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Summary A comparison was made between the proteins in serum and pleural fluid in 52 cases of pleural effusion using the technique of paper electrophoresis. The results showed a marked difference in the proportion of α2 globulin present in the serum and pleural fluid in the majority of cases of pleural effusion associated with neoplastic disease. It is suggested that these changes might be used as an aid in the differential diagnosis of cases of pleural effusion.

Periodic migrainous neuralgia is a clearly defined syndrome and excellent descriptions of it have been given by a number of authors (Harris, 1926, 1936 ; Horton et al., 1939 ; Horton, 1941 ; Ekbom, 1947 ; Kunkle et al., 1952 ; Symonds, 1956 ; Bickerstaff, 1959). Its clinical features are usually so charac teristic that its diagnosis should present no more difficulty than that of trigeminal neuralgia or classical migraine. Various treatments have been advised in the past, and, in particular, Ekbom (1947), Symonds (1956), and Bickerstaff (1959) have described their experience with prophylactic ergotamine preparations. Bickerstaff (1959) suggested that the syndrome was well defined but not widely recognized and that it is often mis diagnosed. He suggested that by describing it in a medical journal with a wide circulation it should become better known and many of the diagnostic difficulties would disappear. We discovered that in our patients the average time from onset of symptoms to diagnosis was 6.5 years ; hence it is clear that no remarkable change has occurred in the speed of diagnosis since Bickerstaff's paper appeared, and we therefore decided to review our own experience. We have done this in two ways : first, we give a brief review of the clinical picture as we have seen it, and then the results of treatment are reviewed.

Seven cases of the “locked-in” syndrome are described. This is a disorder in which a conscious, mute patient is completely paralysed apart from some form of eye movement, usually as a result of an infarct in the ventral pons. Such patients are often assumed to be in coma and as a result may be distressed by inappropriate conversation around the bedside.

The clinical, laboratory, and renal biopsy findings in 47 children with symptomless haematuria are reported. In 41 the haematuria was recurrent. Local causes were excluded by means of intravenous urography, which was normal in all but one child, who had a horseshoe kidney.Since all the patients had presented in a similar manner they were classified into four groups according to the severity of glomerular changes on renal biopsy. In group I the glomeruli were optically normal. In group 2 they showed a variable degree of mesangial thickening with absent or minimal cellular proliferation. In group 3 there was diffuse mesangial thickening and proliferation-an appearance indistinguishable from that of subsiding post-streptococcal glomerulonephritis. Compared with groups 1 and 2, more patients in this group had persistent proteinuria, as well as evidence of streptococcal infection preceding the initial haematuria. Only two patients showed severe proliferative glomerulonephritis on biopsy (group 4); both had heavy proteinuria and one repeatedly had low serum beta1(c)-globulin levels.

Primary amoebic meningoencephalitis is caused by amoebae of the genera Naegleria and Hartmannella (Acanthamoeba), which ordinarily are free-living saprophytes. The infection may be acquired from fresh water—for example, while bathing—the amoebae invading the nasal mucosa and reaching the meninges and brain along the olfactory nerve filaments. The disease is designated “primary” to distinguish it from meningocerebral infection caused by the parasitic amoebae, particularly Entamoeba histolytica, which invade the central nervous system only as a result of dissemination in the blood stream from lesions in other parts of the body. During histological reappraisal of old specimens in a medical museum in London an instance of amoebic meningoencephalitis histologically indistinguishable from the published cases has been found. The specimen dates from 1909. The patient was said to be from Essex. What may have been another case, seen in Northern Ireland in 1937, is also described briefly. These observations may indicate that this disease occurs in the British Isles. Primary amoebic meningoencephalitis should be considered in the differential diagnosis of every case of acute meningitis.

Twenty-six cases of tumoral calcinosis are reported from Kenya. The disease, frequently misdiagnosed, is of unknown origin. It presents as calcified tumours, usually around the hips and buttocks, in muscle and subcutaneous tissue. The tumours are partly solid, partly multiloculated cysts which contain a chalky fluid. They may grow rapidly or very slowly, and are found in children and adults. Both sexes are affected and there is no obvious tribal or geographical localization.

Investigation of a patient with hypercalcaemia, hypophosphataemia, and nephrocalcinosis failed to lead to a clear diagnosis. Neither primary hyperparathyroidism nor primary incomplete renal tubular acidosis could explain all the biochemical features, and it seems that more than one fundamental abnormality may have been present.

Although the respiratory system is directly involved in a large proportion of cases of systemic lupus erythematosus (S.L.E), little is known of the basic underlying pathological changes (Harvey, Shulman, Tumulty, Conley, and Schoenrich, 1954 ; Larson, 1961). Pleurisy and pleural effusions, which are usually bilateral and small, are well recognized (Winslow, Ploss, and Loitman, 1958). The pulmonary lesions of S.L.E. have been decribed radiologically as patchy pneumonitis, linear atelectasis, and diffuse and micronodular infiltration (Israel, 1953 ; Gould and Daves, 1958 ; Myhre, 1959 ; Alarcon-Segovia and Alarcon 1961). These terms presuppose a pathological basis for which there is remarkably little evidence in post-mortem findings (Purnell, Baggenstoss, and Olsen, 1955 ; Larson, 1961). Several writers have also commented on the occurrence of raised diaphragms, not accounted for by associated pulmonary or pleural involvement, which move slowly over a reduced range (" sluggishly ") (Ellman and Cudkowicz, 1954 ; Harvey et al:, 1954 ; Myhre, 1959). A patient with S.L.E. was seen in whom breathlessness, unexplained by physical and radiological examination, had been a major symptom for many years. Lung-function studies per formed early in her illness showed that she had small stiff lungs.

Of 106 patients admitted for investigation to a neurological hospital with a presumptive diagnosis of dementia, 84 were confirmed to have intellectual impairment or loss of learning and memory function or both. A possible aetiology for the dementia was found in 36 of these 84 patients; the commonest causes discovered were intracranial mass lesions, arterial disease, and alcoholism. Fifteen of the 106 patients were found not to be demented but to have some other illness, most commonly depression. Of the whole series some 15% of the patients suffered from conditions that were amenable to treatment.

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.

The ratio of α/β-lipoprotein in serum, as estimated by paper electrophoresis, in eight cases of hydatidiform mole was found to be significantly lower than that in normal women and in pregnant women. The findings are discussed in relation to the differential diagnosis of molar and normal pregnancy.

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 reports a controlled prospective unselected real-time comparison of human and computer-aided diagnosis in a series of 304 patients suffering from abdominal pain of acute onset. The computing system9s overall diagnostic accuracy (91·8%) was significantly higher than that of the most senior member of the clinical team to see each case (79·6%). It is suggested as a result of these studies that the provision of such a system to aid the clinician is both feasible in a real-time clinical setting, and likely to be of practical value, albeit in a small percentage of cases.

In the course of a study of patients with hypochromic anaemia investigated by this unit (Beveridge, Bannerman, Evanson, and Witts, in preparation) a surprisingly large number were found to have unexplained occult alimentary bleeding. Iron-deficiency anaemia associated with unexplained occult blood loss is a recognized clinical problem and has been referred to in several papers (Heath and Patek, 1937 ; Bedford and Wollner, 1958 ; Bel, 1959 ; Retzlaff, Hagedorn, and Bartholomew, 1961 ; Kay, 1962). However, there is little or no information about the long term prognosis. We therefore report the results of a follow-up study on 68 patients in whom this diagnosis was made.

Three cases of cerebellar ectopia first producing symptoms in adult life are reported. This potentially remediable anomaly may not be suspected in adults, in whom associated congenital bony abnormalities of the skull and cervical spine are often absent. In these cases diagnosis depends on radiological contrast studies; in particular it is important to examine the cervical canal in the prone and supine positions.

A Kveim suspension has been shown to inhibit the migration of leucocytes in vitro from 12 out of 18 patients with Crohn's disease but to have no comparable effect on leucocytes from patients with ulcerative colitis or from a group of patients with other diseases. These findings provide further evidence of cross-reactivity or of a possible aetiological link between Crohn's disease and sarcoidosis and suggest a further immunological distinction between Crohn's disease and ulcerative colitis.

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.

A method is described for differentiating the phenylalaninaemias based upon blood phenylalanine (phe) responses to ingestion of natural protein diets with standard phe content. A classification scheme derived primarily from these studies is suggested which includes two forms of phenylketonuria (PKU) and four forms of phenylalaninaemia (variants) unrelated to abnormalities in tyrosine metabolism. Dietary therapy is mandatory for types I and II and possibly for type III, but does not appear to be necessary for types IV or V. Evidence provided by family studies supports the concept that the phenylalaninaemias are genetically distinct. The increased incidence of PKU consequent to newborn blood screening programmes may well be related to misdiagnosis as well as to increased recognition of PKU.

A simultaneous combined pancreatic test can be performed in one morning with only one intubation of the duodenum. The test includes the measurement of exocrine pancreatic secretion of bicarbonate, enzymes, and radioactive selenium, pancreatic scanning, hypotonic duodenography, and cytology of the duodenal aspirate. In the first 70 patients it was found that a single secretion test was of only limited value in detecting pancreatic disease; cytology was the most reliable and scanning the least reliable single test; and that the combined test provided near-complete discrimination between patients with no pancreatic disease, with chronic pancreatitis, and with carcinoma of the pancreas.

Study of 30 patients with raised intracranial pressure whose condition worsened after lumbar puncture emphasizes the danger of carrying this out in the presence of raised intracranial pressure. In half the cases deterioration was immediate and dramatic, and in the other half it occurred within 12 hours. Probably a tentorial or cerebellar pressure cone, or both, had formed before lumbar puncture, and the procedure made this worse and caused the clinical deterioration.A history of progressive headache associated with mental changes, and the development and progression of localizing neurological signs were the two features suggestive of varied intracranial pressure found most constantly in this series. A good quality plain x-ray film is important in the diagnosis of this condition.

The reports of the 15 recorded outbreaks of benign myalgic encephalomyelitis have been reviewed and in one instance the original clinical data studied. We believe that a lot of these epidemics were psychosocial phenomena caused by one of two mechanisms, either mass hysteria on the part of the patients or altered medical perception of the community. We suggest that the name “myalgia nervosa” should be used for any future cases of functional disorder which present the same clinical picture.

Despite the increase in the incidence of early infectious syphilis during the past seven years neurosyphilis is relatively uncommon, and there is, as yet, no satisfactory evidence to suggest that it is increasing in frequency (Laird, 1962). Never theless, cases of neurosyphilis present in many types of medical practice, and lack of experience and familiarity with the clinical manifestations may lead to delay in diagnosis and to permanent damage to the central nervous system. It seems probable that more cases of neurosyphilis may occur in the future because of the rising incidence of early syphilis, not all of which is diagnosed and treated. Neurosyphilis may present as an acute neurological illness, which may not be recognized unless the wide variety of manifestations is appreciated and the possibility of syphilis considered. Recently we have seen four patients with neuro syphilis in whom the presenting symptoms and signs were those of an acute neurological disorder.

Appendicitis is not the only common cause of acute abdominal pain in childhood. Almost equally common is an acute episode which in its early stages resembles acute appendicitis but which subsides without treatment in 24 to 48 hours. The clinical features of this syndrome are contrasted with those of appendicitis. The two conditions cannot always be distinguished on clinical grounds, leading to admission to hospital for observation and the finding of a normal appendix in 14% of operations for suspected appendicitis. Reasons are given for abandoning attempts to diagnose acute mesenteric adenitis at the bedside.

Chemical and histological studies are often unable to differen tiate chronic extrahepatic obstructive jaundice (due to calculi, neoplasia, or stricture) from chronic intrahepatic obstructive jaundice (caused by primary biliary cirrhosis or by drugs, . notably anabolic steroids and phenothiazine derivatives). Oral and intravenous cholangiography are also ineffective when the serum bilirubin is greater than 2-3 mg./100 ml. In such circumstances percutaneous transhepatic cholangiography may be useful, since this method can demonstrate the dilated intra hepatic biliary system which develops in chronic extrahepatic obstruction ; while a negative result may remove the need for laparotomy in a patient with hepatocellular disease. Since Atkinson et al. (1960) remarked on the revival of interest in this investigation numerous authors (Santos et al., 1960 ; Kaplan, et al., 1961 ; Shaldon et al., 1962 ; Arner et al., 1962 ; Flemma et al., 1963) have agreed on its value. Only one of these reports has come from this country, and the British Medical Journal (1964) suggests that percutaneous transhepatic cholangiography has still to gain general acceptance in Great Britain. This report of a small series with a case history and a brief survey of recent studies may be of interest.

Three cases of brain stem astrocytoma and one of a para-stem vascular tumour are described, each showing a history of relapses and remissions. The diagnoses were confirmed by necropsy, and it is suggested that the relapsing course may have been due to oedema and necrosis in both the tumour and the surrounding brain tissue. Features indicating repeated recurrence of a lesion at the same site in the brain stem justify full neuroradiological investigation before a diagnosis such as multiple sclerosis can be accepted.