Abstract: To evaluate the relative importance of the medical history, the physical examination, and laboratory investigations in the diagnosis and management of medical outpatients some physicians recorded their diagnosis and a prediction of the method of managementafter reading the patient's referral letter, again after taking the history, and againafter performing the physical examination. These diagnoses and predictions were compared with the diagnosis and method of management which had been adopted two months after the patient's initial attendance. A diagnosis that agreed with the one finally accepted was made after reading the referral letter and taking the history in 66 out of 80 new patients; the physical examination was useful in only seven patients, and the laboratory investigations in a further seven. In only one of six patients in whom the physician was unable to make any diagnosis after taking the history and examining the patient did laboratory investigations lead to a positive diagnosis.

Abstract: 780 copies were deposited in the hospital in 1933, and vanished. (It has just been reprinted by H K Lewis.) Mr Law deals with the history by subjects rather than in strict datal order, which is an advantage. He gives brief biographies (at the time of his retirement) of each person mentioned, with, and this is most valuable, a photograph. The book is well and generously illustrated with 69 photographs. The author skilfully recounts the complex story of the building, rebuilding, modifications, removals, and amalgamations with other hospitals which make up the development of Moorfields. He describes unobtrusively the advance of the skills and knowledge of ophthalmology during the period, a most creditable amount of which actually originated in the hospital, and although he says \"it is impossible to note each change, each advance, each indication of progress as it occurs\" he makes a good show of doing just that, and very interesting it is. So are some historical details; relevant, such as those about the collection of money in the old \"voluntary\" days, about which the rising generation knows little; and some of more general interest historically, such as those about Lord Avebury. And some things which are well worth recording, such as the observation of The Times in about 1929 that \"Such a hospital service as this [the voluntary hospitals] could not be reproduced by any conceivable effort of public authorities or expenditure of public money . . . it must be preserved intact if its virtue is to continue undiminished.\" If every hospital would produce a history on these lines, the basis of the medical history of this country would be greatly strengthened. CHARLES NEWMAN

Abstract: Eleven patients with asthma and aspirin hypersensitivity have been challenged with eight non-steroidal anti-inflammatory drugs. Each drug was given by mouth in at least three different doses and the patients' symptoms and peak expiratory flow (PEF) rates were observed over a three-hour period. Indomethacin 5 mg caused bronchoconstriction in all patients. Therapeutic doses of mefenamic or flufenamic acid caused bronchoconstriction in most patients. Phenylbutazone 200-400 mg induced a moderate fall in PEF. There were no reactions to therapeutic doses of salicylamide, paracetamol, benzydamine, and chloroquine. Microsomal prostaglandin synthetase, activity was inhibited by aspirin, indomethacin, mefenamic acid, flufenamic acid, and phenylbutazone. The other four drugs had no inhibitory effect. We suggest that precipitation of attacks in asthmatic patients hypersensitive to certain anti-inflammatory drugs is related to drug's ability to inhibit prostaglandin biosynthesis.

Abstract: Sixty-three women discharged from hospital with a diagnosis of myocardial infarction and 189 control patients were studied. All were under 45 years of age at the time of admission. Current oral contraceptive use, heavy cigarette smoking, treated hypertension and diabetes, pre-eclamptic toxaemia, and obesity were all reported by, and type II hyperlipoproteinaemia was found more often in, patients with myocardial infarction than their controls. The relationship between myocardial infarction and oral contraceptives could not be explained in terms of an association between the use of these preparations and the other factors. The combined effect of the risk factors was clearly synergistic.

Abstract: Eight men volunteers each smoked a single cirgarette containing 14C-nicotine and gave arterial blood samples during and for 50 minutes after smoking. The maximum concentration of nicotine in the arterial blood ranged from 31 to 41 mug/l in four regular cigarette smokers who inhaled. Two non-smokers achieved maximum levels of 2 and 4 mug/l. On a separate occasion two of the inhalers received 1 mg. 14C-nicotine in 10 divided doses injected intravenously. In both cases the peak arterial nicotine concentrations bore a similar relationship to the intravenous dose, as did the peak nicotine concentrations to the retained doses during smoking.

Abstract: Some 12% of all geriatric admissions to University College Hospital and Whittington Hospital are for patients whose relatives or friends can no longer cope with them at home. The person principally involved with home support was interviewed in 50 such cases. The causes of inability to cope were identified on a quantitative and qualitative basis. The supporters were asked to assess which of the problems identified would have to be alleviated to restore a tolerable situation at home; 46 (92%) were able to do so. Identification of the "alleviation factors" forms a therapeutic and prognostic guideline in this type of admission and may have far-reaching social and economic implications.

Abstract: We investigated 219 deaths from myocardial infarction in women under the age of 50. Their histories were compared with those of living age-matched controls selected from the same general practices. The frequency of use of oral contraceptives during the month before death was significantly greater in the group with infarction than during the corresponding month in the control group and the average duration of use was longer. No information of cigarette smoking was available but the proportion of women being treated for hypertension or diabetes was greater among those who died than among the controls. This did not alter the overall conclusion that the risk of fatal myocardial infarction was greater in the women using oral contraceptives, particularly in the older age groups.

Abstract: HL-A typing of 150 patients who had developed diabetes mellitus by the age of 30 years showed a significant association with HL-A 8 and W 15. The HL-A genotypes were determined in 17 families in which two or more siblings had this type of diabetes. The zygotic assortment of HL-A haplotypes was found to be significantly disturbed from the expected random pattern, with a reduction in the number of siblings showing no identical haplotypes and an appreciable increase in the number with both haplotypes identical. This appears to be most consistent with the presence of a gene or genes pre-disposing to this type of diabetes at a locus closely linked to the HL-A chromosomal loci. This locus appears to have a fundamental role in the susceptibility to juvenile diabetes.

Abstract: In a double-blind study on the value of equine ("natural") oestrogens 30 patients presenting with menopausal symptoms in a group practice were monitored for possible adverse effects on blood clotting, weight, and blood pressure. The women were randomly allocated to two groups and given either three months' hormone treatment followed by three months' placebo or vice versa. An appreciable amelioration of all symptoms on placebo made it difficult to asses the genuine value of oestrogen treatment during the period of study. Both groups made a dramatic clinical improvement during the first three months. Nevertheless, the symptoms of the 15 women who received oestrogen first returned after the cross-over to placebo without any suggestion of a placebo response. In contrast, the other group who took placebo first did not deteriorate after changing to oestrogen. The menopausal index and the karyopyknotic index were not reliable guides to the need for oestrogen treatment. Hot flushes, however, were proportionately reduced on oestrogen and they seemed to be more readily eliminated in individual cases by oestrogen. The results of blood clotting studies indicated that natural oestrogen administration raised the levels of the extrinsic clotting factors VII and X and accelerated the prothrombin time. The findings were similar to those observed after three months synthetic oestrogen administration with oral contraception. Long-term studies and epidemiological surveys of the clinical incidence of thrombotic and other sequelae are needed before large-scale oestrogen replacement treatment can be recommended.

Abstract: Sensitivity to chromium, cobalt, nickel, molybdenum, vanadium, and titanium was studied by patch tests in 50 patients who had received total joint replacements Nineteen (38%) were sensitive to one or more of the metals In 23 patients non-traumatic failure of the prosthesis had occurred, and 15 of these patients were sensitive to metal Out of 27 patients with no evidence of prosthesis loosening, four were sensitive to nickel and cobalt or nickel only Dermatological reactions occurred in 13 patients after surgery; in only eight, however, was there evidence of metal sensitivity These findings indicate that metal-on-metal total joint replacements may sensitise the patient to metals contained in the prosthesis Although there is a high incidence of prosthesis failure among metal-sensitive patients it remains uncertain whether the loosening causes the sensitisation or vice versa

Abstract: Keratoconjunctivitis sicca, conjunctival scarring, fibrosis, metaplasia, and shrinkage developed in 27 patients as an adverse reaction to practolol. Rashes, nasal and mucosal ulceration, fibrous or plastic peritonitis, pleurisy, cochlear damage, and secretory otitis media also occurred in some cases. Three patients suffered profound visual loss though most retained good vision. Symptoms and signs improved on withdrawal of the drug, but reduction of tear secretion persisted in most patients.

Abstract: The rhesus haemolytic disease story is a particularly fascinating one. In a period of less than 30 years the precise aetiology of the disorder has been worked out, methods for treating the established disease have been developed, and finally a highly successful form of prophylaxis has been established. In this book Sir Cyril Clarke has selected a series of key papers from the rhesus story and has arranged them in three sections, covering the discovery of the rhesus blood group system, methods for treating the disease, and finally the prophylaxis of rhesus immunization. Each paper is preceded by a short critical commentary by the editor. Because of Sir Cyril's particular interest in the prophylaxis of rhesus immunization the third section is by far the longest, and important parts of the story, such as the thorny problem of nomenclature, are dealt with less fully. However, short extracts of some of the leading articles and letters dealing with anti-Rh serum nomenclature are included which serve to whet the reader's appetite for delving further into what was a fascinating combat between the serological giants. The articles have been photocopied from the original publications, and the standard of reproduction, withthe exception ofan occasional x-ray or blood film, is very high, and the whole format of the book is extremely attractive. The editor and publishers have done well to keep the material up to date, and the final section is a reproduction of the summary of an Rh and immunization workshop held at the second congress of immunology at Brighton in July 1974. The early papers on the prophylactic approach to rhesus immunization make particularly fascinating reading. There seems little doubt that the Liverpool and New York groups arrived at a similar scheme for preventing immunization quite independently and for quite different reasons. After descriptions of a few early setbacks on both sides of the Atlantic the papers then describe a series of successful preliminary trials, and finally there are a series of large-scale trial reports from many countries showing that prophylaxis is unequivocally successful. This book underlines the fact that the only way to get real insight into any research field is to go back and read the original papers, and Sir Cyril Clarke has done an invaluable service by setting out the rhesus story in this way. It can be thoroughly recommended to everybody interested in the subject. It should have a much broader appeal, however, and because it highlights the curious mixture of chance, insight, clashes of personalities, and considerable element of good luck which underlies most important scientific discoveries it makes an excellent introduction to medical research for anyone embarking in this rather uncertain pastime. Finally, at a time when money for research is becoming hard to get it is nice to be reminded that an extremely important piece of work cost virtually nothing to get off the ground.

Abstract: Plasma nicotine three minutes after smoking a cigarette was measured in 10 sedentary workers in mid-morning and five hours later on four typical working days. The average mid-morning level after they had been smoking their usual cigarettes (mean nicotine yield 1-34 ng) was 150-4 nmol/l (24-4 ng/ml) (range 95-6-236-7 nmol/l (15-5-38-4 ng/ml)). Despite great variation between smokersthe mid-morning levels of each smoker were fairly consistent over the four mornings and correlated 0-82 with their carboxyhaemoglobin levels. After continuing to smoke their usual brand or switching to a high-nicotine brand (3-2 mg) average afternoon levels of 185-6 and 180-0 nmol/6 (30-1 and 29-2 ng/ml) respectively were not significantly higher than the morning levels, but after switching to low-nicotine cigarettes (0-14 mg) the plasma nicotine dropped to an average of 52-4 nmol/l (8-5 ng/ml). The changes between morning and afternoon while smoking usual or high-nicotine cigarettes showed marked individual variation. The findings suggest that the plasma nicotine level just after a cigarette depends more on the way the cigarette is smoked than on its nicotine yield or the number which have been smoked over the preceding few hours.

Abstract: Urinary N-acetyl-beta-D-glucosaminidase (NAG) activities were assayed in every urine void throughout 24 hours in 17 normal people and in four patients with renal disease. The variation in NAG activity due to changing rates of urine flow was almost eliminated by factoring enzyme activity by the urinary creatinine concentration. Random samples of urine may thus be used for assay. The results of NAG assay in 36 patients with acute and chronic renal diseases showed that NAG was a sensitive indicator of renal damage. This simple test may be valuable in detecting or monitoring renal disease.

Abstract: Diurnal plasma glucose profiles and oral glucose tolerance during pregnancy were studied in normal women, chemical diabetics, and insulin-requiring diabetics. In normal women the mean diurnal plasma glucose rose by only 0.22 mmol/1 (4 mg/100 m1) during pregnancy. Mild chemical diabetes resulted in an increase in both the mean diurnal glucose concentration and the fluctuation of plasma glucose levels during the day. Fluctuation in glucose concentration in insulin-dependent diabetics was about three times that found in non-diabetic women of similar gestation, with relative hyperglycaemia during the day and hypoglycaemia at night. In non-diabetic women and those with chemical diabetes the mean dirunal glucose correlated closely with the total area under the three-hour oral glucose tolerance curve and significantly, but less closely, with the two-hour glucose tolerance test value.

Abstract: In November 1972 the British Diabetic Association sponsored a register to which notification was invited of all new cases of diabetes occurring in children aged 0-15 years in Great Britain and Ireland. More than 2000 cases were notified in the first two years. Notification suggested that there was a minimum yearly incidence of 7-67 cases per 100 000, though incidences varied from year to year and by geographical area. Several reports of simultaneous onset of diabetes in sibs of different ages provided evidence of clustering. A seasonal variation in incidence was found in children aged 5-15 years with peaks in the autumn and winter. The age distribution was bimodal with a main peak at about 11 years and a secondary peak at about 5 years. The sex ratio showed a male excess from 0-4 years and from 11-15 years and a female excess from 5-10 years. Overall there were slightly more male cases. Altogether 11% of patients had a first-degree relative with diabetes. The register and several investigations based on it will continue.

Abstract: In a multicentre trial 456 selected patients with low back pain were randomly allocated to one of four treatments-manipulation, definitive physiotherapy, corset, or analgesic tablets. Patients were reassessed clinically after three weeks9 treatment and again after a further three weeks. Questionnaires were used to find out the patients9 condition three months and one year after admission to the trial. There were never any important differences among the four groups of patients. A few patients responded well and quickly to manipulation, but there was no way of identifying such patients in advance. The response to a corset was slow, but the long-tern effects were at least as good as those of the other treatments. Patients treated only with analgesics fared marginally worse than those on the other three treatments. There is no strong reason, however, for recommending manipulation over physiotherapy or corset.

Abstract: A patient with Goodpasture's syndrome has recovered after treatment with immunosuppressive drugs (cyclophosphamide and prednisolone) and removal of circulating antibodies by plasma exchange. This was performed on seven occasions and seems to have hastened the decline in circulating antibody levels. Undertaken early in the course of the disease plasmapheresis could prove a useful addition to its therapy.

Abstract: A series of 130 consecutive outpatients with recurrent aphthous stomatitis were screened at the oral medicine department, Glasgow Dental Hospital, for deficienciesin vitamin b12, folic acid, and iron. In 23 patients (17.7%) such deficiencies werefound; five were deficient in vitamin B12, seven in folic acid, and 15 in iron. Four had more than one deficiency. Out of 130 controls matched for age and sex 11 (8.5%) were found to have deficiencies. The 23 deficient patients with recurrent aphthaewere treated with specific replacement therapy, and all 130 patients were followed up for at least one year. Of the 23 patients on replacement therapy 15 showed complete remission of ulceration and eight definite improvement. Of the 107 patientswith no deficiency receiving local symptomatic treatment only 33 had a remission or wereimproved. This difference was significant (P less than 0.001). Most patients withproved vitamin B12 or folic acid deficiency improved rapidly on replacement therapy;those with iron deficiency showed a less dramatic response. The 23 deficient patientswere further investigated to determine the cause of their deficiencies and detect the presence of any associated conditions. Four were found to have Addisonian perniciousanaemia. Seven had a malabsorption syndrome, which in five proved to be a gluten-induced enteropathy. In addition, there were single patients with idiopathic proctocolitis, diverticular disease of the colon, regional enterocolitis, and adenocarcinoma of thecaecum. We suggest that the high incidence of deficiencies found in this series andthe good response to replacement therapy shows the need for haematological screening of such patients.

Abstract: The effects of oral bromocriptine in acromegaly have been studied. A dose of 5 mg six-hourly suppressed circulating growth hormone (GH) levels in nine out of 11 patients treated for seven to 11 weeks. This was associated with considerable clinical improvement in all patients, with abolition of excessive sweating, reduction in soft-tissue thichening, loosening of rings, decrease in shoe size, improvement in facial features, and loosening of dentures. Metabolic changes included improvement in glucose tolerance and reduction in hydroxyproline excretion. Unlike the actions of growth hormone release inhibiting hormone the suppression of GH was not accompanied by a reduction in insulin or glucagon secretion, though prolactin levels were suppressed. Side effects other than mild constipation were not seen when the full dose regimen was reached by slowly increasing the dose from 2-5 mg once daily. Bromocriptine holds promise as a safe and orally effective medical treatment to augment surgical or radiotherapeutic measures directed at the pituitary tumour. Its efficacy during longterm administration remains to be established.

Abstract: Heart rate responses to autonomic stimulation and inhibition were studied in 13 diabetic autonomic neuropathy. Parasympathetic function was impaired in all patients and sympathetic function in most. One patient9s heart appeared to be totally denervated. The consequences of cardiac denervation include tachycardia, a fixed heart rate, and a possible tendency to cardiac dysrhythmias, which caused spontaneous cardiac arrests in three patients.

Abstract: Triceps and subscapular skinfold thicknesses were measured in 222 pairs of like-sex twins (78 monozygotic and 144 dizygotic) aged 3-15 years. Log transformations of the measurements were standardized for age and sex and the results used to estimate heritability--that is, the proportion of total variation determined by genetic factors. The overall contribution of non-genetic familial effects was small. There were appreciable differences in heritability between limb and trunk fat and between the sexes and at different ages. Over the age of 10 heritability was high for both sites in boys and girls. In younger children environmental factors contributed more to the variation.

Abstract: The maximum rise in blood glucose after 50 g lactose by mouth was determined in 40 adult Arabs. Out of 30 Bedouin, urban Saudi, and Yemeni and 9 of mixed ancestry (usually partly African), 25 (83%) and 2 (22%) respectively showed an increase of over 1-1 mmol/1 (20 mg/100 ml). In common with most northern Europeans and Hamitic people of northern Africa, Arabs in Saudi Arabia usually have high intestinal lactase concentrations in adult life. This persistence of high levels probably originated in the Arabian peninsula. Its selective advantage may have been associated with the fluid and calorie content of camels9 milk, which is important for survival in desert nomads.

Abstract: On admission to hospital during the acute phase of a stroke presumed due to ischaemic infarction in one cerebral hemisphere 93 patients were examined to determine the factors associated with a poor prognosis for immediate survival. The patients particularly at risk were those who were overtly unconscious and those with any combination of impaired consciousness, dense hemiplegia, and failure of conjugate ocular gaze towards the side of the limb weakness. Necropsy evidence suggested that these signs usually indicate infarction of the whole of one middle cerebral artery territory which is often secondary to internal carotid artery occlusion and commonly produces fatal cerebral oedema.

Abstract: Serum and nasopharyngeal IgA antibody levels were estimated in 20 malnourished children and 20 matched healthy controls after immunization with a single dose of live attenuated measles or poliovirus vaccine. Seroconversion and serum neutralizing antibody titres were comparable in the two groups. Secretory IgA antibody was detected significantly less often in undernourished children; the time of its first appearance was delayed-and its maximum level was significantly lower. Impaired secretory antibody response in malnourished children may contribute to slow inadequate recovery from viral and enterobacterial infections and predispose to lifethreatening complications.

Abstract: The clinical use of uncoated charcoal haemoperfusion systems, despite their efficacy, has hitherto been prevented by the occurrence of a number of adverse effects including charcoal embolism and marked thrombocytopenia. Charcoal coated with a synthetic hydrogel overcomes many of the disadvantages associated with the use of uncoated material in that there is a much reduced thrombocytopenia and no evidence of charcoal embolism. Six patients, severely poisoned as a result of overdoses of either a barbiturate or glutethimide, were haemoperfused using such a system. Four made complete recoveries, and the two patients who died had both suffered cardiorespiratory arrests before perfusion. In contrast to haemodialysis charcoal haemoperfusion is simple to initiate, less expensive in terms of manpower and equipment, and gives superior clearance data for all barbiturates and glutethimide. We believe that this technique may have a significant role to play in the management of the severely poisoned patient.

Abstract: Through gleeding into the lung parenchyma is responsible for morbidity and mortality in patients with leukaemia pulmonary haemorrhage is seldom diagnosed during life. We diagnosed occult pulmonary haemorrhage in five leukaemic patients with unexplained infiltrates on chest roetgenograms by examining alveolar macrophages retrieved by bronchopulmonary lavage. Macrophage haemosiderin content was greatly increased in the patients with pulmonary haemorrhage as compared to normal and thrombocytopenic control subjects. Haemoglobin and intact erythrocytes in alveolar macrophages were taken as evidence of recent haemorrhage. Intrapulmonary bleeding may occur often in patients with leukaemia, and bronchopulmonary lavage offers a safe approach to diagnosis and allows for concomitant identification of pulmonary infection.

Abstract: An analysis of the reports on 16 patients who developed cardiac tamponade, complicating the use of central venous catheters, showed that 14 died. The two survivors were treated by removal of the catheter and needle aspiration of the pericardial fluid. Some patients complained of warning symptoms such as nausea, pain, and dyspnoea, and the combination of tachycardia, hypotension, and raised venous pressure was common. We suggest that awareness of the hazard, radiographic visualization of the catheter tip, and expeditious treatment would reduce the mortality.