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Biomedical subjects

R Peto

Publications and source records attributed to R Peto.

At least 235 records · Page 13Linked to original sources
PubMed1976

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design.

The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers, reporting the results in the medical literature. One unreported result which deserves such publication is the development of the expertise to design and analyse such trials. This report was prepared by a group of British and American statisticians, but it is intended for people without any statistical expertise. Part I, which appears in this issue, discusses the design of such trials; Part II, which will appear separately in the January 1977 issue of the Journal, gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test, including a worked example, and discusses the interpretation of trial results, including brief reports of 2 particular trials. Both parts of this report are relevant to all clinical trials which study time to death, and wound be equally relevant to clinical trials which study time to other particular classes of untoward event: first stroke, perhaps, or first relapse, metastasis, disease recurrence, thrombosis, transplant rejection, or death from a particular cause. Part I, in this issue, collects together ideas that have mostly already appeared in the medical literature, but Part II, next month, is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration. Such trials include the majority of all clinical trials of cancer therapy; in cancer trials,however, it may be preferable to use these statistical methods to study time to local recurrence of tumour, or to study time to detectable metastatic spread, in addition to studying total survival. Solid tumours can be staged at diagnosis; if this, or any other available information in some other disease is an important determinant of outcome, it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive, and more intuitively satisfactory, for it will then only be necessary to compare like with like, and not, by chance, Stage I with Stage III.

Clinical Trials as Topic↗
PubMed1976

Maternal serum alpha-fetoprotein and previous neural tube defects.

A case-control study involving 63 pregnancies showed that women who had previously had an infant with anencephaly or spina bifida did not have raised serum alpha-fetroprotein (AFP) levels in subsequent unaffected pregnancies. The value of a serum AFP determination in such women is discussed. If the serum AFP level is normal and if ultrasonography excludes anencephaly the risk of spina bifida might be low enough (about 1 per cent) to make diagnostic amniocentesis difficult to justify. Conversely, a high serum AFP value in such women should not be acted on without confirmation of an abnormality by ultrasonography and, if that is negative, by diagnostic amniocentesis.

Amniocentesis↗
PubMed1976

Fundamental carcinogenic processes and their implications for low dose risk assessment.

Various possible models of carcinogenesis are analyzed with respect to low dose kinetics. The importance of background carcinogenesis upon the shape of the dose-response curve at low dose is emphasized. It is shown that, if carcinogenesis by an external agent acts additively with any already ongoing process, then under almost any model the response will be linear at low dose. Measures of the degree of linearity are obtained for multistage models of carcinogenesis, where it is shown that throughout the dose range where the extra risk is less than the spontaneous risk linear extrapolation must be quite accurate.

Carcinogens, Environmental↗
PubMed1976

Renal prostaglandin synthesis in experimental renal clip hypertension in the rat.

1. The hypothesis that suppression of prostaglandin E (PGE) synthesis by indomethacin exacerbates renal clip hypertension in the rat was investigated. 2. Indomethacin exacerbated hypertension in renal clip rats. 3. In vitro PGE synthesis determined by gas liquid chromatography (GLC) was suppressed in medullary tissue from the hypertensive animals irrespective of indomethacin treatment. 4. The findings support the concept that PGs participate in blood pressure regulation in experimental renal hypertension.

Animals↗
PubMed1975

Effect of gestational age on screening for neural-tube defects by maternal plasma-A.F.P. measurement.

Maternal plasma or serum alpha-feto-protein (A.F.P.) concentrations were measured once between 8 and 22 weeks of gestation in each of sixty-two pregnancies which resulted in an infant with a neural-tube defect. Between 13 and 22 weeks of pregnancy twenty-two of the forty-one cases tested (54%) had A.F.P. values greater than three times the median value for unaffected pregnancies (which is equivalent to the 97th percentile of normal), and many of these values were very high indeed. However, before the 13th week of pregnancy only one of the twenty-one cases (5%) had an A.F.P. value more than three times the median for unaffected pregnancies, and this value was not very high. This indicates that in antenatal screening for anencephaly or spina bifida, A.F.P. should be measured in blood taken from the mother during the second trimester.

Anencephaly↗
PubMed1975

Controlled trial of repeated halothane anaesthetics in patients with carcinoma of the uterine cervix treated with radium.

39 patients with carcinoma of the uterine cervix who were treated with radium and required repeated general anaesthetics were randomised to halothane and control groups. Their serum-alanine-aminotransferase (S.G.P.T.) levels were measured before each general anaesthetic, and those patients whose S.G.P.T. levels rose above 100 I.U. per litre were freed from the restriction determined by the initial allocation and treated as indicated clinically. None of the 21 patients in the control group had S.G.P.T. levels rising above 100 I.U. per litre. 4 out of 18 patients in the halothane group developed S.G.P.T. levels above 100 i.u. per litre before their third radium treatment. None of these had any symptoms or alteration in other liver-function tests, but liver biopsies in 2 of these patients showed changes characteristic of Hepatitis. Arbitrary selection of 18 out of the 39 patients would only give rise to the degree of abnormality observed in the halothane-treated group with a probability of about 0-02. In the patients studied who required repeated general anaesthetics at short time intervals, the monitoring of S.G.P.T. levels before each operation was useful screen for liver damage and may have reduced postoperative hepatic necrosis by preventing further anaesthetics with halothane when the liver was already damaged.

Adult↗
PubMed1975

Maternal serum alpha-fetoprotein levels in multiple pregnancy.

Maternal serum alpha-fetoprotein (AFP) levels were higher in 10 twin pregnancies and one triplet pregnancy than in 22 control singleton pregnancies matched for maternal age, parity, and the time of gestation at which the serum sample was taken. In twin pregnancies the average AFP levels were double those found in singleton pregnancies and the level in the triplet pregnancy was even higher. Raised maternal serum AFP values due to multiple pregnancy should not cause unnecessary amniocentesis in the diagnosis of anencephaly or spina bifida if an ultrasound investigation is routinely performed first.

Adult↗
PubMed1975

Chronic granulocytic leukaemia: effect of elective splenectomy on the course of disease.

Conventional treatment by drugs or irradiation produces little prolongation of life in patients with chronic granulocytic leukaemia (C.G.L.) because the onset of metamorphosis of the disease from a chronic to an acute or subacute leukaemic process is not substantially postponed. Isolated clinical observations as well as both cytogenetic and cytokinetic evidence suggest that the spleen may play a special though not exclusive role in the development of undifferentiated cell clones which lead to metamorphosis of C.G.L. The results of a study of elective splenectomy during the chronic phase of the disease are reported. Twenty-six patients with C.G.L. underwent splenectomy during clinical remission of their disease, and there were no deaths after the operation. Twenty-one patients were alive at the time of writing, two of them eight years after splenectomy. Five cases of metamorphosis of C.G.L. to a refractory phase occurred whereas 10 would have been expected, a significant difference. After the onset of metamorphosis the quality of life was better in splenectomized than in non-splenectomized patients. These results show that splenectomy is a reasonable and safe procedure in C.G.L., and its apparently beneficial effects on prognosis justify a larger controlled clinical trial.

Adolescent↗
PubMed1975

Cancer and ageing in mice and men.

In an experiment involving 950 mice with a normal lifespan of 2-3 years, in laboratory conditions, regular benzpyrene application to the skin was started at 10, 25, 40 or 55 weeks of age. The incidence rate of malignant epithelial tumours among the survivors in each group increased steeply with time. This increase was associated directly with duration of exposure but, given duration, was independent of age at the start of exposure, as were the growth rates of already established tumours. In our experiment, although age per se was irrelevant, the cancer incidence rate increased approximately as a power of the duration of exposure to benzpyrene. This shows that the observed approximate power-law increase of most human adult cancer incidence rates with age could exist merely because age equals duration of exposure to background and spontaneous carcinogenic stimuli. Thus, no intrinsic effects of ageing (such as failing immunological surveillance or age related hormonal changes) whatever need to postulated to explain the vast increases in old age of the incidence rates of such human cancers. This result can greatly simplify speculation about mechanisms of carcinogenesis.

Age Factors↗
PubMed1975

Renal prostaglandin synthesis in experimental renal-clip hypertension in the rat.

1. The hypothesis that suppression of prostaglandin E synthesis by indomethacin exacerbates renal-clip hypertension in the rat was investigated in four groups of rats. 2. Indomethacin was shown to exacerbate hypertension in renal-clip animals. 3. Synthesis of prostaglandin E, determined by gas--liquid chromatography, was suppressed in medullary tissue from the hypertensive animals irrespective of indomethacin treatment. 4. The findings support the concept that prostaglandins participate in the blood pressure regulatory function of the kidney but pose a number of unsolved questions.

Animals↗
PubMed1975

Renal prostaglandin synthesis in the Goldblatt hypertensive rat.

The role of prostaglandins in blood pressure regulation was studied in normal rats and in animals with renal artery constriction. The effects of chronic inhibition of prostaglandin (PG) synthesis on arterial pressure were observed, and renal medullary PG synthesis was measured in vitro. The prostaglandin synthetase inhibitor indomethacin was given in a dose of 2 mg/kg/day by mouth to one of two groups of male Wistar rats with a unilateral renal artery constriction and the other kidney untouched, and to one of two sham-clipped groups. Systolic blood pressures were higher in indomethacin-treated clipped rats than in non-indomethacin-treated clipped animals, and at 18 days averaged 188 mm Hg (plus or minus SEM 5.9, n = 36) and 162 mm Hg (plus or minus SEM 7.6, n = 34), respectively (P less than 0.005 for data pooled from two experiments). Indomethacin did not affect pressures of sham-clipped animals treated for 40 days. Analysis of PG synthesis by gas-liquid chromatography in renal medullary slices incubated for 30 minutes in Krebs-Henseleit buffer showed: (1) 40% suppression of PGE synthesis in hypertensive animals (P less than 0.001): (2) no differences between clipped and untouched kidneys; (3) chronic indomethacin treatment did not affect PGE synthesis in the in vitro buffer system; and (4) no PGA synthesis was detected. In a further experiment in which medullary slices were incubated in plasma of rats treated with equivalent doses of indomethacin, PGE synthesis was suppressed by 35%. The experiments support the concept that prostaglandins modulate pressor mechanisms which come into play when renal blood flow is drastically reduced. The effects could be mediated by PG synthesis in the kidney and/or in other systemic vascular beds.

Animals↗