Mechanical responses of rat isolated uterine horns to transmural stimulation.

1 Transmural stimulation of rat isolated uterine horns at low pulse width produced contractions. These were antagonized by hyoscine or tetrodotoxin and potentiated by physostigmine. 2 In the presence of hyoscine, and during bradykinin-induced contractions, transmural stimulation produced inhibition. This inhibition was antagonized by guanethidine, propranolol or tetrodotoxin. 3 Hexamethonium or pempidine did not affect responses to transmural stimulation. 4 It is suggested that transmural stimulation is a method of exciting cholinergic motor and noradrenergic inhibitory postganglionic neurones to the rat myometrium.


The effects of prostaglandins E1, E2 and F2alpha on vagal bradycardia in the anaesthetized mouse.

1 In anesthetized mice prostaglandins E1 and E2 reduced the bradycardia caused by electrical stimulation of the sectioned peripheral vagus nerve; prostaglandin F2alpha produced only a slight inhibition of the vagal response. 2 None of the prostaglandins studied affected acetylcholine-induced bradycardia. 3 Prostaglandins modify parasympathetic nerve activity in vivo presumably by a pre-synaptic action.


On the ability of prostaglandin E1, and arachidonic acid to modulate experimentally induced oedema in the rat paw.

1 Prostaglandins E1 and E2 but not prostaglandin F2alpha, arachidonic acid or linolenic acid, produced slight oedema when injected into the rat hindpaw. 2 Prostaglandin E1 potentiated hindpaw oedema produced by carrageenan, kaolin, bradykinin and trypsin but not that produced by 5-hydroxytryptamine (5-HT), histamine, dextran B or compound 48/80. Carrageenan- and bradykinin-induced paw oedemas were also potentiated by prostaglandin E2. Arachidonic acid potentiated responses to carrageenan and kaolin but not responses to bradykinin, trypsin, 5-HT, histamine, dextran B or compound 48/80. Linolenic acid did not potentiate hindpaw oedema induced by carrageenan. 3 Potentiation of carrageenan-induced oedema by prostaglandin E1 was not diminished by pretreatment with indomethacin, hydrocortisone or cyproheptadine. However, arachidonic acid potentiation of carrageenan oedema was reduced by pretreatment with non-steroidal anti-inflammatory drugs but not by anti-inflammatory steroids or by paracetamol. 4 The enhancement of the response to carrageenan and kaolin by prostaglandins E1, E2 and arachidonic acid is discussed in terms of kinin mediation.


Anti-inflammatory action of glucagon in rats.

1 Subcutaneous administration of glucagon (1 and 0.5 mg/kg) 30 min before the injection of carrageenin or dextran into the rat's paw reduced oedema and the local exudation of Evans blue previously given intravenously. 2 The effect persisted after removal of the adrenal medulla but not after adrenalectomy. 3 When glucagon (1 mg/kg, s.c.) was given daily after a local reaction to Freund's adjuvant injected into the paw had developed, a decrease in the reaction was observed up to 12 days. Blood sugar levels remained within the normal range. 4 Glucagon may exert an anti-inflammatory effect through the release of adrenal corticosteroids and thus help modulate inflammatory reactions.


Formation of dopamine and noradrenaline in rat vas deferens: comparison with guinea-pig vas deferens.

1 The formation of [14C]-3,4-dihydroxyphenylalanine (DOPA) from [14C]-tyrosine, in the presence of the amino acid decarboxylase inhibitor, brocresine (3-hydroxy-4-bromobenzyloxyamine dihydrogen phosphate), was greatly enhanced in rat vasa deferentia depolarized by a KCl-enriched Krebs-Henseleit solution (52 mM KCl) compared with tissues maintained in unmodified Krebs-Henseleit solution. 2 When the conversion of tyrosine was allowed to proceed as far as catecholamine (brocresine absent) no significant difference was observed between the accumulation of [14C]-catecholamines (CA) in depolarized rat vasa deferentia and the accumulation in control (non-depolarized) tissues. 3 Endogenous CA levels in the depolarized rat vasa deferentia fell to 67% of the controls after a 1 h incubation period and to 53% at the end of 2 hours. 4 Chromatographic separation on Amberlite CG-120 columns of the newly synthesized CA and catechol metabolites from the rat vas deferens revealed that a very high proportion was present as dopamine. The percentage distribution after 1 h incubation in control Krebs-Henseleit was: noradrenaline (NA): 30.6 +/- 5.2; dopamine 56.9 +/- 5.9; acid metabolites: 12.8 +/- 1.1; and in KCl-rich Krebs-Henseleit, NA: 32; dopamine: 44.7 and acid metabolites 23.3. In contrast to the newly synthesized (14C-labelled) CA, endogenous dopamine comprises only 10% of the endogenous CA stores in rat vas deferens. 5 The distribution of newly synthesized NA and dopamine in rat vas deferens is strikingly different from that of guinea-pig vas deferens where more than 80% of newly formed amine is present as NA. In the latter tissue depolarization with K+ causes a striking increase in CA biosynthesis.


Temperature and behavioural responses induced in the unanaesthetized cat by the central administration of RX72601, a new anticholinesterase.

1 The central effects produced by a new anticholinesterase RX72601 injected into the cerebral ventricles or perfused within circumscribed forebrain structures have been investigated in the unanesthetized cat. 2 When injected into the cerebral ventricles in doses of 1-10 mug, RX72601 produced a dose-related hyperthermia together with behavioural and autonomic responses. 3 Experiments designed to localize the site or sites of these actions demonstrated that hyperthermia could be produced from several diencephalic sites but that the other effects were not normally produced from these same sites.


Influence of some social and environmental factors on the nutrient intake and nutritional status of schoolchildren.

Only children had significantly higher intakes of many nutrients and nutrients/1000 kcal than other children. A higher proportion of only children was found to be obese. There were no significant differences according to birthrank in intakes by children. There were more obese children among the fatherless than those with fathers, in particular among those whose mothers were widowed. However, this was not accounted for by the present dietary findings, since fatherless children had lower intakes of carbohydrate and added sugar. There were no differences in nutrient intake or intake/1000 kcal by mother's country of origin or her level of education, or by disposable income.


Family social characteristics related to physical growth of young children.

Altogether 164 poor families who had children of normal and subnormal weight and height were studied in Bogota, Colombia. Physical growth was found to be positively associated with expenditure on food, sanitary conditions in the home, mother's age, birth interval between surviving children, level of parental newspaper reading, aspirations for children, and socioeconomic status. Physical growth was negatively associated with crowded living conditions and family size. Only mother's age, family size, spacing of births, and sanitary conditions were related to weight and height, independent of socioeconomic status. Food expenditure, crowding, parental newspaper reading, and aspirations for children all reflected the influence of socioeconomic status upon physical growth. The findings emphasized the importance of within-class social differences as they affect the physical growth of young children.


Recall of women in a cervical cytology screening programme. An estimate of the true rate of response.

In a sample of 1007 women from a large cervical cytology screening programme in the Manchester region, the apparent response-rate to a letter inviting women to have a second routine smear three years after their first was 47-6%. After taking account of those who had become ineligible on medical grounds, or inaccessible, a conservative estimate of the true rate of response was 65-7%. When women who had had interim smears or examinations elsewhere were included, 72-2% of the original population of women had continued to make use of facilities for cytological screening.


Bladder cancer mortality in diabetics in relation to saccharin consumption and smoking habits.

The frequency with which diabetes mellitus was mentioned on the death certificates of 18,733 patients dying from bladder cancer has been compared with that of 19,709 patients dying from other cancers (excluding cancer of the lung and pancreas). The estimated relative risk of bladder cancer in diabetics was 0-98 with 95% confidence limits 0-70-1-38. There was no increase in risk of bladder cancer in patients with diabetes of long duration. Diabetics were shown by questionnaire to consume substantially more saccharin than non-diabetics, and the duration of regular saccharin use by diabetics was highly correlated with the duration of diabetes. There was therefore no evidence from this study that consumption of above average amounts of saccharin had led to bladder cancer in diabetics. The proporation of current smokers among diabetics was significantly less than among non-diabetics, and this may account for a low relative risk of lung cancer in the former (0-72).


Mortality from arteriosclerotic disease and consumption of hydrogenated oils and fats.

Consumptions of chemically modified hydrogenated fat are estimated for the United Kingdom standard regions, conurbations, and urban/rural aggregates as well as for the social classes. Consumptions are shown to correlate satisfactorily with mortality from arteriosclerotic disease and account reasonably well for certain peculiarities in the ratio of female to male death rates and for secular changes in mortality patterns.


Incidence of ischaemic heart disease in two cohorts of Belgian clerks.

A study during a five-year period has been conducted on the incidence of ischaemic heart disease (IHD) among two cohorts of Belgian employees who were free of IHD at entry. As regards the final outcome these incidences differ significantly. The chief difference between the two cohorts is their systolic blood pressure. These pressure differences may be attributed to differences in the level of work pressure. The increased work pressure in Cohort I might account, through stress, for the greater incidence of sudden death or myocardial infarction.


Ischaemic heart disease and the water factor. A variable relationship.

A comparison is made between mortality from ischaemic heart disease and the quality of drinking water in the cities of Brisbane and Melbourne. Mortality from ischaemic heart disease is found to be higher in Brisbane where drinking water is harder, than in Melbourne. Moreover, mortality from all causes is higher in Brisbane than in Melbourne.


Genetic hypotheses and environmental factors in the light of psychiatric morbidity in the families of schizophrenics.

The hypothesis that schizophrenia and some non-psychotic abnormalities occurring in the close relatives are both manifestations of a unitary "schizoid state' due to a major dominant gene is further examined. Comparisons are made (1) of the observed and expected frequencies of the different types of parent mating; and (2) of the observed and expected risks among sibs in families with neither, or with one or both, of the parents abnormal. It is concluded that the results do not fit well with the model of inheritance of the schizoid state through a major dominant gene. Since some hereditary contribution in schizophrenia can be regarded as established, the excess of personality disorders and heavy drinking in the families is thought to be due to a combination of polygenic inheritance and environmental influences. The findings are regarded only as tentative, but suggest several hypotheses which could be tested.


Serum copper in schizophrenia in Nigerians.

Serum copper concentrations were determined by atomic absorption spectrophotometry in 102 schizophrenic patients and 95 healthy control subjects. The serum copper concentrations were significantly higher in the schizophrenic patients than in the normal control subjects. The average serum copper in schizophrenic females was higher than in schizophrenic males, but the difference was not statistically significant.


Subjective aspects of alpha enhancement.

Early reports on enhancing occipital alpha through feedback noted that subjects reported the experience as being pleasant and relaxing. This paper reports the subjective experiences of 140 subjects who participated in four studies which examined the alpha enhancement phenomenon. Under both eyes-open and eyes-closed conditions, approximately 50 per cent of the subjects reported that alpha enhancement was "pleasant' and 50 per cent "unpleasant/neutral'. With eyes-open training conditions, about half the subjects stated that the experience was "relaxing' and the other half "not relaxing'. During eyes-closed training, 63 per cent of the subjects noted that enhancing alpha was "relaxing', while 37 per cent reported that the experience was "not relaxing'. However, in the last case the circular relationship between increased alpha and deep relaxation may obtain.


Self-mutilation, obsessionality and narcissism.

A controlled study of the clinical and biographical features of 22 female repeated self-cutters is described. The results of the assessment of these patients, using the Middlesex Hospital Questionnaire and the Obsessive-Compulsive section of the Tavistock Inventory, is presented. The marked obsessionality of these patients is emphasized and the possible implications of these findings for treatment is discussed.


Psychiatric morbidity in a sample of a London coroner's open verdicts.

One hundred and thirty-four deaths recorded as open verdicts in the Inner West London Coroner's District during 1969 and 1970 have been surveyed for evidence of mental illness. For 110 (82 per cent) of these deaths the probable verdicts were suicide or accident and they were reclassified as undetermined deaths. Of these deaths 73 per cent were diagnosed as mentally ill, 54 per cent were receiving medical treatment for psychological symptoms before death, 42 per cent had a history of psychiatric care and 24 per cent had made a previous suicide attempt. In these respects undetermined deaths and suicide deaths resemble each other; both are drawn predominantly from the mentally ill.


The potential difference across the rectal mucosa during depressive illness and lithium therapy.

The potential difference across the rectal mucosa (rectal p.d.) is generated by the active transport of sodium across the mucosa, and it is sensitive to the action of aldosterone. The rectal p.d. values of depressive patients on no treatment, tested whilst depressed or after recovery, were found to be similar to those of control subjects, indicating that sodium transport across the rectal mucosa and the activity of aldosterone were normal in these patients. This contrasts with previous reports of abnormalities of sodium transport and of aldosterone levels in manic-depressive patients. Manic-depressive patients taking lithium carbonate as a prophylactic agent were found to have significantly elevated rectal p.d. values when normothymic. Patients who had become depressed whilst taking lithium, and in whom prophylaxis had therefore failed, were found to have normal rectal p.d. values. Lack of elevation of rectal p.d. in response to lithium administration may be a characteristic of patients who fail to respond to lithium prophylaxis.


Age, persistence and improvement in an open out-patient group.

The ages of 87 patients attending an open out-patient group in a general hospital psychiatric out-patient department are analysed in relation to persistence with treatment. A highly significant correlation (p smaller than .001) is obtained between increasing age and continued attendance, and a significantly greater number are found to attend for six months or more in the age-range 37-47 than at other ages. In a sub-group of 35 patients, all of whom had attended more than four sessions and had returned a questionnaire, significant correlations are obtained between age and symptomatic improvement (p smaller than .05) and between continued attendance and improvement in interpersonal relationships (p smaller than .05).


Psychiatric new-patient clinic non-attenders.

Non-attenders at a psychiatric new-patient clinic were seen and interviewed six weeks after the missed appointment, as were a group of controls who did attend. The non-attenders were more likely to have had frequent changes of occupation or belong to families where this was the case with the family breadwinner; a history of court conviction; and a history of previous psychiatric treatment. They were less likely to have improved since referral to the clinic; and to have a diagnosis of manic depressive psychosis, depressed type. The findings are discussed. There appears to be some self-selection, the most treatable patients keeping their appointments.


Psychiatric referrals from the police.

This is a study of one mode of inception into psychiatric care in Birmingham. Mentally disturbed people coming to the attention of the police are referred to a mental welfare officer and assessed by him, usually in a police station. The mental welfare officer may then refer for a psychiatric decision with regard to further management, and the patient is examined by the doctor in the police station. The annual frequency of use of this referral system was studied from 1962-73 inclusive. It is shown that there was an increase in referral over the years and that such referral from the police became an increasing proportion of new referrals to the Mental Health Department (Social Services Department). The sample of referrals from the police for 12 months is studied in greater detail (252 cases), surveying social characteristics of individual patients, the relationships between such police intervention and areas of the city, the nature of situation requiring intervention and the management and treatment which these patients received. The referrals were traced from contact with the mental welfare officer to hospital where the case notes of those admitted were studied for details of legal status and mental state on admission, diagnosis, duration of stay and disposal. The effectiveness of this method of entering treatment is discussed and some recommendations are made.


Training opportunities for overseas psychiatrists.

The literature relating to the training opportunities offered to overseas graduates in this country and the United States is reviewed. Although overseas trainees in psychiatry do not see themselves at a great disadvantage, the fact that the great majority are working in non-teaching hospitals means by implication that overall their training is not as good as that of home graduates.


Psycho-social transitions: comparison between reactions to loss of a limb and loss of a spouse.

In 21 widows and 46 amputees a psychological reaction to loss designated as "grief' was commonly reported. This included an initial period of numbness, soon followed by restless pining with preoccupation with thoughts of the loss, a clear visual memory of the lost object and a sense of its presence. Defensive processes, reflected in difficulty in believing in the loss and avoidance of reminders, were also evident. Widows differed from amputees in showing more evidence of overt distress in the early post-loss phase, but whereas these features diminished in prevalence in the course of the next year the equivalent features reported by the amputee group remained virtually unchanged.


The treatment of psychotic depression by sleep deprivation: a replication study.

A replication study of the effects of single-night sleep deprivation therapy was carried out as a preliminary to a controlled comparison with orthodox antidepressent measures. The results show that sleep deprivation therapy was acceptable to a majority of the patients studied, and was followed by an improvement in over half those who completed treatment. Adverse effects were minimal. The authors feel that further clinical and physiological study is warranted.


Fertility of the sibs of schizophrenic patients.

This investigation has provided evidence against the hypothesis that heterozygous carriers of schizophrenic gene have a reproductive advantage through enhanced fertility. An advantage arising from lower mortality between birth and the end of the reproductive period was not investigated, but should be examined before we search for other explanations of the apparently stable polymorphism of schizophrenia.


Looseness of associations in acute schizophrenia.

To study looseness of associations and other theoretically relevant variables of speech pathology, 51 acute psychiatric patients, including 26 schizophrenics, were studied at the acute phase of their disorder by means of a free verbalization interview. The results on these 51 patients during the acute period were: 1. There were clear differences between the schizophrenic patient group and the control patient group, the overall index of deviant verbalizations being significant at the .001 level. 2. Many types of looseness were found in non-schizophrenic patients as well as in schizophrenics. Except at the very mildest levels, however, the variants of overt looseness were strikingly more frequent in occurrence and severe in degree in the schizophrenic group (p smaller than .01). 3. Gaps in communication, vagueness of ideas and blocking, though present to some degree in our control group, were much more common in the schizophrenic sample (p smaller than .001). 4. In the control group of patients, private meanings (including neologisms), repetition and perseveration were extremely rare, and current delusional thinking virtually non-existent. Private meanings and current delusional thinking were conspicuously present in the schizophrenic sample; repetition and perseveration were present to a mild degree in this acute schizophrenic sample. 5. Schizophrenic patients tend to show more looseness of associations when faced with a request to talk about topics not related to their illness.


The comparability of suicide rates.

Programmes of suicide prevention require for their planning accurate epidemiological surveys. Doubt has been cast on the accuracy of many existing surveys because of the realization that suicide is under-reported and because of the lack of consistency in the procedure for suicide ascertainment. Two studies are described in this paper which attempt to examine the problem. The first is part of an international study supported by the World Health Organization. In it, Denmark and England are compared, and it is shown that there are striking differences in suicide ascertainment procedure between the two countries. Next, on a blind basis, coroners and their opposite numbers in Denmark examine a sample of each other's case records. It is found that the Danes consistently report more suicides than do the English coroners on the same case material; thus considerable doubt is cast on the supposed difference in suicide rates between the two countries. In the second study, deaths by poisoning are examined for certain coroners' districts in England and Wales. It is shown that there is considerable variation from one district to another in the relative proportions of these deaths which achieve an accident, an open or a suicide verdict. This suggests that in England and Wales coroners may not be consistent in their suicide ascertainment criteria. Hypotheses attempting to account for differences in suicide rate based on such epidemiological surveys should be viewed with great caution.


Trends in the care of psychiatric patients.

This study begins with a detailed analysis of the population of a large psychiatric hospital in South Wales. Attempts are made to determine the incidence of chronicity, with its various underlying causes. This is followed by details of the current admissions to the hospital from a catchment area where general hospital and psychogeriatric units have been established, and estimates of future bed requirements. Finally there is a description of the several facilities of the general hospital unit and of the problems of developing a fully comprehensive mental health service.


Mental health care in rural India: a study of existing patterns and their implications for future policy.

Three separate studies were carried out to examine the patterns of mental health care in an Indian village. The first examined the conceptual frameworks of the various traditional and modern healers. The second was an attitude study inquiring about the type of healer favoured for psychiatric consultation. The third was a population survey in which every person with one or more symptoms was asked if he or she had consulted anyone for relief of distress. Besides the modern doctors there were three types of traditional healers: Vaids, practising an empirical system of indigenous medicine; Mantarwadis, curing through astrology and charms; and Patris, who acted as mediums for spirits and demons. It was found that a large majority (59 per cent) of those with symptoms had consulted someone. The consultation was determined more by the severity of illness than by socio-demographic factors. Modern doctors were more popular, but most people consulted both traditional and modern healers without regards to the latter's contradictory conceptual framework. Literacy and other socio-demographic factors had no influence on the type of consultation. A conclusion was reached that any scheme for introducing modern psychiatry into rural areas should make use of the locally popular healers, both traditional or modern.


Class change in the personal illness hierarchy.

Sixty-eight psychiatric in-patients who had completed the Delusions-Symptoms-States Inventory (D.S.S.I.) on admission were retested after one month. On first testing 92.6 per cent conformed to the hierarchy of classes of personal illness model, and on the second occasion 91.2 per cent. Of those who could improve, 72 per cent did so, most commonly by moving down one hierarchy class, e.g. from the Neurotic Symptoms class to the Dysthymic States class. (On the other hand only 30 per cent of the 61 patients who originally reported symptoms did not do so after one month.) Thus although it is clear that the patients as a group changed markedly, they have not departed from the hierarchy. These results indicate that either the symptoms further up the hierarchy remit before those lower in the hierarchy or they remit together. Certainly those lower in the hierarchy do not go first. It is suggested that the results would be difficult to accommodate within strict disease-entity models, and that they have different implications for both treatment and the assessment of change in current state.


Demographic differences in functional psychoses.

Only Scandinavian investigators have reported on demographic aspects of reactive psychoses. Data from the National Health Service, Denmark, for age at first admission, sex, and length of stay in hospital in reactive, manic-depressive and schizophrenic psychoses are analysed. Differences in sex incidence ratios, age at first admission and length of stay are evident between the three psychoses. The differences noted are considered to provide indirect evidence supporting the separate diagnostic categories.


A phenomenological analysis of symptoms in obsessive-compulsive neurosis.

Eighty-two obsessional neurotics were studied from a phenomenological point of view in order to delineate the various forms and contents of obsessions and compulsions. An attempt was made to ascertain the frequency with which the different forms and content occur and their effect on the final outcome of the disorder. Five types of obsessions were identified: doubts, obsessive thinking, fears, impulses, and images, in order of frequency of their occurrence. Compulsive acts could be classified in two types, depending on whether they yielded to or diverted the underlying obsession. One-fourth of the patients displayed no compulsions. The content of obsession could be classified in five broad categories as relating to: dirt and contamination, aggression, inanimate-impersonal themes, religion, and sexual matters, in order of the frequency of their occurrence. The paper, while offering an interpretation of these findings, emphasizes the part played by socio-cultural factors in the character of an obsession's thought content. The absence of compulsions was found to be associated with good prognosis. A downward gradient was noted in the final outcome of patients without compulsions, those with controlling compulsions alone, those with both varieties of compulsions, and those displaying yielding compulsions alone, in that order. Based on this observation the paper suggests a prognosis-related hierarchical continuum of the severity of obsessional disorder.


A ten-year study of out-patient analytic group therapy.

Ninety-three chronic neurotic patients whose previous psychiatric treatments had proved unsuccessful were included in this study, and selected patients, relatives and G.P.s were briefed to expect stress during therapy. Assessment made by therapist and patients before and after therapy was made on the basis of the acceptability of eight aspects of their life. Follow-up lasted 2 1/2 years. Of the 93 patients, 87 per cent showed positive change, a small number showed temporary negative change and one patient became psychotic but later recovered. The "contamination' of results due to therapist involvement in assessment is offset against corroborative evidence of change, in that 96 per cent of patients became independent of the psychiatric and social services after years of dependency in many cases. There were also marked changes in life situations and relationships. A need for increased facilities for basic and in-service training of group therapists is indicated.


The problem of generalization in the operant conditioning of social speech in the severely subnormal. Use of reversal to establish generalizability.

Many severely subnormal patients talk little to each other. In this experiment, three pairs of subjects were reinforced for talking to each other, and learned to do so quite quickly. Whether social speech would continue to occur without the benefit of external reinforcement was examined by observing the subjects through a one-way mirror in a bare interview room adjacent to the teaching room immediately after each training session. On some occasions untrained subjects were observed in the bare room with the trained subjects. The reinforcement of social speech was demonstrated to be effective by the use of a reversal design (baseline, reinforcement, no reinforcement, reinforcement), where the rate of speech increased considerably when reinforcement was available but decreased when it was discontinued. Generalization of the increased social speech, however, was very poor and only significantly above baseline levels with the pair who seemed responsive to social as well as material reinforcement. The implications of this for training programmes are discussed.


The usefulness of the semantic differential with "mild grade' mental defectives.

Although the semantic differential has been quite widely used with mental defectives, its usefulness (in its traditional form) with such a population has not been conclusively demonstrated. The semantic differential was developed and shown to be valid as an index of representational mediation processes. However, there is also evidence of a mediational deficiency among retardates which, therefore, ought to be reflected in retardates' responses to the semantic differential. Thus, the present study was designed to test two hypotheses: (a) that mild grade retardates, in comparison with subjects of average intelligence, would show less discrimination in the use of the semantic differential, and (b) that such discriminative deficiencies would in turn predispose toward a polarized response bias among the retarded. The results, which support both hypotheses, are discussed in terms of their implications for the usefulness of an unmodified semantic differential with the mentally subnormal.


Schizophrenia in a 47,XYY male.

A case of schizophrenia in a 47,XYY male diagnosed according to strict phenomenological criteria is presented. The authors suggest that the 47,XYY chromosome anomaly should be added to the list of possible causes of symptomatic schizophrenia, and express the hope that future investigations of the effects of an extra Y chromosome in brain function will yield clues as to the aetiology of idiopathic schizophrenia.


Psychiatric morbidity in parents and sibs of schizophrenics and non-schizophrenics.

The aims of this study were to compare the psychiatric morbidity occurring in the close relatives (N = 332) of patients showing nuclear forms of schizophrenia with that of a control group (N = 201), and to consider the findings in relation to the concept of the schizophrenic "spectrum' and to some genetic theories of schizophrenia. About one third of each group were interviewed by a psychiatrist using defined diagnostic criteria, and information of varying degrees of completeness was obtained about the remainder. After considering possible biases, it was concluded that the "spectrum disorders' most likely to be biologically related to schizophrenia were personality disorders of non-neurotic type, either alone or in combination with another diagnosis. The results, however, did not fit well with the model of dominant inheritance of schizophrenia and schizoid disease proposed by Heston (1970).


Information complexity and cross-modal functions.

Intra-modal and cross-modal presentations of a matching procedure were compared at two levels of information complexity in the same subjects. The modalities were visual and somatosensory. Sequence of information type and sex of experimenter and subject were systematically controlled. Pattern of accuracy among the several modality combinations and the effect of sequence varied as a function of information complexity. Sex of experimenter and subject yielded significant differences with simple information but not complex. The results, involving several detailed comparisons, confirmed generalizations derived from a review of prior studies in which only one type of information had been administered to any single group of subjects. Further examination of the relations between type of information and sensory modality is discussed.


Stimulus complexity, EEG abundance gradients, and detection efficiency in a visual recognition task.

Occipital EEG was monitored while subjects inspected 27 projected patterns. The number (N) and variety (V) of elements in the patterns were varied systematically. There were three levels of N (6, 12 or 24 elements) and three levels of V (circles, squares or hexagons occupying all, one half or one third of the element locations for all levels of N). Subjects were instructed that they would be required in a post-test to recognize the patterns, among patterns which had not appeared; they were also informed that the patterns had been constructed according to a set of simple rules, but the nature of these rules was not made fully explicit. The EEG was quantified by means of low-frequency analysis, yielding measures of abundance (theta, alpha and beta) and mean dominant frequency. For the recognition task, nine stimulus items were embedded among 45 items. Recognition efficiency was measured by means of the signal detection theory discrimination index (d'). The results were as follows: (i) Both N and V were inversely related to alpha abundance (P less than 0-01); (ii) the strongest relationship between stimulus parameters and the EEG held for N and EEG beta activity (13-5-19-5 Hz;P less than 0-001), where again the EEG and N were inversely related; (iii) there was a significant (P less than 0-05) direct relationship between N and theta activity; (iv) contrary to prediction, mean dominant alpha frequency decreased as N increased; (v) d' correlated significantly with a number of effects for N, i.e. subjects who exhibited greatest EEG discriminability of items during exposure of the patterns, subsequently obtained the higher detection scores in the recognition task. The work described therefore demonstrates that only only do stimulus parameters have systematic effects upon brain activity as measured by the EEG, but that such effects have functional value and reflect aspects of efficiency. The results are fully compatible with arousal theory constructs relating physiological reactivity and performance.


Anxiety and ritualized speech.

The experiment examines the effects on a number of words that seem irrevelant to semantic communication. The Units of Ritualized Speech (URSs) considered are: 'I mean', 'in fact', 'really', 'sort of', 'well', and 'you know'. Two hypotheses are tested: (i) that URS rate will increase with anxiety; and (ii) that the speaker's preferred URS will increase with anxiety. Subjects were interviewed on topics they had previously rated as anxiety-provoking and non-anxiety-provoking. Hypothesis (i) was supported, but hypothesis (ii) was not. More specifically, the use of 'I mean' and 'well' increases when the speaker is anxious. Explanation for this is sought in the grammatical location of these two units. Sex differences in the use of URSs, correlations between URSs and their relationship to other forms of disfluency are also considered.


The effects of negative relatedness upon word-picutre and word-word comparisons and subsequent recall.

In two experiments subjects were required to compare the meanings of either a word and a picture, or of two words. Different name levels, i.e. category versus superordinate names, had only a small effect on the time to compare a name with a picture. When incongruent stimulus pairs were semantically related, both positive and negative decision times were longer than when the incongruent pairs were unrelated; relatedness also affected subjects' recall of stimuli. Implications for models of semantic decision are discussed.


Visual imagery and the discrimination of differences between altered pictures simultaneously and successively presented.

Ten 'good' visual imagers and ten 'poor' imagers, representing the upper and lower halves of an unselected sample of adult volunteers, were given a task of detecting differences between altered pictures presented in pairs, either simultaneously or successively. Performance was measured by reaction time. 'Good' imagers reacted faster than 'poor' imagers, and the mode of presentation (simultaneous v. successive) did not affect their performances. 'Poor' imagers, on the other hand, reacted significantly slower when the pictures compared were presented successively. The results suggest that self-rated visual imagery can be used to predict the successful recall of visual information required in a discrimination task.


The subliminal perception of movement and the 'suppression' in binocular rivalry.

An analogy is drawn between the perceptual limitation that characterizes the dichotic listening paradigm and the 'suppression' that occurs in binocular rivalry when different stimuli are presented to the two eyes. An experiment is reported which focuses on the fate of the information residing in a suppressed eye (unattended channel) during binocular rivalry. It is demonstrated that the temporal course of rivalry is sensitive to the presence of a subliminal moving stimulus within the currently suppressed field. The effects are seen to confirm a literal interpretation of Levelt's (1966) thesis which relates changes in the 'stimulus strength' of a rivalling field to subsequent changes in the temporal course of the phenomenon. This interpretation is consistent with the hypothesis that, despite phenomenal suppression, a full analysis is undertaken on the currently non-dominant stimulus. The data are related to models of selective attention, and to the notion that there are parallel visual systems.


Experimenter bias and subliminal perception.

It has been suggested that subliminal perception phenomena may be in part due to experimenter bias effects. Two studies that obtained positive evidence of subliminal perception were therefore replicated with experimenters tested under blind  and not blind conditions. There was only marginal support for the subliminal perception hypothesis and, although there were fairly clear indications of diffuse experimenter effects, the evidence for the experimenter bias explanation of subliminal perception was not strong. The need for more extensive replications of subliminal perception researches is noted. It is argued that the experimenter bias hypothesis lacks detail and generality; it is essential for it to be examined in the context of theoretically substantial issues.


National differences in extraversion and neuroticism.

A method is proposed for measuring national differences in extraversion and neuroticism from demographic and epidemiological data. The method is to use national prevalence rates of a number of variables and treat them as indices of the levels of extraversion and neuroticism in national populations. The variables taken are the national rates of divorce, illegitimacy, accidents, crime, murder, suicide, alcoholism, chronic psychosis and coronary heart disease; and the per capita consumption of calories, cigarettes and caffeine. Data for these indices are presented for the advanced western nations. The relationship of these variables to extraversion and neuroticism among individuals is used to set up a model for their relationship among nations. The variables were factored by principal components analysis and this yielded two major factors identified as extraversion and neuroticism. The factor scores of each nation on the two factors were then computed. These indicate that the most extraverted nation is the United States and the most introverted is Japan. The most neurotic nation is Austria and the least neurotic is Ireland.


The personal space of hard-of-hearing children after extended contact with 'normals'.

A group of hard-of-hearing children integrated into a normal public school for a year were found to exhibit similar personal space to that of normal children. Another group of hard-of-hearing children who attended a special institutional school for the deaf, on the other hand, exhibited greater interaction distances under varying dyadic interactions with a 'normal' person. Practical application of the present results is discussed.


The use of current reading ability in the assessment of dementia.

Word-reading ability and general intelligence level were shown to be highly correlated in a group of normal adults; from this data a regression equation was obtained. Using this regression equation, IQ levels were predicted from reading scores in a group of dementing patients. The evidence strongly suggested that these predicted IQ levels provided close approximations to the premorbid IQ levels. Furthermore, the evidence implied that reading ability is potentially a better indicator of premorbid level of functioning than vocabulary level. The advantages and limitations of using the regression equation in the detection and evaluation of dementia in the individual patient are considered.


Arousal and speed of recall.

Subjects were divided into four groups based upon the possible combinations of high or low Extraversion and high or low General Activation. They learned two lists of paired associates in an A-B, A-Br paradigm, with a record being kept of the number of errors and the latency of correct responses. The groups were found to differ considerably more in terms of response latency than in terms of the probability of responding correctly. A number of the analyses indicated an interactive effect of Extraversion and General Activation on retrieval performance, in which high General Activation led to reduced response latencies for extraverts, but to slower latencies for introverts. This finding was interpreted with reference to arousal theory. Additional findings suggested that the poor performance of high arousal subjects was partially due to their tendency to take in information from dominant sources, a hypothesis suggested by Broadbent (1971).


Some characteristics of schizophrenics and their parents.

This study was designed to test four hypotheses: (a) parents of schizophrenics constitute a discrete group amongst the parents of psychiatric patients with regard to aspects of their construing; (b) schizophrenics can be differentiated from other psychiatric patients by aspects of their construing; (c) the construing of parents of psychiatric patients is related to that of their disturbed children; and (d) parents of schizophrenics differ from parents of other psychiatric patients in their personality and attitudes. An experimental group of parents of acute schizophrenics and a control group of parents of acute non-schizophrenic psychiatric patients were given a battery of psychological tests, and their hospitalized children completed a shortened battery. There was some confirmation of each hypothesis. Both experimental groups structured supplied, but not their own personal, constructs more abnormally than the corresponding control groups, and showed more deviant sexual identification, though this latter was a function of social class. The parents' structuring of supplied constructs was related to that of their children. There were also some differences in personality between the groups of parents.


Relationship of mental status, functioning and stress to readmission of schizophrenics.

A study was conducted to determine the interrelations among the variables of patient functioning, life stress, mental status and readmission to the hospital after release. The population consisted of 516 chronic and 125 acute schizophrenic men and women. Stress and functioning were measured by the Social Stress and Functionability Inventory for Psychotic Disorders. Mental status was assessed through the use of a standard Problem Appraisal inventory. Results demonstrated that mental status variables correlated at a low level with readmission, accounting for a minimal amount of variance, and that the factor of patient functioning had more predictive value, but its effectiveness was hampered by the long-standing cycle of admission-release-readmission in regard to chronic patients. Apparently there is no justification for considering mental status as a factor in prognosis, as some researchers have done in the past, based on the same low correlations.


Extraversion and pain.

According to Eysenck's (1957, 1960, 1967) theory of personality, extroverts are posited as having higher pain thresholds and greater pain tolerance than introverts. The evidence for these hypothesized relationships is reviewed. Findings appear inconclusive in both cases. Probability pooling (Mosteller & Bush, 1954) is therefore performed, grouping the comparable studies and carrying out overall tests of significance. Results support the hypothesized relationships between extraversion and pain threshold and between extraversion and pain tolerance. Possible reasons why certain studies failed to find these results are discussed.


Intracavitary metastasis to the left ventricle: an angiocardiographic diagnosis.

A patient with an intracavitary metastasis to the outflow tract of the left ventricle diagnosed prior to the primary tumours is presented. It is unique in location, type and diagnosis. Metastatic disease of the heart is far more common than primary cardiac tumours and usually is diagnosed late in the course of the disease or at autopsy. Angiocardiography is the best method of diagnosing tumours of the heart and should be performed whenever such a diagnosis is considered.


The radiosensitivity of endometrial carcinoma.

An analysis of all cases (121) of endometrial carcinoma treated by pre-operative radium in the uterine cavity revealed that the menopausal status of a patient affects the radiosensitivity of her tumour. It was found that if the patient is more than ten years post-menopausal at time of diagnosis her carcinoma will be more resistant to radiation. The technique used by the authors is adequate in eradicating a considerable percentage (68%) of endometrial carcinomas.


The relationship between mouse arterial partial pressure of oxygen (PaO2) and the effectiveness of localized tumour irradiation.

The effectiveness of localized X-irradiation on the transplantable KHT sarcoma was investigated while the host mice breathed gas mixtures ranging from 5% O2 : 95% N2 to 100% O2. Subcutaneous tumours in the flank of C3H mice anaesthetized with Nembutal (sodium pentobarbitol), Valium (diazepam), or urethane, were irradiated with doses of 1,500 or 2,500 rads and the delay in days for the tumours to grow from 4 to 10 mm in diameter was determined. Measurements of the arterial partial pressure of oxygen (PaO2) were made under conditions identical to the irradiation experiments. For PaO2 values less than 100 mm Hg (animals breathing air), growth delay decreased linearly, while for PaO2 values greater than 100 mm Hg, growth delay increased and reached a plateau at a PaO2 between 200 and 300 mm Hg, (animals breathing congruent to 50% O2). This relationship holds for the two doses and the three anaesthetics studied, and indicates the importance of investigating the Pa02 levels of patients undergoing radiotherapy treatment.


The lymphocyte response and prognosis in cancer of the lung.

One hundred and twenty cases of cancer of the lung have been tested for their lymphocyte transformation to phytohaemagglutinin (PHA) before and after treatment by radical radiotherapy. The average response of these patients was lower than that of the controls. The fall in the lymphocyte response during treatment was calculated. The pre-treatment lymphocyte response with PHA was not related to survival after treatment. The fall in the lymphocyte response during treatment was related to the survival of the patients after treatment.


Traumatic vertebral artery aneurysm. Report of two cases.

Two cases of traumatic vertebral artery aneurysm are described. One followed a stab wound, the other a closed injury. The literature is reviewed. The value of angiography in diagnosis and localization is emphasized.


An anomalous calyx in the mid-kidney: an anatomical variant.

Three cases in which there was an anomalous short calyx without a papilla in the mid kidney are described. This is believed to be a developmental abnormality which is associated with a pelvicalyceal pattern of two major calyces, and with renal "pseudotumour". It is important to recognize this calyceal appearance in order to distinguish it from calyceal disease.


Radiology in chemical sympathectomy.

Chemical sympathectomy is an alternative to surgical sympathectomy when the patient's age or general condition precludes surgery. The indications and rationale in lower-limb arterial disease are discussed, and it is suggested that X-ray control is a valuable adjunct to the procedure.


Repair of radiation damage to capillary endothelium.

Two types of repair occurring in capillary endothelium after irradiation were investigated. The system used was the rat subcutis airpouch, in which the capillary endothelium was stimulated to proliferate by a combined mechanical and chemical stimulus. Assay was by an angiographic technique. The system allows temporal separation between the moment of irradiation and the moment of stimulation to proliferation. The results indicate that capillary endothelium shows the typical "Elkind-type" of time-recovery curve. When the stimulus to proliferation after a single dose of X rays is delayed, however, the D0 value rises from 168 rads (immediate stimulation) to 273 rads (stimulation to proliferation delayed for 32 days). The conclusion can therefore be made that many more endothelial cells survive in the tissues after radiotherapy than one would infer from the simple direct proliferation assays.


Experience in implementing the Mark III Rad 8 system for radiotherapy dose computations.

Rad 8 is a small, in-house computer system for calculating radiotherapy dose distributions, both for multiple field and rotational external beam techniques and for interstitial and intracavitary redium treatments. Implementing the system has its difficulties, particularly in obtaining the necessary beam profile information. Several approaches have been tried and finally a separate profile generator program was written. Other difficulties encountered with beam data storage were overcome by making minor changes to the system programs. The various calculation techniques have been evaluated, and in general found to be satisfactory, and suitable factors to be used in the inhomogeneity correction for 4 MV X rays have been calculated based on previously published measured data. An option to change beam weightings exists and this can be used to renormalize dose distributions to give percentage isodose curves relative to the prescribed tumour dose. If this procedure is followed dose homogeneity over the target volume can readily be assessed, and the exposure times may easily be calculated from the new weightings. Certain shortcomings in the rotating beam program and the radium program may easily lead to error if extreme care is not exercised.


Empirical equations for the representation of depth dose data for computerized treatment planning.

Equations of the form (see article) have been used to represent the variation of central axis percentage depth dose P or tissue-air ratio (TAR) with depth d below the dose maximum. The equations were originally developed for the representation of cobalt 60 depth dose data but have also been fitted to the central axis depth dose data published in the British Journal of Radiology Supplement 11, for radiations ranging in energy from 1-5 mm Cu HVT to 8 MV. Values of the constants Q and M for standard field sizes are presented together with an estimate of the goodness of fit in each case. Two different approaches have been used in determining the dose at points other than those on the central axis. In the simpler method, used for rotation techniques, the off-axis ratio (OAR) is calculated from the equation. (see article) where x is the off-axis distance, w the field width at the depth and k1 and k2 are constants. In the more accurate method, used for fixed field techniques, different equations are used within the main beam, within the geometrical penumbra and outside the beam.


A thermoluminescent method for estimation of effective thyroidal half-life of therapeutic 131I in toxic goitre.

The half-life of radio iodine, in the thyroid gland, was measured using thermoluminescent discs which were placed on the neck surface. Discs placed by hospital staff and by the patient gave self consistent results.


Assessment of regional ventilation by continuous inhalation of radioactive krypton-81m.

A simple technique is described for producing high-quality functional images of regional ventilation during physiological tidal breathing of the inert gas 81mKr. These images are quickly obtained on a gamma-camera without the need of computerized systems for data acquisition and display and are directly comparable with those of perfusion obtained with 99mTc-labelled macroaggregates. The short time required for the procedure, its simplicity, and the extremely low absorbed-radiation dose enable serial images of ventilation to be obtained in multiple views.


Changes in cerebral blood flow during a migraine attack.

Regional cerebral blood flow studies during a typical prodromal phase of a migraine attack in a young woman showed a global decrease of cerebral blood flow in the carotid artery territory. These studies were repeated during the subsequent headache phase of the same attack and hemispheric blood flow increased considerably. Ergotamine tartrate was then administered intramuscularly which brought definite relief of symptoms but no change in cerebral blood flow. Carotid angiography performed immediately afterwards showed retrograde filling of the proximal portion of the basilar artery, which suggested that the brain stem was the site of hyper-perfusion. These findings illustrate certain features underlying both the pathophysiology of migraine itself and its response to ergotamine preparations.


Aeromedical evacuation of the seriously ill.

Almost any patient may be carried by air, but air transport introduces some special problems owing to the effects of altitude, noise, turbulence, and the special environment. Because of these factors it is important to know when considering a patient's suitability for air transport the type of aircraft to be used, the flight profile--its duration and expected cabin altitudes--and the facilities available on board. It is essential to carry all equipment (as simple and as portable as possible), drugs, and diets that may be needed, and to be sure that all the skills and nursing help needed to deal with any possible problems are available.


Intravenous diazoxide in treatment of hypertension associated with recent myocardial infarction.

Twenty patients with blood pressure over 180/110 mm Hg one hour after admission to a coronary care unit with recent acute myocardial infarction were given intravenous diazoxide in a bolus of 300 mg. The average blood pressure before diazoxide was 194/122 mm Hg. Blood pressure fell considerably in all patients, though six patients required two injections. The average fall was 58 mm Hg systolic and 40 mm Hg diastolic. No patient became severely hypotensive. The heart rate increased by an average of 10 beats/min. In nine patients the electrocardiographic changes immediately after the administration of diazoxide suggested an increase in myocardial injury. Though none of the patients seemed to deteriorate clinically from the diazoxide the electrocardiographic changes suggested that the use of intravenous diazoxide to lower blood pressure in patients with acute myocardial infarction might possibly be deleterious.


Effect of breast-feeding on pituitary-ovarian function after childbirth.

Pituitary and ovarian function at the end of pregnancy and during the first six weeks after delivery was investigated serially in women who fully breast-fed their infants and in women who did not. In the women who did not breast-feed the plasma prolactin level decreased rapidly and from the third day after delivery was significantly lower than in the breast-feeding mothers, reaching the normal range of the menstrual cycle by the third week of the puerperium. In the breast-feeding mothers the plasma prolactin was still raised six weeks after delivery. The levels of FSH in both groups were identical and increased over the third week of the puerperium. Plasma oestrogen fell steeply in both groups during the first two weeks after delivery. In the breast-feeding mothers plasma oestrogen remained depressed but increased in the non-lactating women, reflecting follicular development in the ovary in response to FSH; the plasma oestrogen levels were significantly higher in the non-lactating women from the 17th day of the puerperium onwards. These findings support the concept that in breast-feeding women prolactin delays the return of ovulation by inhibiting the ovarian response to FSH stimulation.


Pregnancy, prolactin, and pituitary tumours.

Nine pregnancies are described in patients with pituitary tumours. All patients had definite radiological evidence of a pituitary tumour and no evidence of acromegaly or Cushing's disease. In seven patients serum prolactin levels were estimated before pregnancy and found to be raised.Seven patients had been treated with pituitary implantation of yttrium-90. The remaining two developed complications of the tumour during pregnancy. One developed a bitemporal visual field defect in the second trimester which was successfully treated by emergency yttrium-90 implantation. The other developed diabetes insipidus in the third trimester which resolved spontaneously after delivery.Six patients were treated with drugs to achieve pregnancy. Four took bromocriptine to suppress raised prolactin levels, one was treated with human menopausal gonadotrophin, and one was treated with clomiphene.


Liberty and psychiatry.

The security facilities available in one regional health authority area have been surveyed. The simultaneous run-down of the large mental hospitals and the open-door policy have resulted in a lack of facilities for mentally abnormal offenders, and the increasing scarcity of common lodging houses has exacerbated the problem. Newer psychiatric units associated with general hospitals have been mainly concerned with patients suffering from neurosis or acute psychoses. The failure to develop other services to deal with offenders has seriously overburdened both the penal system and the special hospitals.


Stripes, complex cells and seizures. An attempt to determine the locus and nature of the trigger mechanism in pattern-sensitive epilepsy.

The study concerns an epileptic patient whose absence attacks were contingent on the viewing of striped patterns. A series of experiments demonstrated first that seizures were not due to the intermittent stimulation of retinal cells produced as physiological nystagmus vibrated the image of the pattern, and secondly that seizures were triggered at the cortical level, probably by the firing of complex cells. Spectacles which occluded pattern vision in one eye were highly effective in reducing seizure incidence.


Comprehension and appreciation of humorous material following brain damage.

The effects of brain damage on cognitive and affective status have been assessed separately; however, a dearth of information exists about the interaction of these facets in the brain-damaged patient. Because appreciation of humour involves both cognitive and affective dimensions, an investigation of response to humorous materials should yield information relevant to this issue. In addition, a study of response to humour in aphasic patients can reveal the extent to which appreciation of humour is dependent upon an intact language system. Accordingly a test of humour, in which an individual chose the "funniest" of four cartoons, was administered to a population of brain-damaged and control patients. Ability to detect the most humorous cartoon was impaired in all brain-damaged patients, more in severe than in mild aphasics, but there was no significant difference between patients with left and right hemisphere lesions in their overall performance on the test. A different order of difficulty across items, and a different profile of "mirth" responses to the items did, however, correlate with site of lesion. Right hemisphere patients tended either to laugh throughout or, more frequently, not at all; they often confabulated answers to made impossible inferences; and they performed better on items with captions. Their cognitive reactions appeared "dissociated" from their affective responses. In contrast left hemisphere patients performed better on the captionless items and behaved in a manner which more closely approximated normal subjects in their humorous reactions, their order of item difficulty, and their explanations. All brain-damaged patients found it relatively easier to locate the humorous cartoons when the members of a set differed appreciably from one another. These results provide information about the altered cognitive and affective states of brain-damaged patients, the impairment of cognitive operations in aphasic patients, and the respective "life-spaces" of left and right hemisphere injured patients.


Electrically elicited blink reflex in diagnosis of multiple sclerosis. Review of 260 patients over a seven-year period.

The blink reflex obtained from 260 patients with suspected multiple sclerosis was analysed according to clinical criteria for diagnosis. The R1 component was dealyed on one or both sides in 96 of 145 patients with definite diagnosis (66 per cent), 32 of 57 with probable diagnosis (56 per cent), and 17 of 58 with possible diagnosis (29 per cent). The incidence of abnormal R1 rose with increasing duration of illness in each category. When the reflex was analysed according to the clinical localization of the lesion in the 260 patients, R1 was abnormal in 49 of 63 patients with pontine signs (78 per cent), 59 of 104 with other brain-stem signs (57 per cent), and 37 of 93 with no clinical brain-stem signs (40 per cent). Alteration of R2 was less specific but, when seen in the face of a normal R1, was usually associated with clinical signs suggesting lateral medullary lesions. These fingings offer direct evidence that conduction through demyelinated zones in the central nervous system is indeed slowed and that the degree of slowing can be measured objectively by means of this simple technique in man. The high inicdence of delayed R1 in patients with no clinical pontine signs suggests that the test may be used to document a clinically silent pontine lesion in multiple sclerosis and help to establish the anatomical dissemination of pathology.


Simultaneous recording of absence seizures with video tape and electroencephalography. A study of 374 seizures in 48 patients.

Forty-eight patients, 4 to 24 years of age, with recurring absence seizures were studied prospectively for twenty-seven months. Each patient and his EEG were recorded simultaneously by a multicamera videotape technique and each recording was repeatedly viewed and described in writing by two observers who subsequently resolved any differences by joint viewing. From the 48 patients, 374 clinical absence seizures were recorded and classified according to the International Classification of Epileptic Seizures. Automatisms accompanied at least one attack in 88 per cent of the patients. Mild clonic components occurred in 71 per cent, and decreased postural tone in 41 per cent. Only one patient experienced an attack comprising only "blank staring" accompanied by unawareness and amnesia, but 40 per cent of patients exhibited this type of attack in addition to more complex absence attacks. Seizures of ten seconds or less in duration occurred among 85 per cent of patients. Each of the 374 seizures were readily classified according to the International Classification, but simple absence constituted only 9-4 per cent of the seizures. The others most often contained, in order of prevalence, either automatisms, mild clonic components, or decreased postural tone, or a combination of two or more of these features. The relationship between increased duration of the seizures and the occurrence of automatisms was significant. The findings are discussed in relation to differential diagnosis and mechanisms of automatisms. Absence seizures differ from complex partial (temporal lobe, psychomotor) seizures because an aura does not precede the abruptly beginning absence attack, the seizure usually lasts less than ten seconds, and mental clarity returns instantly at the end of the seizure.


A clinical and genetic study of chronic proximal spinal muscular atrophy.

A study of chronic proximal spinal muscular atrophy was undertaken with the main aim of obtaining empirical recurrence risks for genetic counselling. Thirty-eight patients and their families were studied. Of these, 33 had similar clinical features and onset of disease in infancy or childhood. A division of these 33 patients by onset before or after 2 years (which was equivalent to whether or not they ever walked normally) gave recurrence risks for sibs which were higher with early onset. Among the sibs of patients with onset before 2 years, the incidence of disease was 1 in 5, due to most patients having an autosomal recessive disorder. A few patients, however, were thought to represent new dominant mutations. Among the families of index patients with onset after 2 years, the incidence of disease in sibs was only 1 in 15, but among their children it as 1 in 8. Both autosomal recessive and autosomal dominant forms therefore occurred in this age group, but it was concluded that nearly half the patients with onset after 2 had non-genetic motor neuron disease. The autosomal recessive form of chronic spinal muscular atrophy generally had onset before 2 years, but occasionally after 2. About a third of the patients never walked, and about half were in wheelchairs by age 10. No genetic heterogeneity within this form was demonstrated. Three remaining patients had distinctive clinical features associated with their proximal weakness, external ophthalmoplegia in one, dysarthria in another, and joint contractures in a third. Only 2 patients had onset in adult life, one of a probable recessive disorder and the other a probable dominant disorder.


Chronic progressive external ophthalmoplegia.

The clinical features and investigative findings of 50 patients with chronic progressive external ophthalmoplegia (CPEO) were analysed. The group was found to be clinically, genetically and histologically heterogeneous. With the possible exception of patients with "ophthalmoplegia plus," namely those who in addition to muscular weakness had evidence of central and/or peripheral nervous system abnormality, there was no apparent justification for separating out from among the group patients' subgroups which were distinctive enough to be recognized as syndromes. CPEO therefore seems to represent a number of different degenerative disorders whose common denominator is ophthalmoplegia and for which there are to date no adequate criteria for further classification.


Hemispheric specialization in normal man studied by bilateral measurements of the regional cerebral blood flow. A study with the 133-Xe inhalation technique.

Changes of regional cerebral blood flow (rCBF) during mental activation have so far only been studied unilaterally by means of the intracarotid 133Xe injection technique. In the present study bilateral rCBF measurements were made by the 133Xe inhalation technique during mental activities supposed to engage the hemispheres selectively. The study was carried out on 24 normal right-handed male volunteers by the short 133Xe inhalation method. Fourteen scintilation detectors were placed in parallel overcorresponding regions of the two hemispheres. Four rCBF measurements were made on each subject during three randomized conditions: (1) Rest (two studies); (2) Verbal test (Miller Analogy Test), and (3) Spatial test (Street). The recordings were separated by at least one hour to avoid contamination from previous measurement. The answers to the problems were given either by raising the fingers of the left hand (Verbal test) or after the study (Spatial test). In order to investigate the effects of increased motivation 12 of the subjects were promised an extra money reward in addition to the basic payment, if they performed above a certain level on the tests. Small but statistically significant differences between the average hemisphere flows were recorded during the two tests. In the highest motivated (paid) group the verbal test increased the flow in the left hemisphere by 16 per cent while the right-sided increase was significantly smaller, 13 per cent (P less than 0-001). The corresponding figures for the spatial test were: left 7 per cent, right 10 per cent (P less than 0-01). The same tendencies were seen in the less motivated group although the hemisphere differences were smaller and statistically not significant. Analysis of the regional results showed that the largest interhemispheric differences (about 5 per cent) were seen in occipital and parietal regions during the verbal test and in frontal and parietal regions during the spatial test. It is concluded that bilateral measurements of rCBF can be used with advantage in the study of lateralization of mental functions in the human brain.


Disappearance of supra-ependymal 5-HT axons in the rat forebrain after electrolytic and 5,6-DHT-induced lesions of the medial forebrain bundle.

The present study was intended to demonstrate the origin of supra-ependymal 5-hydroxytryptamine axons in the rat forebrain. Electrolytic lesions and injections of 5,6-dihydroxytryptamine (10 mug in 4 mul) were carried out unilaterally in and close to the medial forebrain bundle in the posterior hypothalamus of rats. Ten to 14 days later, terminal axons and formaldehyde-induced indolealkylamine fluorescence had virtually disappeared supra-ependymally in the lateral ventricles and interventricular foramina ipsilateral to the lesion if the indolealkylamine axons passing through the medial part of the medial forebrain bundle had been destroyed. No changes were observed, electron microscopically or fluorescence histochemically, in ventricles contralateral to the lesion. It is concluded that the supra-ependymal serotonergic nerve terminals in the lateral ventricles and interventricular foramina originate, uncrossed, from non-terminal axons passing through the medial forebrain bundle in the posterior hypothalamus.


Reaction time to square-wave gratings as a function of spatial frequency, complexity and contrast.

Visuomotor reaction time (RT) of normal human subjects to briefly presented square-wave bar patterns were measured. The pattern varied with respect to magnitude and number of spatial frequencies (one cycle/degree of visual angle, 3 cycles/degree, and both combined) with each spatial frequency stimulus presented at 3 levels of contrast. Space-average luminance was held constant. RT increased with the higher spatial frequency and was intermediate in value for the combination stimulus at each level of contrast. RT increased with decreasing contrast levels for each spatial frequency stimulus. There was no interaction between the two parameters. The findings indicate that a behavioral response measure can be employed to study the multiple channel hypothesis of human vision. The results were compared with those of other investigators employing sine-wave gratings, perceptual response measures and the evoked potentials technique.


Loss of chemoreceptive properties of the rabbit carotid body after destruction of the glomus cells.

Glomus cells of the rabbit carotid body were destroyed by local freezing. Electrophysiological recording of baroreceptor afferent activities showed that carotid sinus nerve regeneration was completed after 3 months. Nevertheless, ventilatory reaction as well as chemoreceptor afferent activity were no longer observed in response to the usual stimuli of arterial chemoreceptors (O2 test, NaCN). Results support the view that glomus cells are necessary for chemoreception and question the specificity of their afferent innervation.


The retrograde transport of horseradish peroxidase from the developing limb of the chick embryo.

Chick embryos ranging in age from 4.0 to 18 days of incubation and 1-2-day-old hatchlings received injections of HRP solutions directly into the leg musculature. After survival periods of from 5 to 25 h motoneurons and cells in the spinal sensory ganglia were found to be stained with the HRP reaction product. It was found that the first appearance of a positive HRP reaction coincided with the time when nerve processes are first detected in the limb-bud by silver techniques (i.e. at 4.5 days of incubation). Only neurons with processes in the region of injection showed a positive reaction. The demonstration of a retrograde transport mechanism in neurons and axons which are still undergoing growth and differentiation provides a possible mechanism for the peripheral regulation of certain features of CNS neurogenesis. The application of this technique during development may also allow one to map neuroanatomical pathways during their formation.


A late component of flash-evoked potentials in the cat's optic chiasma and superior colliculus: its appearance due to background illumination.

Flash-evoked potentials (FEPs) in the cat's optic chiasma and superior colliculus were recorded under the following two conditions: complete darkness and background illumination. Special attention was paid to a specific late component of FEP'S and comparison in the behavior of the late component was made between the two conditions. It was found that a late component of FEPs in the optic chiasma appeared in the presence of background illumination while it was not observed under the condition of complete darkness. A corresponding late component of FEPs was detected in the superior colliculus. The late component might be supposed to be driven from a class of W-cells in the cat's retina.


Hippocampal influence on hyperreactivity induced by septal lesions.

Rats were tested for their responses to 4 stimuli in order to measure hyperreactivity. Animals with septal lesions emitted the expected hyperreactivity. Lesions of the postcommisural fornix, precommissural fornix, or anterior hippocampus, administered 16 days prior to a septal lesion, blocked the expected hyperreactivity. Lesions localized to the medial or the lateral fibers of the fornix decreased the magnitude the duration of the expected hyperreactivity following septal lesions but did not block it. Lesions of the posterior hippocampus-entorhinal cortex had no reliable effect on the expected hyperreactivity after septal lesions. These data indicate that the appearance of hyperreactivity following a septal lesion depends upon a circuit involving the septum, precommissural fornix, anterior hippocampus, postcommissural fornix, and hypothalamus, and document an important functional relationship between the septum, anterior hippocampus, and hypothalamus.


Effects of intraventricular 6-hydroxydopamine and replacement therapy with norepinephrine, dopamine, and serotonin on self-stimulation in diencephalic and mesencephalic regions in the rat.

Although 6-hydroxydopamine (6-OHDA) reduced the rate of hypothalamic self-stimulation, it is not known whether the same effect is produced at other reinforcing sites remote from the hypothalamus. This was investigated in rats implanted with rewarding probes in the hypothalamus, in the substantia nigra, in the midbrain, and in the pontine region. Two patterns of self-stimulation emerged in each subject. One, characterized by short, medium and long-stimulus-train durations, was seen in the hypothalamus, in the substantia nigra, and in selected sites in the pons. The other, which comprised only short stimulus-trains, was found in the medial midbrain and in the pontine region. 6-OHDA (250 mug intraventricular route) reduced the rate of responding in the regions where responding was for short, medium, and long stimulus trains. It has a minor effect on responding in regions where the brain rewards were exclusively of short duration. Thus, self-stimulation in the hypothalamus, in the substantia nigra and in the pons was suppressed after 6-OHDA, while self-stimulation in the medial midbrain and at sites in the pons, where selection was for short trains, was only slightly below control levels after 6-OHDA. L-Norepinephrine (L-NE) (10, 20 and 30 mug) injected into the lateral ventricle of the 6-OHDA-treated rats temporarily reinstated self-stimulation in the lateral hypothalamus but not in the substantia nigra and not in the pontine region where the pattern of selection had been for long brain rewards. Dopamine (DA) was not effective as an antagonist of the suppressant action of 6-OHDA. Serotonin (5-HT) reinstated self-stimulation behavior in the lateral hypothalamus but not in the other positive regions. Its action was less than that of NE and did not take place in all animals tested.


Barbiturate spindle activity in functionally corresponding thalamic and cortical somato-sensory areas in the cat.

(1) Spontaneous barbiturate spindles were recorded from a locus in the thalamic nucleus ventralis postero-lateralis (VPL) and the corresponding projection area in the somato-sensory cortex (SI) in the cat. (2) Type I spindles32 recorded from such sites in the thalamus and cortex, regarded as being functionally on line, were cross-correlated. The analysis gave high negative cross-correlation coefficients, indicating that a considerable degree of wave synchrony existed between the spindles. Maximal wave synchrony was present in the first and middle part of the spindle. (3) The thalamo-cortical spindle wave synchrony was reduced by a small displacement of the cortical electrode within the somato-sensory cortex. Starting with a very lightly anaesthetized animal, small amounts of barbiturate did not influence the size of the cortical area which had spindles in synchrony with the thalamic spindles. (4) Spindles recorded from a VPL locus and from its cortical projection site started simultaneously. When the thalamic and cortical electrodes were positioned functionally off line this spindle coincidence decreased. The intervals between the spindle onsets increased with increasing off line positions of the electrodes. Those few thalamic and cortical spindles which occurred simultaneously showed no, or only weak, spindle wave synchrony. (5) These data suggest a point-to-point topographical relation between thalamic and cortical loci engaged in barbiturate spindle activity. (6) Type I and type II spindles32 differed with respect to spindle characteristics (amplitude, duration, incidence) and also with respect to corresponding thalamic rhythmic activity. These spindle types are, therefore, probably produced by different mechanisms. We suggest that type II spindles represent a purely cortical process initiated by type I spindles.


Barbiturate spindle activity in the thalamic lateral ventro-posterior nucleus and the second somato-sensory area of the cortex.

(1) Barbiturate spindles recorded from the second somato-sensory cortical area (SII) were similar to spindles in the primary somato-sensory area (SI) both with respect to incidence, duration of each spindle and per cent spindle time. The spindle wave amplitude was smaller in SII. The highest spindle wave amplitude was observed in the anterior part of SII which receives input from nucleus ventralis postero-lateralis (VPL). No spindle activity was observed in the posterior part of SII which receives input from the posterior nuclear group (PO) of the thalamus. (2) Barbiturate spindles recorded from a locus in VPL and its projection area in SII were cross-correlated. The analysis resulted in high cross-correlation factors, indicating that a considerable degree of spindle wave synchrony existed between the spindles. This wave synchrony was reduced by moving the cortical electrode a short distance. (3) Cortical spindles recorded from corresponding sites in SI and SII were cross-correlated, and gave a high cross-correlation coefficient. This synchrony was markedly reduced if one of the electrodes was moved a few millimetres away from the optimal point. (4) Spindles started simultaneously in corresponding sites of SI and SII. A high degree of coincidence was found also between spindles in a VPL locus and the corresponding projection site in SII. Local anaesthesia applied to or total removal of SI failed to influence the spindle activity in SII and vice versa. Similarly, the SI-SII synchrony survived a deep incision cutting all connections between the two areas. (6) It is suggested that spindles in corresponding sites of SII and SI have a common thalamic pacemaker which probably projects to both areas by axonal branching.


Sleep cycle control and cholinergic mechanisms: differential effects of carbachol injections at pontine brain stem sites.

Muscular atonia and cortical desynchronization, two signs of desynchronized sleep, can be enhanced or suppressed by direct injection of carbachol into the pontine brain stem of cats. The positive effects are graded, being maximal in the gigantocellular tegmental field and less marked in adjacent nuclei. These positive effects are dose-dependent. Suppressive effects of carbachol are maximal in the region of the locus coeruleus and are dose-dependent but do not exceed those of the vehicle alone. The results support the hypothesis that cholinergic mechanisms of the pontine tegmentum are involved in desynchronized sleep generation.


Catecholaminergic mechanisms of the lateral hypothalamus: their role in the mediation of amphetamine anorexia.

The brain mechanisms mediating amphetamine's suppressive effect on feeding behavior were analyzed in rats with chronically implanted brain cannulas. Experiments in which drugs were injected directly into the anterolateral hypothalamus, the region found to be most responsive to amphetamine's action, yielded the following results. (1) Over a dose range of 6.25 nmoles (0.8 mug) to 400 nmoles (51.4 mug), hypothalamically injected D-amphetamine produced a reliable suppression of food consumption (20 percent at 6.25 nmoles, increasing to 88 percent at 200 nmoles) and was found to be approximately 3 times as potent as L-amphetamine in yielding this effect. (2) The anorexic effect of hypothalamically injected D-amphetamine was totally abolished by local administration of alpha-methyltyrosine, an inhibitor of dopamine, norepinephrine, and perhaps epinephrine synthesis, or by local administration of Fla-63, an inhibitor of only norepinephrine, and perhaps epinephrine, synthesis. (3) This effect of hypothalamic D-amphetamine was also antagonized by locally administered dopaminergic or beta-adrenergic receptor blockers but was unaffected by alpha-adrenergic, serotonergic, and cholinergic blockers. (4) Lateral hypothalamic administration of dopaminergic or beta-adrenergic receptor blockers, at quite low doses, was also effective in antagonizing the anorexia induced by peripherally administered D-amphetamine. These results strongly suggest that amphetamine, in suppressing feeding behavior, acts through the lateral hypothalamus, perhaps the anterior region, causing a release of dopamine and norepinephrine (or perhaps epinephrine) from lateral hypothalamic nerve endings and a subsequent stimulation of dopaminergic and beta-adrenergic receptors located in that region.


Biochemical and pathological studies of myelin in hexachlorophene intoxication.

Adult female rats were fed a diet containing 500 ppm hexachlorophene (HCP). Morphological study of brains from these animals showed vacuolation of the myelin sheaths due to separation of myelin lamellae at the minor dense line. However, myelin could be isolated from the brains of these animals in normal yield. The myelin isolated from HCP-fed animals had normal lipid and protein compositions as shown by analyses of the individual lipids and by disc gel electrophoresis of the proteins. Assay of the myelin-specific enzyme, 2',3'-cyclic nucleotide-3'-phosphohydrolase, showed normal specific activity in myelin obtained from HCP-fed rats. Brains of HCP-fed rats showed an increase in wet weight and a decrease in dry weight, with the chloroform-methanol insoluble fraction showing the greatest weight loss. During isolation of myelin from HCP-fed rats material was found floating over 0.32 M sucrose. This "floating fraction" contained a higher ratio of lipid to protein but the same relative proportions of the individual lipids as are found in myelin. The yield of "floating fraction" from each HCP-fed rat was less than 10 percent of the yield of myelin. Disc gel electrophoresis demonstrated the presence of the usual myelin proteins in this fraction, but with a slight increase in the relative amount of the low molecular weight basic protein. The data were compared to reports on the biochemistry of triethyltin poisoning, and it was concluded that vacuolation of myelin in HCP poisoning is probably due to increased permeability of myelin lamellae to water and electrolytes.


Soluble and membrane-bound S-100 protein in cerebral cortex synaptosomes. Properties of the S-100 receptor.

Within cerebral cortex synaptosomes, S-100 protein can be recovered in two forms: soluble and membrane-bound. Synaptosomal S-100 is mainly a soluble protein (85 percent). The membrane-bound S-100 is differently distributed in the synaptosomal membranes, intraterminal mitochondria, and synaptic vesicles. S-100 binds to a specific receptor. The binding is time-dependent, reversible and saturable with respect to S-100. The number of receptors is calculated to be about 9 times 10(12)/mg protein, since saturation is achieved at 31 ng [125I]S-100/0.1 mg protein of disrupted synaptosomes. The rate constant for association of S-100 with its receptor at 37 degrees C, k1, is 4.74 times 10(4) M(-1) sec(-1), and the rate constant for dissociation, k-1, 9.24 times 10(-4) sec(-1).


Tail pinch-induced eating, gnawing and licking behavior in rats: dependence on the nigrostriatal dopamine system.

Mild-tail-pinch induces a syndrome of eating, gnawing and licking behavior in rats in the presence of food. Detailed behavioral, pharmacological and biochemical analyses of this phenomenon resulted in the following conclusions. (1) This is an unusually reliable phenomenon, demonstrable in each of more than 200 animals tested. (2) Eating is by far the predominant response to tail-pinch. (3) Tail-pinch behavior is critically dependent on the nigrostriatal dopamine system. (4) There are striking pharmacological parallels between tail-pinch behavior and schizophrenia.


Perturbations in fluid balance induced by medially placed forebrain lesions.

Acute and chronic effects on the fluid balance of radio-frequency forebrain lesions were studied in the goat. Medial lesions which involved practically the entire anterior wall of the third cerebral ventricle cause persistent loss of thirst and lack of significant antidiuretic hormone (ADH) release in response to hypernatraemia and plasma hyperosmolality. As acute response to such lesions an uncompensated, temporary water diuresis was seen, which rapidly caused pronounced hypernatraemia and hypovolaemia. Lesions extending laterally to encroach upon the supraoptic nuclei resulted in persistent signs of weak, inappropriate ADH secretion (=impaired water diuresis, renal salt wasting, and pronounced hyponatraemia during hydration). Forebrain damage, mainly restricted to the septal region, caused hyperdipsia. In some goats, obvious post-lesioning increase in salt appetite was observed which could not be coreelated to the extent of their forebrain damage. The results are discussed in relation to hypothalamic syndromes in man and previous studies on central control of fluid balance in the goat.


Effects of 6-hydroxydopamine on central noradrenaline neurons during ontogeny.

The effects of the catecholamine neurotoxic compound, 6-hydroxydopamine (6-OHDA) have been investigated on central noradrenaline (NA) neurons after neonatal administration. In agreement with previous studies this treatment (1-3 X 100 mg/kg) led to a pronounced reduction of the in vitro uptake of [3H]NA and the endogenous NA in the cerebral cortex, while these parameters were markedly augmented in the pons and medulla oblongata, regions containing the NA perikarya. The 6-OHDA induced changes in the cerebral cortex and the pons-medulla could be completely prevented by the 'membrane pump' blocker desipramine, indicating that the effects are associated with a specific neurotoxic action of 6-OHDA on  the NA neurons. Consistently, 6-OHDA acutely (within 2 h) produced a marked reduction of the [3H]NA uptake in both the cerebral cortex and pons-medulla. In the cerebral cortex the nadir (approximately 75% reduction) was reached within 6 h and remained so, while in the pons-medulla the [3H]NA uptake rapidly recovered, being maximally elevated after 14 days (50-80% increase) and remained so for at least 6 months. The [3H]NA uptake in the pons-medulla from 6-OHDA treated rats had the same kinetic and pharmacological properties as that of control. Thus the observed differences in [3H]NA uptake are most likely quantitatively related to actual changes in the number of NA nerve terminals. Treatment with lower 6-OHDA doses (10 or 50 mg/kg) resulted in less pronounced reduction of [3H]NA uptake initially, and there was a gradual recovery of tuptake with time in the cerebral cortex, which was more pronounced after the lower dose. These results are indications of regenerative growth, which may be possible when a critical part of the axon is spared from the neurotoxic effect of 6-OHDA. Administration of 6-OHDA on various days after birth disclosed that both the reduction of [3H]NA uptake in the cerebral cortex and the increase of [3H]NA uptake in the pons-medulla did not appear as permanent phenomena when 6-OHDA was given later than on the seventh postnatal day. This is most likely associated with the postnatal development of the blood-brain barrier. It may be concluded that the neonatal 6-OHDA treatment causes a marked NA denervation in the forebrain, e.g. the cerebral cortex, and an increased outgrowth of NA nerve terminals in the pons-medulla, which is preceded by a partial damage. This partial NA denervation is then followed by a regeneration (regenerative and/or collateral sprouting) and a stimulated outgrowth of NA nerve terminals.


Quantitative localization of biogenic amines in the spinal cord.

Recently developed highly sensitive radiometric assays for biogenic amines have been combined with microdissection techniques to localize and quantify these amines in different structures, and at various levels of rabbit and rat spinal cords. Assays were performed for serotonin, norepinephrine, dopamine and epinephrine. It was generally found that the highest concentrations of those biogenic amines were found in the lateral and ventral horns, slightly lesser concentrations were found around the central canal, and still lower concentrations were found in the dorsal horns. Relatively low amine concentrations were found in the white matter. These biochemical measurements correlate well with localizations indicated by histofluorescence methods but provide precise quantification. Comparisons with previously available, less sensitive biochemical measurements are discussed.


The effect of diethylstilbestrol on the rate of osseous repair, bone integrity, and plasma calcium in the adult avian.

The effect of diethylstilbestrol on healing experimental osseous defects in adult roosters was studied by means of I-125 photon absorptiometry. Although the two dose levels utilized in this study both resulted in elevated plasma calcium and lipid levels and significantly increased the mineral and organic fractions of femoral bone, diethylstilbestrol treatment over a six-week period had no effect on the rate or magnitude of mineralization in the repairing osseous defect.


The metabolism of labeled parathyroid hormone. II. Methodological studies.

Further studies on the preparation of 125I-labeled, biologically active parathyroid hormone have resulted in improvements in the procedure, in the storage of the labeled product, and in the establisment of the location of the label in the polypeptide chain. Approximately 95% of the label is on the single tyrosyl residue, amino acid 43, in the bovine hormone. New procedures have also been developed for the isolation and quantitative gel filtration of the labeled hormone deposited in tissues (liver, kidney and bone).


The metabolism of labeled parathyroid hormone. III. Studies in rats.

A series of experiments indicated that 125I-parathyroid hormone administered to the rat i.v. was deposited very rapidly in three organ systems only, bone, kidney and the liver. As indicated by increasing solubility in trichloracetic acid, the hormone seemed to be rapidly metabolized at the sites of deposition. The experiments were in part repeated employing quantitative extraction and gel filtration procedures. It was found that intact hormone predominated (82%) in the circulation but was cleared very rapidly: 91, 97, and 99% having left by 10, 30 and 60 minutes respectively after injection. The intact hormone was found at 10 minutes to be principally in kidney, bone, and liver. Although there was evidence of fragmentation preferentially to polypeptides of molecular weights of 6000, 4500 and 2500 these cannot be claimed to represent real molecular entities. By one hour, only a few per cent of the injected hormone remained intact, the bulk having been degraded to fragments of small molecular weight.


The metabolism of labeled parathyroid hormone. IV. Autoradiographic studies.

Autoradiographs were prepared from tissues of rats sacrificed 10 minutes after injection of biologically active 125I-labeled parathyroid hormone. No radioactivity was seen in intestine and muscle. Deposition in liver was diffuse showing some sinusoidal concentrations. Depostion in kidney was high and, nearly all activity appeared in selected tubules (presumably proximal tubules) in the outer third of the cortex. Specific localization was also seen in bone particularly in the cellular layers of periosteum and endosteum adjacent to bony matrix and to some extent in osteocytes.


The metabolism of labeled parathyroid hormone. V. Collected biological studies.

Biologically active 125I-labeled parathyroid hormone (125I-PTH) was used in a series of studies in dogs and chickens designed to confirm and augment earlier studies in rats. As in rats, a three exponential equation was required to describe disappearance of 125I-PTH from the blood in the dog. The first two "half-lives" (1.8 and 7 min) accounted for the bulk of the dose. Also as in rats, deposition of apparently intact hormone took place rapidly in kidney, liver and bone in both the dog and the chicken. Degradation occurred very rapidly in all three target organs. Three labeled hormones of different biological activities were compared in the rat. Inactive, oxidized hormone was rejected by the liver but showed markedly increased deposition in kidney and the higher the purity of the hormone the higher was its uptake by liver. Exploration of a wide range of dosages revealed few effects on distribution (smaller deposition in liver and kidney at highest dosages, 65 mug/rat). Fresh sera did not degrade hormone rapidly or extensively. There was no deposition of hormone in intestinal mucosa, marrow, and red cells. Nephrectomy increased deposition in liver and bone. Finally, the perfused liver was capable of extensive degradation of the hormone.


The metabolism of labeled parathyroid hormone. VI. Effects of vitamin D status.

Labeled 125I-PTH with full biological activity was utilized to investigate the interrelationship between vitamin D and parathyroid hormone (PTH) function. The distribution of labeled PTH was studied in rats and chickens on diets containing various amounts of vitamin D and calcium. The effects of vitamin D deficiency were found to be minor. There was a slightly delayed (10--30%) blood clearance of the hormone and a smaller deposition in the liver (20--30%) in the D-deficient animals. Deposition in bone and kidney appeared to be essentially normal. It is concluded that any failure of PTH to evoke a bone response in the deficient animal is not due to the failure of binding of hormone at the target organ.