Prognostic classification of Hodgkin disease in pathologic stage III, based on anatomic considerations.

Fifty-two patients with pathologic stage III Hodgkin disease were studied in an effort to determine whether location of involved abdominal nodes influenced survival. Treatment consisted of total nodal radiotherapy with or without subsequent combination chemotherapy. Th initial radiation field was the "extended mantle," which included supradiaphragmatic nodes, the splenic hilar area, and paraaortic nodes to the level of L2-L4. Subsequently, lower paraaortic and iliac regions were treated ("lower inverted Y"). Patients with disease limited to the spleen and/or splenic, celiac, or portal nodes ("anatomic substage" III1) had a more favorable 5-yr survival than did patients with involvement of paraaortic, iliac, or mesenteric nodes ("anatomic substage" III2): 93% versus 57%, respectively (p less than 0.05). The addition of combination chemotherapy to total nodal irradiation was associated with improved survival of patients in stage III2, but not of those in stage III1.


Induction of serum stimulation and plasma cell proliferation during chemotherapy of multiple myeloma.

Sequential sera from 45 patients with multiple myeloma (MM) and from 6 patients with solid tumors but normal bone marrows who received cyclophosphamide, 15 mg/kg/day for 4 days, were assayed for their effects on tritiated thymidine (3H-TdR) incorporation by normal bone marrow cells and malignant plasma cells. Pretreatment sera from 23 of the 45 patients with MM inhibited normal marrow cell proliferation relative to the effects of normal sera. Of these 45 sera, 30 inhibited plasma cell proliferation. This humoral inhibition was overcome by the induction of humoral stimulation at a predictable time during chemotherapy. The sera obtained sequentially from patients with MM and patients with  normal bone marrows increased 3H-TdR uptake by both cell types by days 12-15 of therapy. Sequential changes in malignant marrow plasma cell 3H-TdR labeling indices paralleled the changes in serum activity, with an increased tumor cell growth fraction occurring at the time of peak serum stimulatory activity. The relationship between serum stimulation and malignant plasma cell proliferation was confirmed in vitro.


Role of transferrin in determining internal iron distribution.

The behavior in vivo of transferrin in loading and unloading iron from its two sites was examined in rats. Radioiron entering the plasma from the gastrointestinal tract in iron-deficient, normal and iron-loaded rats did not differ in its subsequent tissue distribution between erythroid marrow and liver of normal recipients from a second isotope added to the same plasma in vitro. Loading studies in vitro were then carried out employing a reticulocyte incubation model designed to place one isotope predominantly on one site of transferrin, more available to the erythron, and the second isotope on the other site, more available to the liver. In 15 groups of animals in which 3 different iron salts were employed to load transferrin with iron, the mean isotope ratio in the erythron was 1.03 (+/-0.06 SD) and the mean liver ratio was 0.75 (+/-0.21 SD). It was found that the incubation of plasma with reticulocytes resulted in contamination of the plasma by radioactive hemoglobin. After allowance was made for hepatic uptake of radiohemoglobin in the 13 groups in which proper correction could be made, the isotope ratio in the liver became 0.97 (+/-0.17 SD). It is concluded that iron atoms from the two sites of transferrin have similar tissue distributions in vivo in the experimental situations examined.


Red cells in sickle cell crisis: observations on the pathophysiology of crisis.

The pathophysiology of the occurrence and resolution of sickle cell crisis is unknown. The molecular abnormality is constant, while crisis is episodic. In the present study, red cell filterability and sickling with deoxygenation have been measured during sickle cell crises. Recovery from sickle crisis is associated with an increased filterability of the circulating red cell and a decreased susceptibility of the red cell to sickle with deoxygenation (p less than 0.05). The possibility that these changes are responsible for the resolution of crisis is suggested.


Frequencies of thalassemia in American blacks.

The frequency of thalassemia was determined in a group of 541 healthy adult black males. Individuals with decreased mean corpuscular hemoglobin (MCH) values were evaluated further with hemoglobin analysis, iron studies, and globin chain synthesis. Of the males screened, 13.4% had MCH levels below 27.0 pg, while 1.4% had heterozygous beta thalassemia, 2.3% had iron deficiency, and 5.7% had globin synthesis findings compatible with the diagnosis of alpha thalassemia trait (alpha thalassemia-1). This study suggests that thalassemia is one of the most frequent hematologically depictable abnormalities in American blacks.


Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood.

A patient with recurrent pulmonary abscess, weight loss, and alcoholism was found to have extremely high serum vitamin B12 and unsaturated vitamin B12-binding capacity (UBBC) levels. While transcobalamin (TC) II was also increased, most of his UBBC was due to an abnormal binding protein which carried greater than 80% of the endogenous vitamin B12 and was not found in his saliva, granulocytes, or urine. This protein was shown to be a complex of TC II and a circulating immunoglobulin (IgGkappa and IgGlambda). Each IgG molecule appeared to bind two TC II molecules. The reacting site did not interfere with the ability of TC II to bind vitamin B12, but did interfere with its ability to transfer the vitamin to cells in vitro. The site was not identical to that reacting with anti-human TC II antibody produced in rabbits. Because of this abnormal complex, 57Co-vitamin B12 injected intravenously was cleared slowly by the patient. However, no metabolic evidence for vitamin B12 deficiency was demonstrable, although the patient initially had megaloblastic anemia apparently due to folate deficiency. The course of the vitamin B12-binding abnormalities was followed over 4 yr and appeared to fluctuate with the status of the patient's illness. The IgG-TC II complex resembled one induced in some patients with pernicious anemia by intensive treatment with long-acting vitamin B12 preparations. The mechanism of induction of the antibody formation in our patient is unknown.


Resolution of lipid-containing atherosclerotic lesions induced by injury.

In previous experiments, injury-induced atherosclerosis has been shown to be associated with the development of fatty streaks. The findings suggested that fatty streaks might represent a stage in healing of intimal injury evolving to fibrous plaques, free of lipid. The present experiment was designed to study the incidence and evolution of these lesions during a 2-week period of lesion retrogression following removal of a catheter placed in the aorta for 1 week. The findings indicate that as fat-containing lesions, either of the thromboatherosclerotic or fatty streak varieties, decreased, the amount of nonlipid-containing fibrous lesions increased.


Effects of prolonged hemorrhagic hypotensive stress on catecholamine concentration of mesenteric blood vessels.

Norepinephrine (NE) and epinephrine (E) concentrations were determined fluorometrically as an index of functional adrenergic innervation in small mesenteric arteries, veins, and superior mesenteric arteries of dogs and rats subjected to a period of prolonged hemorrhage at a constant mean arterial pressure of 35 mm Hg. In nonhemorrhaged animals, highest catecholamine concentrations were found in the small principal arteries, next highest in the small veins, and least in superior mesenteric arteries. A significant decrease occurred in the NE and E concentrations of all three vessel types in the dog during the decompensatory phase of the hypotensive stress (defined as the hypotensive period beyond the time at which maximum bleedout volume occurred). In the rat significant decreases were detectable only in the NE concentrations of the small arteries and veins during this phase. It is concluded that the increase in neurogenic vascular tone accompanying severe hemorrhagic stress is lost simultaneously on the arterial and venous sides of compensatory vascular beds. Such loss is closely related to transmitter depletion at the adrenergic neuromuscular junction and, if allowed to continue uncorrected, can contribute significantly to irreversible cardiovascular collapse.


Effect of chronic denervation on the activities of monoamine oxidase and catechol-O-methyl transferase and on the contents of noradrenaline and adenosine triphosphate in the rabbit ear artery.

When assayed on homogenates of the rabbit ear artery up to 192 h after sympathetic denervation, the activity of monoamine oxidase (MAO) showed a small but significant decrease (maximum 9%). The activity of catechol-O-methyl transferase (COMT) appeared unchanged, although it is possible that the small and variable nature of this enzyme activity compared with that of MAO may have masked a comparable effect of denervation. The maximum decreases in noradrenaline (NA) and adenosine triphosphate (ATP) contents were greater than 90% at 48 h, and 32% at 96 h after denervation. These results confirm the presence of neuronal as well as extra-neuronal MAO, and also the presence of extraneuronal comt in this artery. The decline in ATP contents after denervation suggest that part of the ATP is neuronal. However, the estimated ratio of NA to neuronal ATP is far in excess of that reported for isolated noradrenaline storage vesicles, suggesting that the major portion of the neuronal ATP was not present in these vesicles.


Basis and results of chemotherapeutic treatment of gliomas.

Brain tumor chemotherapy has improved in recent years with increasing knowledge of the requirements for effective drugs (such as lipophilicity and low molecular weight in order to enter brain tissue, and ability to kill proliferating and non-proliferating cells) and the evolution of criteria for statistically evaluable studies. In Phase II studies BCNU is the best single agent so far, giving a response rate of 51 per 100 for a median duration of 9 months. CCNU and procarbazine are also effective, while epipodophyllotoxin, DTIC, BIC, methotrexate and vincristine are somewhat less so. Recent Phase III studies have shown unequivocally that radiotherapy is effective; BCNU and radiation therapy together appear at present the best available treatment following surgery. Combinations of drugs as well as new drugs are a major source of hope for the future in these tumors with their still inexorably fatal courses.


[Hormone therapy in the treatment of primary brain tumors of the adult].

After considering the principle effects of corticosteroids on human fluids and tissues their action in the treatment of cerebral tumors is reviewed. Corticosteroids have a definite effect on cerebral and intra-tumoral edema and thus help to restore local circulation as well as C.S.F. circulation. Through these effects they diminish intracranial hypertension and reduce clinical symptoms to those of the tumor itself. They increase the time necessary for neuro-radiologic, isotopic and other investigations and make them safer, they diminish the surgical and and post-operative risks as well as those of radiotherapy. Their action on the growth of cerebral tumors remains incertain and increased survival in patients with inoperable or recurrent malignant gliomas may be due to their anti-edema effect more than to an antitumor action which remains to be determined.


[Basocellular epithelioma of the back with metastases of the axillary ganglia].

In a 52-year old woman, basal cell carcinoma of the back skin recurs after excision and the axillary lymph nodes are involved. This case is to be added to the list of basal cell carcinomas with metastatic evolution. The histologic study of a series of sections allows to show the migration of neoplastic cells in the vessels. Though exceptional, the ability of the basal cell carcinomas to yield metastases must be taken into account.


[Demonstration of osteoclastic acid phosphatase in the serum of patients with giant cell tumors. Preliminary study].

Starting from the fact that an ultrastructural cytochemical study of the Giant-Cell Tumour demonstrated the presence of a large amount of lysosomic acid phosphatase in the tumour cells, an attempt was made to evidence the presence of this enzyme in the serum of patients bearing such a type of bone tumor. Acrylamide gel electrophoresis of the serum allowed one to separate a number of isoenzyme with acid phosphatase activity and to characterize at least two bands different from those secreted by prostate, blood platelets, liver or spleen. The comparison between zymograms of normal and pathological sera, more particularly in Paget disease, led to consider that these two bands had an osteoclastic origin. Besides, these bands vanish after tumor eradication. Acrylamide gel electrophoresis of serum provides therefore a means to support the preoperative diagnosis of Giant-Cell Tumor and, eventually, to detect an early recurrence of the disease.


[Esophageal cancer in Ille-et-Vilaine in relation to levels of alcohol and tobacco consumption. Risks are multiplying].

A retrospective case-control study of 200 male cases of oesophageal cancer and 778 population controls has been carried out in Ille-et-Vilanine (France). The logarithms of the relative risks of developing the disease increase linearly with daily consumption of alcohol and tobacco independently. The combined effect of both fit with a multiplicative model which is proposed. This model could be applicable to other situations. It explains the sex ratio and the urban/rural differences observed in Ille-er-Vilaine. The practical implications for public health purposes are briefly discussed.


[Esophageal cancer in Western France. Retrospective analysis of 1400 cases].

A retrospective review was made of 1 400 cases of cancer of the esophagus treated at the Centre "Francois Baclesse" between 1964 and 1975. The disease appeared at an earlier age and more frequently in men (95%) than in women. The lesions were located predominantly in the middle third of the esophagus. There was a high frequency of local, regional and general extension of the disease due to late diagnosis. Less than one-third of the patients were eligible for surgery--which was excluded in the other cases because of age or the presence of associated pathology or secondary neoplasm--and only 10 per 100 of this group were potentially curable.


[Cancer information of the general practitioner].

Inquiries among more than 1 000 general practitioners in the South-West area of France permitted us to precise their needs and wishes about information in the cancer field. The aim of these data is to adapt in a better way the teaching for students and graduates on the base of a close collaboration between general practitioners and cancer specialists.


[Evaluation of the results of radiotherapy in 14 cases of malignant thymoma. Therapeutic prospects].

The authors present a critical review of 14 cases of malignant thymomas. They point out that the development of the tumours is similar to Hodgkin disease's (13 relapses in contiguous areas), that surgery is never sufficient for cure and that radiosensitivity is high (in 8 patients radiotherapy alone results in a total and early regression of the tumour). Therefore the authors propose a complementary post-operative treatment by limited irradiation and MOPP type polychemotherapy. This temporary choice of treatment can be reevaluated after further case studies. To facilitate this they wish that a cooperative project could gather the rare and dispersed observations of different centers.


Changes in activity of malate dehydrogenase and glucosephosphate isomerase in serum of rats exposed chronically to inorganic mercury and its aryl and alkyl compounds.

In course of prolonged exposure [14 weeks] to various mercury compounds [MetHg - a fluid seed-dressing preparation 0,8. Phenyl and Ethyl chlorides and HgC1(2) in doses corresponding to 5% of DL(50)[3 times weekly], enhanced levels of activity of malate dehydrogenase [MDH] and glucosephosphate isomerase [PHI] in blood serum were observed. After 7 weeks of exposure about fourfold increase of MDH and 2-3-fold enhancement of PHI activities were found relative to controls. After 14 weeks of exposure in livers of rats, given MetHg and EtHg, organic mercury was found at concentrations of 28.8 and 4 microng/g tissue, respectively. Inorganic mercury in liver was found in animals given all coumpounds and concentrations were in the range of 1,2 - 4,7 microng/g tissue.


Fate of labeled n-alkanes in the blue crab and stripped mullet.

Results of these studies demonstrate that the blue crab was readily able to take up and discharge labeled n-alkanes, but it was not able to metabolize them. In contrast, it appears that n-alkanes taken up via the digestive tract in mullet are readily metabolized, probably via microorganisms in the gut. More limited metabolism was observed in mullet when n-alkanes were taken up via the gills.


Starvation-pesticide unteraetions in juvenile brown pelicans.

Nineteen 9-week-old brown pelicans (Pelecanus occidentalis), obtained from a colony in Vero Beach, Florida, containing environmentally acquired p,p'-DDE residues, were subjected to a food deprivation experiment. Samples of brain, liver, muscle, and fat taken after one and two week periods of starvation indicated that starved birds contained significantly greated residue levels in fat compared to non-starved controls. Such differences were not observed in residues in the other tissues. The significance of these findings is discussed in relation to the biology of brown pelicans.


Steroids as Sewage Specific Indicators in New York Bight sediments.

Sediments of the New York Bight were examined for steroidal compounds and found to contain relatively large amounts of coprostanol and 24 beta-ethyl coprostanol. These steroids were found to be derived from sewage, and it is suggested that they be used as sewage tracers in marine sediments.


Toxicity to fish of flame retardant fabrics immersed in their water. Part I.

A number of commercial and candidate flame retardants were studied with regard to their toxicity to fish when released from fabrics immersed in their water. Immersion of laundered or unlaundered flame retardant 100% polyester or polyester blend fabrics used in children's sleepwear in water containing goldfish resulted in release of the anticholin-esterase flame retardant TDBPP (tris (2, 3-dibromopropyl) phosphate) and death of all fish within 24 hours. TDBPP undergoes loss of HBr in water and production of a metabolite.


Reduced mercury excretion with feces in germfree mice after oral administration of methyl mercury chloride.

When methyl mercury chloride was administered orally the amount of mercury excretion with feces of germfree mice was noticeably lower than that of the control mice. Germfree mice excreted 24 percent of the administered mercury within 10 days of administration while the control mice excreted 46 percent. Mercury retention in the organs of germfree mice was slightly higher than in the control mice. These results suggest that the existence of microorganisms in animal intestines are concerned with mercury excretion in the animal body.


Precision of analysis for waterborne chrysotile asbestos by transmission electron microscopy.

Detailed examinations of water samples were carried out to determine the precision of analysis for chrysotile asbestos by transmission electron microscopy (TEM). Since the frequency distribution of counts fits a Poisson distribution, several statistical inferences were made, including (1) an estimate of precision, and (2) a model for determining the probability of observing chrysotile as a function of its concentration in water and magnitude of area scanned by TEM.


Mercury accumulation by largemouth bass (Micropterus salmoides) in recently impounded reservoirs.

Mercury levels of largemouth bass from three reservoirs in the southeastern United States were highest in the younger, relatively oligotrophic reservoirs and were significantly lower in an older, more eutrophic reservoir in the same drainage system. The reservoir with the highest mercury levels in bass is the reservoir farthest upstream, and is not subject to inputs of municipal or industral wastes. The source of mercury in these reservoirs appears to be the soil which formed theri original sediments. Preliminary data indicate that mercury levels in largemouth bass in these systems decline as the reservoirs age. televated mercury levels in fish appear to be a transitory phenomenon in newly impounded, relatively oligotrophic reservoirs.


The making and breaking of affectional bonds. II. Some principles of psychotherapy. The fiftieth Maudsley Lecture.

An account is given of how a clinician guided by attachment theory approaches the clinical conditions to which the theory is held to apply, which include states of anxiety, depression and emotional detachment. Assessment of a patient is in terms of the patterns of attachment and caregiving behaviour which he commonly shows and of the events and situations, both recent and past, which may have precipitated or exacerbated his symptoms. The problems posed by relevant information being suppressed or falsified are noted. Viewed in this perspective a psychotherapist is seen to have a number of inter-related tasks: (a) to provide the patient with a secure base from which he, the patient, can explore himself and his relationships; (b) and (c) to examine with the patient the ways in which he tends to construe current interpersonal relationships, including that with the therapist, and the resulting predictions he makes and actions he takes, and the extent to which some may be inappropriate; (d) to help him consider whether his tendencies to misconstrue, and as a result to act misguidedly, can be understood by reference to the experiences he had with attachment figures during his childhood and adolescence, and perhaps may still be having.


Prospective study of airway obstruction in a population with small airway disease.

In this paper, we discuss results showing an increase of bronchial obstruction due to exposure in an iron foundry. The research has been conducted in two steps: in the first, we selected a sample of 100 subjects, all working in the iron foundry, who were affected only by small airway obstruction. In a second step, 30 months later, 99 of these subjects were re-examined and the present airway condition determined. In 43 subjects we found abnormal results of the tests indicating total airway obstruction after the 30 months. After properly accounting for ageing, we found that even in the subsample of non-smokers a deterioration had occurred, showing an effective contribution of environmental pollution. The use of RV, MMEF, CV, DLCO for detecting small airway obstruction is evaluated. The combination of RV, MMEF and CV is the most efficient mosaic of tests for the selection of subjects with small airway obstruction (89%) and with high probability of developing total airway obstruction (44%).


On the prevalence, diagnosis and management of lithium-induced hypothyroidism in psychiatric patients.

Fifty-three psychiatric patients who had been receiving treatment with lithium continuously for more than two years were examined to estimate the prevalence of lithium-induced hypothyroidism. It was found to be 20 per cent among women. No men were affected among these patients. In order to study the characteristics of the disorder further cases were drawn from another population. One third of the patients developed hypothyroidism during their first year of treatment, others not until after 9 years. About two thirds of the female patients with hypothyroidism had thyroid antibodies. All cases with lithium-induced hypothyroidism showed elevated levels of serum thyrotropin, which in our experience is the laboratory examination of choice in these as well as other cases of "primary" hypothyroidism. Since the probability of detecting these cases at a given control visit was found to be low, we feel that such visits need not include extensive laboratory investigations. Hypothyroid patients responding well to lithium treatment should continue their medication combined with appropriate thyroxine substitution.


The effect of mild hyperventilation on red cell sodium.

Control subjects voluntarily overbreathed to produce end-tidal PCO2 levels similar to  those found in patients suffering from neurotic or endogenous non-retarded depression. Red cell sodium content was found to decrease during overbreathing in all the subjects. The changes were similar to those usually reported for depressed patients. The results imply that red cell sodium levels are in part dependent on respiratory behaviour. They suggest a need for considerable caution in interpreting red cell sodium values from psychiatric patients.


The significance of dopamine for the mode of action of neuroleptics and the pathogenesis of schizophrenia.

Animal experiments have demonstrated the likehood that all known neuroleptics inhibit transmission in central CA-ergic systems, regardless of their chemical structure and via different mechanisms. For clinical psychiatry this fact prompts a number of questions: (1) is this phenomenon also to be found in human individuals; (2) if so, is it of importance for the clinical (side) effects of neuroleptics; (3) do patients with (schizophrenic) psychoses show signs of central CA-ergic hyperactivity? This article presents a survey of clinical research focused on these questions which, for the sake of brevity, is confined to DA metabolism. The available data indicate the plausibility of a correlation between inhibition of DA-ergic transmission on the one hand, and on the other hand the therapeutic effects of neuroleptics and the occurrence of hypokinetic-rigid symptoms. The hypothesis that DA-ergic hyperactivity is an important pathogenetic mechanism in schizophrenic psychoses can be based only on indirect arguments; direct studies of the DA metabolism have so far failed to reveal supporting evidence. The possible causes of this failure are discussed.


Airway obstruction in pulmonary sarcoidosis.

To determine the physiological basis of airway obstruction, we studied mechanical properties of the lung in 21 patients with various stages of pulmonary sarcoidosis. Forced expiratory flow at 50% vital capacity (VC) was significantly decreased in nine patients. Determining factors of the flow reduction factors of the flow reduction in addition to the decreased VC were: 1) low peripheral airway conductance in four patients; 2) loss of elastic recoil in three patients; 3) combination of 1) and 2) in two patients. These findings could be explained by a concept that in pulmonary sarcoidosis the lungs are a composite of inhomogeneously distributed normal, granulomatous, or fibrotic tissue, with or without hyperinflated tissue in various proportions.


Follow-up of pulmonary function after "shock lung".

Long-term follow-up of pulmonary function has been performed in four patients having recovered from "shock lung". In three patients there is a progressive normalization of lung volumes and lung compliance, whereas the pulmonary diffusing capacity improves but without attaining predicted levels. In the fourth patient, a delayed reduction of total lung capacity, lung compliance and diffusion capacity occurred. During the follow-up period (from one month to four years) there was no complaint and physical examination, electrocardiogram, chest roentgenogram, conventional pulmonary perfusion scintigraphy and arterial blood gases at rest were quite normal. These results are compatible with the persistence of some degree of interstitial lung disease after recovery from "shock lung".


Aspects of outcome in a therapeutic community setting. How patients are seen by themselves and others.

How patients are seen by themselves and others close to them may influence the process of re-integration in the community after discharge. In a study in a psychiatric admission unit employing a therapeutic community approach, patients who sought little or no contact with the unit after discharge saw themselves, and were seen by others, as less "pleasant" but less "ill" than those who continued more regular contact. Perceptions were measured with the semantic differential technique. Patients' social class and household position were found to have a marked effect on the level of contact and on its association with how patients were seen. Diagnosis did not appear to influence hospital contact.


Maximum expiratory flow-volume curves in children: changes with growth and individual variability.

Environmental factors may affect the lungs of children by retarding growth of ventilatory capacity. To detect retarded growth, we recorded maximum expiratory flow-volume (MEFV) curves in boys and girls aged 8-14 years observing the normal patterns of growth. The accuracy with which deviations from the normal patterns of growth may be measured was also determined. Expiratory flow rates and timed expiratory volumes were less reproducible in the same child than was forced vital capacity. At all ages the shape of girls' MEFV curves was different from that of boys curves in that girls had greater maximum expiratory flow rates (Vmax.) when differences in forced vital capacity (FVC) had been taken into account. The ratio of Vmax. 50% FVC to FVC decreased in both boys and girls as they grew older. The rates of growth of the MEFV curve measurements and estimates of their reproducibility were used to calculate minimum sample sizes required to detect retarded growth of ventilatory capacity. To detect a change of 10% in the normal growth rate in Vmax. 50% FVC between ages 8 and 14 years, nearly 2,000 children would need to be studied annually. Smaller samples could be used if changes in FVC growth rates were of primary concern.


The effect of holidays on a token economy regime.

This preliminary study investigates the effect on patients' performance of a set time off, in the form of a short holiday, from a strict reinforcement (token economy) regime. Assessment was by the patients' mean token earnings before and after the holiday and their self-care and work performance throughout. The results suggest that a holiday from a token economy has beneficial effects for patients.


Rehabilitation of the institutionalized patient: description of a programme and follow-up of 60 patients.

The programme in an intensive rehabilitation unit in a large psychiatric hospital is described. Features include the use of non-medical staff as primary therapists, the use of a mini-bus to facilitate regular visits by patients to their home areas, the inclusion of the mini-bus driver on weekly staff conferences, the use of sociodrama, the re-organization of hospital money payments to patients, the promotion of relations with community-based facilities through occasional "teach-in" days, and a special liaison social worker providing intensive follow-up after discharge. Rehabilitation was prolonged (average stay about one year) and about half of those selected for rehabilitation from the long-stay wards were discharged. Follow-up showed that these patients benefited from discharge, in spite of a relatively high incidence of psychopathology and of social problems. Those transferred back to long-stay wards showed increased institutionalization.


Kibbutz civilian population under war stress.

During the Arab-Israeli war of 1973 measures had to be taken by the kibbutz civilian population in Israel to cope with the stresses of war. The measures adopted, and the specific characteristics of an organized cohesive group, appear to have succeeded in reducing the severity of the reactions to stress and in lowering the incidence of psychiatric casualties among children and adult members of the kibbutzim.


Perinatal complications in offspring of psychotic parents.

The birth records of 78 subjects born to psychotic parents and 72 subjects born to normal parents were studied. No significant differences in the rates of pregnancy and birth complications (PBCs) were found between the offspring of psychotic parents and normal control parents. There were no differences between offspring born to psychotic mothers compared to psychotic fathers. Neither the onset of the parent's illness, nor the mother's age at delivery, nor the sex of the offspring seemed to influence the rate of PBCs. The offspring of chronic schizophrenic mothers and manic-depressive fathers had lower PBC rates than the offspring of parents of other diagnostic categories. The parents of these two groups, which were of a limited size, did not differ on any variable of significance, excepting the time of their first psychiatric hospital admission.


Survival of nieces and nephews of schizophrenic patients.

Evidence was found against the hypothesis that heterozygous carriers of a schizophrenic gene have a reproductive advantage through enhanced fertility. In consequence an investigation was made of the possibility that an advantage is gained through diminished early mortality among the off-spring of carriers. The results were equivocal. While an observed deficit of infant deaths was attributable to under-reporting, the possibility of a true advantage could not be ruled out, because of the statistical unreliability of the findings in a sample of the size available. A plea is made for a collaborative effort to settle the issue.


The effect of varying the rate of presentation on the information transmission of schizophrenic and control groups.

Groups of subjects were tested on a paced serial reaction-time task in order to study the effect of varying the rate at which information was presented. The groups were: two groups of patients with acute schizophrenia but differentiated on the basis of primary symptoms, a group of institutionalized schizophrenic patients, a group of neurotic patients and a normal group. All groups showed a reduction in efficiency when the presentation rate was increased. The groups most adversely affected were the non-integrated and institutionalized schizophrenic patients. The integrated schizophrenic and the neurotic groups were affected to a lesser degree, the normal groups being least affected. These results favour a dimensional view of personal illness, in which deficits are most marked in patients with non-integrated schizophrenia.


A survey of sports injuries in Birmingham.

7% of the injuries presenting to the Birmingham Accident Hospital during 1975 occurred during sport. Of those injuries which could be classified 98.3% were due to extrinsic causes. These figures would not seem to justify a sports injury clinic. However we believe that this presents the service available rather than the service required.


Meralgia paraesthetica--a sports lesion in girl gymnasts.

Investigation into thigh pain in two girl gymnasts has established the likely relationship between the point of impact on the thighs during exercises on the asymmetric bars and mild neuropathy of the lateral femoral cutaenous nerve. The clinical and biomechanical steps taken to elucidate the problem are described. Local infiltration of anaesthetic has confirmed a definitive diagnosis of meralgia paraesthetica in one case.


Will the olympics survive?.

The United States of America dominated 58 events in athletics, field and swimming, which between them accounted for 35 per cent of all events in the Munich Olympiad. 1972; these events favour taller individuals. But, in 25 per cent of other events (1) cycling, (2) fencing, (3) gymnastics, (4) judo, (5) weightlifting and (6) Graeco Roman wrestling the U.S.A. did not win a single medal. The failure of the U.S.A. to maintain her lead in Munich was largely due to weaknesses in these other events in many of which the potential medallists can be derived from the lower half of the height distribution (events 3 to 6). These weaknesses are Russia's strength and they continued to remain unstrengthened at Montreal. Also, the domination held by the U.S.A. in swimming was seriously challenged by East Germany. The present trends indicate that the U.S.A.'s ranking is likely to slip further to the third position in Moscow 1980. Factors inhibiting the survival of the Olympics are pointed.


On the choice of fluid for the hydration of middle-aged marathon runners.

Nine subjects (five well-trained post-coronary patients and four other middle-aged joggers) paticipated in a 42 km "Marathon" race. The course was covered in an average of 212 minutes under pleasantly warm conditions (Maximum 21.7 degree C, 69% relative humidity). Subjects were given initial hyperhydration and repeated subsequent doses of water, "Erg" (Na+ 19mE/l K+ 10.7mE/l, glucose 5.3g/100 ml) or a "Special Solution" (during the race Na+ 21mE/1 glucose 4.1g/100 ml; after the race Na+ 20 mE/l, K+ 4.7mE/l., glucose 4.1 g/100 ml). Weight loss averaged 2.2 kg and sweat production 3.3l taking account of water liberated from the hydration of glycogen and the oxidation of food stuffs, it was estimated that most subjects suffered relatively little dehydration over the race (0.4--0.8l). This was confirmed by a sustained urine production of greater than 100ml/hr. Nevertheless, rectal temperatures showed substantial elevation over the race (final readings 38.3 - 40.2 degree C). In terms of fluid balance and stability of plasma mineral composition, the runners drinking water performed slightly better than those receiving the other two solutions. Nevertheless, there may be merit in giving potassium solutions during recovery from vigorous effort.


Effects of exercise on free serum cholesterol.

Two age groups (young and old, n = 12) matched for physical fitness and two physical fitness groups (high and old, n = 12) matched for age participated in a four month physical fitness programme. Blood samples were drawn at four stages of metabolic stress at the pre-test and five stages at the post-test. The blood samples were analyzed by colorimetric methods for total cholesterol and free cholesterol. Statistical analysis revealed that: (1) Short-term exercise increased total cholesterol, free cholesterol, and the percent free cholesterol from the resting state to the submaximal and maximal exercise states. (2) There was no change in free serum cholesterol from the pre- to post-tests. (3) The high-fit group, compared with the low-fit group, had a lower free cholesterol level but had similar percent free cholesterol values. (4) There was no significant difference between age groups for either total serum cholesterol, free cholesterol, or the percent free cholesterol levels.


Rugby football injuries.

A review of one thousand injuries due to Rugby Football is reported. There is a high incidence of fracture (15.7%) and head injury of various types (14.0%) in this series although only four adults required immediate hospital admission for the head injury.


"Pulseless" femoral arteriography.

Direct needle arteriography of "pulseless" femoral arteries is described. The information obtained, and the excellent detail of the arterial tree, is discussed in cases of collateral filling of the femoral artery. Evaluation of occluded by-pass grafts is also mentioned.


Effect of cobalt-60 gamma rays and DTIC (5-(3,3 dimethyl-1-triazeno)-imidazole-r-carboxamide) on human malignant melanomas grown in athymic nude mice.

The effects of 60Co gamma rays and DTIC on two human malignant melanomas, inoculated and passed serially in athymic mutant nude mice, were studied in vivo. Dose-response curves determined after single exposures to 60Co gamma radiation indicate that human malignant melanomas remain radioresistant after transplantation in mutant nude mice. A fractionated irradiation régime, used in the treatment of patients suffering from malignant melanomas, had a considerable effect but did not cure. A corresponding treatment régime with DTIC inhibited the tumour growth, but less effectively than 60Co gamma rays. These two treatments combined were more effective than either alone. The results obtained show no disagreement with results from clinical practice regarding treatment of disseminated malignant melanomas. This suggests that human malignant tissue, transplanted to mutant nude mice, retains its properties with respect to response to therapy. The mutant nude mouse may therefore be valuable in developing new treatment régimes for cancer.


The effect of radiation on tumour growth delay, cell survival and cure of the animal using a single tumour system.

The response of a murine tumour to single doses of X rays has been measured using three different assays--animal cure, cell survival in vitro after irradiation in vivo, and tumour growth delay. The dose to cure 50% of the animals, the TCD50, was 79.0 Gy. This was not affected by clamping the tumours to render all the cells hypoxic at the time of irradiation, implying that most of the cells in the tumour were hypoxic already. The enhancement ratio for the hypoxic cell sensitizer Ro-07-0582 was 2.1. The cell survival assay gave an enhancement ratio of 1.6 and an hypoxic fraction of 5%. The discrepancy in the estimates of the hypoxic fraction can be explained by the ability of the naturally hypoxic cells, but not the oxic ones, to recover from potentially lethal damage in vivo. Neither the cell survival assay nor the growth delay assay agreed with the TCD50 assay as to the effect of the hypoxic cell sensitizer, even allowing for recovery from potentially lethal damage. It is doubtful whether the measured survival curve would predict the measured TCD50.


Absorbed doses in the marrow during 131I therapy.

Absorbed doses to red marrow and blood from 131I therapy have been re-evaluated using data which has become available more recently. Uncertainties in the calculations are discussed and a comparison is made with previously published dose estimates. The mean dose to red marrow from the treatment of hyperthyroidism is estimated to be 0.59 rad mCi-1, compared with 0.36 rad mCi-1 for the euthyroid state.


Radioisotopic study of the adrenal glands using 131I-19-iodocholesterol.

Scintigraphy of the adrenal gland with 131I-19-iodocholesterol has recently been added to radiological techniques in adrenal imaging and has been used successfully to demonstrate anatomical and functional disorders of the adrenals in a variety of clinical situations. A review of the authors' experience stresses the diagnostic value of this method. Radiological findings and results of scintillation imaging are complementary: their comparison improves and clarifes indications for scintigraphy. Hyperadrenal cortical diseases always gave satisfactory scintigrams, the most interesting results being obtained in adrenal cortical hyperplasia and unilateral hyperfunctioning adenomas. In these cases the evaluation of the response to stimulation or suppression tests was very useful. On the other hand scintigraphy was less valuable in demonstrating malignant and non malignant tumours.


Idiopathic megacolon: a review of 42 cases.

Forty-two patients with idiopathic megacolon who were seen at St Mark's Hospital over an 18-year period are reviewed with regard to presentation, investigation and management. The differential diagnosis is discussed with particular reference to Hirschsprung's disease. The important aspects of medical treatment are outlined and the possible reasons for failure in more than one-half of the patients are discussed. The indications for surgical intervention in 14 patients are reviewed. The results following subtotal colectomy were better than following a localized sigmoid resection.


Adult Hirschprung's disease.

Hirschprung's disease (aganglionosis) in the adult is a rare condition but needs to be considered as a diagnosis in any case of intractable constipation. A series of 35 cases of probable aganglionosis seen at St Mark's Hospital since 1954 is reviewed. Diagnosis is discussed and operative management evaluated.


Organic constipation in adults.

Four cases of non-Hirschsprung megacolon in adults are presented. The histology of the myenteric plexus suggests that this may be an anomaly of development.


Prevention of wound sepsis in gastro-intestinal surgery.

After gastro-intestinal operations wound infection is usually caused by the inoculation of bacteria present within the intestinal tract into the incision during the surgical procedure. In theory, wound sepsis may be minimized by the following methods: (a) avoiding intestinal contamination of the incision; (b) altering the normal flora of the intestinal tract by adding oral antimicrobials to bowel preparation; (c) using topical or systemic prophylactic antibiotic administration for certain high-risk patients. The relative importance of these methods of prophylaxis is described.


Preoperative diagnosis in carcinoma of the breast.

Two methods of obtaining a preoperative diagnosis of breast lumps have been evaluated by simultaneous use on 131 patients. Tru-Cut needle biopsies gave a reliable diagnosis in 75 per cent of those suffering from primary carcinoma of the breast. No cases of benign disease were wrongly reported as carcinoma by this method. Fine-needle aspiration cytology gave no helpful information in one-half of the patients with malignant disease and in addition 5 cases of benign disease were falsely reported as carcinoma. Tru-Cut needle biopsy is a valuable preoperative investigation in patients with primary carcinoma of the breast.


Occlusion of the subclavian vein associated with cephalic vein pacemaker electrodes.

Thrombosis and occlusion of major veins have been described following the use of transvenous pacing electrodes for the establishment of permanent cardiac pacing. The frequency of such complications is, however, not well known. A series of 125 patients was therefore reviewed, all of whom had been paced with permanent transvenous electrodes through a cephalic vein. There was clinical and venographic evidence of subclavian vein occlusion in only 3 of these patients. A further 20 of these patients were also subjected to venography and showed no radiographic evidence of venous occlusion although minor thrombosis associated with the pacemaker electrode was found in one patient. It is concluded that the convenience of using the cephalic vein as a route for the insertion of transvenous pacing electrodes outweighs the small risk of major venous occlusion.


The place of transthoracic vagotomy in the management of recurrent peptic ulceration.

For the successful treatment of recurrent peptic ulceration confirmation of the presence of the ulcer by fibreoptic endoscopy is essential. Further investigation by barium meal and gastric acid secretion studies allows a rational surgical approach to be formulated. This process is illustrated by discussion of the investigative findings and the results of treatment in a series of 20 patients with recurrent peptic ulcer over a 5-year period. In one-half of these patients a second abdominal operation was necessary, but in the other half a transthoracic vagotomy alone gave equally good results.


Relative risk of stump cancer following partial gastrectomy.

The relative risk of stump cancer following partial gastrectomy for a benign gastroduodenal condition was estimated using an individually matched retrospective study design based on autopsy material. Data on all patients dying with gastric cancer and autopsied at the Central Laboratory of Pathology, University Central Hospital, Helsinki, during 1961-75 were collected. Matched pairs of the same sex and age were used as controls. Of the 464 patients dying with gastric cancer, 9 had undergone previous partial gastrectomy, while the respective number among the controls was 5. This result suggests that the risk of cancer in the gastric stump was not significantly increased as compared to the normal unoperated population.


Chylothorax: a complication of Dwyer's anterior instrumentation.

The authors report the development of an extensive right chylothorax several days after Dwyer's anterior instrumentation in a 6-year-old girl with a severe progressing infantile scoliosis. Instrumentation extended from T11 to L4 with removal of the tenth rib and with splitting of the diaphragm. The postoperative course was initially without any problems. However, respiratory distress on the tenth day after surgery was accompanied by mediastinal shift and the symptoms were relieved with aspiration of 600 ml of chyle from the right pleural cavity. The literature on this complication of chylothorax is reviewed; it has been observed in cardiothoracic surgery. The management of the case is reported in detail and methods of detection and treatment are discussed.


The neutrophil count in childhood acute appendicitis.

A study was made of the total leucocyte count, neutrophil percentage and absolute neutrophil count in 100 consecutive children with acute appendicitis and in 25 children from whom, following a provisional diagnosis of acute appendicitis, a normal appendix had been removed, no other infective or inflammatory lesion having been found. In the first group there was a raised total leucocyte count in 42 per cent, a raised neutrophil percentage in 93 per cent and a raised absolute neutrophil count in 77 per cent. In the second group the corresponding figures were 4, 24 and 16 per cent. Acute appendicitis is associated with changes in the total leucocyte and neutrophil counts and a correct interpretation of the results of these investigations requires that account be taken of the age of each child. A probable maximum absolute neutrophil count has been calculated. An explanation has been suggested for the presence of normal total leucocyte counts in certain cases in spite of acute appendicitis.


The role of the surviving pancreas in late fatalities of acute pancreatitis.

The necropsy findings in 3 patients who died between 4 and 14 weeks after episodes of acute pancreatitis are described. The most striking features were the extent of extraperitoneal necrosis and the comparative normality of residual portions of the pancreas. It is suggested that when the duct system is disrupted, the secretions of the surviving pancreas cause progressive enzymatic destruction of extrapancreatic tissues and thus contribute to the mortality of the disease.


Dissolution of retained bile duct stones using heparin.

Five cases of retained bile duct stones treated with heparin in normal saline are reported. In 2 cases the stones were retained in the left hepatic duct, proximal to the T tube. Infusion of heparin in normal saline was found to be simple and effective in treating retained bile duct stones without obvious side-effects. If stones are inadvertently left in the common bile duct following surgery, attempts should be made to encourage them to pass by heparin infusion through the T tube before a second operation is contemplated. Sufficient time must be allowed before the treatment is considered to have failed.


The implications of scrotal interference for the preservation of spermatogenesis in the management of testicular tumours.

Seminal analyses have been performed in 14 patients who have received radiation therapy following unilateral orchidectomy for testicular tumours. In patients receiving scrotal in addition to para-aortic and pelvic lymph node irradiation azoospermia occurred in 17 out 18 specimens examined, whereas in those patients not requiring scrotal irradiation, restoration of spermatogenesis occurred. The difference is a result of the increased dose of radiation received by the remaining testicle when the contralateral side of the scrotum is irradiated. Following scrotal aspiration, trans-scrotal biopsy or scrotal orchidectomy for testicular tumour, the scrotum becomes a possible site of recurrence and it should be electively irradiated. In order to give the patient the best chance of preserving fertility it is essential that scrotal interference in the management of testicular tumours must be avoided.


Fissure-in-ano: the initial management and prognosis.

The results of treatment of 188 consecutive new patients with a primary diagnosis of fissure-in-ano presenting to the Outpatient Department of St Mark's Hospital are reviewed. One-third underwent operation as the primary treatment and were not studied further. Of the remaining patients who underwent non-operative treatment only, one-half were initially cured. Follow-up at 4 years showed that this cure was maintained in half of these cases, suggesting that there is a place for treatment with a dilator in the correctly selected case. The presence of a sentinel skin tag or a fibrous anal polyp is shown to have a statistically significant association with operative treatment. The use of a paediatric sigmoidoscope to diagnose a fibrous anal polyp is recommended.


The results of arterial reconstruction utilizing the profunda femoris artery in the treatment of rest pain and pre-gangrene.

Arterial reconstruction utilizing the profunda femoris artery was performed for rest pain and pre-gangrene in 45 limbs. The preoperative mean ankle arterial pressure index of 0-21 (s.d. 0-12) was increased to 0-52 (s.d. 0-16) in the 22 limbs salvaged by the reconstruction. In 38 limbs a proximal reconstruction was necessary in addition to profundaplasty. At a mean follow-up time of 15-4 months 41-6 per cent of the 36 patients were dead.


The value of profundaplasty in the management of severe femoropopliteal occlusion.

A series of 45 patients with advanced occlusive arterial disease of the femoropopliteal segment underwent profundaplasty as the sole operative procedure. The value of this technique as a salvage procedure for the severely ischaemic limb is discussed.


The long term results of profundaplasty in femoropopliteal arterial occlusion.

The long term results of profundaplasty in the treatment of femoropopliteal arterial occlusion have been reviewed. Fifty patients have been studied with a mean follow-up period of 4 years (range 6 months to 8 years). Intermittent claudication was abolished or substantially improved in 5 of the 25 cases (20 percent); rest pain was relieved in 10 of the 25 cases (40 per cent), the remainder requiring a major amputation. Lumbar sympathectomy produced little additional benefit in either group. The mortality rate in the rest pain group was high and only 5 patients survived for more than 3 years with both legs intact. The state of the distal 'run-off' and the degree of preoperative profunda stenosis appeared to have little influence on the clinical outcome. After operation pedal pulses were restored in 16 per cent of those presenting with claudication. Profundaplasty was without significant effect on the ankle systolic pressure index both in patients with claudication and those with rest pain.


Doppler ultrasound in the functional assessment of extended deep femoral angioplasty.

Twelve patients who have had an extended deep femoral angioplasty (EFDA) for severe lower limb ischaemia have been assessed. The patients underwent a standard exercise ankle pressure test before operation and 6 months after operation. The test included the measurement of resting brachial and ankle pressures, walking distance on a treadmill and the post-exercise pressure response. A limb ischaemic score was derived from these measurements; 8 patients showed an improved score, 3 patients exhibited no change and 1 was worse. The mean improvement in walking distance of the successful cases was 182 per cent (s.d. 96 per cent). There were no amputation during the period of study.


The efficacy of graduated compression stockings in the prevention of deep vein thrombosis.

The incidence of deep venous thrombosis (DVT) was studied by the 125I-fibrinogen technique in 70 patients who had had major abdominal operations and who were wearing graduated static compression stockings on one leg, the patient's other leg being used as a control. In the whole group 7 patients developed bilateral DVT, 19 patients developed unilateral DVT in the control leg and only one patient developed unilateral DVT in the stockinged leg. The difference between stockinged and control legs was highly significant (P = 0-0003). In the 19 patients with malignant disease the incidence of DVT in the stockinged leg remained significantly less (P = 0-037). It is concluded that graduated static compression stockings do reduce the incidence of postoperative deep venous thrombosis.


Resection of the manubrium.

Direct exposure of the superior mediastinum is essential when resecting subglottic tumours of the larynx, neoplasms of the cervical trachea or cervical oesophagus. This facilitates low resection of the trachea and clearance of the paratracheal nodes. This may best be carried out by removal of most of the manubrium sterni and both sternoclavicular joints and this operation has been performed in 22 patients with minimal morbidity or long term disability.


Cefoxitin: a hospital study.

Cefoxitin is a new cephamycin antibiotic that has recently become available for clinical trial. We report here the results of an uncontrolled trial of cefoxitin treatment in 31 hospital patients with various acute infections, 20 of whom were cured. Serum, urine, and bile concentrations of cefoxitin greatly exceeded the minimum inhibitory concentration (MIC) required for clinically important Gram-negative organisms. We conclude that cefoxitin will have a place in the management of serious infections, particularly in the abdominal cavity and renal tracts.


Self-poisoning with barbiturates in England and Wales during 1959-74.

Hospital admissions due to acute barbiturate poisoning per million population in England and Wales have decreased since 1965 at about the same rate as NHS prescriptions for barbiturates. Admissions due to poisoning with other drugs have increased, but, largely because the benzodiazepine hypnotics and tranquillisers are much less toxic than the barbiturates that they are replacing, deaths from poisoning with all solids and liquids have decreased. The risk of death from self-poisoning associated with each barbiturate prescription has increased two and a half times since 1961, perhaps partly because greater quantities of barbiturate are being dispensed with each prescription and partly because patients for whom these drugs are still being prescribed would, in the event of an overdose, be unlikely to be found and admitted to hospital in time owing to their age and social circumstances. There is now little to justify prescribing barbiturate hypnotics or sedatives for anyone.


DNA synthesis by jejunal mucosa in responsive and non-responsive coeliac disease.

DNA synthesis by jejunal biopsy specimen from patients with coeliac disease and from controls was measured by an organ culture technique. The rate of synthesis in the mucosa of patients with untreated coeliac disease was almost eight times that in normal mucosa. Patients whose jejunal mucosa remained flat despite prolonged gluten withdrawal showed a rate of DNA synthesis significantly lower than that of the untreated patients, while those whose jejunal mucosa had responded to gluten withdrawal showed a rate similar to that of normal subjects. Impaired enterocyte production in nonresponsive coeliac disease may be responsible for the failure to regenerate villi after gluten withdrawal.


Biracial study of arterial pressures in the first and second decades of life.

The blood pressures of young Black and White American schoolchildren were measured and compared with those of Nigerian children of similar ages. Both diastolic and systolic pressures were consistently higher in the Nigerian children than in the Americans, both Black and White. The White children had the lowest pressures at each age. The mean weights and heights at each age were not significantly different in the three groups. Although the blood pressure of African children was higher than that of Black Americans, mean adult pressures are known to be similar in both groups. This suggests that the difference in childhood pressures must be due more to environmental factors than to genetic ones.


Paget's disease of bone in 14 British towns.

The radiological prevalence of Paget's disease was studied in 14 towns. Routine radiographs showed that the disease was present in 5.4% of people aged 55 years and over. The disease was more prevalent in men than in women at all ages, and the prevalence increased with age. The three Lancashire towns studied (Preston, Bolton, and Blackburn) had higher rates than elsewhere. This probably reflects a real geographical variation in the prevalence of Paget's disease in England and Wales.


Changes in breast sensitivity at puberty, during the menstrual cycle, and at parturition.

Sensitivity to pain and touch was measured in the nipple, areola, and cutaneous breast tissue of prepubertal boys and girls, postpubertal men and nuliparous women before and after delivery. Before puberty there were no differences between the sexes, but after puberty the tactile sensitivity of all areas of the women's breast was significantly greater than the men's. Tactil sensitivity of all areas also varied during the menstrual cycle, with maximal sensitivity at midcycle and at menstruation; the mid-cycle peak was absent when the women were taking oral contraceptives. But the most dramatic changes occured within 24 hours of parturition, when there was a great increase in breast sensitivity. This may be the key event for activating the suckling-induced discharge of oxytocin and prolactin and inhibiting ovulation during lactation.


Undescribed toxin in pseudomembranous colitis.

A girl aged 12 developed pseudomembranous colitis after a short course of oral penicillin. She had no history of adverse reaction to penicillin before or after the illness. No pathogenic bacteria, mycoplasmas, or viruses were found in her faeces, but they did contain a toxin. Toxin was also found in four of five other patients with pseudomembranous colitis but not in six specimens obtained from patients with diarrhoea caused by other disorders. Further studies may show that pseudomembranous colitis is caused by a bacterial toxin.


Recurrent laryngeal nerve paralysis in patients receiving vincristine and vinblastine.

Three patients receiving vincristine or binblastine developed recurrent laryngeal nerve paralysis, which resolved when the drug was withdrawn. The presence of mediastinal lymphadenopathy in patients with lymphoma may obscure the correct diagnosis, with the danger that the condition will produce respiratory distress if vinca alkaloid treatment is continued.


Control of blood glucose during labour in diabetic women with combined glucose and low-dose insulin infusion.

During 15 labours in diabetic women blood glucose concentrations were controlled with simultaneous infusion of insulin and glucose. The mean insulin infusion rate was between 1 and 2 U/h. No infant showed evidence of neonatal hypoglycaemia. The procedure is simple to use and may be carried out in any labour ward.


Comparative study of alkaline phosphatase isoenzymes, bone histology, and skeletal radiography in dialysis bone disease.

Liver, intestinal, and bone alkaline phosphatase isoenzymes were measured using heat stability and L-phenylalanine inhibition techniques in 78 patients on intermittent haemodialysis. Fifty-five patients had abnormalities in one or more of the isoenzymes. Changes in bone and intestinal alkaline phosphatase activities seemed to be related and raised liver isoenzyme activity was associated with the development of liver disease. Abnormal histological and radiological findings were better correlated with bone alkaline phosphatase levels than with total alkaline phosphatase, and serial estimations of bone isoenzyme activity were useful in assessing the response of renal osteodystrophy to treatment with a vitamin D analogue. Serum alkaline phosphatase isoenzyme measurement provides another useful and non-invasive index for monitoring metabolic bone disease in patients with chronic renal failure.


25-Hydroxycholecalciferol absorption in steatorrhoea and postgastrectomy osteomalacia.

Post-absorption levels of 25-hydroxy vitamin D (25-OHD) after oral administration of 25-hydroxycholecalciferol (25-OHD3) were measured in 11 subjects. Five had presented with steatorrhoea of various causes while six had post-gastrectomy osteomalacia. Post-absorption levels of 25-OHD were low in four of the patients with steatorrhoea but normal in five of those with post-gastrectomy osteomalacia. There was a significant inverse correlation between peak post-absorption 25-OHD levels and faecal fat excretion. All patients with active post-gastrectomy osteomalacia had subnormal baseline plasma 25-OHD levels, which indicates that the condition is due to a deficiency of vitamin D. Only two of the patients with osteomalacia had estimated dietary vitamin D intakes ofer 1-75 microng/day. These findings suggest that an oral 25-OHD absorption test may be a valuable measure of small intestinal function and that poor dietary vitamin D intake rather than impaired absorption of the vitamin may be the major cause of post-gastrectomy osteomalacia.


Premature baby statistics.

For 27 years annual figures have been kept of all infants weighing 2500 g or less born in the maternity department of the Northern General Hospital, Sheffield. The initial neonatal mortality rate (death within the first four weeks after birth) was then around 30% and is now 10%. This reduction is partly due to a decreased mortality rate among the individual weight groups but also to an increasing number of larger infants and a decreasing number of infants of low birth weight in the "high-risk" category.


Evoked potentials, saccadic velocities, and computerized tomography in diagnosis of multiple sclerosis.

One hundred and two patients with suspected or established multiple sclerosis (MS) were investigated by one or more of the following techniques: measurement of visual evoked potentials (VEP); measurement of cervical and cortical somatosensory evoked potentials (SEP); measurement of horizontal saccadic eye movement velocities (SV); and computerised axial tomography of the cranium and orbits (CT). Each of the techniques was valuable in detecting abnormalities, some of which were subclinical, in many patients. More abnormalities were found in patients studied by more than one technique, the most being detected in patients who were studied by all five techniques. We conclude that the techniques have a complementary role in investigating suspected MS.


Immunoreactive beta-melanocyte-stimulating hormone in cerebrospinal fluid and plasma in hypopituitarism: evidence for an extrapituitary origin.

Immunoreactive beta-melanocyte-stimulating hormone (beta-MSH) was measured in the plasma of 19 patients with hypopituitarism and in the cerebrospinal fluid (CSF) of five of these patients. In neither plasma nor CSF were the beta-MSH concentrations significantly different from those in normal controls. These observations raise the possibility that beta-MSH may be produced by and secreted from neural tissue; this is supported by the findings of beta-MSH in high concentrations in many parts of the brain.


Is cowpox misnamed? A review of 10 human cases.

Twelve separate outbreaks of confirmed cowpox, 10 involving humans, were reviewed. Six of the patients, including three children, had severe infections and five were admitted to hospital. In three outbreaks both people and cows were affected but it was not known how the infections entered the herds. In seven outbreaks no direct contact with cattle was established and clinical and serological examination failed to show evidence of cowpox in the bovine population. Comparison of these data with information about infections known to be enzootic in cattle leads to the suggestion that cows are not the natural reservoir of cowpox. This should be remembered when diagnosis is considered. The role of small wild animals as hosts and vectors of "cowpox" should be investigated.


Casualty departments and the monitoring of drug dependence.

In a month-long prospective survey of patients attending London casualty departments with drug-related problems, 395 drug-dependent patients were identified. A check against the official Home Office index of notified addicts showed that 226 (57%) were not known to the Home Office. Of 92 patients who used narcotics only 53% were known with certainty to the Home Office, and when the source of notification was checked it became clear that in at least 77% of incidents involving narcotic addicts in casualty departments the addict was not reported. Repeated research in casualty departments could play a valuable role in monitoring drug dependence and might provide information supplementary to that obtained from the specialised drug treatment clinics and other sources of notification.


Antipyrine, paracetamol, and lignocaine elimination in chronic liver disease.

The plasma half lives of antipyrine, paracetamol, and lignocaine given by mouth were measured in 23 patients with stable chronic liver diseases of varying severity. Fifteen patients received all three drugs and 19 at least two. The half life of paracetamol was abnormally prolonged in nine out of 17 patients (mean 2-9 hours, normal 2-0 hours), of antipyrine in 10 out of 19 patients (mean 30-4 hours, normal 12-0 hours), and of lignocaine in 19 out of 21 patients (mean 6-6 hours, normal 1-4 hours). Prolongation of the half lives of all three drugs was significantly correlated with an increase of the vitamin-K1-corrected prothrombin time ratio and a reduction in serum albumin concentration. There was no correlation with serum bilirubin concentration or serum alanine aminotransferase activity. This suggests that impaired drug elimination was related to depressed hepatic protein synthesis. Considerable prolongation of the half life of one drug was invariably associated with delayed elimination of the others. The half life of lignocaine, however, was always the most prolonged and was a highly sensitive indicator of hepatic dysfunction. The pharmacokinetic characteristics of a drug as well as the severity of liver disease should be taken into account when considering drug dosage in patients with chronic liver disease.


Vaccination scar with soft-tissue atrophy restored by local insulin treatment.

A woman who had a deep scar on her left arm as a result of an influenza vaccination was treated with insulin. Monocomponent porcine insulin was injected into each quadrant of the pit. After 82 days' treatment her arm appeared normal and has remained so over seven months. Using insulin's ability to promote fat and protein synthesis is a simple and effective way of treating atrophied scars.


Sclerosing peritonitis due to practolol.

Six patients developed intestinal obstruction from sclerosing peritonitis due to practolol. Complete surgical removal of the abnormal membrane appears to be necessary.


Delivery of postgraduate medical education--who pays?

As the cost of academic postgraduate medical education increases the DHSS may sometimes need to fund established academic posts or sessions within universities, and it must recognise the need for salaried sessional commitments by clinical tutors and encourage universities to integrate them more effectively into regional medical schools. Such activities will otherwise increasingly impose on undergraduate departments teaching demands that are neither practicable nor proper.


Mortality among doctors in different occupations.

A total of 20540 male doctors who replied to a questionnaire on their smoking habits that was sent to them on 1 November 1951, and who were aged 35 years and over, were classified according to their occupation as listed in the Medical Directory for 1952 and followed up until 1 November 1971. Examination of the mortality rates in 11 occupational groups showed gross heterogeneity for smoking-related diseases but not for all other diseases grouped together. On average, general practitioners smoked 37% more cigarettes than did hospital physicians and surgeons and the overall death rates among general practitioners were about 23% higher than among physicians and surgeons of similar ages. This excess death rate was chiefly accounted for by a 38% excess mortality from smoking-related diseases such as lung cancer, chronic bronchitis, and ischaemic and pulmonary heart disease. The few other statistically significant associations between occupation and disease were thought to be due either to chance or to the effect of the disease on the choice of specialty.


Current management of hypertension in hospital.

A study of the notes of 1784 patients new to two London hospitals found a blood-pressure recording in 1027 (58%). Only 423 (32%) of all outpatients had had a blood-pressure recording on their first visit. Of 144 patients with hypertension (systolic greater than or equal to 160 mm Hg or diastolic greater than or equal 100 mm Hg or both) a check recording was made in 89 (62%) and 18 (12%) were put on treatment. We conclude that the opportunity that a hospital visit provides for blood-pressure screening is being incompletely used, and that the discovery of hypertension often does not lead to further action.


Current management of hypertension in general practice.

An examination of the notes of 697 patients in a random sample of seven general practices in one part of inner London showed that 164 (24%) of 669 had had a blood-pressure recording in a five-year period. Proportions varied between 4% and 36% in the different practices. The blood pressure was raised (systolic greater than or equal to 160 mm Hg or diastolic greater than or equal to 100 mm Hg or both) in 74 patients (45%) whose blood pressure had been recorded, and another recording had subsequently been made in 45 (61%) of these patients. Fifteen (21%) of those with hypertension had not had a blood-pressure recording during the five years before the study. Tranquillisers or sedatives were the commonest drugs used in the treatment of hypertension. As in a study of the management of hypertension in hospital, opportunities provided by visits to the general practitioner were not commonly used for blood-pressure screening, and the discovery of hypertension often did not lead to further action.


Diabetic cardiomyopathy: the preclinical phase.

Left ventricular function was assessed by measuring sytolic time intervals in insulin-requiring diabetics with and without significant microangiopathy. The results were compared with those in normal controls. Significant microangiopathy was defined as proteinuria over 3 g/24 h or proliferative retinopathy. Left ventricular function was also assessed one and a half years later by echocardiography in four patients with microangiopathy. Patients with angina, previous myocardial infarction, hypertension, and alcoholism were excluded. All had normal electrocardiograms and chest radiographs. Diabetics with microangiopathy had impaired left ventricular function, whereas those with uncomplicated diabetes had normal function. This finding supports the existence of a specific diabetic cardiomyopathy due to microangiopathy rather than the metabolic defect. The association of microangiopathy and impaired left ventricular function may explain the high immediate mortality and the high incidence of cardiogenic shock and congestive heart failure after myocardial infarction in diabetics.


Psychologically mediated abdominal pain in surgical and medical outpatients clinics.

Ninety-six patients complaining of recurrent or persistent abdominal pain were referred consecutively to a surgical clinic and a medical clinic, respectively. They were examined psychiatrically after their initial physical investigation. The psychiatric examination included rating scales for depression and anxiety, a personality inventory, life-events schedule, scale of verbal expressivity, and family and personal patterns of pain and invalidism. Only 15 patients (15-6%) had organic disorders that could be responsible for their symptoms. In the remainder, psychiatric factors were considered primarily responsible for their abdominal pain: 31 were depressed; 21 had chronic tension; in 17 hysterical mechanisms were prominent; and 12 were found to be unrecognised alcoholics. Follow-up at three and six months and recognition by 80% of the psychogenic group that a psychological explanation was plausible, confirmed the diagnoses, and over half responded favourably to psychiatric management. Features distinguishing the organic and psychogenic groups were delineated. Psychiatric assessment has a place among the investigations of non-acute abdominal pain; certainly it should not be condisered simply as "a last resort."


Cardiac arrhythmias that masquerade as epilepsy.

Over six months 10 patients, representing 20% of those referred to a neurological department with possible idiopathic epilepsy, were subsequently considered to have cardiac arrhythmias that caused or significantly contributed to their symptoms. In some cases relevant arrhythmias were shown only after prolonged electrocardiographic monitoring. Although several theoretical and practical factors need to be assessed when considering the cardiac basis for cerebral disturbances, unsuspected cardiac arrhythmias may underlie "epilepsy" in many patients.


Uses of barium meal examination in dyspeptic patients under 50.

No abnormality was found in 76 of 100 dyspeptic out-patients under the age of 50 who underwent barium meal examination, while various non-malignant lesions were found in the remaining 24. Only 10% of those under 30, and 10% of those with symptoms for less than a year proved to have any abnormality. Because of the radiographic results treatment was altered in only 11 patients, and most of these changes were small.


Recovery patterns and prognosis in aphasia.

Ninety-three aphasics were studied with repeated language assessment by a scorable test (the Western Aphasia Battery). Recovery rates were determined by measuring language performance (Aphasia Quotient) at nought to forty-five days post-onset, and three, six and twelve months and yearly after. Recovery rates were higher in post-traumatic than in cerebrovascular cases. When the stable infarcts were separately studied, the greatest recovery was seen in "Broca's" aphasics, followed by the "conduction" group. Anomic aphasia appeared to be a common end-stage of evolution. Long-term follow-up (twelve months or more) demonstrated that global aphasics have a poor prognosis, while Broca's and Wernicke's have an intermediate one. Complete recovery occurred frequently among anomic, conduction and transcortical aphasics and in more than half of the traumatic cases. Initial severity and outcome correlated significantly. Age and rate of initial recovery showed a trend of negative correlation; younger patients recovered better, but there were frequent exceptions, depending on other factors, such as the initial severity of aphasia. Although some cases recovered exceptionally well while under therapy, there was no significant difference between the treated and untreated groups, where such a comparison was possible.


Perceptual, semantic and phonetic aspects of elementary language processes in split-brain patients.

Patients with total forebrain commissurotomy were examined on three tests of elementary linguistic ability. We found that the right hemisphere was dominant for the visual recognition of words when no semantic or phonetic decoding was required. The left hemisphere assumed control of behaviour when written words had to be matched semantically to pictures, though the right hemisphere was also competent at this task. On a test of rhyming, the left hemisphere was not only dominant, but was vastly superior to the right which displayed little, if any, ability. We suggest that the two hemispheres are basically differentiated with respect to their generative, constructive capacities in language, as in other functions of intelligence.


The comparison of small-size rectangle and checkerboard stimulation for the evaluation of delayed visual evoked responses in patients suspected of multiple sclerosis.

The use of foveal small-size rectangle stimulation to elicit visual evoked responses was compared with VERs elicited by the standard checkerboard pattern. Foveal stimulation achieved a significantly better discrimination of optic nerve lesions in the early diagnosis of multiple sclerosis. Sources of misdiagnosis due to different neurological disorders are discussed.


The effect of posterior column lesions on servo responses from the human long thumb flexor.

Lesions of the posterior column pathways, in which muscle spindle afferents run towards the brain, are associated with loss of servo responses in the long flexor of the thumb, in the absence of motor weakness and with tendon jerks preserved. This evidence is consistent with the hypothesis that the long-latency stretch reflex (on which servo responses are based) uses a supraspinal, possibly a transcortical, reflex arc.


Abnormalities of the auditory evoked potentials in patients with multiple sclerosis.

Fifteen components of the auditory evoked potential can be recorded within 300 ms of a click stimulus and these can be classified by latency in early (0-8 ms), middle (8-60 ms) and late (greater than 60 ms) components. Follwing a click stimulus of high intensity these components have been studied in 45 normal subjects and in 88 patients with definite multiple sclerosis. Component V, thought to arise from brain-stem structures, was the most consistently abnormal in patients and there was a correlation between the abnormalities and clinical evidence of a brain-stem lesion. Thus in 79 per cent of patients with definite evidence of a brain-stem lesion and in 51 per cent of those without clinical signs related to the brain-stem, component V was abnormal. Abnormalities were also detected for components Pa, Nb and P1 of the middle components, and in 12 per cent of these the early components were normal. The late components were normal in all but 3 patients. Evidence is presented to show that pairs of click stimuli, 5 ms apart, presented at a fast stimulus rate, stress the auditory system in normal subjects. Using this technique abnormalities of component V in patients became more marked and the proportion of abnormalities detected was increased. The contribution of the reflex muscle responses to the click to the middle components of the auditory evoked potential has also been studied. It is concluded that components Pa, Nb and P1 are independent of these reflexes.


Peroneal muscular atrophy (PMA) and related disorders. II. Histological findings in sural nerves.

Biopsy of the sural nerves distinguished two groups of patients with peroneal muscular atrophy (Charcot-Marie-Tooth): a hypertrophic type and a neuronal type. In patients with the hypertrophic type (10 nerves), 30-100 per cent of teased fibres of the sural nerve had demyelinated segments, numerous onion-bulb formations and often an increase in endoneurial space. Large and small fibres, with a diameter of more than 7 micron and less than 5 micron were diminished in number. Regeneration was scarce. There were more fibres with 60-120 myelin lamellae than in normal nerve, suggesting an atrophy of the axon. Biopsy of 19 sural nerves of patients with the neuronal type of PMA showed loss of large fibres (more than 7 micron in diameter). The number of small fibres was normal, presumably due to regeneration, since there were many "clusters" of small myelinated fibres. Fibres with demyelinated segments and onion-bulb formations were absent or rare and the endoneurial space was normal or slightly increased. Neither in the hypertrophic nor in the neuronal type did fibre loss occur selectively among the very largest fibres. Nine nerves from patients with hereditary spastic paraplegia and from a family with tremor and spasticity in addition to PMA showed changes similar in type but often milder in degree than nerves of the neuronal type of PMA. The number of unmyelinated fibres was normal in 12 of 21 nerves from patients with PMA; it was increased in 5 and diminished in 3 nerves.


Cognition and commissurotomy.

Cognitive functioning was extensively evaluated in a recent callosum-sectioned patient. A number of standardized and specialized experimental memory tests, as well as a sophisticated hypothesis testing task, were administered both before and after operation. No post-operative deficits were obtained. In fact, this patient showed marked improvement on almost every measure utilized. These results demonstrate that the cognitive processing of complex information is not necessarily dependent on the integrity of the corpus callosum, but rather suggest that cognitive functioning is largely an intrahemispheric process.


Effect of post-impulse depression on background firing of sympathetic preganglionic neurons.

(1) Many of the preganglionic neurons responsible for sympathetic tone in the cat exhibit a characteristic irregular background spike activity with a low repetition rate. The properties of this activity, described by the interspike interval histogram, can be explained as the result of the responses of the neurons to random synaptic imputs. (2) Serial interspike interval correlation was used to show that additive post-impulse depression in preganglionic neurons does not enter into the timing of typical low-rate, irregular background firing. However, if cells are accelerated by anitdromic tetanization, a depressive recovery process accumulates to cause a prolonged silent period after driving of the cells has ceased. If cells are accelerated, by the action of their synaptic inputs, to rates higher than their usual basal rates, serial post-impulse depressions overlap, and summate to cause a temporal interaction between neighboring pulses which is observable by serial interval correlation. (3) By observing the effect of antidromic responses occurring at various intervals after a background spike, we showed that the time course of the summative part of post-impulse depression is shorter than the interspike intervals typically encountered in background firing. (4) At higher-than-basal levels of sympathetic activity, occurring spontaneously or during antidromic stimulation, successive post-impulse recovery periods overlap and sum to impart a negative correlation of serial interspike intervals. At the levels of sympathetic activity existing in waking animals, the damping effect of cumulative post-impulse depression is probably an important factor in stabilizing sympathetic tone.


Effect of insulin hypoglycemia upon cerebral energy metabolism and EEG activity in the rat.

Anesthetized ventilated rats were subjected to insulin-induced hypoglycemia (50 units/kg i.v.) while EEG, ECG, mean arterial pressure, blood gases, arterial pH and rectal temperature were controlled. Animals were sacrificed by rapid transcalvarial freezing of the brain in situ. Glucose, pyruvate and lactate were measured in blood, CSF and cortical tissue, in which additionally glycogen, phosphocreatine, ATP, ADP, AMP, aketoglutarate (aKG), glutamate, oxalacetate, aspartate, ammonia and water content were estimated. ATP/ADP ratio, energy charge (ECh) energy reserve, NADH/NAD+ quotient and intracellular pH were calculated. ECh does not correlate with either dysfunction of carbohydrate depletion, but declines in a threshold fashion when tissue glucose has fallen by over 97% and glycogen by over 60%. The EEG correlates with the degree and duration of carbohydrate depletion in cortical tissue. An isoelectric EEG occurs pari passu with the fall of the ECh. Increase in ammonia and decrease in aKG and Glut are supportive evidence of intrinsic substrate. Lactate decrease during hypoglymecia is not reversed by super-imposed hyqoxia.


Microwave alteration of the blood-brain barrier system of rats.

Rats were exposed to 1.3 gHz microwave energy to assess the uptake of several neutral polar substances in certain areas of the brain. A quantitative, radioactive isotope method, which uses an internal standard, was employed to measure the loss of test substances to brain tissue. Single, 20 min exposure, to either pulsed or continuous wave (CW) microwave energy induced an increase in the uptake of D-mannitol at average power densities of less than 3.0 mW/sp. cm. The permeability change was greatest in the medulla, followed, in decreasing order, by the cerebellum and hypothalamus, with small or negligible changes in the hippocampus and cortex. Permeability increases were observed for mannitol and inulin but not for dextran. Increased permeability was observed both immediately and 4 h after exposure, but not 24 h after exposure. After an initial rise, the permeability of cerebral vessels to saccharides decreased with increasing microwave power. Differences in the level of uptake occurred between CW energy and pulsed energy of the same average power. Microwaves of the same average power but different pulse characteristics also produced different uptake levels. Our findings suggest that microwaves induce a temporary change in the permeability for small molecular weight saccharides in the blood-brain barrier system of rats.


Impairment of DNA synthesis in Gunn rat cerebellum.

Brain DNA synthesis was developmentally investigated in Gunn rat with marked cerebellar hypoplasia due to hereditary hyperbilirubinemia. In this mutant rat, the Purkinje cell was nearly selectively affected in the cerebellar cortex by bilirubin. The impaired DNA synthesis was observed in homozygous (jj) Gunn rat cerebellum, in which the DNA content and [3H]thymidine incorporation rate into DNA decreased after 10 days of age compared to those in the heterozygous (Jj)littermate. In contrast, these impairments were not found in the non-cerebellar parts of the brain and liver of jj Gunn rat. The activity of cerebellar thymidine kinase in jj Gunn rat decreased from a very early stae, being 80% of Jj rat at 6 days, and 50% at 10 days of age. The enzyme activity was not affected in the non-cerebellar parts of the brain. Although bilirubin competitively inhibited cerebellar thymidine kinase activity in vitro (15% at 10(-5) M), such bilirubin level was found to be about 1000-fold that in vivo. Moreover, photo-degradation of bilirubin in jj cerebellum exhibited no improvement in thymidine kinase activity, and the presence of an enzyme inactivator was not suggested in jj cerebellum. These results seem to indicate that the induction of thymidine kinase might be affected in jj Gunn rat cerebellum. The possibility that the impaired DNA synthesis in the external granular cells in jj cerebellum may be due to Purkinje cell damage is discussed.


Subcellular distribution of radioimmunoassayable somatostatin in rat brain.

A specific, sensitive and reproducible radioimmunoassay is described for measurement of somatostatin in brain tissue. The sensitivity of the assay is 10 pg/tube and recovery of synthetic somatostatin added to brain homogenates was 95.8 +/- 6.2%. Dilution of tissue extracts from various brain regions showed parallelism in standard curves with labelled somatostatin. Somatostatin is shown to be widespread in the central nervous system with highest concentrations in hypothalamus, particularly the median eminence. Subcellular preparations of medial basal hypothalamus, preoptic area and amygdala indicate that over 70% of somatostatin immunoreactivity is localized to the synaptosome fraction. Recovery of activity in  the P2 pellet prior to separation on sucrose gradient is approximately 100%. It is hypothesized that somatostatin, in addition to being released into blood vessels of the median eminence, may also be liberated from nerve terminals in other brain regions.


Olfactory and vomeronasal deafferentation of male hamsters: histological and behavioral analyses.

Deafferentation of the vomeronasal system by cutting the vomeronasal nerves severely impaired mating behavior in 44% of male hamsters over a 1--2 month period of postoperative testing, but the remaining males mated normally after the surgery. Damage to the main olfactory bulbs, concomitant to vomeronasal nerve cuts, did not account for this behavioral difference. Subsequent deafferentation of olfactory system by intranasal infusion of zinc sulfate solution (5 g ZnSO4--7H2O in 95 ml 0.5% NaCl) had no effect on intromission or ejaculation latencies of sham vomeronasal cut males but eliminated mating behavior 2 days after treatment in males with bilateral vomeronasal nerve cuts. Some of these males recovered the behavior in 1--3 weeks of post zinc sulfate testing. Histological analyses of the olfactory mucosa in 7 males on day 2 after zinc sulfate showed that 89--97% of the mucosa had been destroyed in 6 out of 7 of the males and 78% in the seventh. We conclude that destruction of the vomeronasal system irreparably reduces arousal necessary for mating in some hamsters but in other males sufficient arousal for this behavior to occur is mediated through the olfactory system, presumably in conjunction with other sensory inputs. Subsequent removal of the olfactory input in these animals eliminates the behavior.


Rat hippocampal neurons in dispersed cell culture.

An in vitro system has been developed for the study of isolated hippocampal neurons from 18- or 19-day rat fetuses. Following trypsinization the cells are plated out at low density on polylysine-treated coverslips in an enriched medium. The isolated neurons rapidly attach to the substrate and initiate process extension. Little reaggregation occurs and the number of non-neuronal cells present is minimal. Unless co-cultured with tissue explants the neurons survive for only a few days; in the presence of hippocampal explants the initial growth of the isolated cells is improved and their survival in culture is extended to about two weeks. Some of the cells in such cultures develop a characteristic branching pattern closely resembling that of maturing hippocampal pyramidal cells in vivo. There is a clear relationship between the stage of the cells' development and their growth in culture. Cells which had completed DNA synthesis about 48 h before dissociation, and which were in the process of migration to the cortical plate, survived best in our cultures. Early post-mitotic cells which were still within the ventricular zone and cells which had already reached the cortical plate grew poorly. This system should permit the study not only of process formation by these cells, but also of their capacity to form specific synapses in vitro and of the biochemical constituents of their surfaces.


Unit activity of amygdala and hippocampal neurons: effects of morphine and benzodiazepines.

The effects of morphine sulfate and two benzodiazepine derivatives, chlordiazepoxide HCl and diazepam, were evaluated upon single unit activity of the amygdaloid nuclear complex and hippocampal formation in immobilized cats. All surgical procedures were performed under halothane anesthesia and all wound margins were infiltrated with Lidocaine after halothane withdrawal. Single unit activity was recorded extracellularly with platinum-iridium microelectrodes. Chlordiazepoxide HCl, 10.0-20.0 mg/kg i.v., or diazepam, 0.05-0.20 mg/kg i.v., suppressed spontaneous firing rates of the amygdala and the hippocampal neurons. In contrast, the spontaneous firing rates of neurons in these limbic structures were augmented by morphine sulfate, 0.50-2.00 mg/kg i.v. The morphine-induced augmentation of hippocampal neuronal activity was effectively antagonized by naloxone, 0.10-0.20 mg/kg i.v. However, naloxone, 0.20-0.40 mg/kg i.v., only partially suppressed the morphine induced augmentation of amygdala neuronal activity. In a dose-dependent fashion, chlordiazepoxide and diazepam administration prevented or antagonized morphine-induced augmentation of amygdala and hippocampal neuronal activity. Our results suggest that, in the cat, the amygdala and hippocampus may play an important role for morphine-induced behavioral responses. Moreover, our data imply that these two limbic structures may be the sites of tranquillizing actions of diazepam and chlordiazepoxide.


Nucleus raphe magnus inhibition of spinal cord dorsal horn neurons.

In decerebrate cats, electrical stimulation of nucleus raphe magnus (NRM) of the medulla produced marked inhibition of spinal neurons in lumbosacral dorsal horn. Only neurons with high threshold inputs were inhibited. These cells were located in lamina I and in or near laminae V and VI. The duration of inhibition produced was related to the stimulus train length. An ipsilateral lesion of the dorsolateral funiculus at L1 markedly reduced the inhibition of neurons caudal to the lesion. Although NRM stimulation was the most effective, inhibition from more lateral sites could be obtained at higher stimulus intensities. NRM induced inhibition is probably mediated by a direct projection via the dorsolateral funiculus to spinal dorsal horn laminae I, II, V and VI. The results are discussed in relation to proposed mechanisms underlying the analgesia produced by NRM stimulation.


Specificity of adhesion between cloned neural cell lines.

We have investigated the phenomenon of intercellular adhesion using cloned cell lines derived from the rat central nervous system. Adhesion is assayed by measuring the rate at which a suspension of labeled (probe) cells of one type adheres to monolayers of other cell types. In general a given probe cell such as the nerve line B50 will adhere rapidly to most other cell lines, providing little information about the specificity of the interactions. However, we discovered several methods of pretreating the B50 cells which specifically alter their rate of adhesion to various types of monolayers. Treating the B50 cells with trypsin, coating them with an antinerve antiserum, or simply lowering the assay temperature from 20 degrees C to 0 degrees C were 3 separate procedures which resulted in slower rates of adhesion of the B50 probe cells to 3 distinct subclasses of monolayers. These data suggest that different mechanisms are involved in the adhesion of B50 cells to the various other cell lines. To account for the differences, we postulate the existence of pairs of interlocking or complementary surface components on the cell lines, a concept that has also been valuable in understanding interactions in other systems. We discuss the characterization of these proposed components and outline their usefulness in categorizing the cell lines.