Detection of factor VIII inhibitors with the partial thromboplastin time. Variations of the partial thromboplastin time (PTT) were tested to determine the best screening method for detection of inhibitors of factor VIII. Variables tested included the duration of preincubation of a mixture of patient plasma and factor VIII source (normal plasma), the ratio of the patient plasma to the normal plasma, and the duration of incubation of the normal plasma-patient plasma mixture with kaolin-cephalin suspension prior to recalcification. The following conclusions were reached: (1) The PTT performed on a mixture of equal amounts of patient and normal plasma without preincubation of the mixture was inadequate to detect many factor VIII inhibitors. (2) Factor VIII inhibitors of more than 0.5 Bethesda units could be detected if the PTT was performed on a mixture of four parts patient plasma and one part normal plasma, with preincubation of the mixture for 60 min at 37 degrees C. (3) Factor VIII inhibitors as weak as 0.1 Bethesda units could be detected if the PTT was performed on a mixture of four parts patient plasma and one part normal plasma incubated with kaolin-cephalin suspension for 120 min at 37 degrees C before recalcification. The last method may make detection of mild factor VIII inhibitors possible in routine clinical laboratories not equipped to perform the more technically difficult Bethesda inhibitor assays.


Induction angiometer. Electromagnetic magnification of microscopic vascular diameter variations in vivo. It is possible to obtain continuous linear recordings of changes in vascular diameters on the basis of the electromagnetic induction principle. An extracorporeal coil energized by an alternating current generates an AC magnetic field and acts as a transformer primary. An intravascular loop of fine wire acts as transformer secondary. The EMF induced in the loop is proportional to the diameter of the vessel which confines the loop. Relative measurements do not require a calibration. Absolute measurements require radiographic determination of vessel diameter. Changes of less than 0.1% in vascular diameters can be easily recorded. Variations in pulsatile diameter changes as well as pharmacologically induced changes in mean diameter have been studied.


Absence of renal circulatory autoregulation during perfusion with paraffin oil. Autoregulation of vascular flow as a function of arterial pressure was studied in isolated dog and rat kidneys, perfused serially with an oxygenated aqueous colloidal medium and with oxygenated paraffin oil. Square wave elevations in arterial pressure eleicited autoregulatory adjustments in flow within the first few seconds of elevated pressure during colloidal perfusion but not during oil perfusion of the same kidneys. Before oil perfusion, the steady state autoregulatory efficiency ratios (% flow change/% pressure change) over pressures ranging from 95 to 180 mm Hg averaged 0.37 +/- 0.13 and 0.51 +/- 0.16 (mean +/- SD) in dog and rat kidneys, respectively. During oil perfusion, the autoregulatory efficiency ratios exceeded 1.0 in every instance. Following oil perfusion, vasoactive autoregulation of colloidal perfusate flow returned, at very low organ flows. Our results do not confirm the previous findings of LEICHTWEISS, SCHRODER, and WEISS [Pflügers Arch. ges. Physiol. 293: 303 1967] concerning the presence of autoregulation during oxygenated renal oil perfusion. Our findings suggest that renal circulatory autoregulation is either primarily myogenic or else primarily dependent upon a rapidly acting tubulovascular feedback mechanism.


Pulmonary distributions of lead in human subjects. The concentration of lead in five lung segments and in regional lymph nodes was determined post mortem in ten subjects by atomic absorption technique. In each case there was a considerable variation in the concentration of lead in different lung segments, and, in general, the apical segment in the upper lobe tended to be more contaminated than segments in the lower lobes. With one exception, the lead levels in the regional lymph nodes exceeded those of the lung segments. Individual differences in the distribution of lead in the lungs may be due to differences both in exposure and physiological response. When comparative analyses are made, we suggest that samples be taken from the same and preferably the basal segments of the lung.


Study on the post-mortem identification of pollutants in the Fish killed by water pollution: detection of arsenic. Careless Herbicidal aerial spray of a field for weed control and defoliation of cotton before machine picking, resulted in the contamination of an adjoining reservoir, killing large volume of fish. The dead catfish, along with water and Amarantha weed leaves analyzed contained relatively high levels of arsenic concentrations, indicative of arsenic being the probable cause of fish killing. The arsenic absorbed by fish was irreversable and its bioaccumulation continued in the surviving fish though the water arsenic level fell during the following weeks.


Polymyositis.

Polymyositis. Polymyositis is a treatable and curable disease. Unfortunately, patients with polymyositis are still frequently diagnosed as having muscular dystrophy. It is important to have a high index of suspicion of polymyositis, and to recognize that the detailed symptoms and signs and the overall picture are different from the relatively clear-cut pattern of the muscular dystrophies. Treatment of polymyositis is rewarding, although it frequently requires considerable resilience from both patient and doctor to achieve the best results. A detailed search for an underlying aetiology should be made, and a carcinoma should be suspected in elderly patients and those with dermatomyositis. In patients in whom polymyositis is related to a carcinoma, the latter may be at a stage where total excision is possible.


Neuromuscular syndromes associated with malignant disease. Malignant disorders may produce neuromuscular syndromes in a variety of ways, for some of which it is still difficult to determine the exact pathophysiology. In the myopathic and neuropathic disorders, one possible explanation is that they are due to a virus such as is found in the rare "progressive multifocal leukoencephalopathy". This is seen in association with the malignant lymphomas and with other conditions such as sarcoidosis where immune responses may be altered by either the disease or the treatment. No viral material has been found in the nonmetastatic neurological disorders apart from progressive multifocal leukoencephalopathy. An alternative theory is that there may be an autoimmune process, the nervous system sharing some antigenic determinant with the neoplasm (Urich, 1967). The prognosis in the paraneoplastic neurological disorders is usually poor. As well as the direct threat to life posed by the malignant disease, when the neurological disorder is due to destruction of neurones (for instance cerebellar degeneration or sensory neuronopathy) recovery of function is impossible. Spontaneous remissions have been recorded in cases of proximal muscle weakness and sensorimotor neuropathy, but it is difficult to know whether the remissions have been truly spontaneous or related to treatment (excision of the neoplasm or administration of steroids). Further immunological and virological studies will probably reveal the answers to some of the outstanding problems. In the meantime the clinician must continue to investigate patients with muscular weakness for evidence of an occult neoplasm, and to repeat investigations if no other cause for the neurological disorder is found. Also, in patients with known malignant disease, apart from trying to differentiate forms of neuromyopathy from the effects of metastases the various metabolic disorders must be considered because the therapeutic possibilities are a little more promising in the paraneoplastic endocrine disorders. Ross (1975) wisely said that "cancer has replaced syphilis as the great imitator".


An evaluation of child health clinic services in Newcastle upon Tyne during 1972-1974. The community child health clinics continued to provide an important and popular service for mothers with young children in Newcastle during 1972-1974, supplementing the primary care services of general practitioners as only a minority of them had undertaken the preventive aspects of child care. Most of the work of the community clinics was done by health visitors and it consisted of advice, support, and reassurance about the everyday problems of children. Although an appreciable amount of the work of the community doctors was developmental screening (birthday checks) most mothers consulted them about relatively minor medical complaints--such as feeding difficulties, specific developmental problems, and immunisation. There was no attempt to do a birthday check on all the children in the city and those that were done revealed few significant undetected abnormalities because most of the children had already attended clinics. In a poor area of the city, family and social problems were often found but very little consultation took place between health and social services, indicating the need for better liaison between these services. The community child health clinics will need to be maintained if general practitioners cannot provide these services and are unable to include preventive as well as curative child care within their practice.


Cigarette smoking patterns during the working day. The rates at which people smoke cigarettes during different periods of the day were obtained from three occupational groups. Group 1 consisted of those working at the main London production site of a food processing factory, Group 2 consisted of those in the administrative offices of the same company; there are smoking restrictions at both. Group 3 consisted of workers in the offices of a London borough where there are no smoking restrictions. Replies were received from 3174 people, or 88% of those approached. There was a higher proportion on non-smokers (over 70%) among the two groups of office workers than among the food processing workers (about 55%). Smokers in Group 3 recorded somewhat higher average cigarette consumption than those in Groups 1 and 2. During different periods of the day, the maximum hourly rate of cigarette smoking was about three times the minimum rate. For Groups 1 and 2 the maximum rate was consistently during the interval between leaving work and going to bed. In contrast, the maximum rate for Group 3 was consistently during the afternoon, while at work, and the rate between leaving work and going to bed was similar to the rate for the day as a whole. Results will help in deciding the time of day at which blood for carboxyhaemoglobin estimations should be taken.


Health norms in pregnancy.

Health norms in pregnancy. A study was conducted on a sample of pregnant women. The study had two aims: to develop a method of measuring social expectations (norms) and to find out how far women conform in their behaviour to these norms. The areas of behaviour were smoking, exercise, diet, alcohol, and medication. Pregnancy was found to be appropriate for this study because of the high degree of formalisation that this state enjoys in our society. The methods used for measuring norms in this study are an improvement on earlier methods, but further refinements are needed. The findings show that women generally do conform to the social expectations and that their behaviour is in accordance with three types of norms--that is, general, specific, and transitional. The implications for health education interventions are discussed.


Self-administration of a questionnaire on chest pain and intermittent claudication. A total of 18 403 men aged between 40 and 64 years took part in a screening examination which included a self-administered version of the London School of Hygiene questionnaire on chest pain and intermittent claudication. The yield of positives for "angina" and "history of possible infarction" was about twice as high as with interviewers, but the positive groups obtained by the two techniques differed little in their association with electrocardiographic findings or in their ability to predict five-year coronary mortality risk. This risk ranged from 0-9% in men negative to questionnaire and electrocardiograms (ECG), to 4-3% for those with positive ECG but no symptoms, 4-5% for those with angina and negative ECG, up to 16% for those with angina and positive ECG. The self-administered version of this questionnaire provides a simple and convenient means of identifying individuals with a high risk of major coronary heart disease.


Randomised controlled trial of anti-smoking advice in pregnancy. In a randomised controlled trial intensive individual anti-smoking advice given in parallel with hospital antenatal care did not influence the outcome of pregnancy. The belief that retardation of fetal growth caused by maternal smoking occurs in late pregnancy is not well based, and the advice may not have been given in time to be effective. Other possible interpretations of the results, that maternal smoking is merely an index of some other factor that retards growth or that those counselled did not reduce their smoking sufficiently to influence outcome, cannot be excluded.


Sex differences in the emotional behaviour of laboratory mice. Three laboratory strains of mice (C57, BALB/c, Porton) were tested in an open field using a number of measures taken during the initial 2 min of testing and after a loud bell had sounded. The mice were tested either in a clean field or in one containing an odour of a same-sex conspecific. Over all three strains, several measures indicated that females showed high leveles of 'emotional' or 'fear' responses than did males. This sex difference was found in C57 and BALB/c strains but not in the Portons; it could not be attributed to activity or response-specific sex differences. Conspecific odours did not influence the direction of the main findings.


Hypnotic susceptibility and personality: the consequences of diazepam and the sex of the subjects. It was suggested by Gibson & Curran (1974) that the rather complex relationships found to obtain between hypnotic susceptibility and the personality parameters of extraversion and neuroticism might be understood by considering neuroticism as a moderator variable (as had been suggested by Furneaux & Gibson, 1961). They made the hypothesis that if a tranquillizing drug were administered the operative level of neuroticism would be decreased, and as a consequence the level of susceptibility of neurotic extraverts would be raised, and that of neurotic introverts lowered. This study reports the test-retest data on a sample of 71 subjects on the Stanford Hypnotic Susceptibility Scales, half of whom were retested with diazepam and half with nicotinic acid. The hypothesis was confirmed and additional data are given on the drug/placebo effects on each item of the scale. The significance of drugs on different aspects of hypnotic susceptibility in relation to personality is discussed.


Sequential contrast effects with retarded subjects after discrimination learning with and without errors. Four retarded adults were exposed to a multiple variable interval-extinction schedule of reinforcement. The 2 min components were presented in a random order. Two subjects acquired the discrimination with an errorless procedure. The two other subjects learned the discrimination with errors. The schedule generated sequential contrast effects under both training procedures: response rates during periods of reinforcement were higher when a reinforcement period followed an extinction period than when it followed another reinforcement period. These results were confirmed in a second observation where eight retarded children were exposed to a multiple fixed ratio-extinction schedule of reinforcement. This study is the first demonstration of sequential contrast effects with human subjects during the acquisition of a discrimination without errors. The results are discussed in terms of Terrace's theory of errorless learning.


Sclerosing peritonitis due to practolol: a report on 9 cases and their surgical management. Nine patients with an unusual and serious intraabdominal complication of the beta-adrenergic blocking agent practolol seen since 1973 are reported. The striking and bizarre peritoneal changes induced by the drug have distinctive features that are not shown by other forms of peritoneal disease. The cases presented with small bowel obstruction, usually chronic in type and often associated with profound weight loss and an abdominal mass. Characteristic radiological features were present. The abnormalities at laparotomy were impressive, with a gross proliferation of the visceral peritoneum which formed a dense white cocoon which encased, constricted and markedly shortened the small bowel, usually from the duodenojejunal flexure to the ileocaecal valve. The obstruction was relieved by mobilizing the small bowel from the ensheathing tissue. Restoration of alimentary function after surgery was delayed but the long term result was satisfactory with full relief of symptoms and the absence of recurrent obstruction during the follow-up period. This complication may arise after treatment with the drug has been stopped, and although long term oral therapy has been discontinued, further cases will almost certainly present for some time to come.


Nine years' experience with internal arteriovenous fistulas for haemodialysis: a study of some factors influencing the results. Data were collected concerning 314 internal arteriovenous fistulas created in 242 adult patients (92 women and 150 men). The immediate failure rate for the various techniques used ranged from 7-7 to 12-0 per cent, except for ulnar fistulas which had a rate of immediate thrombosis of 20-7 per cent. Survival rates were significantly lower for patients submitted to a combined therapy of dialysis and kidney transplantation when compared with patients treated with dialysis alone. The probability of survival of an arteriovenous fistula was lower in women than in men but the difference was significant only in patients undergoing transplantation. Survival rates at 2 years in dialysed patients were 87-6 per cent for distal radial-cephalic side-to-side fistulas, 100 per cent for radial-cephalic end-to-side fistulas located in the mid-forearm, 78-5 per cent for radial-cephalic end-to-side fistulas created near the wrist, 53-1 per cent for distal radial-cephalic end-to-end fistulas and 60-9 per cent for ulnar fistulas. Thrombosis was responsible for 87-2 per cent of 109 late failures. The incidence of infection was 1 case/11 patient years of haemodialysis.


Protection of the skin around intestinal fistulas. The use of two recently introduced skin protective preparations in the treatment of perifistular skin inflammation is described. Karaya gum in paste form (karaya paste) and a compressed wafer of gelatin, pectin and methyl cellulose (Stomahesive) were used, alone or in combination; with drainable collecting appliances. The method protects the inflamed skin from fistula discharge and allows healing to proceed beneath the dressing. A technique to improve the adhesion of the appliance, in spite of large fluid losses, is outlined. Healing of skin excoriation was obtained in nearly all cases. Complete control of leakage was achieved in a group of patients with a high output fistula.


The early mobilization of the elderly amputee. A policy of early mobilization of elderly leg amputees using a simple temporary prosthesis has been assessed in the context of a district general hospital. Close cooperation between members of the hospital management team, adequate rehabilitation facilities and close liaison with the limb-fitting centre and domiciliary services were found to be essential to support this policy. Of 42 elderly amputees, 34  were supplied as early as possible with temporary prostheses. Nearly 80 per cent of them were able to walk without assistance on discharge from hospital care. Delays in discharge were mainly for socio-domestic reasons. Early prosthetic mobilization in this aged and often frail group of patients led to a reduced morbidity and mortality. There was improved morale in patients and staff, rapid clearance of acute surgical beds and the all-important early achievement of domestic mobility and independence for the amputee.


Torsion of the testis.

Torsion of the testis. A series of 56 proved cases of torsion of the testis is reviewed. The condition is rare, only 2 patients per year being admitted to a large general hospital of 800 beds. The aim of this study was to assess the fate of testes in relation to the duration of symptoms: if less than 12 hours the outlook is good, between 12 and 24 hours survival of the testis is possible, over 24 hours the testis is most likely to be beyond salvage and beyond 48 hours there is virtually no hope of testicular survival and orchidectomy will be necessary.


Some surgical aspects of homozygous beta-thalassaemia. The surgical aspects of the management of patients with homozygous beta-thalassaemia are reviewed, and the operative findings in 10 patients with the disease who underwent splenectomy are described. Postoperatively, blood consumption was reduced and there was a longer time interval between transfusions needed to maintain the haemoglobin level. Hyperplastic lymph nodes containing erythropoietic elements are always present, and the first reported case of extrabiliary obstructive jaundice caused by this tissue is included. All the patients survived for 2-3 years after treatment and there were no serious infections. All received prophylactic oral penicillin after surgery. Cholelithiasis was not found. Two malleolar ulcers were successfully grafted with split skin after preparation of the craters with silver sulphadiazine cream.


Plasma glucagon levels in haemorrhagic shock. Eleven healthy dogs were subjected to haemorrhagic shock for 90 min. after which shed blood was reinfused. Detailed studies were made of cardiopulmonary function. Samples of blood were taken at frequent intervals for the measurement of glucagon, insulin and glucose. Three dogs had samples taken for catecholamine levels. The glucagon level rose during haemorrhagic shock but there was no relationship between this rise and the change in cardiorespiratory measurement, but there was a relationship between the plasma glucagon level, the blood glucose and the catecholamine level. It is suggested that the release of glucagon in haemorrhagic shock is mediated by sympathetic stimulation of the alpha cell and that the rise in glucagon is in part responsible for the hyperglycaemia which is found in shock.


Unsuspected exposure to asbestos and bronchogenic carcinoma. Two hundred and fifty men admitted to a thoracic surgical centre and matched controls were questioned in detail about their occupations after leaving school and their smoking habits. Of 201 men with confirmed bronchial carcinoma 58 gave a history of occupational exposure to asbestos, whereas only 29 out of 201 men matched for age and residential area who were admitted with other diseases gave such a history. This difference was statistically highly significant. The usual association of bronchial carcinoma with heavy smoking was observed, but asbestos exposure increased the risk of carcinoma whatever the level of smoking. These results are consistent with the hypothesis that asbestos exposure and the level of smoking act independently in causing bronchial carcinoma. The patients with carcinoma who had been exposed to asbestos presented on average three years earlier than those who had not been exposed. Asbestos regulations have eliminated the risk of exposure to workers in scheduled industries, so asbestos-induced diseases will probably be increasingly found among the many workers who have had incidental exposure to asbestos. It is therefore important to take a full occupational history.


Rubella vaccination of schoolgirls: factors affecting vaccine uptake. In a national sample of 16-year-old girls who were aged 12 when the rubella vaccine programme was implemented in 1970, 71% were reported to have received rubella vaccine. There was a high regional disparity in the uptake of rubella vaccine: 81% of girls living in Scotland had been vaccinated but only 61% of girls living in Wales. Similarly there was a difference in reported vaccine uptake according to the family social background, the lowest proportion vaccinated came from professional and unskilled manual families. Girls attending independent schools also had a lower vaccine uptake than girls in schools maintained by the local educational authorities. If rubella immunisation is to be effective uptake of vaccine must increase to almost 100%.


Changing patterns and mortality of acute myocardial infarction in a coronary care unit. Three groups of patients who had been admitted to a coronary care unit with infarction at different periods since 1963 were reviewed to assess whether the outcome in such patients had improved over 12 years. There was a significant reduction in mortality among consecutive patients with mild or severe infarction between 1969-70 and 1974-5. Classifying the patients in all three groups according to their risk factors showed that for each risk factor mortality had decreased since 1963. The incidence of arrhythmias and conduction defects decreased between 1969-70 and 1974-5, and mortality among patients with each arrhythmia also fell. The reduction in mortality may reflect a changing pattern in the natural history of the disease as well as a benefit of improved treatment.


HLA patterns in pernicious anaemia.

HLA patterns in pernicious anaemia. The pattern of HLA antigens was studied in 127 patients with Addisonian pernicious anaemia. The pattern in the whole group of patients differed significantly from that in 586 controls. But different subgroups of the patients had different HLA antigens. Among 27 patients with anaemia associated with endocrine disease there was an increased frequency of HLA-B8, B18, and BW15. The remaining 100 patients, who did not have endocrine disease, showed increased frequencies of HLA-B7 and B12. The positive association with HLA-B12 among this subgroup was confined to 62 patients with severly impaired vitamin B12 absorption, including 13 patients with vitamin B12 neuromyelopathy, who had the highest frequencies of HLA-B7 and B12. The significant heterogeneity in HLA patterns in different clinical subgroups of these patients indicates genetic heterogeneity in pernicious anaemia and explains previous discrepancies in the associations between HLA antigens and pernicious anaemia.


Problems in using basal body temperature recordings in an infertility clinic. Basal body temperature recordings are extensively used to diagnose and treat infertility, but too great an emphasis on the interpretation of these charts might be counter-productive in managing these patients. Several gynaecologists who use temperature charts clinically were asked to score 60 charts taken from a selection of normal and infertile women, and their results were compared with those obtained by a group of non-experts. Since the full hormonal profiles had been obtained for each of the 60 charts the accuracy of the predictions could be assessed. About 80% of the temperature charts were correctly interpreted by both groups as being either ovulatory or anovulatory but the day of ovulation was predicted correctly for only about 34% of the charts. When the charts were examined retrospectively the thermal nadir was found to coincide with the luteinising hormone surge in 43% of the charts from normal subjects but in only 25% of those from the infertile patients. Predicting the day of ovulation from the temperature recording, particularly in infertile women, is clearly unjustified.


Asthma: analysis of sudden deaths and ventilatory arrests in hospital. The incidence of episodes of unexpected ventilatory arrest, some of which led to sudden death, was studied in 1169 consecutive hospital admissions for asthma. Of the most acute cases, 458 were initially managed in a special care unit where only one ventilatory arrest occurred. A further nine cases of arrest, three of which proved fatal, happened on general wards. Accepted clinical criteria of a severe attack were not present in those episodes occurring outside the unit, which were apparently mild attacks. The risk of sudden death could not be related to the severity of the attack but it did correlate with the presence of excessive diurnal variation in peak expiratory flow rate (PEFR). Special treatment of patients with this sign might reduce mortality.


Icarus's syndrome: new hazards in flight. The British Hang Gliding Association accident report for 1975 reported two deaths. The remaining cases were predominantly limb fractures. The major causes of the injuries were inexperience, high wind speed, turbulence, and stalling. It is contended that the sport is no more risky than is rock climbing, motor-bike racing, skiing, or potholing, yet against these undoubtedly dangerous sports no threat of prohibition exists. The current accident rate in hang gliding could be reduced dramatically by the provision of proper courses of instruction.


Variations in GP night visiting rates: medical organisation and consumer demand. Specially obtained data for night visiting fees show a considerable increase in the number of claims made per general practitioner and per 1000 patients. There were also considerable variations between the 116 executive councils: in 1973-4 the range was from 3-8 to 17-0 per 1000 patients. To explain these variations, their relations with the local characteristics of family practice and of the population was explored using regression analysis. The factors most strongly associated with variations in implied visiting rates were found to be deputising services and the proportion of social class V in the population.


Dermatitis herpetiformis: effect of gluten-free diet on skin IgA and jejunal structure and function. To clarify the controversy about the effectiveness of a gluten-free diet in dermatitis herpetiformis, 10 highly motivated patients were investigated. The indices used to assess improvement included deposition of sub-epidermal IgA in unaffected skin, counts of intraepithelial lymphocytes, deposition of IgA in jejunal villi, and electrical tests of glucose absorption. In every patient subepidermal IgA concentrations fell after gluten withdrawal. In all but one patient the dose of dapsone necessary to control symptoms was reduced. Indeed, six patients stopped taking the drug completely within a year. In nine patients biopsy specimens were taken from the jejunum; seven showed abnormalities in jejunal morphology, eight had increased numbers of intraepithelial lymphocytes, and five had increased numbers of IgA-reactive cells in the lamina propria. Two of these three indices improved after gluten withdrawal, which confirmed that all nine patients were adhering to their diet. Routine screening for malabsorption proved to be unsatisfactory for showing the mild jejunal disease found in patients with dermatitis herpetiformis. The electrical test of glucose absorption showed subnormal results in all eight patients tested, however, and in six the results improved after gluten withdrawal.


Idiopathic recurrent superficial thrombophlebitis: treatment with fibrinolytic enhancement. Sixteen patients with idiopathic recurrent superficial thrombophlebitis were shown to have a defect of blood and tissue fibrinolytic activity. After six months' treatment with stanozolol their mean dilute blood clot lysis time and plasma fibrinogen fell significantly and the mean fibrin plate lysis area increased. Attacks of thrombophlebitis stopped completely in 13 patients, though five patients later suffered recurrences and phenformin had to be added to their treatment. Fibrinolytic enhancement with stanozolol seems to be effective in this previously intractable condition, and regular blood studies will indicate which patients also need phenformin.


Anaesthetic waste gas scavenging systems. The Department of Health and Social Security has recently recommended that waste anaesthetic scavenging systems should be installed to reduce pollution in operating theatres. Three passive and two active systems were compared to see how effectively they reduced concentrations of halothane in the atmosphere. All five systems reduced halothane levels significantly, the combination of an active system and semiclosed circuitry being the most effective. All obvious leaks from equipment were controlled in this study, but normally such leaks contribute significantly to atmospheric pollution. Some of the benefits of a scavenging system may be lost if gases can still escape through leaks.


Breakfast and Crohn's disease.

Breakfast and Crohn's disease. The breakfast habits in adult life of 34 patients with Crohns disease were compared with those of 68 matched controls. Cornflakes were being eaten at least weekly by 23 of the patients (67--6%) at the time that their symptoms began, compared with 17 (25%) of the controls at the corresponding time. Only one of the 34 patients had not eaten cornflakes at all, compared with half of the controls. A significant but weaker association was found between Crohn's disease and the eating of wheat cereals. However, in both patients and controls the taking of cornflakes and of wheat cereals were correlated, and the observed preponderance of wheat eating among the patients was almost entirely ascribable to this association of habits. Eating of rice cereals and of porridge was not associated with Crohn's disease, though it was correlated with eating cornflakes. There was an excess of bran eaters among the propositi, but this, too, was attributable to their being also cornflake eaters. Other breakfast foods were taken with equal frequency, and omission of breakfast was equally common. Six of the 68 controls, but none of the patients, ate cornflakes later in the day but not at breakfast. The results need confirmation. There was no evidence that bias could have caused the correlation found. The association of Crohn's disease with the eating of cornflakes is strong and unlikely to be indirect. Variable digestive secretory behaviour after waking may play a part in determining susceptibility to Crohn's disease.


Medical audit in practice.

Medical audit in practice. A stage by stage approach was adopted to solve some of the problems of diagnosing and managing acute abdominal pain. Audit started in hopsital and was extended, with the help of a community physician, to cover the practice of a group of general practitioners. Referrals to the accident and emergency department for acute abdominal pain were analysed, and the diagnostic accurancy of general practitioners, accident department staff, and ward staff was assessed. The accuracy of hopsital staff was improved by issuing guidelines and checklists to help in diagnosis. The general practitioners' problems were defined and discussed with the surgeons. The audit continues with the aim of improving the general practitioners' diagnostic accuracy.


Suspension of non-viable fungal spores as a standard for platelet counting. In the search among biological particles for a standard for counting human platelets, a strain of Absidia corymbifera was found to have spores that resembled platelets. After fixing in formalin and autoclaving the spores had a similar mean cell volume to that of human platelets. A suspension of these killed spores was tested in 100 laboratories and gave consistent results as a standard for human platelet counting. The Absidia corymbifera standard can be used in electronic counting methods but not in sedimentation methods, as the spores will be removed by centrifugation.


Outside Europe. Is poliomyelitis a serious problem in developing countries?--the Danfa experience. Children were examined for lameness in the Danfa Project district of rural Ghana to assess the impact of endemic poliomyelitis and to test a widely held hypothesis that paralytic poliomyelitis is relatively rare in such districts (less than 1 per 1000 children affected). The observed prevalence of lameness attributable to poliomyelitis was 7 per 1000 school-aged children, and the annual incidence is estimated to be at least 28 per 100 000 population. Although no evidence for an epidemic was found, these rates are comparable with those in the USA and Europe during the years of severe epidemics and indicate that a high price is being paid in the Danfa district for the natural acquisition of immunity. As a result, immunisation against poliomyelitis has been given high priority. A teacher questionnaire was also tested for use in postal surveys as a rapid means of estimating the prevalence of lamenes attributable to poliomyelitis in countries with a reasonable network of primary schools.


Is poliomyelitis a serious problem in developing countries?--lameness in Ghanaian schools. A postal survey of lameness in schools throughout Ghana showed an estimated prevalence of lameness attributable to poliomyetitis of 5-8 per 1000 school-aged children and an estimated mean annual incidence of paralytic poliomyelitis of 23 per 100 000 population. Official reported incidence rates range from 0-1 to 2-1 per 100 000 population, indicating that at least 90% of cases are not reported. No evidence of epidemics was found to account for these high rates. These suggest that mean annual incidence rates in tropical endemic countries have always been as great, if not greater, than those experienced by temperate countries during epidemic periods in the twentieth century and that the total number of cases of paralytic poliomyelitis occurring in the world each year has been reduced by only 25% since the advent of polio vaccine. Immunisation against poliomyelitis must have a high priority in Ghana and other tropical countries where the disease is endemic.


Naming of neurones. Classification and naming of cat retinal ganglion cells. Many schemes of ganglion cell classification seek to classify the cells by some particular characteristic, such as the time course of the cells' physiological responses or their dendritic morphology. It is here argued that such schemes are based on the Aristotelian concept of "essences" and raise the same difficulties as have arisen with the essentialist approach to animal taxonomy. A better approach to the classification of neurones, it is proposed, is to base the classification on as many features of the cells as possible, and to regard the classification as an hypothesis, subject to testing and modification by experience, about the "functional niches" occupied by the cell types distinguished.


Responses of thoracic dorsal horn interneurons to cutaneous stimulation and to the administration of algogenic substances into the mesenteric artery in the spinal cat. The effects of the injection of algogenic substances (bradykinin, acetylcholine) into the inferior mesenteric artery were studied at the thoracic level on 47 dorsal horn interneurons responding to cutaneous stimulation. Each unit was characterized by its electrophysiological properties and carefully located within the cord by extracellular injection of pontamine sky blue. Twenty cells, driven only by non-noxious cutaneous stimulation and mainly located in lamina IV, were not affected by the administration of algogenic substances. The activity of 25/27 cells, excited by both non-noxious and noxious cutaneous stimulation and mainly located in lamina V, was strongly modified by nociceptive visceral stimulation, induced by bradykinin and acetylcholine: 8/27 cells were activated, 14/27 were inhibited, 3/27 had a mixed inhibitory-excitatory response. From our study it clearly appears that nociceptive visceral messages only project on dorsal horn cells receiving noxious cutaneous afferents. Thus viscerosomatic convergence seems only to concern nociceptive messages; the existence of this kind of convergence reinforces the hypothesis suggested by several authors to explain referred pain from a neurophysiological point of view.


Activity of the crayfish caudal photoreceptor submitted to a conditioning paradigm. The activity of the crayfish caudal photoreceptor (Ph) was studied during the application of a classical conditioning paradigm. This cell is a primary photoreceptor and, at the same time, a secondary neuron in the mechanoreceptive pathway. The electrical stimulation of afferent mechanoreceptor fibers, the analog of the conditioned stimulus (ACS), produced a slight increase in the Ph firing rate. The photic stimulation, the analog of the unconditioned stimulus (AUS), produced a marked increase in the Ph firing rate. After ACS-AUS pairing, a decrease in the Ph firing rate appeared during the ACS-AUS interval, and it was considered the analog of the conditioned response (ACR). This inhibitory response gradually vanished during extinction. The application of ACS or AUS series alone did not produce a response similar to the ACR, this excluding sensitization as a possible cuase. The ACR meets several conventional criteria accepted in learning, supporting the idea that the crayfish caudal photoreceptor is part of a small neuronal network able to learn in the isolated nerve cord preparation.


The subunit structure of bovine brain 14-3-2. Two aspects of the subunit structure of the bovine brain specific protein 14-3-2 have been examined. On the one hand, native 14-3-2 has been separated into two fractions by hydroxylapatite chromatography. One eluted at the same position when chromatographed on the same column, while the other redistributed into the same two fractions again. Amino acid analysis of these two forms of 14-3-2 gave results that were not significantly different under the condition of analysis. Furthermore, when each peak was subjected to cyanogen bromide cleavage, very similar elution profiles of the resultant fragments were obtained. The two pools also cross-reacted with antiserum to 14-3-2. Reaction of purified 14-3-2 with dimethylsuberimidate caused the formation of covalently bound protein units of 100,000 molecular weight when measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis, as opposed to the 50,000 minimal molecular weight normally detected. On the other hand, analysis of the soluble tryptic peptides of S-[14C]carboxymethyl 14-3-2 yielded only three distinct radioactive peptides, each with one residue of S-carboxymethylcysteine whereas 8 are expected on the basis of the amino acid composition of the 50,000 molecular weight polypeptide chains. Thermolysin digestion of a similarly modified 14-3-2 preparation yielded all of the radioactivity in 5 S-carboxymethylcysteine-containing peptides. The partial amino acid sequence of these peptides indicates that they represent 4 unique areas of the polypeptide chain. Since 8 such peptides were expected, that is, double the number found, the minimum structural unit of the protein must be of 25,000 molecular weight. The results of these experiments do not permit distinction between a duplication of the structure within a single polypeptide chain or the alternate possibility of two polypeptide chains bound by unusually strong non-covalent bonds. These results suggest that 14-3-2 is a covalently linked dimer of 25,000 mol.wt. units that can aggregate to form larger species of 100,000 mol.wt. and higher.


The involvement of the noradrenergic system arising from the locus coeruleus in the postnatal development of the cortex in rat brain. The effect on the developing cerebral cortex and hippocampus of removing the noradrenergic input was investigated in 3-month-old rats following unilateral electrolytic lesions performed semistereotaxically at 15 h postnatal. In 5 animals there was a significant reduction (mean = 74%) in noradrenaline in the cortex ipsilateral to the lesion, and the neuronal morphology on the two sides was studied with the Golgi technique. There was no apparent difference in the morphology of pyramidal cells in parietal cortex with respect to soma depth, apical dendritic length, number of basal dendrites or number of spines on selected dendritic regions. There was a small but significant increase in the number of dendritic branches of pyramidal cells in layers II and IV on the side ipsilateral to the lesion. No layer VI cells were identified which had retained their contact with layer I. An examination of the cell morphology of CA1 pyramidal and dentate granule cells in the hippocampus revealed no obvious differences between the two sides. These results suggest that the trophic influence of the noradrenergic innervation on the postnatal development of cells in the cerebral cortex and hippocampus, if it exists at all, is relatively minor.


Glutamate decarboxylase (GAD) and gamma-aminobutyric acid (GABA) in discrete nuclei of hypothalamus and substantia nigra. The distribution of L-glutamate decarboxylase activity (GAD) and gamma-aminobutyric acid (GABA) was investigated in the hypothalamic nuclei and in parts of the substantia nigra in the rat. GAD varied markedly among these areas. The reticular part of the nigra showed the highest activity two-fold higher than any other nucleus. Among the hypothalamic nuclei, a 5-fold difference was found between the poorest and richest nuclei. High GAD was measured in the preoptic, anterior and dorsomedial nuclei. Low activity was found in arcuate and supraoptic nuclei. The lowest GAD activity was measured in the median eminence with only half the activity of the whole brain homogenate. This suggests that GABAergic neurones might not be involved in neuroendocrine regulation at the median eminence level. GABA was determined using the sensitive cycling microassay. The rats were killed by microwaves, procedure which was found to inactivate enzymatic processes within two sec without affecting the level or the distribution of GABA. Postmortem increments during the first 3 min following decapitation ranged up to 5 times the endogenous levels, and were proportional to the GAD activity of the corresponding nucleus. This confirms that GAD is the limiting factor in GABA synthesis and suggests that GABA turnover might be rapid. Endogenous GABA showed a uniform distribution within hypothalamic nuclei and nigra. No relationship appeared between endogenous GABA levels and GAD activities in the various nuclei. These results suggest that while GABA synthesis is likely to occur in non-evenly distributed nerve cells, most GABA may be stored in surrounding cells, presumably glia cells.


Oscillation of acetylcholine during nerve activity in the Torpedo electric organ. The amount of transmitter in the electric organ of Torpedo was measured with a time resolution of 1 sec in the course of stimulation. In parallel, the modifications of the electrophysiological response were analysed by determining the conductance increase (deltaG) and the electromotive force of electroplaques. Large changes in the level of total acetylcholine (ACh) were seen during stimulation. These changes were two-fold: a slow wave and, superimposed on it, a rapid oscillation. The slow wave raised total ACh to the initial level, or even higher. It was probably related to modifications in the amount of ACh released since it corresponded to characteristic inflections in the evolution of the deltaG curve. The slow wave and this physiological parameter were similarly affected when the experiments were performed at a reduced temperature. The rapid oscillation had an amplitude of about 20-40% of the total ACh. It was undamped and its period was 4-5 sec. In contrast to the slow wave, no clear physiological change associated with the rapid oscillation has been observed. The slow wave and rapid oscillation occurred in the 'free pool' of ACh, whereas bound ACh, the fraction associated with synaptic vesicles, was not affected by these changes. A dynamic description of synaptic activity is proposed. The content of 'free' ACh is used and renewed completely after a few tens of impulses, so that transmission seems to imply the continual recycling of the same pool of transmitter rather than utilization of a large preloaded store. The release process must then be integrated in rapid metabolic loops.


Ipsilateral utricular and semicircular canal interactions from electrical stimulation of individual vestibular nerve branches recorded in the descending medial longitudinal fasciculus. Interactions from electrical stimulation of individual vestibular end organ nerves recorded from second order vestibular neurons projecting caudally in the medial longitudinal fasciculus (MLF) have been investigated in unanesthetized, decerebrate decerebellate cats. Canal-canal and utricle-canal interactions were recorded using various condition-test parameters. The brain stem was sectioned to eliminate influence of the contralateral vestibular nuclei, and the condition-test experiments were repeated. The type of interaction observed (inhibition or facilitation) and the degree to which it occurred were dependent on the MLF recording site. Also, in the case of utricular interactions, these were dependent on the site of utricular stimulation. These dependencies indicate a topological arrangement from receptor cell through the second order neuronal projection pathways. Sectioning of the brain stem produced changes in the interaction patterns, indicating masking and/or balancing of the ipsilateral interactions. In interactions between the anterior and posterior canals, instances of no apparent interaction occurring before sectioning converted to inhibition after sectioning. This indicates that some facilitative interaction occurs involving feedback from the contralateral vestibular nuclei, and this facilitation masks or balances ipsilateral inhibition. In interactions between the anterior and horizontal canals, contralateral inhibitory influence masks ipsilateral facilitatory interactions. Contralateral facilitatory influence again balances ipsilateral inhibition in interactions between the horizontal and posterior canals. The degree of inhibition and facilitation observed indicates that considerably more polysynaptic ipsilateral convergence on second order vestibular neurons occurs than has been demonstrated in intracellular studies. Only inhibition was observed when the anterior canal was conditioned by stimulation of the utricular nerve after sectioning. In all other pairings, mixed effects were observed. It is suggested that this is related to known functional connections of semicircular canal second order neurons with neck motoneurons. Not only is canal output affected by utricular activity, but each canal affects utricular output in a different manner.


Short-term modulation of endogenous bursting rhythms by monosynaptic inhibition in Aplysia neurons: effects of contingent stimulation. A presynaptic neuron fires a high-frequency train of spikes that produces long-lasting synaptic inhibition that modulates the bursting rhythm in a small population of endogenous bursting neurons in the left upper quadrant of the isolated abdominal ganglion of Aplysia. Single inputs decrease or increase the duration of the burst cycle as a function of the precise phase of the input (the phase response curve). Two phases of the burst cycle were used to analyze the effects of repeated contingent (phase-locked) stimulation. One contingency involved synaptic input early in the burst cycle that inhibited spikes and decreased the duration, whereas the other contingency involved input late in the cycle that increased the duration. Under both contingencies of stimulation, buildup and short-term persistence were found, however these cumulative effects were not dependent upon the phase of the burst cycle. The locus of the short-term plasticity that underlies the buildup and persistence is in the pacemaker properties of the postsynaptic cell rather than in the synapse. The plastic change appears to involve a nonspecific postinhibitory rebound that follows a single input and builds up with repetition. These results support the suggestion that endogenous rhythms of pacemaker cells can undergo plastic changes and can therefore serve as a means of short-term information storage in the nervous system. However, this neuronal circuit does not have the specificity required to mediate operant conditioning.


The Ranvier nodes in the neurogenic electric organ of the knifefish Sternarchus: a freeze-etching study on the distribution of membrane-associated particles. The two types of Ranvier nodes (type I with narrow gap, type II with giant gap) and internodes in nerve fibers composing the Sternarchus electric organ have been studied by means of freeze-etching electron microscopy. Numerical analysis of the distribution of membrane-associated particles revealed the following features: (1) the P-faces of both types of nodes and of the internodal axon bear a similarly high density of particles (1000-1200 particles/sq. micron on the average). (2) particle density is differential in E-faces: the histogram for type I nodes has a wider range of particle concentrations (114-1522 particles/sq. micron) than that for type II nodes (45-576 particles/sq. micron) whose density values are in the same range as those of the internodal axon. At least some type I nodes (narrow gaps) generate spikes and probably have a low resistivity; these nodes may be those with high particle density on E-faces. The low particle density on E-faces of type II nodes may be associated with high resistivity and absence of excitability. Similarly, the low particle density in internodes may reflect inexcitability. There is evidence that the transition from one nodal type to the next is gradual: as the gap width of type I nodes increases, there is an occurrence of surface elaborations and the density of E-face particles tends to drop towards the range of type II nodes.


Protein synthesis in regenerating motor neurons in the cockroach. Protein synthesis was studied in the thoracic ganglia of the cockroach. All the motor neurons leaving the metathoracic ganglion were axotomized by cutting the nerve roots. In vivo experiments demonstrated that within two days of the operation those ganglia with cut nerve roots had an increased [3H]leucine incorporation into protein resulting from an increased uptake and labeling of the leucine pool. These effects were non-specific responses to the damage and trauma produced by the operation. In vitro labeling experiments failed to demonstrate any change in incorporation or uptake of [3H]leucine up to 16 days after the operation. Autoradiographic experiments were done on ganglia in which only nerve root 5 on one side was cut. Grain densities and cytoplasmic areas were measured for the ipsilateral, axotomized, identified, fast motor neuron, Df and the homologous, contralateral, intact cell of the same ganglion. The first statistically significant increase in grain density in the axotomized Df was observed 12 days after the operation. This may be compared with the 13 day lag period after the operation before the nerves start growing from the proximal stump. The significance of this relatively long lag period before the increased [3H]leucine incorporation and the start of nerve growth is discussed in terms of the ability of regenerating neurons to specifically reinnervate the cells to which they were originally connected.


Behavioral effects of spinal cord transection in the developing rat. Albino rats, 0, 9, 12, 15, 18, 21 or greater than 90 days of age, were given a mid-thoracic spinal cord transection. Evaluation of responses of the hindlimbs to a variety of behavioral tasks was begun on the day of surgery and at intervals throughout the postoperative survival period (up to 300 days). Two investigators, independently and without knowledge of the animals' ages or survival times, rated the response data. Histological study showed all transections to be complete. Large differences in behavior are observed when animals trasected at the neonatal stage (0-4 days of age) are compared with animals transected at the weanling stage (21-26 days of age)37. Results of the present investigation indicate a critical period near 15 days of age; animals lesioned prior to this age (0, 9, 12 days of age) show response development and recovery similar to the neonatally lesioned animal, whereas those animals lesioned at a later age (18, 21, greater than 90 days of age) show little recovery and are behaviorally similar to the weanling transected animal. In animals lesioned prior to the fifteenth postnatal day, postural responses appear depressed for a brief period but recover rapidly while most responses of animals in the older groups are depressed for longer periods and never attain the degree of recovery characteristic of the neonatally transected animal. Finally, like the neonatally transected animal, rats lesioned on the ninth and twelfth postnatal day develop certain responses at appropriate times relative to normal response development. If, however, these responses are mature and supraspinal control is present at the time of lesioning, they appear to be permanently depressed and fail to recover.


Brightness discrimination learning under conditions of cue enhancement by rats with lesions in the amygdala or hippocampus. Three groups of rats, one with amygdala lesions, one with hippocampal lesions and a control group were trained on a brightness discrimination task under one of three different conditions, enhancement of the negative cue, enhancement of the positive cue or a non-enhanced condition. Animals with amygdala lesions showed retarded learning compared with normal animals and those with hippocampal lesions under the positive cue enhancement condition. Under the negative cue enhancement condition animals with hipocampal lesions were significantly handicapped compared with the other two groups. Results are discussed in relation to the Douglas and Pribram concept of a reciprocal linking of the amygdala and hippocampal systems in discrimination learning with the amygdala functioning as a reinforce register system and the hippocampus as an error evaluation system.


Evidence for substance P in the striato-nigral tract. The highest concentration of substnace P yet found in the mammalian brain is in the reticular part of the substantia nigra. The effect of various lesions on the substance P content of that region has been examined in the rat in order to determine the possible sources and paths of nigropetal substance P-containing fibers. Unilateral knife cuts which transect the medial forebrain bundle and medial portion of the crus cerebri at a premammillary level lead to a 90% reduction in substance P in the ipsilateral reticular part of substantia nigra, with no significant effect on contralateral values. Incomplete electrolytic lesions of the globus pallidus lead to a 50% decrease. These data indicate that descending uncrossed pathways provide most of the substance P in the reticular part of the substantia nigra, with the striato-nigral tract providing an important component.


Presence of free, sulfate and glucuronide conjugated 3-methoxy-4-hydroxyphenylglycol (MHPG) in human brain, cerebrospinal fluid and plasma. The concentration of the free, glucuronide and the sulfate conjugated forms of 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in human plasma, cerebrospinal fluid (CSF) and brain by mass fragmentography. All three forms of MHPG were detected in the media analyzed. Free MHPG was found to be the predominant form in both the brain and the CSF. The sulfate conjugate of MHPG constitutes about 15% of the total MHPG in the CSF while in the brain the percentage varies between 30% in the hypothalamus and cortex and 80% in the substantia nigra. The concentration of the glucuronide conjugate of MHPG measured in the brain and CSF represents about 5% of the total MHPG concentration. In the plasma free MHPG and its glucuronide and sulfate conjugates are present in about equal concentrations. The relative concentrations of the three forms of MHPG measured in plasma, CSF and brain were compared with their concentrations in the urine from previously published results. From this comparison the diagnostic significance of each of the three forms of MHPG in the clinical assessment of central norepinephrine metabolism is discussed.


Glutamate decarboxylase localization in neurons of the olfactory bulb. Glutamate decarboxylase (GAD), the enzyme that synthesizes the neurotransmitter gamma-aminobutyric acid (GABA), has been localized in the rat olfactory bulb by immunocytochemical methods with both light and electron microscopy. The light microscopic results demonstrated GAD-positive puncta concentrated in the external plexiform layer and in the glomeruli of the glomerular layer. In addition, GAD-positive reaction product stained the dentrites and somata of granule and periglomerular cells. The electron microscopic observations confirmed the presence of GAD-positive reaction product within granule and periglomerular somata and dendrites. In electron micrographs of the external plexiform layer, the gemmules which arise from the distal dentrites of granule cells were also observed to be filled with reaction product, and these structures corresponded in size and location to the puncta observed in light microscopic preparations. The gemmules were observed to form reciprocal dendrodentritic synaptic junctions with mitral cell dentrites which lacked reaction product. In the glomeruli, GAD-positive reaction product was observed in the dentritic shafts and gemmules of periglomerular cells which also formed reciprocal dendrodentritic synaptic contacts with mitral/tufted cell dentrites. The localization of GAD in known inhibitory neurons of the olfactory bulb supports the case that these local circuit neurons use GABA as their neurotransmitter. The present study demonstrates that GAD molecules located within certain neuronal somata and dentrites can be visualized with antisera prepared against GAD that was purified from synaptosomal fractions of mouse brains. This finding suggests that the lack of GAD staining within somata and dentrites of GABA-ergic neurons noted in previous studies of the cerebellum and spinal cord was probably due to low GAD concentrations, rather than to antigenic differences among GAD molecules located in different portions of the neuron. A striking differences among GAD molecules located in different portions of the neuron. A striking difference between the granule and periglomerular neurons of the olfactory bulb and the neurons of the cerebellum and spinal cord is that the former have presynaptic dentrites while the latter do not. Since GAD-positive reaction product can be detected in the somata and dentrites of GABA-ergic neurons which have presynaptic dentrites, it is suggested that these neurons may differ from other GABA-ergic neurons with respect to either transport or metabolism of GAD.


Factors affecting the electrophoretic analysis of myelin proteins: application to changes occurring during brain development. Several factors affecting the sodium dodecylsulfate (SDS)-electrophoretic analysis of myelin proteins were investigated. It was observed that complete solubilization of proteins with SDS-containing solutions required either that the lyophilized myelin sample was pretreated with organic solvents or that reducing agents were added to the solubilizing solution. The SDS-electrophoretic pattern of myelin proteins was strongly dependent upon the ionic strength of the resolving gel since the mobility of the large basic protein appeared to increase as the ionic strength was decreased. Attempts were made to measure ratios of the major myelin proteins as a function of pretreatment of myelin with organic solvents followed by visualization of the protein bands with different stains. These studies revealed that lowered ratios of the proteolipid to each of the basic proteins was obtained if the myelin was delipidated with ehter-ethanol mixtures followed by staining with either Fast green or naphthol blue black (amido black). The most consistent results were obtained when myelin was not delipidated, solubilized in an SDS solvent containing dithiothreitol as the reducing agent, and gels were stained with Coomassie blue. Studies on developmental changes in the protein composition of myelin using this technique revealed that as mouse myelin matured the membrane became increasingly enriched in the small basic protein with the ratios of proteolipid/large basic protein/small basic protein changing from about 2:1:1 at 8-10 days to 2:1:2 at 16-17 weeks. Furthermore, the ratios of proteolipid/large basic protein remained essentially the same at all ages examined, suggesting that these proteins may be incorporated into the membrane at about the same rate during maturation.


Effects of neonatal deafferentation on the superficial laminae of the superior colliculus. The effect of neonatal unilateral enucleations or combined enulcleations-visual cortex ablation on the neurons of the superior colliculus has been studied, Enucleation alone leads to a shrinkage of neurons in the upper portion of the stratum grieseum superficiale but does not affect those in the lower half. The ratio of asymmetric/symmetric synaptic terminals is decreased from 85/15 to 75/25. A small number of abnormal synapses is also found. When both eye and contralateral visual cortex are removed at birth, neurons throughout the stratum griseum superficiale are reduced in size 20-25%. The synaptic ratio is reduced further to 55/45, and about 15% of the post-synaptic structures encountered have abnormal presynaptic profiles attached. It is concluded that the extent of transneuronal atrophy and synaptic disruption is proportional to the amount of afferent input removed. Also, the synaptic modifications made in the upper layers of the superior colliculus appear to be local in nature and there is no evidence of a significant sprouting or new growth of the remaining axons.


The effects of early hypo- and hyperthyroidism on the development of rat cerebellar cortex. III. Kinetics of cell proliferation in the external granular layer. The effects of early hypo- and hyperthyroidism on the rates of cell acquisition and proliferation have been studied in the external granular layer (EGL) of the developing rat cerebellar cortex at 10 days of age using quantitative autoradiographic methods. Both altered thyroid states reduce the rate of cell acquisition in the EGL, but appear to do so for different reasons. Hyperthyroidism shortens the average length of the cell cycle by decreasing the duration of the pre-DNA synthetic phase (G1),  indicating that excess thyroxine may exert a direct effect on the EGL. This action involves the early onset of neuronal differentiation (cessation of proliferation)46 which presumably leads to the observed decrease in the rate of cell acquisition (increased doubling time). Such differentiating cells do not, however, leave the proliferative zone or the EGL prematurely, resulting in a reduced labeling index, mitotic index, and growth fraction as non-dividing cells dilute the proliferating cell population. Hypothyroidism, on the other hand, leads to no significant change in the length of the cell cycle or in the mitotic index, but causes a decreased labeling index and growth fraction, as well as a reduced rate of cell acquisition (increased doubling time). No significant change in the amount of cell death in the EGL could be found to explain this apparent discrepancy between the rate of cell proliferation (cell cycle length) and cell acqusiition. The answer to this puzzle appears to lie in the mitotic index, which is not affected to the same extent as the labeling index, although it is also slightly reduced. If cells were to remain longer in mitosis, this could result in a decreased labeling index and growth fraction but nearly normal mitotic index and cell cycle length (as measured using the % labeled mitoses method), since those cells dropping out of the cycling population would be counted as mitoses...


Sex differences in dentritic patterns in hamster preoptic area. Sexual dimorphism is described in the dentritic field pattern of Golgi-stained neurons from the dorsomedial preoptic  area of adult golden hamsters (Mesocricetus auratus). Data were obtained through a mathematical reconstruction of dentritic densities of neurons sampled from this area in males and females. Males tended to have a central concentration, while females showed an irregular dendritic density distribution with concentrations dorsolateral, ventral and medial to the area of highest dentriic density in the males. These results suggest sex differences in the afferent inputs to neurons in the dorsomedial preoptic area which may be related to functional sexual dimorphism in physiology and behavior.


Binding of [3-H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by antiestrogens. The antiestrogens MER-25, CI-628, and nafoxidine inhibit the uptake of [3H]-estradiol in whole homogenates and isolated cell nuclei tissues and the pituitary, and inhibit estradiol-induced female sexual behavior. The antiestrogens were injected intraperitoneally 2 h prior to an intravenous injection of [3H]estradiol, and the animals were killed 2 h after the estradiol. CI-628 reduces radioactivity in whole homogenates and isolated cell nuclei of cerebral cortex, hypothalamus, preoptic area -septum and pituitary. Nafoxidine reduces uptake in cell nuclei of the hypothalamus, preoptic area-septum and pituitary. In this paradigm, MER-25 inhibited uptake only in the pituitary. In the analogous behavioral experiments, with antiestrogens injected 2 h prior to an intravenous injection of unesterified estradiol, CI-628 and nafoxidine totally inhibited lordosis responding. MER-25 shows no inhibition of behavior in this paradigm. However, when MER-25 is injected 12 h prior to the estradiol, it inhibits retention of [3H]estradiol at 2 h in brain and pituitary cell nuclei, and lordosis responding is also inhibited. Additionally, the antiestrogens can apparently displace previously bound [3H]estrdiol. When the antiestrogens are injected 2 h prior to an injection of [3H]estradiol, MER-25, CI-628 and nafoxidine all show greater inhibition of nuclear estradiol retention at 12 h after the [3H]estradiol injection than 2 h. Analogously, when CI-628 is injected 2 h after an intravenous injection of [3H]estradiol, it displaces most of the radioactivity present in hypothalamic-preoptic area nuclei at 12 h after the estradiol injection. These results indicate that antiestrogens can prevent or reverse the nuclear concentration of estradiol in brain cells and are consistent with a role of the cell nucleus in the induction of estrous behavior by estradiol.


Tree host range and world distribution of the extomycorrhizal fungus Pisolithus tinctorius. The natural occurrence of Pisolithus tinctorius has been confirmed in 33 countries of the world and in 38 states in the United States. This ectomycorrhizal fungus is found associated with various tree species in nurseries, urban areas, orchards, forests, and strip-mined spoils. Experiments have proved that this fungal symbiont forms ectomycorrhizae with Abies procera, Betula pendula, Carya illnoensis, 11 species of Eucalyptus, 30 species of Pinus, Pseudotsuga menziesii var. meniziesii, 2 species of Quercus, and Tsuga heterophylla. Pisolithus has also been reported growing under natural conditions in association with three additional species of Betula, two species of Eucalyptus, nine species of Pinus, and eight species of Quercus, Populus tremuloides, Pseudotsuga grandidenta, and Salix humilis. This fungal symbiont has great potential in forestation efforts because of (1) the availability of practical techniques for artificially introducing in into nursery soils; (2) its ability to improve tree survival and growth in the nursery and the field; (3) its near worldwide distribution on a variety of sites; and (4) its broad host range encompassing many of the world's most important tree species.


[Study of the initial parasitic relationship between a virus of the Gourlay group L 1 and the cellular population of Acholeplasma laidlawii]. The study of the relationship between MVL 51 virus, of the Gourlay group L 1, and the Mycoplasma cells of A. laidlawii during the first 35 min of infection leads to the conclusion that a "carrier state" has been established, free virus as well as infected and noninfected cells being present at the same time in the cultures. The evidence of a virus growth after 20 min of infection and the high level of remaining viable cells (1.15 x 10(8) CFU) at the end of the experiment also indicate that the carrier state should persist, at least for some time, being probably an important factor of the virus-cell relationship in the viral group L 1.


Effect of detergents and chemicals on purified vaccinia virus: analysis by SDS polyacrylamide gel electrophoresis and electron microscopy1,2. Vaccinia virus particles were dissociated into their constituent polypeptides and analysed by sodium dodecyl sulfate (SDS) gel electrophoresis. Thirty-three distinct polypeptide bands were identified and their molecular weights ranged between 11 000 and 150 000 daltons. Specific staining of gels containing polypeptides of dissociated virions revealed the presence of eight glycopeptides. No lipopeptides were detected. Analysis of chemical extracts (urea, guanidine hydrochloride, and alkali treatment) of the virus by SDS gel electrophoresis indicated that a total of 10 to 14 different polypeptides ranging in molecular weights from 11 000 to 70 000 daltons were solubilized. Analysis of detergent extracts and of the remains of extracted viral particles has shown that the detergent Nonidet P-40 (NP-40) solubilized a total of 11 polypeptides of which 6 were glycopeptides. The other detergents sodium deoxycholate (SDC) and cetyl trimethyl ammonium bromide (CTAB) were not as selective. both solubilizing more than 25 of the polypeptides composing the virus. Gel electrophoresis results also indicated that most of the small molecular weight (11 000-70 000 daltons) polypeptides were readily solubilized by NP-40, SDC, and CTAB, while those with molecular weights of 70 000  daltons and higher were not well solubilized. The effects of detergents were also analysed by electron microscopy. Evidence was obtained for subpopulations of viral particles having different susceptibility to detergent extraction.


Glutamate uptake in Thiobacillus novellus. Properties of the glutamate uptake system of Thiobacillus novellus were investigated using intact cells. Two kinetically distiguishable components were found and designated at the high-affinity (HA) component with an apparent Km of 33 micronM, and the low-affinity (LA) component with a Km of 18 mM. Glutamate accumulation was temperature-sensitive and could be inhibited by the addition of wide range of inhibitors including cyanide, dinitrophenol (DNP), iodoacetate, mercuric chloride, sodium azide, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), and dicyclhexylcarbodiimide (DCCD). The complex kinetics of the uptake process may be due to the rapid incorporation of added glutamate into a small peptide. This soluble peptide was formed rapidly after glutamate addition, and accumulated in whole cells.


Nitrate reduction nitrogenase activity in Spirillum lipoferum1. Nitrate and nitrite reduction under aerobic, microaerophillic, and anaerobic conditions was demonstrated in Spirillum lipoferum (ATCC 29145). Nitrite did not accumulated during assimilatory nitrate reduction in air. The nitrite produced during dissimilatory nitrate reduction accumulated in the medium but not in the cells. On exposure of the bacteria to nitrate and anaerobiosis, a low initial rate (lag) was followed by accelerated rates of nitrite accumulation. A 3-h anaerobic pretreatment, in the absence of nitrate, did not a void the lag phase. No nitrate reductase activity (NRA) developed in the presence of chloramphenicol. The data suggest that induction of anaerobic NRA in S. lipoferum required nitrate and protein synthesis. Anaerobic N2-ase by S. lipoferum was greatly stimulated in the presence of nitrate. The time course of nitrate reduction was coincidental with the pattern of nitrate-stimulated N2-ase activity inidcating that a relationship exists between these two processes.


Effects of temperature on the macromolecular composition and find structure of psychrophilic Arthrobacter species. A facultatively psychrophilic bacterium, Arthrobacter SI 55, grows at 20 degrees C, but growth, as measured by increase of viable cell count, is inhibited at 32 degrees C. Corresponding temperatures for an obligate psychrophile, Arthrobacter glacialis SI 137, are 10 degrees C and 19-20 degrees C. At the higher temperatures for each organism increases of cell mass, as measured by turbidity and of DNA, RNA, and protein, were not inhibited. At the upper temperatures, fewer septa were formed in Arthrobacter SI 55, and cells appeared as distorted filaments with irregular brancehs. Arthrobacter glacilis grew as single cells at the lower temperature, but as clumps of coccoid cells with well marked septa at the higher temperature. It appears that in Arthrobacter SI 55 septum formation may be inhibited at the higher temperature. In contrast, in A. glacialis septation occurs but the cells do not separate.


Dorsal frontal, orbital and mesial frontal cortical lesion and amygdaloid kindling in cats. Bilateral anteromesial or orbital cortical lesions do not affect sequential pattern of amygdaloid seizure development. However, orbital cortex lesions appear to significantly participate in the elaboration of a Stage 6 seizure pattern. Amygdaloid kindling ipsilateral to the side of anterodorsal cortical lesion or in animals with the same bilateral lesion appears to predispose them for the development of spontaneous, nonconvulsive (partial complex) seizures. It also significantly modifies clinical ictal patterns with practical ommission of Stages 2, 3 and 5, and largely lateralizes AD propagation to the stimulated hemisphere. The latter two features are strikingly reminiscent of the electroclinical manifestations of secondary site AM kindling in intact animals or AM kindling in animals with forebrain commissure bisection. Nonconvulsive (partial complex) status epilepticus was readily arrested by placement of electrolytic lesions ipsilateral to the AM stimulation, suggesting that MRF is essential for the perpetuation of the recurrent spontaneous seizure. Finally, the presence and absence of positive and negative aftereffects respectively, in animals with anterodorsal cortical lesion is consistent with the view that transfer and interference effects are mediated through the brain stem and forebrain commissures respectively.


Ribonuclease activity of human cerebrospinal fluid. The ribonuclease activity of cerebrospinal fluid of 219 patients was studied. The normal level was 269 +/- 95 units/ml. Consistent elevations above 550 units/ml were found in: 1. Chronic cerebrovascular disease; 2. Spinal cord compression; 3. Tumors. The molecular weights of the ribonucleases in the cerebrospinal fluid are approximately 33,000; 21,000 and 15,000; the major species is the one with m.w. 33,000. Although the increase in the CSF ribonuclease activity is not disease specific, the measurement has provided corroborative help in cases when the CSF protein is normal. The increase in CSF RNAase is not due to red or white blood cells and the immunologic data suggest that the CSF enzyme activity is derived from the blood stream. Further studies are necessary to rule out a nerve cell origin of the CSF ribonuclease activity.


Relevance in undergraduate neurological teaching. About 10% of patients consulting a family practitioner have neurological complaints, and about 2% ultimately receive a neurological diagnosis. As it is not possible to train enough neurologists for these patients, graduating medical students must be competent and confident in assessing neurological problems, particularly those that are common, treatable or require emergency management. An evaluation was made of the neurological problems commonly seen in family practice, the difficulties in managing neurological problems by the family practitioner and the criteria for referral to a neurologist. To evaluate the teaching of medical students and house staff, the types of problems seen in a teaching hospital neurology service were examined. As a result of this study an approach to the training of physicians is outlined to assist them to handle confidently and competently the neurological problems they will see in daily practice.


Metabolic balance studies in patients with Paget's disease receiving salmon calcitonin over long periods. Metabolic balance and calcium kinetic studies were performed in four patients with Paget's disease before treatment with salmon calcitonin and during the early and late stages of the treatment, which lasted 9 to 19 months, A significant decrease in bone turnover and 24-hour urine hydroxyproline and serum alkaline phosphatase values was observed in all patients. In contrast, the calcium, phosphorus and magnesium balances did not change significantly. In agreement with this, the partial body calcium, measured by in vivo neutron activation analysis, did not change. Intestinal calcium absorption increased initially, but returned to baseline levels 9 to 19 months after the study began. During the initial period there was a small, significant, but transient decrease in tubular reabsorption of phosphorus; this was accompanied by a significant decrease in serum phosphorus values--probably a direct effect of calcitonin rather than evidence of secondary hyperparathyroidism. Administration of salmon calcitonin to patients with Paget's disease decreases bone turnover without affecting calcium and phosphorus balances.


Nurse practitioners in primary care. VII. A cohort study of 99 nurses and 79 associated physicians. Long-term surveillance of the employment experience and developing roles of 99 nurses and 79 associated physicians who participated in the first 5 years of the McMaster University educational program for family practice nurses was undertaken with a descriptive survey. Data were gathered by mailed questionnaires; a 97.8% response rate was attained. Sociodemographic profiles of both groups and characteristics of the practice setting where copractitioner teams functioned were determined. Selected noteworthy results show that 92.7% of the nurses were currently employed, and that 82.5% of the graduates continued in their original practice. Nurses' time invested in patient care activities increased by 105%; time devoted to clerical and housekeeping duties decreased by 42%. Changes in roles for both categories of copractitioners were important. The interdisciplinary arrangements resulted in appreciable financial disadvantages to physicians and only modest income incentives to nurses. A series of successes of the model of practice under assessment has been identified; offsetting ongoing difficulties and problems have also been enumerated. The data from this project and preceding studies can facilitate the solution of unresolved problems on the basis of evidence rather than opinion.


Physical and psychological complications after intestinal bypass for obesity. Cognitive changes, depression, arthralgia and dermatitis developed in a 33-year-old woman 5 years after a jejunoileal shunt for massive obesity, The dermatitis and low serum carotene and vitamin C values suggested vitamin deficiencies, The serum magnesium concentration also was low. Vitamin and mineral replacement led to amelioration of the physical and psychological symptoms; the improvement has been maintained at 18-month follow-up. The favourable changes were documented with the Wechsler Adult Intelligence Scale, the Minnesota Multiphasic Personality Inventory and test performance ratings. It is concluded that the surgical procedure caused vitamin and magnesium deficiencies and that these resulted in the patient's symptoms.


Psychiatric hospitalization in Ontario: the revolving door in perspective. Ontario government statistics have indicated that during the 1960s the proportion of readmissions to psychiatric hospitals doubled to form two thirds of all admissions. Since this pertained to events rather than to individuals, a cohort of patients first admitted in 1969 was followed for 4 years to trace the pattern of readmission and the characteristics of patients at risk of readmission. Routinely returned data were linked and a sample from the greater metropolitan Toronto area was randomly selected. Of the cohort, 31% were readmitted, 8% three or more times. Age and diagnosis distinguished those readmitted. Most with multiple readmissions were under 25 years of age. Although diagnoses were equally distributed on first admission among psychotic, neurotic and other nonpsychotic disorders, with no significant change on readmission or multiple readmission, there was a predictably greater proportion of functional psychoses among the high-risk group and also an equal representation of personality, addictive and the remaining nonpsychotic conditions. The vulnerable few are identifiable early in their intermittent hospital career. It can be concluded that statistics suggesting that two thirds of admissions are readmissions are misleading.


Penetrating chest wound: a case report.

Penetrating chest wound: a case report. An unusual penetrating chest injury was caused by a ball-point pen. Because of apparent penetration of the heart, preparations were made for an emergency open-heart procedure before emergency thoracotomy was undertaken, with the pen still in situ. The pen had bruised the epicardium but had not penetrated the pericardial sac. After removal of the pen, the wound was closed and a chest tube left in place. Recovery, apart from minor degrees of basal atelectasis, pleural effusion and wound infection, was uneventful. The outcome was consistent with that associated with current aggressive management of penetrating chest injuries. Management is based on three approaches. The primary one is intercostal thoracostomy tube drainage and fluid and blood replacement. In cases of massive hemorrhage or air leak, thoracotomy is necessary. The third approach is to prevent post-traumatic pulmonary insufficiency by using fine, high-efficiency filters during blood transfusion, avoiding excessive administration of intravenous fluids, performing tracheostomy after prolonged endotracheal intubation, and using a volume respirator with positive end-expiratory pressure. The average mortality for penetrating wounds of the heart is 25%.


[Implantation of behavior therapy in the psychoanalytic milieu]. In French-speaking Quebec, implantation of behaviour therapy in psychiatric hospitals has been difficult because psychiatrists' training was and still is almost exclusively based on psychoanalytic therory. For this reason, many psychotherapists do not use the knowledge derived from laboratory experiments and only rely on their clinical judgement. Prejudiced by their professional identity, many psychiatrists believe that behaviorists manipulate and control patients, mechanize therapy, deny the importance of interpersonal relationships and only use punitive techniques. After refuting these arguments, the author describes the practical difficulties encountered when implanting behaviour therapy in a psychoanalytic milieu, as well as the advantages of a better understanding between these two schools, which might lead to psychiatry becoming more scientific, more human and closer to daily reality.


A developmental hierarchy of dyadic relationships. With the work of Mahler, Bowlby and others it has been increasingly recognized in recent years that there is a sequential progression in the nature of the first dyadic relationship which forms the basis for the type and quality of subsequent interpersonal transactions. Four levels of development of dyadic relationship may be recognized. To begin with the infant is in a state of not recognizing the existence of the other individual - the autistic phase. At the toddler stage there is awareness of a separateness of physical attributes between the child and the significant other, but the persistence of the symbiotic belief that there is substantial co-extension of mental processes between the two. With further separation and individuation in the pre-school and early school-aged child, a period of magical thinking prevails for varying durations in the child, in which there is an attempt made to retain an omnipotent control of the thinking of the significant other by the mechanism of projection of thought. In the mid-elementary school-aged child the decentering process emphasized by Piaget, together with the emerging capacity for making allowance for the context within which events occur, leads to the dyadic relationship being seen by the child as being mediated through the transactions of two autonomous mental apparatuses. Dependent upon the quality of the first dyadic relationships, the nature of the communication which occurs in them, of traumatic psychological events and of the integrity of the integrated forces of personality formation, residues of earlier modes of perceiving the dyadic relationship may be encountered.  Examples of these in adolescent and adult patients are given. The recognition of the possibility of shifts in the perception of the levels of the dyadic relationship is of importance in the conduct of individual pschotherapy, as the therapist can then deal more realistically with such topics as the establishment of goals, the management of the modes and quality of communication, as well as of transference and counter-transference relationships. This is particularly true of the treatment of patients with poorly integrated personalities. The fluctuations referred to are seen most dramatically with some schizophrenic patients.


Patterns in the delivery of psychiatric care in Saskatchewan 1971-1972 (II). Types of contacts and some patient career characteristics. A previous paper dealt with an overview of service sectors and patient volumes (2), whereas this one concentrates on types of contacts and some patient career characteristics. Analysis of a comprehensive psychiatric care utilization data file for Saskatchewan for the 1971-1972 period shows that 'public' sector patients were hospitalized for a greater average length of time than were 'private' sector patients. This may reflect differences in the styles of practice, exigencies of the demand for hospital beds in the 'private' as opposed to the 'public' sector and/or intrinsic differences in the nature of the problem treated in each sector. Some interesting facts regarding patterns of contact were uncovered. The bimodal nature of the 'psychiatric population' was further evident from the data which show that the majority of patients used relatively few services whereas a few used a large number of services. This suggests that the majority of the people seen for psychiatric reasons by medical practitioners were suffering from relatively minor psychiatric disorders. Heavy users of services were much more likely to have had some'public' or University Hospital-based contact. Conversely, light users were predominantly private sector patients. In the 'public' sector, those who had had some in patient treatment were consistently higher users of all services. It is evident that psychiatrists held a dominant position in this community-oriented public sector, having seen a large number of patients, but having had a low average rate of services per patient. In contrast, community nurses saw relatively few patients but saw them very often. This no doubt reflects their role in providing 'maintenance' services to chronic patients in approved homes in the community. In the 'private' sector, 69 percent of the services were delivered by GPs and 23 percent by psychiatrists were more likely to have had 'public' sector activity than were those seen only by GPs; also once in the 'public' sector, they were likelier to have had in patient as well as outpatient treatment. This suggests a 'sifting' of the more "difficult" patients through the private specialist sector into the public sector.


Improvement of cis-dichlorodiammineplatinum (NSC 119875): therapeutic index in an animal model. Cis-Dichlorodiammineplatinum (CPDD) NSC 119875 was given at toxic doses (3 mg/kg) to three groups of dogs. The renal toxicity was avoided with massive prehydration and with mannitol induced diuresis. The bone marrow toxicity was unaltered by either manipulation. The data presented indicate that a better therapeutic index has been achieved by osmotic diuresis with mannitol. Blood levels and urine levels measurements show that the pharmacokinetics of the drug are unaltered, the urinary concentration of drug being low in the first few hours, but with similar urinary drug recovery in all three groups.


High dose cis-platinum diammine dichloride: amelioration of renal toxicity by mannitol diuresis. A clinical trial was undertaken to improve the therapeutic index of cis-platinum diammine dichloride with a concomitantly administered mannitol induced diuresis. Sixty patients, heavily pretreated, were entered; fifty-one are evaluable. The technique of concomitant osmotic diuresis and CPDD administration is described in detail. Doses ranged from 3 mg/kg to 5 mg/kg. At 5 mg/kg, dose-limiting renal, marrow and ototoxicity were seen, and resulted in one drug death. Marrow toxicity was moderate. Renal toxicity was limited to transient elevations in serum creatinine levels, except in some patients who had renal impairment prior to CPDD treatment. These patients had moderate renal toxicity. Serial treatments as frequently as once every 3 weeks were used to maintain responses. Serial high dose CPDD produced only mild renal dysfunction. Ototoxicity, usually subclinical, was quantitated audiometrically, and found to be dose related, but not clinically prohibitive at 4 mg/kg or less. The overall response rate (PR/MR) was 42%. Clinically significant responses in epidermoid carcinoma of the head and neck, adenocarcinoma of the ovary, and germ cell tumors of the testis were seen. All six responding patients with germ cell tumor of the testis, had been resistant to low dose (1mg/kg) CPDD. Two responding patients with ovarian adenocarcinoma had been resistant to alkylating agents.


Adriamycin cardiomyopathy--risk factors. The records of 53 patients treated with Adriamycin, 17 of whom developed congestive heart failure and 36 of whom received a similar total dose of Adriamycin without developing congestive heart failure, were analyzed for factors associated with Adriamycin cardiomyopathy. The risk of cardiomyopathy was significantly greater in patients who developed a larger than or equal to 30% decrease in limb-lead QRS voltage. Concurrent cyclophosphamide and mediastinal radiotherapy lowered the cumulative Adriamycin dose necessary for the development of cardiac toxicity. Uncontrolled hypertension also appears to be a risk factor in potentiating the development of Adriamycin cardiomyopathy at lower doses. Congestive heart failure was more likely to be fatal if it developed shortly after the last dose of Adriamycin. These findings can be utilized to increase the safety of Adriamycin therapy in the future.


Hypocalcemia with hypoparathyroidism and renal tubular dysfunction associated with aminoglycoside therapy. Seventeen patients with malignant disease developed a complex metabolic syndrome of 2-8 weeks' duration characterized by hypocalcemia, hypomagnesemia and hypokalemia following administration of the aminoglycoside group of antibiotics. Gentamicin, Tobramycin, Amikacin, and Sisomicin were all involved. Other features noted were hypoalbuminemia, hypophosphatemia, and hypouricemia. Low immunoreactive parathyroid hormone (i-PTH) levels in the presence of hypocalcemia and absence of hyperplastic changes in the parathyroid gland examined at postmortem confirmed a diagnosis of hypoparathyroidism. Immunoreactive calcitonin levels (i-CT) were not elevated. Renal tubular wasting of potassium and magnesium was documented in six patients and excessive urinary loss of sodium, phosphate, and uric acid was noticed. Twelve patients died before recovering from the metabolic stress and five patients developed progressive renal impairment. A possible potentiating action of chemotherapeutic agents, especially Adriamycin, is suggested.


Radiotherapy results for nodular sclerosing Hodgkin's disease after clinical staging. Certain features of nodular sclerosing Hodgkin's disease predispose toward achievement of excellent radiotherapeutic results using clinical staging rather than currently advocated surgical staging including laparatomy. These include a distinct pattern of contiguous lymphatic involvement and the infrequent dissemination of disease to extranodal sites in early stage patients. Only three of 58 consecutive Clinical Stage I-III patients initially treated with radiotherapy alone between 1965 and 1969 have died from Hodgkin's disease. The 10-year survival rates corrected for intercurrent deaths are 97%, 90%, and 86% for Stages I-IIA, IIB, and III respectively. The usual prognostic influence of "B" symptoms was not evident following extended prophylactic irradiation. Likewise, there was no discernible influence of the subtype (lymphocyte predominant, mixed cellularity, lymphocyte depletion) on survival with these nodular sclerosis patients. There was a single extension of disease to iliac nodes in 46 patients with supradiaphragmatic involvement for whom prophylactic irradiation did not extend below the aortic bifurcation, providing justification for modified total nodal irradiation. Development of extranodal dissemination was observed in only 4/58(7%) patients, indicating that adjuvant chemotherapy is not warranted or justified in the early stages of nodular sclerosing Hodgkin's disease.