Nevertheless their findings are of considerable interest.

soning displays

33 Hawthorn Gardens,

Kenton,

E. N. WARDLE

Newcastle upon Tyne NE3 3DE

as Dr Dixon’s letter (Jan. 3, describe p. 35), paracetamol (acetaminophen) overdose accompanied by renal damage. Up to now this has not been a finding in animal studies3 but this is probably because laboratory animals were fed the wrong diets. If rats are given 15% herring oil in their diet and then given the treatments that usually produce moderate to severe liver injury (phenobarbitone lg/1 in drinking water plus a single oral dose of Ig/kg paracetamol),4 then we find that definite renal damage is regularly produced. Appearances are those of patchy acute proximal tubular necrosis with regeneration, complicated by acute internal hydronephrosis (due to obstruction of collecting ducts by desquamated tubular cells). These are found within 48 h of dosage. Kidney injury in response to paracetamol is found less frequently in rats given fats other than herring oil. There are many possible explanations for this observation. Addition of fat to the diet certainly increases oxidative metabolism of drugs in the kidney’ and can lead to more toxic metabolites in the kidney; the highly unsaturated fatty acids in herring oil will alter membranes in kidney cells; and the herring oil may cause a vitamin-E deficiency. But whatever the mechanism, the experiment points to the need to study drug toxicity in animals fed diets that resemble those eaten by man, with 40% of calories from fat, rather than the usual rat diets which contain 5% or so of their calories as fat.

SiR,-Clinical reports, such

Departments of Morbid Anatomy and

Experimental Pathology, University College Hospital Medical School, London WCIE 6JJ.

R. CHENERY

C. FISHER A. E. M. MCLEAN

PAY BEDS

SiR,-Dr Andrews (Jan. 10, p. 87) rightly calls attention to the desirability of siting private beds in the major hospitals. In 1971 I indicated6 the dangers and difficulties of conducting private care, especially in surgery, in small hospitals often remote from medical centres, and with the more recent threat of 1. Wardle, E. N. Q. J Med. 1975, 44, 389. 2. Wardle, E. N. Archs 1974, 109, 741. 3. Calder, I. C., Funder, C. C., Green, C. R., Ham, K. N., Tange, med. J. 1971, iv, 518. 4. McLean, A. E. M., Day, P. A. Biochem. Pharmac. 1975, 24, 37. 5. Paine, A. J., McLean, A. E. M. ibid. 1973, 22, 2875. 6. Shepherd, J. Lancet, 1971, i, 903.

Surg.

J. D. Br.

Letter: Nomenclature of peptide hormones.

190 euphemism for strike. Without waiting to see the effects of last fall’s State legislation which, among other things, sharply restricted the right...
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