Showing papers in "QJM: An International Journal of Medicine in 1966"

The pathology of diabetic neuropathy

Abstract: The chapter attempts to describe the expected diversed underlying pathological alterations in patients with diabetes mellitus and to relate the changes to the clinical syndromes. Keywords: perikaryal; nerve fiber; horn cell; ganglia; tissue; vascular

Exercise-induced asthma.

Abstract: Exercise maintained for approximately eight minutes results in a fall in F.E.V.1 a rise in airway resistance, and impaired gas distribution in asthmatic subjects. These effects are usually maximal within 15 minutes after cessation of exercise and recovery takes place over the next 30 minutes. Measurement of airway resistance before and after exercise in normal subjects suggests that the same mechanism is operating in them. Hyperventilation stimulated by the inhalation of carbon dioxide has failed to produce a similar effect. Chlorpromazine, atropine, mepyramine maleate, and hydrocortisone administered before exercise have failed to block the effect but adrenaline has succeeded. It has been possible in a few subjects to lessen the effect of exercise by repeated exercise on the same day and we interpret this as pointing towards the depletion of a bronchoconstrictor substance released in the earlier periods. The possible substances are discussed.

The association of peptic ulceration, chronic renal disease, and analgesic abuse.

Abstract: Patients are described who have both peptic ulcers and chronic renal disease together with a history of prolonged analgesic abuse. Psychological instability may predispose to the high analgesic intake. The symptoms of peptic ulceration were frequently resistant to medical management and a gastrectomy had been performed in more than half the patients studied. The renal features are those of renal papillary necrosis and bacterial invasion of the kidney did not seem to play an important role. Although urinary tract infection was present at some time in two-thirds of the patients the most frequent urinary finding was a sterile pyuria. Patients with renal papillary necrosis showed a much higher incidence of hypertension than has been previously recorded. Anaemia is a prominent feature and seems to be due to occult gastrointestinal blood loss and uraemia. The diagnosis is frequently missed if only one radiological examination is made. Progressive changes in serial radiographs more often reveal it.

The incidence of osteoporosis in normal women: its relation to age and the menopause.

Abstract: The spine, hands and femur were X-rayed in 152 normal women between 19 and 83 years of age. Metacarpal and femoral cortical thickness and vertebral density all tended to fall with age, particularly after the fifth decade. Vertebral biconcavity, on the other hand, did not develop. When the indices of osteoporosis were related to the menopause it was observed that the fall in vertebral density occurred about five years after the menopause, metacarpal cortical thickness started to fall about 10 years after the menopause and femoral cortical thickness about five years later still. The results suggest that the osteoporotic process commences or accelerates in women soon after the menopause but cannot be taken to signify that this process is necessarily a normal or physiological one.

Acute barbiturate poisoning—a review of two years experience

Abstract: The results of therapy in 776 patients with acute barbiturate poisoning over a two-year period are studied. The mortality was 0.8 per cent. 94.9 per cent. were treated successfully by a regime of supportive therapy. This routine is described in detail and the differences from the ‘Scandinavian Method’ are discussed. Only 5.1 per cent. required measures to enhance removal of the poison. The indications for instituting this therapy are considered in the light of present knowledge and with regard to current practice elsewhere. The results show that the vast majority of these patients can be managed adequately by supportive treatment and that additional measures should be reserved for very severely poisoned patients.

Anticonvulsant therapy, megaloblastic haemopoiesis and folic acid metabolism

Abstract: A clinical, haematological, and biochemical investigation of 62 epileptics is reported. Fifty-four of the patients were receiving anticonvulsant drugs and eight were untreated. None of the treated patients was anaemic, but 17 (38 per cent.) of 45 in whom the bone marrow was examined showed megaloblastic haemopoiesis. Treatment with folic acid in seven patients restored normoblastic haemopoiesis in all. Only seven of the 54 treated patients showed macrocytosis and only five showed hypersegmentation of the neutrophils in the peripheral blood. Serum folate concentrations were subnormal in 76 per cent. of the treated patients. With one exception, serum vitamin B12 concentrations were within the normal range, though significantly lower in the megaloblastic group than in the untreated patients. Only a small proportion of the treated patients excreted excess Figlu after a histidine load. Serum lactate dehydrogenase concentrations were normal in all patients. It was found that neither morphological changes in the peripheral blood nor biochemical investigations were reliable indications of megaloblastic haemopoiesis. All three major anticonvulsant drugs (phenobarbitone, phenytoin, and primidone) appear to be capable of causing folate deficiency. The possible mechanisms are discussed, and it is suggested that there may be a relationship between the anti-folate effect of the drugs and their therapeutic action. Attention is drawn to the possible consequences of prolonged drug-induced folate deficiency, which may be responsible for producing mental symptoms.

The liver lesion of the epping jaundice

Abstract: An outbreak of jaundice in the Epping district, involving at least 84 people, had been traced previously to eating bread made from flour accidentally contaminated with 4,4'-diaminodiphenylmethane. In this paper the clinical, biochemical, and liver-biopsy findings are described. There were three modes of presentation according to presence or absence of upper abdominal pain and its severity, but this could not be correlated with the probable amount of toxin eaten. Rigors, limb pains, malaise, and obstructive jaundice followed. Jaundice sometimes lasted for months. Differential diagnosis included cholelithiasis. Serum bilirubin, serum alkaline phosphatase, and serum aspartate transaminase were raised to a varying and generally moderate degree. In a few cases there was blood eosinophilia. Seven patients had liver biopsies. These showed portal inflammation, eosinophil infiltration, cholangitis, cholestasis, and hepatocellular damage at different stages. Fibrosis appeared to be slight. All patients have now made a good clinical recovery.

Parathyroid function in chronic renal failure

Abstract: A collection has been made of 134 personal and published cases of azotaemic osteodystrophy in which adequate information was available concerning the pathological state of the bones. Measurements were available of the plasma calcium, plasma phosphate, and blood-urea-nitrogen in all cases, and of plasma bicarbonate and plasma proteins in a representative sample. The plasma levels of calcium and phosphate in the whole series of 134 cases were not related reciprocally but were correlated directly. These data were further analysed by allocating each case to either of two sub-groups, according to the type of pathological lesions present in the bones. In one group there was evidence of defective mineralization of skeletal tissues, in the form of either rickets or osteomalacia, and the plasma-calcium was found to be statistically sub-normal. In the other group there was no primary defect of mineralization but the lesions of generalized osteitis fibrosa were present and the plasma calcium was statistically normal. There was no significant correlation between the plasma levels of calcium and phosphate in either sub-group; and the plasma phosphate was significantly higher in the group with the higher plasma calcium levels. The data indicate that in patients with renal osteodystrophy, contrary to general belief, the plasma calcium varies independently of the plasma phosphate. Since these results imply differences in parathyroid function among patients with azotaemic osteodystrophy, a survey has also been made of the recorded parathyroid weights in chronic renal failure. Generalized osteitis fibrosa and the accompanying normal levels of plasma calcium are associated with greater parathyroid hypertrophy than is found in most cases of chronic renal failure or cases with defective mineralization. The various data are interpreted in relation to the known metabolic disturbances and natural history of azotaemic osteodystrophy. By analogy with states of simple vitamin D deficiency, it is suggested that hypocalcaemia and relative unresponsiveness to the calcaemic action of parathyroid hormone are related to an acquired resistance to vitamin D. The group of cases with a statistically normal plasma-calcium prove that the parathyroid glands can function effectively in some patients with chronic renal failure, irrespective of the level of the plasma phosphate. The size of the glands and the effects of sub-total parathyroidectomy in patients of this group suggest that the normal plasma calcium results from an increased production of parathyroid hormone. The more advanced renal failure in the normocalcaemic, as compared with the hypocalcaemic, cases could mean that the development of an effective degree of secondary hyperparathyroidism is a function of the duration of the renal disease. It seems likely that when the parathyroid response is sufficient to overcome the effects of the vitamin D resistance it also entails the development of generalized osteitis fibrosa, healing of the defect of mineralization and an increased liability to metastatic calcification.

Autonomic failure with orthostatic hypotension due to intermediolateral column degeneration

Abstract: Two patients who had autonomio failure with orthostatic hypotension are described. Physiological studies indicated a preganghonic sympathetic lesion in the central nervous system. Post-mortem examination in both cases showed severe nerve-cell loss in the intermediolateral columns (preganghonic sympathetic cells) of the spinal cord. One case also showed the lesions of olivo-ponto-cerebellar atrophy. Both patients are considered to have been suffering from a primary neuronal degeneration.

General alveolar hypoventilation: a syndrome of respiratory and cardiac failure in patients with normal lungs.

Abstract: Chronic alveolar hypoventilation has been considered in terms of its pathogenesis. Distinction has been made between general alveolar hypoventilation, which arises from failure of the ventilatory apparatus, and net alveolar hypoventilation which is secondary to bronchopulmonary disease. Examples are presented to ifiustrate the pathogenesis of general alveolar hypoventilation in various disorders of the ventilatory apparatus. The common end-points for all of these are arterial hypoxaemia and hypercapnia; these abnormalities in the blood gases are responsible for the cardiorespiratory failure of chronic alveolar hypoventilation. However, the clinical expression of these abnormal blood gases is modified by the pathogenetic background: in failure of the respiratory centre, the consequences of arterial hypoxaemia and hypercapnia are manifest in the purest forms, free of the complications of abnormal lungs or mechanics of breathing; in severe kyphoscoliosis, the compressed distorted lung restricts the pulmonary hypertension and cor pulmonale ; in obesity, the hypermetabolic and hypervolemic states provide a background of left ventricular, as well as right ventricular overload, for the consequences of arterial hypoxaemia and hypercapnia. The clinical importance of recognizing the syndrome of general alveolar hypoventilation lies in its reversibility following adequate relief of the hypoxaemia and hypercapnia.

Construction of a model for computer-assisted diagnosis: application to the problem of non-toxic goitre

Abstract: This study describes the construction of a model for the computer-assisted diagnoses of non-toxic goitre. From a study of 53 patients with Hashimoto's disease, 51 with simple goitre and 51 with thyroid cancer, information was obtained which was used in the construction of a probability matrix. The diagnosis was confirmed histologically in all of these patients. The probability matrix was constructed from 30 pieces of information relating to the results of history taking, clinical examination, and laboratory investigations and consisted of a table of the observed incidence of each piece of information in each of the three diseases. This probability matrix was then fed into an Elliott 803 automatic digital computer and formed the memory of the computer for these three diseases. A fresh series of 88 patients, 43 with Hashimoto's disease, 26 with simple goitre, and 19 with thyroid cancer were then studied. Clinical information and the results of laboratory studies were provided as data to the computer to calculate a diagnosis for these patients. Two slightly different applications of probability theory were used for each calculation. In one (Bayesian probability) the ratio of the prior probabilities that any patient would have Hashimoto's disease, simple goitre, or thyroid cancer before any tests or observations had been made, were taken to be 10:89 and 1 respectively on the basis of observations previously made on a population of patients attending a thyroid clinic. In the other application of probability theory (relative likelihood) the prior probabilities of occurrence of the three diseases were assumed to be equal. The diagnoses given by both methods were compared with each other and with the diagnosis of a clinician experienced in dealing with thyroid disorders. In all patients in whom discordence of opinion occurred a histological diagnosis was accepted as the final diagnosis. The method using relative likelihood was considered to be superior to the method using Bayesian probability for in no patient did relative likelihood miss a diagnosis of thyroid cancer when the clinician diagnosed thyroid cancer. This was not true for Bayesian probability which missed three cases of clinically obvious cancer. The possible reasons for this superiority of relative likelihood are discussed in the paper. The results given by relative likelihood agreed with the clinician's correct diagnosis of Hashimoto's disease in 26 of 28 patients. The calculated diagnosis was wrong in two of these patients in whom the clinician made the correct diagnosis. In another 12 patients in whom the clinician made a wrong diagnosis, the calculations based on relative likelihood gave the correct diagnosis. In a further three patients the clinical and calculated diagnoses were both wrong. In 24 of the 26 patients with simple goitre the clinician made the correct diagnosis. In 21 of these patients the diagnosis calculated by relative likelihood was correct and in three patients it was wrong. In two patients both the calculated and clinical diagnoses were wrong. Of the 19 patients with thyroid cancer 16 were correctly diagnosed by relative likelihood and by clinician alike. The remaining three patients in this group were incorrectly diagnosed by both. It is concluded that the results of this study support the contention that a correct diagnosis can be calculated using the theory of conditional probability. Many difficulties remain to be overcome in what still remains a highly experimental approach to the problem of diagnosis.

Cushing's syndrome: adrenocortical hyperactivity secondary to neoplasms arising outside the pituitary-adrenal system

Abstract: Nine cases of Cushing's syndrome associated with non-adrenal-pituitary malignant neoplasms are described. The findings are compared and contrasted with 50 cases of non-malignant Cushing's syndrome previously described. In eight cases the primary carcinoma was bronchogenic in origin, whereas in one ease the primary arose in the parathyroid glands. Eight of the nine cases pre sented with a hypokalaemie alkalosis and all were found to have markedly elevated urinary 17-ketogenic steroids and plasma 1l-hydroxycorticosteroids, both at 9 a.m. and at 12 midnight. The possible mechanisms producing excess adrenocortical activity are considered. The therapeutic approach to the management of cases with the syndrome is briefly discussed.

Corticotirophin-secreting carcinomas

Abstract: The syndrome of adrenal cortical overactivity resulting from corticotrophin producing malignant tumours is reviewed. The primary neoplasm is most commonly an oat-cell carcinoma of the bronchus. The patient's appearance does not resemble that seen in Cushing's syndrome. Common symptoms include muscle weakness, oedema, mental disturbance, and skin pigmentation. The diagnosis is often suggested by the presence of a hypokalaemic alkalosis believed to result from the very high level of cortisol production. Other types of tumour include atypical thymomas, mediastinal neoplasms, malignant bronchial carcinoids and islet-cell carcinoma of the pancreas. In these cases the progress of the disease is slower and the classical picture of Cushing's syndrome more often seen. Five cases are described. Three were due to oat-cell carcinomas of the bronchus, one to a mediastinal neoplasm of uncertain origin and one to a medullary carcinoma of the thyroid. One of these patients was treated by total adrenalectomy and two others by the long-term administration of metyrapone. A case of Cushing's syndrome associated with a benign bronchial carcinoid is also reported. This association has been described before, but there is in sufficient evidence to show whether there is any causal relationship between the two conditions.

Cardio-respiratory aspects of trophoblastic tumours

Abstract: In a group of 60 patients with trophoblastio tumours, 52 had pulmonary metastases and these caused serious symptoms in 12 patients. Six patients presented with cardio-respiratory symptoms, and four of these had no symptoms of a gynaecological nature. Three main forms of pulmonary metastases have been distinguished. The commonest metastasis is the easily recognized discrete mass. This is normally asymptomatic, but confluent growth may progress to a fatal respiratory acidosis. Miliary metastitio involvement of the lungs is the least common form, and may be associated with hyperventilation and tachycardia. Tumour emboli of sufficient size, number, or growth potential to occlude the pulmonary arteries cause pleuritio pain, dyspnoea, hyperventilation, signs of pulmonary hypertension, and large pulmonary arterio-venous shunts. Gross functional disturbances may be corrected by specific chemotherapy.

The absorption of iron after partial gastrectomy

Abstract: Iron-absorption tests were performed in 31 patients who had had a partial gastrectomy, and 18 of these were anaemic. Tests were also performed in 14 patients before and after partial gastrectomy. The absorption of haemoglobin iron was impaired in patients with postgastrectomy anaemia. Some of these also absorbed less inorganic iron than anaemic control subjects but the majority absorbed it well. Absorption of iron when taken orally and when introduced into the jejunum was measured in five normal volunteers. Although inorganic iron was absorbed equally as well from the jejunum as after oral administration, the absorption of haemoglobin iron from the jejunum was impaired. Absorption of inorganic iron was increased in three subjects with postgastrectomy anaemia when a whole hog stomach extract was added to the ingested iron. The significance of these findings in relation to the development of postgastrectomy anaemia is discussed.

Bacterial Endocarditis A Changing Disease.

Abstract: Sixty-eight acceptable cases of bacterial endocarditis were obtained from hospital records for the 20-year period 1945 to 1964 inclusive. Cases were classified according to age, nature of any underlying heart disease, and type of infecting organisms. Two main groups emerged with a very significant mean age difference; the younger were patients with chronic rheumatic heart disease, and a preponderance of Streptococcus viridans infection, while the older very often had no clear antecedent heart disease at all, and were infected predominantly with organisms more virulent than Streptococcus viridaus . Comparison of these two main groups over the 20-year period showed that the disease was occurring progressively more commonly in older patients without antecedent heart disease. Analysis of the Registrar General's statistics for deaths from bacterial endocarditis for the same period shows a progressively rising mean age, and a steadily increasing percentage of deaths in the over 60's. This trend has continued despite a stable over-all mortality since 1954, suggesting a real increased incidence of the disease in the older age-groups. It is concluded that a change in the pattern of bacterial endocarditis has occurred. Possible factors involved in this change are discussed, and its clinical implications stressed.