Showing papers in "BMJ in 1963"

Psycho-Analytic Study of the Child

Abstract: There is a wealth of experimental observation, some of it available previously only in Russian. The subjects were most often dogs and cats, but there are many pertinent observations on the behaviour of children and patients deprived of one of the senses with which images of the outside world are formed -blind people, deaf-mutes, and patients with disorders of development of some central nervous structures. It is very likely that this book contains something of interest and something to think about for every neurologist, psychologist, and physiologist.

Intrauterine Transfusion of Foetus in Haemolytic Disease

Abstract: In the management of the pregnancy complicated by rhesus sensitization the guidance given by amniotic-fluid pigmentation (Bevis, 1956 ; Walker, 1957 ; Mackay, 1961 ; Liley, 1961,1963) has greatly reduced the perinatal mortality from haemolytic disease. In the National Women’s Hospital, Auckland, with a policy of selective induction based on amniocentesis findings, this perinatal mortality has fallen steadily from 22% in 1957–8 to 9% in 1962. It was obvious that no further reduction could be expected from conventional treatment when of 7 perinatal deaths in 80 consecutive rhesus-sensitized pregnancies one baby had multiple congenital abnormalities and the other six were all hydropic before 34 weeks’ gestation. Transfusion in utero appeared the logical procedure for these very severely affected babies early in the third trimester, and intraperitoneal transfusion seemed the simplest technique.

Natural History and Prognosis of Cervical Spondylosis

Abstract: It is now fi**ffftn years since cervical spondylosis was clearly defined (Brain, Knight, and Bull, 1948), but this is not long in terms of natural history, and it is not surprising that little has been written on this aspect of the disease. Brain (1962) considered that the natural tendency of cervical spondylosis was to become arrested, but most of those affected were left with a variable degree of disability. Wilkinson (1962) wrote that the prognosis of cervical spondylosis was good, provided that the condition was recognized early, appro priate treatment was given, and the patient was told how to cope with his disability.

Hypoplasia of lung with congenital diaphragmatic hernia.

Abstract: Hypoplasia of the lung-the term applied to subnormal lung volume-is commonly associated with conditions which affect the volume of the thorax available to the lung. Diaphragmatic hernia encroaches on and therefore reduces it; anencephaly and spina bifida impair the development of the ribs. Polycystic kidneys and renal agenesis may be associated with hypoplastic lung, though the nature of the relationship is less obvious. Potter (1962) stated that with moderate degrees of hypoplasia the foetal lung is less mature than might normally be expected, and that the bronchi are disproportionately numerous, the alveoli and alveolar ducts being reduced in number. She did not specifically count bronchial generations. Campanale and Rowland (1955) describe the necropsy findings in five cases of congenital diaphragmatic hernia in which there was hypoplasia of the lung, and mention the same structural disparities as does Potter. In three of the five cases operation was performed, within 45 minutes, two hours, and 21 hours of birth, respectively and in each case it was found that on the side of the hernia the lung did not inflate properly. Similar behaviour of hypoplastic lungs on inflation at operation had been mentioned by Barrett and Wheaton (1934) among others who have operated in this condition, but they also described operation at four and a half months on a child who survived for 17 days in whom at necropsy it was found that the affected lung had expanded \" almost to normal.\" Tolins (1953) also reported a case operated upon at 22 hours, when attempts to reinflate the lung failed, so that immediately after the operation a pneumothorax was present, the lung being airless until the sixth day. when a large amount of thick mucus was aspirated at bronchoscopy. After this the lung gradually aerated and at 19 months the radiograph was normal. No investigation of the functioning of these lungs subsequent to operation has been reported. In order to establish the effect of diaphragmatic hernia on the lung and the pulmonary structure on which the effect is greatest, the number of bronchial generations (or orders of branching) and the depth of the subpleural alveolar layer in both lungs of two foetuses have been investigated. Recently the antenatal development of the lung has been described (Bucher and Reid, 1961a, 1961b) at different states of gestation by reference to the number of bronchial generations and the level to which cartilage and glands have extended, and these results have been used as the criteria of normal development. *Present address, Central Chest Hospital, Bangkok, Thailand Material

Spontaneous regression of cancer.

Abstract: SIR,-I hope I may be allowed to comment on the provocative paper of Drs. R. E. Kendell and J. Marshall on the genesis of transient focal cerebral ischaemic attacks (August 10, p. 344). Because these authors were unable to reproduce the patient's focal symptoms as a primary manifestation by the production of falls of blood-pressure by tilttable with infusion of hexamethonium they conclude that hypotension is not normally a causative factor in the genesis of such attacks and disparage our hypothesis of focal cerebral haemodynamic crisis. Yet focal symptoms were produced in 20 of the 37 cases, and in 12 of these were relevant to those of spontaneous attacks. The authors decline to attribute such signs to a localized haemodynamic crisis because subjective symptoms of oncoming faintness, deep respiration, clammy skin, etc., occurred first, and were attributed to general cerebral ischaemia. They appear to be unaware that such pre-syncopal symptoms commonly accompany any severe local cerebral haemodynamic crisis occurring spontaneously as a result of blood loss, cardiac arrhythmia, or shock, and relate to the steepness of fall of blood-pressure. Such symptoms do not of themselves necessarily indicate cerebral ischaemia, being commonly produced directly by carotid sinus stimulation, but in any case the first paralytic symptom clearly associated with ischaemia comes from the vulnerable focal cerebral arterial area. This was our original contention, which the findings of these investigations in no way deny. I have elsewhere' discussed the effect of established infarct on such attacks, and would consider the cases listed under group III by Drs. Kendell and Marshall as irrelevant to the general problem. In their groups I and 11 12 of 23 developed focal signs with hypotension, six of them signs of the kind which occur spontaneously. The remainder developed no focal sign before syncope or near syncope. I would maintain that in these 11 the absence of reproducibility of attack means either that cerebral ischaemia had no part in their causation or that any ischaemic factor underlying the attacks was no longer operative. In the absence of any information as to how recently the spontaneous attacks had occurred it is not possible to resolve this alternative. Nevertheless the prime criterion of haemodynamic crisis (reproducibility of attack) was absent, so that by our definition that physiological state is excluded in this group. There are clearly many causes of recurrent cerebral symptoms. On general principles we doubt that cerebral ischaemia, whether focal or general, can occur as frequently as 200 to 1,000 times without catastrophe, as in five of the patients who were cited. The transient disorders of extreme hypertension, as in the one case cited in detail, are also irrelevant to the problem, so that I question the validity of the word \" ischaemic\" in the title of the paper. Finally, since \" general cerebral ischaemia\" to the point of syncope (with generalized convulsions in three) was produced by these authors at bloodpressures as high as 95 mm. Hg in one patient, 90 mm. Hg in three, and 70-80 mm. Hg in nine, I challenge the statement of these authors that \"hypotension is remarkably well tolerated\" in hypertensive states. For all these reasons I submit that the findings do not warrantthe sweeping generalizations that are made in relation both to the complex problems of cerebrovascular stenosis and to the equally potentially catastrophic states of hypertension.-I am, etc., D. DENNY-BROWN. Department of Neurology. Harvard University Medical School, Cambridge. Mass., U.S.A.

Effect of penicillamine on cystinuria.

Abstract: the practice to return patients from the operating suite to a cool bed in order to avoid peripheral vasodilatation -and consequent hypotension. We have found that a little warmth is a useful adjunct to the treatment of 'iypertension post-operatively. Much attention is given, and rightly so, to urinary jutput in the post-partum period, especially in patients who present with an accidental haemorrhage. One is led to wonder how great or significant an effect the administration of ergometrine exerts on the renal bloodvessels of such patients. Byrom and Pratt (1952) state hat \" as long as the causation of renal cortical necrosis tin pregnancy remains obscure, all vasoconstrictors . . . must be suspect.\" The choice of anaesthesia exerts considerable nfluence on the pressor response to ergometrine. One severely toxaemic patient who was delivered of twins and was deeply sedated with tribromethanol showed no elevation of pressure following ergometrine. A study being conducted in this department at the moment shows that the hypertensive response to ergometrine in preaclamptic women is modified greatly by ether or halothane anaesthesia.

Pelvic Recurrence after Excision of Rectum for Carcinoma.

Abstract: were not of a restorative nature. Moreover, all these operations were " radical " in the sense that in each case it was thought by the surgeon that the primary growth and all known metastases had been completely removed. Palliative Excisions.-These include those operations of the excision type in which the surgeon was of the opinion that growth had been left behind, mostly because of incomplete local excision or because of the presence of hepatic metastases. During 1928-52 there were 200 operation survivors in this group. Anterior Resection.-There were 217 survivors after anterior resection during the 10-year period 1948-57. Of these, 177 were " radical " and 40 " palliative " as defined above. In this group the operations were nearly always palliative because of the presence of hepatic metastases. The attempt to follow up all these patients has been successful in 98.5% of the cases. Approximately half the patients continued to attend the out-patient department at regular intervals and thus received experienced aftercare. The remainder, usually living at a considerable distance from London, were followed up by means of biannual questionary letters. When death occurred in the absence of recent examination at St. Mark's Hospital, the opinion of the local practitioner on the cause of death was requested. Obviously only a thorough post-mortem examination in each case could establish beyond doubt whether or not there was a recurrence, and this was possible in only a very few patient.s.

Further experimental studies on the prevention of Rh haemolytic disease.

Abstract: In a previous report (Finn et al., 1961) we gave reasons for thinking that the rapid removal of Rh-positive foetal erythrocytes from the circulation of a mother who was Rh-negative would prevent her from becoming immunized and producing Rh antibodies. We have now investigated the matter further, and the present paper describes the completed results of the earlier work (Experiment I) and then gives details of some subsequent observations (Experiments II and III). The reasoning involved and the scope of the investigations are first discussed.

Indomethacin: a new non-steroid anti-inflammatory agent.

Abstract: Reports have been published of the successful treatment with ampicillin of a carrier of Salm. typhi, but of failure in six carriers of Salm. typhimurium (Stewart et al., 1961; Trafford et al., 1962). Ampicillin has failed in three carriers of salmonellae, but a fourth patient remained negative one month after cholecystectomy and ampicillin therapy (Tynes and Utz, 1962). The five relapses in the present series of 10 patients may have been due to the use of an inadequate dose, as they all occurred after treatment with less than 1 g. six-hourly. The administration of a larger dose in two of them resulted in a clinical and bacteriological cure. It has been suggested that ampicillin may not reach the lower ileum in a concentration inhibitory to pathogenic bacteria, owing to rapid absorption from the upper part of the small intestine, and possibly to local destruction by penicillinase (Stewart and Harrison, 1961). This may contribute to failure of the drug in acute salmonelloses. Chronic salmonella infections are notoriously difficult to treat (Main, 1961). In acute salmonelloses chlorainphenicol is unsatisfactory in preventing the development of the carrier state (Douglas, 1950; Good and Mackenzie, 1950; Woodward et al., 1950). This is due to the bacteriostatic action of chloramphenicol and the low concentrations achieved in bile. Ampicillin, being bactericidal and highly concentrated in bile, may be a useful drug in carrier states when given in an adequate dose of at least 1 g. six-hourly for 21 days. It probably represents no advance in the treatment of acute salmonelloses, although more extensive trials are necessary (Brit. med. J., 1961). At the time of writing there was a large epidemic of paratyphoid infection in the Edinburgh area and ampicillin treatment was being compared with chloramphenicol for both the acute infection and the carrier state in over 130 patients. It is hoped to publish the results of this trial after adequate long-term follow-up studies have been completed. Side-effects similar to those seen with other penicillins occurred in seven (19%) of the patients but were readily reversible. It seems likely that cross-sensitization exists among all penicillins, and it is important that patients should be questioned about previous penicillin allergy before ampicillin or any other penicillin is given. Summary Forty-eight patients were treated with ampicillin, 37 suffering from infections of the urinary tract, 10 from salmonelloses, and one from KI. pneumoniae septicaemia. The ampicillin sensitivity of the causative organisms has been studied, and concentrations of ampicillin in blood and urine have been estimated. In the treatment of infections of the urinary tract ampicillin should be reserved for infections due to Proteus spp. It is not the drug of first choice for E. coli infections, being less effective and more costly than cycloserine. The majority of strains of Klebsiella are resistant. A follow-up study showed a 38% long-term failure rate, the possible causes of which are discussed.

The Hereditary Factor in Arterial Blood-pressure

Abstract: The current conflict of views about the nature of essential hypertension reflects our ignorance of arterial pressure in the general population. Though reliable apparatus for the indirect measurement of bloodpressure has been available for over half a century we still do not know how arterial pressure increases with age in the population at large; we know little of the influence of environmental factors and there is disagreement about the mode of inheritance of hypertension. Investigations of these questions cannot easily be initiated from hospital practice, and it seems highly probable that the long-term study of representative populations by the modern techniques of epidemiology will contribute much to the understanding of the factors affecting blood-pressure within the next decade. Two such long-term epidemiological studies are in progress in South Wales, and this report summarizes the analyses of the genetic data derived from them. Other papers will deal with the influence of environmental and personal factors. The results reported here include data derived from the original \" cross-sectional \" surveys, and from the follow-up surveys which were undertaken four years later. Some of these data have been published previously (Miall and Oldham, 1955, 1957, 1958; Miall, 1962), but

Eighty-six cases of addison's disease.

Abstract: Hypoadrenalism is a not uncommon condition nowadays: a defective function of the adrenals occurs as the result of hypopituitarism-a greater or less degree of which condition is more common than used to be supposed, and becoming more so as the result of the activity of the neurosurgeons in this sphere; adrenocortical activity, of course, ceases completely after bilateral adrenalectomyan operation unknown till comparatively recent years, but now increasingly undertaken for Cushing's syndrome, metastatic mammary cancer, and even, occasionally, for hypertension; lastly, defective function for a variable and unknown period always follows long-continued corticosteroid therapy and constitutes one of the great problems of modern medicine. A knowledge of the diagnosis and management of hypoadrenalism is thus of importance nowadays, and creates one of the many new burdens which modern doctors have to assume and of which we were comparatively free in my young days. It is not, however, of these types of hypoadrenalism which I wish to discuss here, but of the disorder first described so beautifully by Thomas Addison in 1855-a state of chronic adrenal insufficiency resulting from primary disease of the adrenals due to tuberculosis or idiopathic atrophy (possibly the result of an autoimmunizing reaction similar to Hashimoto's goitre); occasionally to infarction and malignant disease; and very rarely to syphilis, the reticuloses, and giant-cell granuloma. Since 1928 1 have personally looked after 86 cases of Addison's disease, and hoped that an account of the experience so acquired might be of some interest, if only from a historical point of view. Pathology During 1928 to 1938 1 saw 34 cases, but, though all these patients died, 1 was able to secure necropsies on only 24 of them (Table I). In 19 (79%) of these the disease had resulted from tuberculosis-a higher tuberculous incidence than in other published series. For example, Guttman (1930), reviewing 333 necropsies on patients with Addison's disease conducted in different centres between 1900 and 1930, reported a tuberculous aetiology in 68%, atrophy in

Evolution of Natural Resistance to the Newer Penicillins

Abstract: We wish to thank Dr. E. T. Knudsen, of Beecham Research Laboratories, for the generous supply of methicillin. Our thanks are also due to Dr. I. A. Tounjer and Sisters B. M. Shelton and P. J. Gower for their very efficient ward work. We also thank Mr. G. L. C. Usher, the chief technician, Mr. V. van Geersdaele, the senior laboratory technician, and their staff for dealing with the increased bacteriological work.

Autoimmune Phenomena in Pernicious Anaemia

Abstract: was obvious that very substantial relief of pain was obtained in most cases. Each patient was also carefully questioned, but, in order that the results could be judged with the least possible bias, no comment was made to the patient at the time of the injection, save to explain that an examination was to be made. Ten minutes after the injection the result was assessed by asking the patient, \" How are the pains ? \" without giving any suggestion of 'expected relief. When recorded and analysed the answers indicated \" complete\" or \" very good \" relief of pain in 71%, \"partial relief \" in 25%, and \"no relief \" in 4%. These results may be compared with those of other workers, which for this purpose are expressed under similar headings, and on a percentage basis to the nearest unit.

Studies of Urinary Tract Infections in Infancy and Childhood

Abstract: that benefit is derived after splenectomy in occasional patients with thalassaemia. The investigations of McFadzean et al. (1958) on Chinese with cryptogenic splenomegaly suggest that this anaemia responds to splenectomy through this mechanism also. I have tried in this lecture to adopt a physiological approach to the pathological problem of the production of anaemia by the spleen by considering firstly our knowledge of the splenic circulation. I think this approach is

Mineral metabolism in melancholia.

Abstract: comparisons between the treatments are unbiased and independent of any general trend in scores, which applies to all treatment groups during the trial. From the clinician's viewpoint the results are bound to be regarded as somewhat less satisfactory. It is obvious that, taken as a whole, the anticipated clinical course of multiple sclerosis is not one of clinical improvement, and from this point of view the standard of measurement we have employed in these trials has failed us. In seeking the reasons for these anomalous results the short duration of the gammaglobulin trial imposed on us by the limited availability of the substance should be noted. The tonic effect of any new form of treatment in a chronic disease is notorious, and six months might well not be long enough for such a non-specific psychological effect to be dissipated by subsequent disappointment. The clinical examinations in the two trials were carried out by two different observers, but the observer was the same throughout each trial, and it is improbable that the mean improvement observed in treated and control patients in each trial was due to an overall simultaneous change in the standard of scoring of both observers. Again, a placebo effect seems to be the likeliest explanation: in a chronic and fluctuating disease, where the subjective component of the patient's disablement represents a variable moiety of the total incapacity, the detailed interest and attention shown and the rituals attendant on taking part in such a trial often have a striking effect on the patient's attitude towards his disability. Such a patient not infrequently carried out activities previously thought to be quite beyond his capacity. We believe that such factors probably account for the results described above. Most of our previous trials have covered longer periods of time, when the inexorable progression of the organic process inevitably comes to outweigh the subjective effects of early optimism. In one such trial (Miller et al., 1961a) re-examination after six months did fail to reveal any significant deterioration in both control and treated cases, though we have not previously encountered the slight clinical improvement observed here. It should also be mentioned that the doctors and nurses engaged in treating and examining the patients in the present study were an entirely different group from those concerned in previous trials and may well have exuded more optimism. The therapeutic effect of suggestive measures in chronic disease is the basis of a great deal of unorthodox treatment in these disorders, and it is unfortunate that our observations could be used to furnish ammunition for the view that at the present time-possibly with the solitary exception of corticotrophin in acute episodes of the disease (Miller et al., 1961b)-treatment with inert substances accompanied by suggestion has at least as much to offer as any of the more rational lines of therapy which we have tried during the past few years. Summary Two separate controlled therapeutic trials are reported. The first, employing 57 patients, was designed to measure the effects of dosage with chloroquine (250 mg. daily) and also with soluble calcium aspirin (54 g. (3.5 g.) daily) on the clinical course of multiple sclerosis over a period of 14 months. The second, employing 21 female patients, was designed to measure the effect of 500 mg. of gammaglobulin, given intramuscularly at fortnightly intervals, on the course of the disease during a six-months period. Disability was scored numerically and clinical examinations were carried out by an observer unaware of the patient's treatment group. In the dosages and over the respective periods involved none of these three substances could be shown to influence the clinical course of the disease. The only patients who showed assessable deterioration during these two observations were those on chloroquine, who deteriorated by 13.3 points over a 14-months period.

Haematopoietic Chimera in Man After Allogenic (Homologous) Bone-marrow Transplantation

Abstract: In 1958 we were able to demonstrate the possibility of transient grafting of allogenic bone-marrow in the human subject accidentally exposed to whole-body irradiation,28 and between 1959 and 1963 we confirmed this possibility in patients with leukaemia who were irradiated intentionally.26 27 In the latter series of experiments there have been several cases of failure, which after a subsequent experimental investigation8 we are inclined to attribute to a cross-immunization resulting from previous blood transfusions. In those cases where grafts were found to take, some were relatively well tolerated-that is, they were complicated by a secondary syndrome which was of moderate intensity-but of a rather brief duration (approximately three months),26 whereas others were complicated by a secondary syndrome that ran a rapidly fatal course. During a recent experiment in mice we found that the use of a mixture of bone-marrow from several donors offers certain advantages: the frequency of the myeloid restoration and the incidence of the secondary syndrome in such cases are approximately the same, as can be observed, for the same number of transfused cells, with the bone-marrow of the donor who has shown the best histocompatibility; the cause of this is that the host organism spontaneously selects the best donor, as could be demonstrated in a study of the specific tolerance due to chimerism.\"1 20 These observations have guided us in the test case reported below.

Chlorinated Insecticide Content of Human Body Fat in Southern England.

Abstract: FIG. 4.-Plasma thromboplastin times and levels of factors influencing the extrinsic clotting system in women on enavid. Summary Anticonceptive therapy with enavid in five healthy women was followed by increased blood coagulability, as evidenced by shortened plasma cephalin time, marked increase in the activity of the antihaemophilic A factor (factor VIII), and a slight increase in proconvertin (factor VII) activity. No significant changes were observed in blood samples collected at intervals during one menstrual cycle in five non-treated normal women.

Beta-adrenergic Receptor Blockade in Cardiac Arrhythmias

Abstract: Black and Stephenson (1962) reported that beta-adrenergic receptor blockade with pronethalol produced marked bradycardia in animals. They suggested that this substance might prove helpful in the management of atrial fibrillation and in ventricular and atrial tachycardias by reducing the cardio-sympathomimetic responses to emotion and exercise. The purpose of this paper is to report our experiences with this drug in a variety of cardiac arrhythmias and to discuss its possible therapeutic applications.

"Hairbrush Diagnosis" in Detection and Eradication of Non-fluorescent Scalp Ringworm.

Abstract: Nor is it helpful to qualify the extent of the growth with such terms as \" scanty \" or \" moderate\" (Fig. 2). On the other hand, the absence of growth on routine culture appears to be a reliable indication that the urine is not infected. To decide whether a positive routine urine culture is due to contamination or infection it is a common practice for the urinary content of white cells to be used as a guide. The tendency of some laboratories to refuse to culture a urine unless it contains more than a \" normal\" number of white cells is an admission of this fact. Moreover, a positive urine culture is often ignored by the clinician if the number of white cells in the urine is not raised. But the results of routine methods for examining the white-cell content of the urine can be misleading; for instance, it has been shown that of 155 urines in which one to five white cells were seen per high-power field the white-cell excretion rate was raised in 42 (Little, 1962). In addition it has been shown above that even when the white-cell excretion rate is normal the urine may contain a large number of organisms, particularly in patients with chronic pyelonephitis or asymptomatic bacteriuria. The patient's symptoms can be equally misleading in distinguishing between contamination and infection. Among the patients discussed above there were 29 with no urinary symptoms at the time when their urine contained more than 100,000 organisms per ml., and the presence of an asymptomatic bacteriuria in up to 8% of pregnant women is well recognized (Kass, 1959; Turner, 1961). Conversely, Boshell, MacLaren, and Metcalfe (1962) have described how 24 out of 99 pregnant women were treated with antibiotics for urinary-tract symptoms although only six had an infected urine. Sumntary The number of organisms found on a quantitative urine culture has been compared with the report of a routine culture in 205 urines. In many instances it was not possible to distinguish from the routine report whether the urine was infected or contaminated. In some patients with chronic pyelonephritis or asymptomatic bacteriuria the urine may contain large numbers of organisms though the white-cell excretion rate is normal. It is concluded that the only consistent way to distinguish between contamination and infection in the urine is to use some form of quantitative culture.

Tissue transplantation: a new approach to the "typing" problem.

Abstract: on purely immunological considerations-that is, of how to choose the donor whose tissues are least foreign to the future recipient. Such a choice may be crucially important, for experience with laboratory animals has shown that when the transplantation of tissues is opposed only by weak immunological barriers it is a matter of no great difficulty to induce a state of immunological tolerance, even in adult life (Martinez, Shapiro, Kelman, Onstad, and Good, 1960; McKhann, 1962; Medawar, 1963). The test of compatibility we propose here is founded on the observation that the homograft reaction in guinea-pigs and human beings can be made to display itself as a cutaneous inflammatory reaction of delayed onset, essentially similar to a tuberculin reaction (Brent, Brown, and Medawar, 1958, 1962; Merrill, Friedman, Wilson, and Marshall, 1961). Let R be the intended recipient of a homograft and D}, D2, D3, etc., a panel of possible donors. Lymphocytes are extracted by differential sedimentation from the defibrinated blood of R and injected intradermally into each member of the panel of donors, whereupon they give rise to small but otherwise typical \" delayed reactions \" of unequal intensities. Experiments on guinea-pigs have shown that the order of the strengths of the inflammatory reactions excited by R blood lymphocytes in the skins of D1, D2, D3, etc., is almost exactly correlated with the order of breakdown of skin grafts subsequently transplanted from D1, D2, D., etc., to R. The weakest reactor is the donor of the most long-lived homograft and therefore the donor of choice. The existence of this correlation makes it very likely that the inflammatory reaction provoked by R lymphocytes in D skin is, in fact, an R-versus-D homograft reaction, but

Blood Fibrinolytic Activity in Diabetes Mellitus and Its Bearing on Ischaemic Heart Disease and Obesity

Abstract: The clinical approach to occlusive vascular disease has been so dominated by coagulation on the one hand and by lipid metabolism on the other that many clinicians are unfamiliar with an enzymatic system in blood whose function seems to be the removal of deposited fibrin. Freshly obtained blood has spontaneous fibrinolytic activity-that is, the capacity to dissolve fibrin (Fearnley and Tweed, 1963 ; Fearnley and Lackner, 1955 ; Fearnley and Ferguson, 1958); and attention has been drawn to its probable role in maintaining vascular patency (Fearnley, 1953, 1960, 1961). An apparent link between fibrinolysis and carbohydrate metabolism has been revealed by the response of blood fibrinolytic activity in diabetics to insulin (Fearnley, Vincent, and Chakrabarti, 1959) and in nondiabetic atherosclerotic patients to the sulphonylurea drugs (Fearnley, Chakrabarti, and Vincent, 1960; Tsapogas, Cotton, Flute, and Murray, 1962). Complementary perhaps is the abnormal carbohydrate metabolism found by Wahlberg (1962) in atherosclerotic patients free from clinical diabetes mellitus. For these reasons, and because of the well-recognized tendency of diabetics to ischaemic disease, we have studied blood fibrinolytic activity in 100 diabetic patients and in 100 age-matched controls free from diabetes and from detectable complications of atherosclerosis. The incidence of myocardial ischaemia in the diabetics hasbeen classified in relation to their fibrinolytic activity.

Obesity and the heart.

Abstract: Part I of the Schedule describes the conditions of pasteurization. The temperature-time relationship of 1480 F. (64.40 C.) for 24 minutes was worked out experimentally both by laboratory experiments and in a commercial plant. Such treatment eliminated the most heat-resistant salmonella strain so far described, S. senftenberg 775W,3 in numbers far exceeding those encountered in \"naturally \" contaminated material. Moreover, the enzyme a-amylase of egg yolk was also inactivated under these conditions. Details of the experiments which led to these conclusions and of the pasteurization plants required for heat-treatment, as well as of baking tests with the pasteurized liquid egg, have been reported.4-7 Thirteen plants for pasteurization of egg in the U.K. and Northern Ireland are already following this technique with satisfactory results in regard to the cz-amylase test, freedom from salmonellac, and use of the pasteurized material for confectionery; by the end of the year there will be 30 such plants installed in the country. In one instance the pasteurized material is piped straight into the bakery. Most if not all countries exporting egg to the U.K. are already equipped for pasteurization and they have been waiting only for regulations to put into effect the extra procedure required for safety. It has been calculated that there will be an additional cost of perhaps ld. per lb. of egg to cover pasteurization, but this will surely be more than compensated for by the assurance of safety, and by the cessation of large-scale condemnation, which in the past must have caused much financial loss to the industry. The regulations assume that adequate sampling will still be carried out at the ports and by the medical officers of health in whose areas breaking-out plants are situated. Public-health laboratories, public analysts, and industrial laboratories will be responsible for carrying out the a-amylase test. It is hoped that, at least in the initial stages of production from any new plant, laboratories will continue to examine for salmonellae, because the a-amylase test may still be satisfactory despite 2-3% recontamination with raw egg. In the event of salmonellae being isolated, condemnation of the egg under the Food and Drugs Act, 1955, or the Public Health Imported Food Regulations, 1937, will follow. Conversely, a longer heating time at a lower temperature may kill salmonellae without complete inactivation of the a-amylase, and this would result in condemnation of the egg even though it were free of salmonellae. However, such a product might not be acceptable to the baking trade because prolonged heating may cause the egg to thicken. The regulations do not indicate how to dispose of egg batches that fail to satisfy the a-amylase test. There is an urgent need now for other egg products to be made safe, though further experimental work is required on the best methods to use. It should not be long before similar regulations can be applied to spray-dried whole egg and yolk and frozen yolk, all of which may present dangers similar to those of bulked whole egg. Experiments are in progress on hen egg albumen, which is more difficult to pasteurize because it coagulates at a lower temperature than mixed whole egg, and it presents a further difficulty in that a test other than that of destruction of a-amylase is required to monitor the efficiency of heat-treatment. Nevertheless a method must be found, and investigations planned for the ensuing year will in all probability provide an answer to the heat-treatment of hen egg albumen; but it may take longer to devise a simple routine test to indicate that this pasteurization has been carried out satisfactorily. In the meantime all will watch with keen interest the results of the Ministry's first step towards making egg products safe. It is to be hoped that, as for the pasteurization of milk, the years ahead will justify these measures.

Effect of Smoking on Blood Coagulation and Platelet Survival in Man

Abstract: or mechanisms these processes are related. Kershbaum et al. (1961) have found that smoking produces a rise in the plasma free fatty acid; the effects of smoking on the blood-pressure and cardiovascular dynamics have been extensively documented; and there is evidence that smoking influences blood coagulation (Horwitz and Waldorf, 1960). The studies of Shimamoto and associates (personal communication) in rabbits on the effects of inhaling cigarette smoke on the adhesion of platelets to the endothelium in the microcirculation are of particular interest. They have found that the endothelium cells are structurally altered in the process.

Amphetamine and Phenmetrazine Addiction

Abstract: thiazines in obstetrics, in which they assessed the patients' response after one dose of the drug under test and demonstrated a significant difference between the phenothiazines and the placebo. These present trials were, however, designed to assess therapy under normal labour ward conditions, which is a more realistic method than the single-dose test. So far as promazine was concerned the double-blind trials confirmed the safety suggested by a pilot study and showed it to be an effective agent for controlling agitation and potentiating analgesics in labour. An anti-emetic effect was also shown. Maternal tachycardia was the only adverse effect, but this did not appear to have any clinical significance. Hypotension is a recognized risk of phenothiazine administration, but although no serial blood-pressure readings were made there were no cases of clinical hypotension in the 785 patients in the series treated with promazine.

Role of Hypotension in the Gnesis of Transient Focal Cerebral Ischaemic Attacks

Abstract: --(1958b). Ibid. 13, 524. and Tsang, K. C. 11956a). Brit. J. Haemat., 2, 355. (1956b). Trans. roy. Soc. trop. Med. Hyg., 50, 433. (1958). Ibid., 52, 354. McIntosh, J. F (1932). Clint. med. J., 46, 992. Musgrave, W. E., Wherry, W. B., and Wooley, P. G. (1906). Johns Hopk. Hosp Bull., 17, 28. Pan, Y. C., and Wong, C. C. (1962). Unpublished observations. Ravin, H. A. (1956). Lancet, 1, 726. Smith. C. H., Erlandson, M E., Stern, G., and Hilgartner, M. W. (1962). New Engl. J. Med., 266, 737.

Oral Contraception and Blood Coagulability

Abstract: The fact that oral contraception mimics the hormonal effects of pregnancy which is associated with high levels of certain clotting factors prompted the authors to investigate whether changes in blood coagulability might be induced by oral contraception. 10 normal healthy women aged 22-42 with regular menstruation and no previous hormonal therapy served as volunteers in the study. 5 of the women received oral enavid (norethynodrel + ethinyloestradiol 3-methyl ether) medication in the standard contraceptive dosage of 5 mg a day from Menstrual Day 5 to be applied for 20 days. The other 5 women served as controls for analyzing possible physiological variations in blood coagulability during the menstrual cycle. Plasma samples were prepared according to a standardized technique as described for the methods used and stored at minus 20 degrees centigrade until assayed. Results of the coagulation study showed no definite changes occurring in the coagulation activities of the blood samples from nontreated women. Plasma samples from the women on "enavid" medication showed a shorting of the cephalin time and a definite increase in the activity of the antihemophilic A factor. The measured proconvertin activity increased slightly but significantly. These changes developed during the first and second weeks of therapy and the values showed a tendency to return to pretreatment levels soon after the drug was discontinued. It is noted that the number of women treated was small but the change in coagulability was marked and uniform.