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In two papers (Finn et d., 1961; Clarke it al., 1963) we described experiments which were successful in preventing Rh immunization in Rh-negative male volunteers. The basis of the procedure was to remove rapidly from the circulation previously injected chromium-tagged Rh-positive red cells by giving hightitre incomplete anti-D either as an infusion of plasma or as gamma3-globulin. In our second paper we stated that the next steps should be to find out whether foetal red cells could be cleared equally well as adult and whether female volunteers could be protected in the same way as men. The results of experiments to test these points form the first part (I) of the present paper. The second part (II) concerns two factors of great importance in the application of the technique to preventing Rh immunization due to pregnancy. These are the frequency with which transplacental haemorrhage from foetus to mother occurs during pregnancy as distinct from at delivery, and the relation of the production of immune antibodies to the size of transplacental haemorrhage assessed after delivery. In the third part of the paper (III) we discuss some of the details of the clinical trial, recently started in Liverpool, of anti-D gamma2-globulin injection given to Rh-negative Women after delivery.

This paper gives an account of five patients with glomerulonephritis complicating subacute infective endocarditis. In three patients with focal (segmental) glomerulonephritis granular deposits of immunoglobulin and C3 and reduced serum complement suggested an immune-complex aetiology; but in two patients with a diffuse proliferative glomerulonephritis no Ig or C3 was detected in the diseased glomeruli and the pathogenetic mechanism remained undetermined. Four of the five patients developed renal failure needing dialysis.

This paper reports our experience in monitoring gentamicin therapy during the treatment of 68 episodes of serious Gram-negative sepsis in 65 hospital patients. Most of the patients had major underlying disease. Of those who were adequately treated (peak serum concentrations of 5 mug/ml or more in 72 hours for septicaemia, urinary tract infection, and wound infection; and 8 mug/ml or more at some time during the course of treatment for pneumonia) 84% (46 out of 55) were cured. These serum concentrations could be achieved only by starting with a regimen of 5 mg/kg/day in three divided doses in all adult patients, subsequent dosage being determined by the results of rapid serum assay. The incidence of nephrotoxicity and symptomatic ototoxicity was no greater than in previous series. The main reason for assaying serum gentamicin is to ensure that an adequate dosage is achieved as soon as possible. In patients with impaired renal function or receiving prolonged high dosage assays also serve to guard against an excessive accumulation of gentamicin and an increased risk of toxicity.

The use of an extracorporeal circulation in open-heart surgery is now standard practice, and deaths directly attributable to perfusion are unusual. Nevertheless, a significant morbidity may be associated with such procedures, and in recent years more attention has been directed to the causes of such morbidity. Kreel et al. (1960) were the first to comment on the presence of atypical lymphocytes in the peripheral blood of patients two to three weeks after perfusion. A clinical post-perfusion syndrome of fever and splenomegaly with atypical lymphocytes in the peripheral blood was described by Seaman and Starr (1962). This syndrome has been further amplified by the reports of Perillie and Glenn (1962), Wheeler et al. (1962), Holswade et al. (1963), and Anderson and Larsson (1963). So far 33 examples of the syndrome have been described. The present paper presents a further nine examples and compares the findings in these patients with those previously described.

Pain is an apperceptive mental experience which can only be studied in man. It cannot be measured or even satisfactorily described except to those who have suffered like pain, and the similarity is always an assumption. The purpose of this paper is to propound the following hypothesis, which consists of two main parts: (1) that pain is meant to subserve a purely protec tive function and merely to cause sufficient discomfort to warn of noxious stimuli and to make the animal take appropriate action, such as to move from harm or rest a limb ; and (2) that the affective or cortical component of pain, or the pain image, can be envisaged as a panel comparable with a multi-channel electromanometric recording apparatus, which allows the size of the image or the amount of deflection of the pen to be varied by turning knobs on the panel which change its sensi tivity. It will be shown that pain sensitivity can be affected by (a) psychical, and (b) peripheral factors, and that it may also be modified in the spinal cord. The thesis will be supported by gynaecological experience, which gave it birth.

This paper reports the outcome of 60 pregnancies in 40 women, all of whom had concomitant Crohn's disease. Detailed analysis of pregnancy rates in Crohn's disease supports in outline the hypothesis that some patients with bowel symptoms may be rendered temporarily subfertile by the activity of their bowel complaints. In contrast there is little or no evidence of any adverse effect during pregnancy on mother or child. Most pregnancies went normally to term and, if anything, Crohn's disease tended to improve during the period of confinement.After delivery, however, over 40% of patients suffered a relapse of Crohn's disease. Such a situation might well constitute a logical indication for the administration of corticosteroid therapy.

The levels of aetiocholanolone, androsterone, and 17-hydroxycorticosteroids were measured in women without known disease of the breast, in women with benign breast disease, and in women with primary and advanced breast cancer. Statistical analysis showed there was no difference in the excretion of urinary 17-hydroxycorticosteroids in the various groups of patients. Detailed analysis of the aetiocholanolone and androsterone levels, however, indicated that patients with advanced localized disease excreted significantly less of these 11-deoxy-17-oxosteroids than those in the other groups.

While barium enema is the most useful investigation in the primary diagnosis of diverticular disease of the colon, this paper presents further evidence that the terms “diverticulosis” and “diverticulitis” are unsatisfactory and shows that a radiological classification on the traditional criteria is not accurate in determining whether or not inflammation is associated with colonic diverticula.

This paper describes a system of computer-aided diagnosis using an English Electric KDF9 computer linked to a terminal in a busy clinical department. Data from a series of patients were recorded, coded, and entered into the computer, which then performed a Bayesian analysis and displayed diagnostic probabilities in an adaptable format. Experience in this setting suggests that computer diagnosis may be a valuable aid to the clinician.

A system has been devised which records direct arterial pressure, electrocardiogram, and other variables in man with no restriction of activity. The advantage of this system is that the record is on magnetic tape, and it is possible to replay the records at various speeds to analyse each beat or to produce an entire 24-hour record on a few feet of paper. A marker allows the timing of relevant events. Initial experience with this procedure indicates that is is safe and reliable.

This paper describes our experience with cyclophosphamide in the treatment of systemic lupus erythematosus. Since 1965 42 such patients have been treated either singly with cyclophosphamide or in combination with steroid. Serious complications have been rare except for amenorrhoea, which occurred in 14 out of 32 patients within the reproductive period. Our experience suggests that cyclophosphamide has an important, though not primary, part to play in the therapy of this disease.

In a coronary care unit patients and electrocardiographic monitors are under almost continuous observation by trained personnel. This paper suggests that in a general medical ward without this facility routine cardiac monitoring with E.C.G. oscilloscopes is unlikely to lower the overall mortality from acute myocardial infarction. A mortality of 25% for acute myocardial infarction was the same for a hospital without a coronary care unit where monitoring was routinely performed and for two neighbouring hospitals which did not routinely use monitoring during the period of analysis. The need to train personnel in the recognition of E.C.G. monitor tracings and the difficulties associated with monitor alarm systems are emphasized.

The Scribner shunt (Quinton, Dillard, Cole, and Scribner, 1962) (Fig. 1) is an artificial arteriovenous fistula made of inert plastic tubing which is used for repeated haemodialysis. When dialysis is required the U-tube connecting the arterial and venous limbs of the shunt is removed and the patient is con nected to the dialyser. At the end of dialysis the U-tube is replaced. The use of the Scribner shunt in intermittent haemodialysis for chronic renal failure is well recognized, and Chisholm (1961) has advocated its use in some patients with acute renal failure and especially those who have few available veins, it is our belief that it should be used in all patients with acute renal failure who are likely to require more than one haemo dialysis ; certain patients with acute renal failure may be alternatively managed successfully by peritoneal dialysis. It is the purpose of this paper to show that the routine use of the Scribner shunt, as opposed to repeated cannulation, saves time and trouble in a busy artificial kidney unit and increases the safety of dialysis. Now that all parts of this shunt are manufactured in Great Britain the increase in cost is not significant. Improvements in the technique of insert ing the shunt, the experience of the first year, and the com plications encountered are also outlined.

It is surprising that, so far as we can ascertain, no trial has been reported in which the efficacy of a modern "anti depressive " drug has been compared with that of a combina tion of drugs (dexamphetamine and amylobarbitone) widely used in the treatment of depressive illness before the newer drugs were introduced five or six years ago. Proprietary mixtures of dexamphetamine and amylobarbitone are still advertised as of value in depression, and the lack of any comparative trial is perhaps more surprising when it is remembered that the basic cost to the National Health Service of a week's treatment with the ingredients of such mixtures (dexamphetamine sulphate 5 mg. and amylobarbitone sodium 50 mg. t.i.d.) is 5d., while that of the currently most popular antidepressant (imipramine hydrochloride (" tofranil ") 50 mg. t.i.d.) is about 11s. 6d. In this paper we report a controlled comparative trial of imipramine and a proprietary mixture of dexamphetamine and amylobarbitone ("drinamyl"), in the treatment of depressive illness.

Among 123 Nigerians with migraine seen at one clinic 49 (40%) had complicated migraine, with ophthalmoplegia in 20 and amaurosis or field defects in 13. Haemoglobin AS was found in 60% of patients with complicated migraine, compared with 20% of those with simple migraine.

The treatment of active tuberculosis during pregnancy is complicated by the problem of the safety of the drugs employed. In order to prevent the emergence of drug-resistant organisms it is customary during the initial stages to give streptomycin as well as isoniazid and p-aminosalicylic acid, and, while the mother is of course subject to the risk of ototoxic damage due to streptomycin, it is not entirely clear how far this risk extends to the foetus. Certainly streptomycin does cross the placenta : this was established in 1945 by Woltz and Wiley and indepen dently by Heilman et al. (1945). Subsequent work (Bernhard et al, 1950 ; Riskaer et al., 1952 ; Charles, 1954) confirmed that, although the effectiveness of the placental barrier varies, streptomycin and dihydrostreptomycin (Jacobsen, 1953) are present in foetal blood in up to 50% of maternal concentrations. The effect of these drugs on the foetus was studied experiment ally by Riskser et al., using guinea-pigs ; no disturbance of auditory or vestibular function was apparent. Watson and Stow (1948) were the first to examine this ques tion clinically ; they found no obvious abnormality in two children born after high maternal doses of streptomycin during pregnancy. Later reports agreed, and Kreibich (1954) was able to collect from the literature 35 cases in which children at risk seemed to be unaffected. Since 1950, however, several case reports have appeared of deaf children born to mothers treated with streptomycin for tuberculosis. Leroux (1950) described the case of a child aged 2\ with deafness (and normal caloric responses) whose mother had received 30 g. of streptomycin in the last month of pregnancy. Bolletti and Croatto (1958) reported the case of a girl of 5 with severe deafness and impaired vestibular function, the maternal dose of streptomycin having been 1 g. daily for 85 days prior to delivery. Kern (1962) described the case of a 6-year-old girl with severe deafness in the left ear and total deafness in the right. A caloric test evoked very little response. In this case the mother had been treated with 20 g. of dihydrostreptomycin in the first four months of pregnancy. Finally, in a study of the causes of deafness in 300 children, Robinson and Cambon (1964) dis covered two further children with severe deafness and absent caloric responses. The first mother fiad been given 1 g. of streptomycin twice weekly for eight weeks in the first trimester, and the second a similar dosage for the last four months of pregnancy. Apart from these isolated cases there have been three papers describing the otological findings in small groups of children at risk. Rebattu et al. (1960) found two cases of high tone loss among six children they examined, and in one the caloric tests were abnormal. Lenzi and Ancona (1962) studied 10 children aged 7-10 years and their mothers. Audiograms showed that three of the children were deaf ; all the mothers were normal. Grande and Vespa (1963) examined nine mothers and their 14 children, then aged 7-11 years. In this instance all the mothers had received dihydrostreptomycin, the dose ranging from 5 to 80 g. Four mothers and three children had perceptive deaf ness ; five more children had mixed deafness. Vestibular function was studied with galvanic and caloric tests, of which no details were given ; all the children were stated to be normal. These three series suggest a relatively high incidence of deaf ness (possibly related in the last one to the use of dihydro streptomycin, which is more apt than streptomycin itself to damage cochlear function), and it is therefore surprising that so few children with deafness caused in this way have been reported. The present investigation was undertaken in an attempt to reassess the incidence of deafness in children at risk. Furthermore, in theory one would expect labyrinthine rather than cQchlear damage to be the commoner finding after the use of streptomycin, and accordingly vestibular function was examined in detail.

For over 25 years sporadic reports have been appearing in the literature of cases of eosinophilic granuloma arising in various parts of the gastro-intestinal tract. Kaijser (1937) described the first cases. In a search of the literature, which although extensive is not claimed to be exhaustive, 47 papers were found, describing a total of 89 cases. They occurred through out the alimentary tract from pharynx to rectum, though the majority were in the stomach and small intestine, and they

The first trials of measles vaccines in the United Kingdom were reported in 1961 by Aldous et al., when three living attenuated vaccines derived from the Edmonston strain (Enders et al., 1960) were compared at the Fountain Hospital. In many cases vaccination reactions were too pronounced for the vaccines to be suitable for routine use. However, in view of the high complication rate of measles in young children (Miller, 1964), it was considered important to continue clinical trials of measles vaccine rendered less toxic by further attenuation. The present paper describes four subsequent trials of vaccines prepared from the Edmonston strain but which had undergone a further series of passages in chick-embryo or chick-cell tissue cultures. In some of the trials the vaccines were given alone, and in others concurrently with gamma-globulin.

Evidence of cell-mediated immunity to gastric intrinsic factor was present in 86% of patients with pernicious anaemia and in at least 13% of patients with hyperthyroidism, 21% of patients with atrophic gastritis, and four out of nine (46%) patients with hypogammaglobulinaemia. Controls gave negative results. The four patients with hypogammaglobulinaemia and cell-mediated immunity to intrinsic factor had evidence of impaired gastric function.

Twenty-five patients with perennial rhinitis completed a double-blind cross-over trial of intranasal beclomethasone dipropionate 200 mug daily and placebo. Of these patients 19 preferred the active drug and two preferred placebo. There were significant reductions in symptom scores for nasal obstruction and rhinorrhoea and in the use of decongestant nasal drops when using the active drug. No changes in morning plasma cortisol levels occurred during the three-week treatment period.

Two different types of commercially available bran were studied. One of these was composed of flake-like particles (coarse bran) whereas the other had smaller, finer particles with a floury component (fine bran). The effectiveness of the two preparations in lowering intraluminal pressure and decreasing transit time in patients with constipation and diverticular disease was assessed. Only coarse bran promoted changes at the dose used. The physical properties of the brans were examined in an effort to explain their differing effects. It is concluded that water-holding capacity, upon which the beneficial effect of bran may depend, is a function of particle size. The greater water-holding capacity of coarse bran makes it preferable for the treatment of colonic disorders.

Oil-aspiration pneumonia is a common cause of mortality and morbidity in infants and young children in South India. The high incidence of this condition results from the local custom of giving oil baths to infants and of cleansing the mouth, throat, and nose with oil. The clinical findings in 12 cases, 10 of them in babies aged under 8 months, are described. The signs range from an acute segmental collapse of the lung, clearing in a few days, to a chronic picture mimicking pulmonary tuberculosis or mucoviscoidosis. Mothers in South India should be advised to abandon the practice of cleansing their baby9s mouth and nose with oil.

Immunological investigation of four patients with meningococcal meningitis who developed arthritis or cutaneous lesions showed circulating meningococcal antigen at the time of presentation in each patient. It was cleared from the circulation over the next few days. Circulating antibody was detectable in three of the four patients about a week after the onset of the illness. A marked fall in the serum C(3) level occurred in two patients at about that time. Deposits of meningococcal antigen, immunoglobulin, and C(3) were detected in the synovial fluid white cells of the two patients studied and in one of three skin biopsies examined. These findings suggest that the arthritis and cutaneous lesions of meningococcal meningitis may be due to immune complex formation.

A new drug, AH 7725, with properties similar to those of disodium cromoglycate (Intal) has the additional feature of being effective when taken by mouth. Six patients with allergic asthma were studied by bronchial challenge tests with antigen. In every one the drug was found to inhibit (either partially or completely) the immediate-type asthmatic response. Late responses were not influenced. The results were significant at the 0·5% level. These findings suggest that AH 7725 given by mouth may be able to inhibit naturally occurring asthmatic attacks in allergic patients. In this case its particular advantage as a prophylactic drug would lie in the treatment of very young asthmatic children and other patients who cannot take drugs by inhalation.

This study was undertaken to examine the possibility that IgE is not the only immunoglobulin responsible for immediate allergic reactions. A group of asthmatics were investigated in whom immediate allergic reactivity of the bronchi to common inhalant allergens had been confirmed by provocation tests. Their sera were fractionated and the reaginic activity of the immunoglobulin classes was studied by passive cutaneous anaphylaxis testing in monkeys. The results showed that the immediate allergic reactions were due to IgE antibodies in most patients, but there was a group with reactions due to short-term anaphylactic IgG antibodies. It was not possible to inhibit the IgG-mediated responses with disodium cromoglycate. As these two groups had clearly different serum IgE levels the estimation of IgE provided an important guide to the management of these patients.

We have monitored two pregnancies from families at risk for galactosaemia. The fetus was diagnosed as having galactosaemia in one and to be unaffected in the other. The accuracy of the predictions was confirmed postnatally. Assays for galactose 1-phosphate uridyl transferase involving the reduction of the coenzymes NAD or NADP are unsuitable for amniotic cells whereas estimation of (14)C-UDP-galactose produced from (14)C-galactose 1-phosphate detected the homozygous mutant fetus.

The dermatoglyphics of 135 children with acute leukaemia differed significantly from those of normal controls, and examination of 174 of the patients' first degree relatives indicated that familial factors were involved. The findings suggested that within the racial group studied dermatoglyphics may partly identify a population subgroup which is at increased risk of leukaemogenesis. While these observations may not have immediate clinical application, they are likely to contribute to a greater understanding of individuals who have increased constitutional susceptibility to leukaemia.

The use of many different antibiotics to treat chest infection has led us to test the sensitivity of 68 strains of Haemophilus influenzae to 15 different compounds. These included established compounds such as ampicillin and tetracycline and newer agents such as cephalosporins and clindamycin. The minimum inhibitory concentrations of the compounds for H. influenzae were then compared with blood levels attained after the usual dose regimens. There has been a significant increase in tetracycline resistance in the last few years, but all strains were sensitive to ampicillin, chloramphenicol, sulphamethoxazole, and trimethoprim, Several antibiotics were found to be microbiologically unsuitable for treating H. influenzae infections.

During the first 12 months of a total population survey 249 patients were seen with viral hepatitis. A total of 215 of these were tested for hepatitis B antigen (HB Ag) by radioimmunoassay and 32 (15%) were positive. More than five times as many men (27) as women (5) were HBAg positive and 19 of the men were between the ages of 20 and 39 years. There were only four drug addicts among those tested, two of whom were positive, as were two of the four patients who were tattooed. Sixty out of 86 children (under 15 years) were tested for HBAg and none was positive.

A method is reported by which the “in utero” crown-rump length of the fetus may be determined by sonar in the first trimester of pregnancy. The accuracy of the technique was assessed by comparing the sonar and the direct postabortum measurements of fetuses in cases of missed abortion. A normal curve of fetal crown-rump length was derived from 214 examinations on 80 patients and by using these values in a further “blind” series it was found possible to predict the maturity of pregnancy to within three days, between the sixth and the 14th weeks of pregnancy.

Seven cases are reported in which drugs of the tetracycline group produced a fall in the glomerular filtration rate. In six patients there was a primary underlying renal disease and renal impairment. All seven patients were made seriously ill by the antibiotic. Two patients required immediate haemodialysis; one died and the other continued on dialysis until transplanted. Another patient initially responded to intravenous fluids and protein restriction but his renal function deteriorated and four months later he began maintenance haemodialysis. Three patients required peritoneal dialysis. The seventh patient responded satisfactorily to conservative management. The medical and medicolegal complications arising from the use of tetracycline in patients with renal disease are discussed. Yet another plea is made that drugs of the tetracycline group other than doxycycline should not be given to patients with chronic renal failure.

Six patients suffering from recurrent chest infections were found to lack antibodies to a pooled antigen obtained from six different serotypes of commensal Escherichia coli bacteria. All had normal serum IgG concentrations, but five subsequently benefited from regular gammaglobulin injections. We suggest that the absence of such E. coli antibodies usually indicates a clinically significant defect in antibody production. This simple screening test is of use in the diagnosis of primary and secondary immunodeficiency disorders.

Twenty-eight patients with multiple myeloma have been treated with a quadruple chemotherapeutic regimen consisting of 1, 3 bis (2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide, melphalan, and prednisolone. Nineteen new patients and nine who had escaped from previous single-agent therapy were included in the study. The results to date, on eight criteria of response, seem to be superior to those obtained from previous chemotherapeutic regimens. The study has been in progress for 18 months and only three patients have died. Only one who had not received previous therapy died, and she had complicating hyperparathyroidism, which almost certainly contributed to her death.

From 1,156 insertions of the copper 7 contraceptive device with 15,044 women-months of use we conclude that it offers advantages in intrauterine contraception. Continuity is improved for all users. It is a useful method for those who have not been pregnant and as an exchange device for patients having problems with other intrauterine devices or contraceptive methods. These advantages must be set against the necessity of replacing the copper 7 after a limited life span. In no cases in our series did cervical cytological examination show anything abnormal, and a 98·1% follow-up was achieved.

Subungual malignant melanoma developed on both great toes of a 61-year-old woman. The lesions had been diagnosed elsewhere as ingrowing toenails and had been treated as such for two years. The difficulty in clinical diagnosis is illustrated by the description of three other patients with subungual malignant melanoma. The tumour should be considered as a possible cause of any persistent abnormality of the nail bed or the nail itself, especially if it is pigmented.

In late 1971 410 consultant general surgeons and urologists—74% of a national random sample—responded to a postal survey about vasectomy. Probably about 50,000 vasectomies were performed by surgeons in England and Wales in 1970. The service was largely a private one: 60% of consultants9 hospital vasectomies were not done under the National Health Service, and, in addition, 26% of the consultants who worked in relevant specialties performed vasectomies elsewhere than in hospital (usually in private nursing homes). Based again on consultants9 estimates, probably 6,000 men in 1970 had their requests for vasectomy turned down by surgeons, or more than one turned down for every 10 done. The most common reason was that patients were “too young.” About 90% of the consultants thought vasectomy could normally be performed safely and adequately as an outpatient procedure, yet only 64% said that 90% or more of their hospital vasectomies were done on this basis. While 69% regarded services in their areas as adequate, most were in favour of more special vasectomy clinics.

Relations between expiratory reserve volume (ERV), closing volume (CV) as a percentage of vital capacity (CV/VC%), and pulmonary gas exchange have been investigated in the sitting and supine postures in eight severely obese subjects before and after substantial weight loss. CV/VC% exceeded predicted values but did not change with posture or weight loss; the increase could have been owing to the smoking habits of the subjects. Arterial oxygen pressure (PaO(2)) was significantly less in the supine than in the sitting posture and improved after weight loss in six subjects. The reduction in PaO(2) was correlated with the extent to which dependent airways were closed within the range of tidal breathing, shown by increasing negativity of ERV-CV as a percentage of VC. A good correlation was also found between PaO(2) and ERV, an easier measurement for routine use. Improvement of pulmonary gas exchange occurred only in those patients who lost weight to within 30% in excess of ideal.

Management of a patient with snake bite is influenced by the nature of the offending snake. Species diagnosis based on the patient's history and physical signs is often unreliable and the possibility of making a species diagnosis by immunological means has therefore been investigated. Wound aspirates, blister fluids, sera, and urine samples from patients with snake bite were examined for the presence of species-specific venoms using immunodiffusion. A positive species diagnosis was made in 40 out of 101 patients. Immunodiagnosis was especially successful in patients bitten by the puff adder, Bitis arietans, and the African spitting cobra, Naja nigricollis. A higher success rate could probably be achieved using more specific antisera and more sensitive assay techniques.

Metiamide, an antagonist of histamine H(2) receptors, was administered intravenously to normal subjects and to patients with a peptic ulcer during vagal stimulation with a constant infusion of insulin. In normal and peptic-ulcer subjects there were reductions of 70% and 71% respectively in gastric-acid output compared with control tests on the same subjects. The decreased acid output resulted from a reduction in both volume of secretion and acid concentration. Metiamide is therefore a potent inhibitor of vagally-induced gastric acid secretion.

Carcinoembryonic antigen (C.E.A.) estimation has been used in the preoperative assessment of colorectal carcinoma patients and has been shown to give a useful guide to the presence of metastatic disease and ultimately to a poor prognosis if the serum concentration is 100 ng/ml or more. C.E.A. has been shown to be a more reliable index of tumour spread than either clinical examination or serum alkaline phosphatase estimation. Raised C.E.A. levels of less than 100 ng/ml do not, however, necessarily imply a poor prognosis. Routine C.E.A. estimation may have a valuable role in the assessment of the colorectal cancer patient by identifying those likely to benefit from postoperative chemotherapy.The test has also been assessed in a group of patients attending cancer follow-up clinics after radical resection of a colorectal tumour. Raised C.E.A. occurred in most of those developing recurrent disease, and in several patients a rising C.E.A. level preceded clinical or biochemical evidence of recurrence. C.E.A. estimation is a superior guide and of clinical importance when applied to the follow-up of the colorectal cancer patient.

An objective radiographic study of erosions, fractures, and periarticular and vascular calcification was made in a series of 135 patients over 10 years of maintenance haemodialysis therapy. The four lesions progressed at different rates, consistent with variation in the response of tissues to a changing biochemical milieu and deficiency in vitamin D metabolites. The half time for development of individual radiographic signs was 3·4 years for vascular calcification, 9 years for fractures, 16 years for periarticular calcification, and 22·9 years for erosions. Calcification of the dorsalis pedis artery seen as a developing ring or tube was an early and valuable sign of disturbed calcium metabolism. In these patients renal osteodystrophy is a chronic condition with a prolonged time course.

Analysis of the results of two cross country races, one on foot and one on skis, in which nearly 10,000 men competed showed that performance is very closely matched with age. There is a decrease of 5-10% in the performance every 10 years from optimum age for the event. This optimum varies for different types of physical activity. Studies in a small group of women showed similar variations.

The results of treatment with frusemide in 105 patients with established acute renal failure admitted during the past six years were reviewed and compared with control groups. Daily doses of 2,000 mg of frusemide administered from the day of admission onwards produced a significant increase in the number of patients who attained a diuresis and decreased the duration of oliguria.The reduction in the time spent in hospital and in the number of dialyses required suggests that the use of frusemide in these large doses is indicated in patients with severe established acute renal failure.

Calciferol therapy for 12 months in white, Asian, and West Indian schoolchildren resulted in a highly significant increase in height and weight when compared with schoolchildren not so treated. The rate of fall of serum alkaline phosphatase was similar in both the treated and untreated schoolchildren and in other children treated in hospital for rickets. Dietary studies on 9% of the total survey by weighed inventory methods showed a low average intake of vitamin D, while random estimates of 25-hydroxycalciferol levels on 6% of the children were less than 3.8 ng/ml in 40% of those studied (principally Asian). It was concluded that there was a significant problem of vitamin D deficiency among Asian and West Indian teenagers and that white children were also affected to a less degree.

A total of 43 episodes of tuberculosis lymphadenitis were treated in 32 adult patients. In 12 instances the affected lymph node was excised without any chemotherapy; there were 10 relapses. The treatment was local excision of the affected lymph nodes together with antituberculosis chemotherapy with at least two drugs in 30 instances; there were no relapses following such therapy.Presumably patients with tuberculosis lymphadenitis are still sometimes treated with surgery alone because that was at one time the orthodox line of surgical teaching. Such a view is out of date: these patients should always be given antituberculosis therapy in addition to any surgical measures.

A national sample of several thousand children has been followed longitudinally from birth. At the ages of 7 and 11 years physical and mental retardation due to smoking in pregnancy has been found, and this deficit increases with the number of cigarettes smoked after the fourth month of pregnancy. Children of mothers who smoked 10 or more cigarettes a day are on average 1·0 cm shorter and between three and five months retarded on reading, mathematics, and general ability compared with the offspring of non-smokers, after allowing for associated social and biological factors.

The cardiovascular responses to forcing acrylic bone cement, Plasticine, or soft paraffin wax into the medullary cavity of the femur have been studied in rabbits and cats. An acute fall in blood pressure, occurring within a few seconds of insertion, was demonstrated with each substance. In a few of the animals the blood pressure response had a second more protracted component and it is suggested that more than one mechanism is involved. The cardiovascular effects that have been observed in man when acrylic cement is used in prosthetic hip surgery also may be due to more than one mechanism.