Dichotic listening in psychotic patients. Patients recently recovered from schizophrenic or manid-depressive psychoses showed larger ear difference scores than normal controls on a dichotic listening test, i.e. when asked to identify dissimilar words fed synchronously to the two ears. The possible significance of the finding is discussed, in relation both to hemispheric organization and to other aspects of cognitive activity which may underlie performance on the task.


Immunoglobulins and viral antibodies in psychiatric patients. The serum and CSF of 66 patients with functional psychoses were tested for immunoglobulins and antibodies to measles, HSV-I, CMV, and rubella viruses. Ten surgical and 80 neurological patients were controls. There were no significant findings in the serum, consistent with most previous studied. In the CSF 6 of 17 multiple admission schizophrenic patients had definite elevations of IgG or measles antibody and differed significantly from the surgical controls. Immunologically this group resembled the seriously ill neurological patients. No previous study has been made of immunoglobulins or viral antibodies in the CSF of psychiatric patients. It is concluded that further work is warranted in a search for biological subgroups of schizophrenia.


A controlled evaluation of the therapeutic effectiveness of a psychiatric day centre for pre-school children. The progress over one year of 25 children aged 2 1/2 to 3 1/2 years attending a psychiatric day centre was compared with that of 25 similarly disturbed 3-year-old children identified in a total population study. There were few differences in outcome, and thost that were found did not particularly favour either group. Implications for the organization of treatment servides are discussed in terms of the need to lay down clear objectives and to pursue systematic controlled evaluation.


Familial nature of reading disability.

Familial nature of reading disability. An extensive psychometric test battery was administered to 125 children with a reading disability, to their parents and siblings, and to members of 125 matched control familes (N = 1,044). In addition to expected differences in spelling and reading, probands obtained significantly (P less than or equal to .01) lower scores than controls on tests of other cognitive abilities. Manifold deficits were also found in siblings and parents of probands, conclusively demonstrating the familial (genetic and/or common-family environmental) nature of the disorder.


The contingent negative variation in antisocial behaviour: a pilot study of Broadmoor patients. Using a classical click/flash paradigm, the CNV was recorded from the following three groups of subjects at Broadmoor Hospital: (1) 14 'psychopathic' patients selected by use of the 4/9 MMPI profile and confirmed by independent clinical diagnosis; (2) 15 'non psychopathic' patients, all psychotic and mainly schizophrenic; (3) 14 healthy staff control subjects. All three groups were matched for age and sex; the two patients groups were also matched for length of stay. Two series of 32 paired stimuli were used, separated by an interval of 30 minutes. The mean CNV voltage was significantly lower in the 'non-psychopathic' patients. The amplitude of the 'psychopath's' CNV response did not differ significantly from that of the staff controls, but the response variability between the first and second series of trials was much greater in the 'psychopathic' patients than in the other two subject groups. The 'psychopathic' subjects tended to show more rapid initial development of the CNV.


Resting levels of alpha and the Eysenck Personality Inventory. The number of microvolt seconds of alpha rhythm emitted during a five-minute period were collected for 30 male and 30 female subjects. This measure of alpha abundance was then compared in subjects who scored high and in those who scored low on the E and N scales of the Eysenck Personality Inventory. Subjects who scored low on the E scale tended to have a significantly greater number of microvolt seconds of alpha than did subjects who scored high on the scale. No differentiation on the basis of emitted alpha was possible for subjects scoring high and low on the N scale.


Validity of the Zung Self-rating Depression Scale. The Zung Self-rating Depression Scale (ZSDS) correlated well (0.69) with the treating physician's global rating in 26 depressed out-patients during the six weeks of treatment with a tricyclic anti-depressant. In a larger sample of 41 patients, a high correlation was found between the ZSDS and the Hamilton Rating Scale. The sensitivity of the ZSDS was found to be adequate. The scale was able to differentiate, at the 0.05 level, four severity groups classified on the basis of the global rating. The importance of the direct relationship between the range of severity studied and the value of the correlation coefficient was discussed. Previous investigations and the results of this study indicate that the ZSDS is a valid and sensitive measure of clinical severity in depressed patients and support its continued use as a research instrument.


Glucose metabolism in unipolar depression. Glucose utilization, serum insulin, human growth hormone, and free fatty acids were studied in 18 unipolar depressed patients and 14 normal controls, using the intravenous glucose tolerance test. Patients were kept drug-free for at least two weeks before testing, and physical activity and diet were carefully controlled. Previously described abnormalities in the balance between glucose and free fatty acids were not seen, but endogenous depression was associated with lowered glucose utilization rate with insulin resistance. Changes in kinetics of membrane transport in endogenous depression which could account for this finding are discussed.


Teaching psychotherapy in mental hospitals. This paper deals with the early results and problems of establishing and developing a regional training programme in psychotherapy, using peripatetic senior lecturers. The difficulties of a psycho-analytic approach to psychotherapy in mental hospitals are discussed, and a model of psychotherapy more suitable for general application in mental hospitals and district general hospital psychiatric units is proposed.


An unusual case of the Capgras syndrome. A variant of the Capgras syndrome is described in a 43-year-old woman who had vitiligo and multinodular goitre. The unusual feature of the case was that the patient not only misidentified members of her own family but also claimed that she herself had been replaced by a double.


Late meningeal effects of myelographic contrast media with special reference to metrizamide. Two hundred and fifty-six myelograms in 192 patients were following by repeat myelography using a water-soluble contrast medium. The films of these re-examinations were analysed for signs of meningeal changes. Adhesive arachnoiditis had developed in five of 46 cases after methiodal sodium, in 24 of 96 cases after iothalamate meglumine, in seven of 12 cases after iocarmate meglumine, in seven of ten cases after iodophendylate, but in none of 90 cases after metrizamide. Dose of contrast medium, observation time and protein concentration of the CSF were found to be factors of importance for the development of adhesive arachnoiditis.


Osteonecrosis in Hodgkin's disease.

Osteonecrosis in Hodgkin's disease. Four patients suffering from Hodgkin's disease developed osteonecrosis following therapy and both femoral heads were involved in each case. Retrospective review of abdominal radiographs taken for follow-up lymphography demonstrated that the earliest radiological changes in bone were evident between five and 18 months after treatment was started and between six and 21 months before the onset of symptoms. The clinical implications are discussed.


Needle aspiration/biopsy of the spine in suspected disc infection. Closed needle aspiration/biopsy was performed in 19 patients with suspected spinal disc space infection. A precise diagnosis was made, from the material obtained in 13 (68%); the infecting organism was isolated in 11 and malignant tumour diagnosed histologically in two. There were no important complications. The procedure which is described in detail is simple to perform and can be carried out early in the course of a patient's stay in hospital, thereby enabling prompt treatment.


The metacarpal index in Jamaican children and adults. The metacarpal index was measured in radiographs of the hands of 615 male and 667 female Jamaicans aged over two years. The index increased with age from two years to adulthood, and was greater in females than in males, and greater in the left hand than the right hand. Means and standard deviations of the index for the left hand are presented as standards. An index of 9.6 for males and 10.1 for females over the age of 13 years is suggested as the upper limit of normal (three standard deviations above the mean). These standards are higher than those previously reported, and are probably applicable to other black populations outside Jamaica.


Tuberculous erosion of the sphenoid bone. Sphenoidal erosions due to tuberculosis are reported in four young coloured children. The lytic destruction is emphasized for refence texts indicate that tuberculosis produces a sclerotic reaction when extending to the skull base. Tuberculous osteitis of the skull occurs particularly in coloured children and adolescents. It should be considered when destructive skull lesions are seen in these patients.


Two regimes with the same TDF but differing morbidity used in the treatment of stage III carcinoma of the cervix. As an alternative to five daily fractions per week, one large fraction per week has been used to treat patients with stage III carcinoma of the cervix. This regime was greatly appreciated by our village women who could attend for weekly treatment from their homes. The weekly dose was matched with our previously acceptable daily fractionation using NSD, TDF and CRE values. In 24 patients the early reactions and tumour response were acceptable. Late rectal complications commencing seven months after treatment have, however, developed in all surviving patients with the new regime. The complications have been far more severe than those of a matched group of 24 patients treated with daily fractions and the schedule using one fraction per week has been abandoned. "Iso-effective" doses for the two techniques were selected from the NSD, TDF and CRE tables. This study clearly indicates that for one fraction per week the doses predicted are not "iso-effective" as far as the normal tissues of the pelvis are concerned.


Further experience with radiotherapy by multiple daily sessions. Since 1972 over 100 patients have been treated by frequent daily sessions of radiotherapy with a short overall time. Cobalt 60 teletherapy and 250 kV X-ray beams have been used with radical or palliative dosage. The tolerance to these regimes of the skin, breast, chest wall, neck, lung and pelvis is discussed and the tumour responses described. Radiotherapy by multiple daily sessions is clinically possible and often an advantage. Its therapeutic ratio is not inferior to comparable regimes using longer intervals.


The complication probability factor: a method for selection of radiation treatment plans. The problem of selecting the best radiation treatment plan from several that may offer subtle differences has been considered. A method is introduced in which the concept of a complication probability factor (CPF) can be used to quantify the relative merits of such treatment plans. The CPF is a variant of integral dose and consists of a weighted volume of irradiated normal tissue which may relate to radiation-related complications. Treatment plans for irradiation of a pelvic tumour volume using parallel opposed, 360 deg rotational and four-field techniques with X-ray beams of 4, 8, 22, and 45 MV have been analyzed to demonstrate the utility of the method. This analysis suggests that complex radiation delivery techniques may offer a substantial improvement in dose distribution characteristics, while higher beam energies are relatively less advantageous.


On the nature and significance of the radiation outside the beam in neutron therapy. Measurements have been made of beam profiles at 10 cm deep for the neutron beam of mean energy 7.5 MeV produced by the MRC cyclotron at Hammersmith Hospital. Neutron and gamma-ray doses in water were measured with a tissue-equivalent chamber and a Geiger-Müller counter. Far outside the beam the radiation consists mostly of gamma rays penetrating the shielding. Perfect shielding would reduce this but the profile of biologically effective dose would still be worse than that from conventional X- and gamma-ray generators owing to the high RBE of small doses of neutrons. The main hazard to the patient is probably that of carcinogenesis. An approximate assessment is made of this hazard which is compared with that estimated in previous publications.


The radiosensitizing effect of metronidazole and misonidazole (Ro-07-0582) on a human malignant melanoma grown in the athymic mutant nude mouse. The radiosensitizing effect of two electron-affinic nitroimidazoles, metronidazole and misonidazole (Ro-07-0582), has been tested on a human malignant melanoma grown subcutaneously in the athymic mutant nude mouse. A 60Co therapy unit was used for local irradiation of the mice. Metronidazole in doses of 750 mg/kg and misonidazole in doses of 500 mg/kg were administered intraperitoneally to the animals 45 min before exposure to 1250 rad. The time necessary for the tumours to regrow to their original sizes was compared with that of tumours treated with 1250, 1875 and 2500 rad without drug. The enhancement ratios were found to be 1.2-1.3 and 1.4-1.5 for metronidazole and misonidazole respectively. It is concluded that misonidazole is a more efficient hypoxic cell radiosensitizer for this human malignant melanoma than metronidazole. The former may prove to be of value in human radiotherapy.


Preparation of the patient for abdominal ultrasound scanning. The value of dietary restriction and laxatives both separately and in combination for the reduction of bowel gas has been investigated and compared with unprepared patients. No significant difference was found between the results from prepared and un-prepared patients.


Highly selective vagotomy using tantalum clips. A technique is described for performing highly selective vagotomy in cases of duodenal ulcer. Tantalum clips are used instead of conventional ligatures for securing the nerves and blood vessels that pass to the lesser curve of the stomach. With this technique the author has found the operation of highly selective vagotomy quicker and easier to perform.


Peroperative grading of pyloric stenosis: a long term clinical and radiological follow-up of patients with severe pyloric stenosis treated by highly selective vagotomy and dilatation of the stricture. Highly selective vagotomy (HSV) is now an accepted form of surgery for uncomplicated duodenal ulcer. Highly selective vagotomy and dilatation has been successfully used in some cases of pyloric stenosis, but many would regard severe pyloric stenosis as a contraindication to this procedure. Eleven patients with severe pyloric stenosis, measured objectively at operation, have been treated by HSV and dilatation of the stenosis and reviewed for periods of up to 3 years. The clinical results, immediate and long term, were good in all cases. Barium studies and histopathological findings were slower to return to normal. With intensive preoperative preparation to restore the tone of the dilated gastric muscle and gentle, controlled dilatation of the stricture, HSV in these patients should be as satisfactory as in those patients with uncomplicated duodenal ulcer.


Closure of gastrojejunostomy for the relief of post-vagotomy symptoms. When dumping, diarrhoea or bile vomiting follows vagotomy and gastrojejunostomy, simple closure of the stoma, without alternative drainage, has been performed in 19 patients. Thirteen patients, 5 with truncal, 7 with selective and 1 with proximal gastric vagotomy, have been followed up for 1-6 years. Five were completely relieved of symptoms, 7 improved and there was only 1 complete failure. Bile vomiting was more often relieved than dumping or diarrhoea. The procedure is safe and significant gastric retention does not occur provided that at least one year is allowed to elaspse after the primary operation.


The clinical significance of gallstones and their radiological investigation. The symptoms of 122 patients with gallstones were correlated with the radiological findings. No specific indigestion was present which could be termed 'flatulent dyspepsia'. Sensitivity to fatty foods occurred in 69 per cent, heartburn in 42 per cent, regurgitation of of acidtasting or bitter fluid to the mouth in 31 per cent and increased passage of flatus from the stomach upwards in 38 per cent. If the gallbladder concentrated contrast medium or an oral cholecystogram but did not contract after a fatty meal, the patients suffered less heartburn than if the gall bladder functioned normally. However, since surgeons rarely perform a cholecystectomy for flatulent dyspepsia alone, knowlege of gallbladder function may be unnecessary.


Small bowel melaena: 2 cases diagnosed by angiography. Two cases of small bowel tumour presenting with melaena are reported. Selective visceral arteriography was found to be invaluable in the management of these cases. The first case presented with intermittent bleeding causing anaemia. Conventional barium studies of the small and large bowel revealed no abnormality. Superior mesenteric angiography revealed a mass lesion in the jejunum, with features characteristic of a leiomyoma. The second case presented with massive gastrointestinal bleeding. Selective visceral angiography was performed initially and revealed a large, mainly avascular, mass lesion in the ileum. Pathological examination showed a leiomyoma which had undergone cystic degeneration. The value of selective angiography in patients with suspected small bowel bleeding is discussed..


Vascular malformations of the parotid region. Five adult patients with vascular malformations in the parotid region are described. Three of these patients had lumps in the parotid gland clinically indistinguishable from parotid tumours: one had a diffuse swelling of the check, and the fifth had a pulsatile tumour in the deep lobe of the gland. Two patients had a characteristic sign-the lump in the cheek became more obvious, both visually and on palpation, when the masseter muscle was tensed. In 3 of the patients calcified opacities, resembling phleboliths, were demonstrated on plain X-ray examination. This is only the third report of vascular malformations of the parotid region in the British literature; no other report of a pulsating tumour within the parotid gland has been found in a search of the world literature.


Transection of the trachea secondary to blunt trauma. Tracheal injuries secondary to blunt trauma are not common and complete tracheal transection is even more unusual. Because the incidence of these treatable, but often lethal, injuries is increasing, more surgeons will encounter them. A report of the treatment of a case of tracheal transection due to blunt trauma with emphasis on avoiding unnecessary tracheostomy is presented, with a review of the literature.


Non-recurrent laryngeal nerve.

Non-recurrent laryngeal nerve. Two cases of a right non-recurrent nerve were encountered in 203 thyroidectomies. In its abnormal, non-recurrent course the nerve passes transversely from under the carotid sheath and takes a position which is at right-angles to the normal recurrent laryngeal nerve.


An assessment of the accuracy of modern endoscopic diagnosis of oesophageal stricture. The results of 135 fibreoptic endoscopic examinations of oesophageal strictures carried out in a district general hospital are reported. The endoscopic diagnosis was correct in 90 per cent, uncertain in 3 per cent and incorrect in 7 per cent of these cases. This study indicates that endoscopic examination should include tissue sampling; this not only allows a precise tissue diagnosis to be made but also is shown to increase the accuracy of diagnosis. Tissue sampling should include cytological as well as histological material. Analysis of cases of stricture correctly diagnosed has shown that target biopsy and brush cytology each makes a significant contribution to diagnosis. The routine collection of cytological specimens in addition to the more commonly obtained histological specimens in addition to the more commonly obtained histological speciments is strongly advocated. The natural history of malignant oesophageal strictures in this study is reviewd. The mean survival in 58 cases was 6.9 months.


Tuberculous fistula between the 5th lumbar vertebra and the colon presenting as a left thigh abscess. An abscess of the left thigh due to a fistula between a tuberculous 5th lumbar vertebra, the sigmoid colon and the muscles and subcutaneous tissues of the left thigh is described. This appears to be a unique occurrence and was only diagnosed at post-mortem. The  treatment and diagnosis are discussed.


Cell viability studies on the exfoliated colonic cancer cell. Suspensions of desquamated colonic cancer cells were obtained from patients with cancer of the large bowel by colonic exfoliative cytology and from resected specimens of colonic cancer by an exfoliative technique. In addition, a tumor suspension was obtained from the resected specimens. Cell viability studies were performed on these cell suspensions. Whereas 23 of the 25 tumour homogenate cell suspensions were shown to exclude trypan blue, none of the exfoliated colonic cancer cell suspensions had viable cells. This finding would cast some doubt on the hypothesis that suture line recurrence following large bowel cancer surgery is due to the implantation of cells desquamated from the surface of the growth.


The patient's opinion of day care vein surgery. A questionnaire was sent to 181 patients whose varicose veins had been operated on as day cases. A good response was obtained that showed that day care was generally acceptable except in those cases requiring multiple incisions or stripping.


The importance of plasma lipid, glucose, insulin and fibrinogen in femoropopliteal surgery. Fasting blood levels of cholesterol, triglyceride, glucose insulin and fibrinogen were measured preoperatively in 44 patients who had reconstructive operations for occlusive disease in the femoral and popliteal arteries. Comparison of these preoperative biochemical measurements with the results of surgery over a 4-year period indicated that failure was associated with significantly higher mean preoperative levels of both glucose (P less than 0.01) and fibrinogen (P less than 0.01). High fasting blood glucose was associated with early failure (occlusion between 3 and 12 months) and high plasma fibronogen was associated with late failure (occlusion between 1 and 4 years). The results of operation were not influenced significantly by preoperative blood levels of cholesterol, triglyceride or insulin.


The bruit-occlusion test: a clinical method for localizing arterial stenosis. The bruit-occlusion test is accomplished by listening to a bruit whilst occluding and releasing an efferent artery, e.g. bruit in the groin, occluding the superficial femoral artery. If the bruit disappears, that efferent artery is stenosed. Changes in intensity of the bruit imply stenosis in the parent or alternate efferent vessels. The test is useful in the follow-up of aortofemoral and particularly femoropopliteal vein grafts. It can be applied in the abdomen and neck. This simple manoeuvre can be added to a vascular examination whenever a bruit is discovered. It often allows specific anatomical diagnosis and can be more reliable than arteriography.


The mechanism of calf claudication: studies of simultaneous clearance of 99Tcm from the calf and thigh. Simultaneous clearance of 99Tcm from the gastrocnemius and quadriceps muscles has been studied in 74 limbs of 62 patients with claudication and in 20 normal limbs of 15 volunteers. The local decay curve for 10 min at rest and for 20 min after a 3-min treadmill walk at 4.5 km/h was recorded. The changes in blood flow which occurred after exercise were characteristic of the arteriographic lesions and they explain the haemodynamics of claudication.


Intermittent claudication in the foot and Buerger's disease. The objective of this investigation was to study the pathogenesis of intermittent claudication in the foot and to determine whether it could be used as a diagnostic manifestation of Buerger's disease. In 30 limbs with foot claudication and 20 limbs without foot claudication, systolic pressures at various levels of the leg were measured by a photoelectric technique, and the significance of collateral circulation in the foot on the development of claudication was studied. Although there was a significant difference between blood pressures at the foot and toe, considerable overlapping was seen between the two groups. This finding might indicate that muscle circulatory insufficiency in limbs with foot claudication results from occlusion of the nutrient arteries supplying the plantar muscles as well as poor collateral circulation in the foot. Hospital records of 48 patients with foot claudication were reviewed and the question of whether these patients could be diagnosed as having Buerger's disease was discussed. On the basis of clinical findings and arteriographic appearances, the diagnosis of Buerger's disease was made in all patients except one with hypercholesteraemia. From the results obtained here, foot claudication could be considered to be almost specific to Buerger's disease and a useful guide in the clinical diagnosis of this disease.


Two cases of giant intestinal gas cyst.

Two cases of giant intestinal gas cyst. Large gas cysts of the colon are uncommon and only some 30 cases have been reported (Moss, 1975). They usually arise from the sigmoid colon and are always associated with diverticular disease (Schenken and Cochran, 1972). In view of their rarity, 2 further cases with different presenting factors are discussed.


Meconium ileus equivalent an adult: a case report. A case is described of meconium ileus equivalent presenting as a small bowel obstruction in an adult patient with cystic fibrosis. The importance of conservative management with acetylcysteine and intravenous fluids is emphasized.


The nature of hypocalcaemia in acute pancreatitis. A retrospective and prospective study was made of 82 attacks of acute pancreatitis occurring in 80 patients. Attacks were defined as mild (55) or severe (27) according to clinical criteria. Severe attacks were associated with significantly low levels of uncorrected calcium and calculated ionized calcium, both at the time of admission and 48 h later. Patients with severe attacks were found to have lower levels of parathyroid hormone than either those with mild attacks or other patients who had undergone an abdominal operation. These results indicate that severe pancreatitis is associated with true hypocalcaemia, and that deficiency of circulating parathyroid hormone may be a factor in its production.


Cushing's syndrome: 20 years after adrenalectomy. The long term results (over 20 years) of our first 13 patients treated by adrenalectomy for Cushing's syndrome are described. Twelve survived operation and 5 of these died within 5 years, but thereafter the expectation of life of the treated patients was similar to that of the general population. At 20 years 7 patients were alive and 6 were well. If modern therapeutic measures to control adrenocortical function before operation has been available 20 years ago, some of the early deaths might have been prevented.


Inhibition of aldosterone response to surgery by saline administration. The renin-angiotensin system, ACTH and hyperkalaemia are known to induce increased plasma levels of aldosterone. In order to assess the relative significance of these mechanisms during surgical stress, aldosterone, cortisol and electrolytes in plasma were measured in 12 otherwise healthy women during and after cholecystectomy. The patients received either isotonic sodium chloride or 5 per cent glucose in water during the experimental period of 22 h. The results showed that the pronounced increase of aldosterone and the concomitant decrease of sodium in plasma found in patients given glucose in water could almost be inhibited by the administration of saline. Cortisol and potassium concentrations were identical in the two groups of subjects. It is concluded that the aldosterone response to surgery is mainly mediated via the renin-angiotensin system. This response is probably due to a reduced sodium content or volume of extracellular fluid, since it could almost be inhibited by administration of sodium chloride. The rationale of saline restriction during and after surgery is questioned.


Anorexia nervosa and Crohn's disease.

Anorexia nervosa and Crohn's disease. Two cases of anorexia nervosa who were subsequently found to have Crohn's disease are presented. The difficulties in determining whether they had anorexia nervosa and Crohn's disease concomitantly or whether the Crohn's disease alone was responsible for their condition are discussed without definite conclusion. The importance of excluding occult organic disease before assuming a diagnosis of anorexia nervosa is stressed.


Cure of intractable watery diarrhoea by excision of a vipoma. A 56-year-old man suffered unexplained watery diarrhoea for 5 years which ultimately produced quadraparesis due to serve potassium depletion. All investigations were negative until demonstration of elevated plasma vasoactive intestinal peptide (VIP) indicated the presence of a vipoma. Removal of the VIP-producing tumour tissue--an adrenal ganglioneuroma--resulted in complete cure. Plasma VIP measurement is thus a valuable diagnostic screen in such cases and can be used to predict prognosis and to guide further therapy.


Postoperative recurrence of hydatid disease. Since larval scolices of the parasite Echinococcus granulosus are capable of developing in vivo into mature hydatid cysts in the human intermediate host, operative spillage of cyst contents can lead to local regrowth of hydatid cysts after a suitable interval. The overall rate of postoperative recurrence of hydatid cysts of soft tissue organs in 106 patients, followed-up from 6 months to 3 years, was 11.3 per cent. Both host and parasite factors determine recurrence. Serosal and surgical wound surfaces, unlike mucosal surfaces, provide fertile ground for the development of implanted scolices into hydatid cysts. No correlation was found between the size of removed cysts and postoperative recurrence. The risk of recurrence and associated morbidity was highest in patients with multiple intra-abdominal cysts. Certain technical problems increase the chance of inadvertent operative rupture and spillage of cyst contents, with subsequent regrowth of cysts. Routine measures against operative spillage of hydatid fluid are mandatory, but the actual method of surgical treatment must be individualized for every case.


Acute non-calculous cholecystitis in burns. Seven burned patients developed acute cholecystitis within 10-37 days of injury, associated with jaundice in 5. There were 6 males and 1 female, with 5 patients aged 28-40 years, the others being 56 and 69 years. Cholecystectomy was performed in all patients with 1 death. It is suggested that the cause of post-burn cholecystitis is traumatic and septic shock with consequent biliary stasis.


The selective use of combined supraduodenal and transduodenal exploration of the common bile duct. The results of combined supraduodenal and transduodenal exploration of the common bile duct in 42 selected cases are presented. The indications for this operation were: the presence of multiple calculi in the common bile duct; stones impacted in the ampullary region; residual stones in the common bile duct following previous surgery on the biliary tract; stricture at the papilla and pancreatitis associated with cholelithiasis. After the procedure no patient had residual stones in the common bile duct. Serious complications were infrequent; there were no postoperative deaths and post-operative pancreatitis occurred in only one patient.


The treatment of haemobilia.

The treatment of haemobilia. This paper describes 4 cases of haemobilia. The use of hepatic arterial ligation in its management is discussed. Attention is drawn to the raised serum amylase level in the 2 patients in whom it was measured.


The use of endoscopy in the surgical treatment of the Mallory-Weiss syndrome. Fibreoptic endoscopy has provided a new dimension in the diagnosis and management of oesophageal and upper gastrointestinal disorders. Its value as an aid to surgery of the lower oesophagus is demonstrated in a case of the Mallory-Weiss syndrome.


Oesophageal resection with cervical oesophagogastrostomy for corrosive oesophageal stricture. An 8-year experience of the surgical treatment of 28 patients with corrosive oesophageal stricture is reviewed. Eight patients underwent oesophageal bypass using colonic or jejunal graft with one death (12.5 per cent mortality). The single death (5 per cent mortality) among 20 patients undergoing oesophageal resection was not related to the technical difficulty of the operation. In 17 of these patients reconstruction was by cervical oesophagogastrostomy and in 2 by pharyngogastrostomy. One case of oesophageal carcinoma occurred among 5 cases of corrosive stricture exceeding 20 years in duration. Oesophageal resection for severe corrosive stricture is not a hazardous procedure as generally believed and is desirable in view of the pre-malignant nature of corrosive stricture. Reconstruction by cervical oesophagogastrostomy after oesophageal resection is advantageous because of its relative simplicity and safety.


Fibrinolytic activity in the vein wall after surgery. The fibrinolytic system, including the fibrinolytic activator activity of vein wall and fibrinolytic activity in blood after venous occlusion, was analysed in 43 patients before and on the third day after operation. Twenty-two of the patients underwent abdominoperineal amputation of the rectum and 21 had a cholecystectomy. The incidence of postoperative thrombosis was asssessed by means of the isotope method and phlebography. The results indicate that a decrease in fibrinolytic activity of the vein wall and/or in the release of fibrinolytic activator from the vein wall is a regular postoperative phenomenon, especially after major surgery. Malignant tumour of the rectum did not have any depressing effect on the fibrinolytic activator. All the patients with thrombosis after operation had a postoperative fibrinolytic defect of the vein wall compared with about 60 per cent of the other patients. It is concluded that postoperative changes in the parameters studied might be of significance for the development of thrombosis after operation.


The assessment of aorto-iliac disease by static isotope angiology. In 48 patients with severe claudication isotope images of the aortofemoral arteries have been assessed for the severity of disease in 417 anatomical segments and compared with arteriography. An overall correlation of 80 per cent was found; 87 per cent of patent and 76 per cent of occluded segments were correctly identified, but only 68 and 54 per cent of segments with minor and major disease respectively. Underestimation of disease occurred in only 6 per cent.


The effect of smoking on the late patency of arterial reconstructions in the legs. In a retrospective study of 217 patients, smoking habits were related to the late patency rates of arterial reconstructions performed for ischaemia of the legs. Patients who had stopped smoking or who smoked no more than 5 cigarettes per day after the operation had late patency rates of approximately 90 per cent for aortofemoral reconstructions and 80 per cent for femoropopliteal vein grafts. Patients who continued to smoke more than 5 cigarettes per day were approximately three times more likely to block an aortofemoral reconstruction and four times more likely to block a femoropopliteal vein graft. The results were similar for males and females, for various age groups, for claudicants and patients with severe ischaemia and for aortofemoral endarterectomy and Dacron grafts. The late patency rate was approximately inversely proportional to the number of cigarettes smoked per day after the operation. There was no such correlation with the number smoked per day before the operation.


Assessment of suture materials for intestinal use by an extramucosal implant technique and a quantitative histological evaluation. Six suture materials, 5 of which are in common use for intestinal suture, were implanted in the small and large bowel of the rabbit, and thereafter the durability of their tensile strength and the histological reaction produced were assessed at standard times over 64 days. Absorbable sutures (catgut and polyglycolic acid) lose strength too rapidly to provide reliable sole support, though the synthetic absorbable produces only a slight reaction. Non-absorbables maintain their strength. Only minor differences exist between the reactions produced by different non-absorbables. Other considerations such as handling characteristics or the results of clinical work should be borne in mind in the selection of the optimum suture material.


Clinical course and outcome of pregnancies in amenorrhoeic women with hyperprolactinaemia and pituitary tumors. Seventeen term pregnancies occurred in 14 amenorrhoeic women with hyperprolactinaemia and radiological evidence of pituitary tumour. The abortion rate was high (32%). All but one of the term pregnancies occurred after ovulation-inducing treatment with human gonadotrophins and bromocriptine (four and 12 pregnancies respectively). Two of the 14 women had visual complications during pregnancy, but neither had serious residual visual impairment. Two patients had possible pituitary enlargement during pregnancy.Bromocriptine may be the most suitable primary treatment for many infertile women with prolactin-secreting tumours. Tumour complications during pregnancy are a definite risk, but most pregnancies went uneventfully to term. Patients with pituitary tumour should be carefully evaluated before starting ovulation-inducing treatment with bromocriptine alone, and they should be told of the possible risks and of the advantages and disadvantages of pretreatment with irradiation or surgery. Patients should be carefully monitored during pregnancy and have their visual fields checked frequently. If visual complications due to tumour enlargement occur during a pregnancy, reinstituting bromocriptine may be the treatment of choice. If this fails, other forms of treatment such as induction of labour, high-dose corticosteroid treatment, pituitary implantation of yttrium-90, or surgery may be effective.


Interrelation of age, obesity, cigarette smoking, and blood pressure in hypertensive patients. The relations between age, obesity, cigarette smoking, and blood pressure were investigated in 637 men and 835 women who had attended the Glasgow Blood Pressure Clinic with untreated hypertension. In contrast to results of population surveys of mainly normotensive people no relation was found between cigarette consumption and either systolic or diastolic blood pressure. Moreover, contrary to results of epidemiological studies a relation between adiposity and blood pressure was found in only male non-smokers. Thus the relations established for largely normotensive populations do not apply to hypertensive patients.


Place of ultrasound and radiography in obstetrics. In the two years after an ultrasound service was introduced at this hospital obstetric referrals for abdominal radiography decreased by over 55%. Most of these were for estimation of fetal maturity. Out of 349 such patients subjected to radiography in 1976, 176 had already been examined by ultrasound; in only four did radiography appear to influence management. We believe that if a satisfactory ultrasound scan is obtained before 30 weeks of gestation subsequent radiological estimation of fetal maturity is unjustified. Radiography may still be necessary, however, for diagnosing fetal abnormalities.


Lung function in asthmatic children after year or more without symptoms or treatment. Lung function was examined in 24 children who for a year or more had not received treatment for asthma or had any asthmatic symptoms. Although clinical recovery from asthma was apparent, increased bronchial smooth-muscle tone remained present, which probably renders such children susceptible to obstructive lung disease in adult life. These children should be given guidance on treatment of their symptoms and instructed in preventive measures.


Intellectual impairment in chronic renal failure. In a dialysis centre with a high tap water aluminium content and a known high incidence of dialysis encephalopathy, 29 patients undertaking regular home dialysis, without clinical evidence of encephalopathy, were studied with a battery of psychological tests that have proved useful in detecting early organic intellectual deterioration in other conditions. Full-scale intelligence quotient, as measured by the Wechsler Adult Intelligence Scale, did not differ significantly from that of the normal population, but the patients showed significant deficiencies in three tests of performance--namely, digit symbol, block design, and picture arrangement. The ability to acquire new information in relation to performance was impaired and the abnormality increased with time on dialysis. Such tests should be useful in early detection of dialysis dementia at a reversible stage.


Endometrial assessment with Isaacs cell sampler. The value of the Isaacs endometrial cell sampler in the cytologic assessment of the endometrium was studied in 121 unanaesthetised patients aged over 40. Satisfactory aspirates for cytological diagnosis of endometrial state were obtained in 111 patients (91%) whereas endometrial specimens for histological diagnosis were obtained in only 89 patients (79%). In only four out of 83 cases were there diagnostic discrepancies between the aspirates and the curettings. It is concluded that the technique is safe, quick, comfortable, and reliable for assessing endometrial state. It should therefore prove valuable for screening, particularly in the management of menopausal women requiring oestrogen treatment.


Transmission of HBsAg from mother to infant in four ethnic groups. Antenatal screening in the West Midlands during a three-year period identified 297 mothers who were chronic carriers of hepatitis B surface antigen (HBsAg)--a prevalence of about 1 in 850. About half of their infants had HBsAg in the cord blood, but of 122 infants followed up for over three months (mean 8.5 months) only 17 (14%) were still positive for HBsAg. Cord-blood HBsAg-positivity was evenly distributed among different ethnic groups, but the transmission rate was highest among the Chinese, and no carriers were discovered among 39 European infants. Raised serum transaminase concentrations were found in some of the carrier infants who were otherwise healthy. The results suggest that adequate follow-up of HBsAg-positive infants may be achieved by tests at 4 months and 1 year of age, and that the role of breast-feeding in mother-to-infant transmission of HBsAg is unimportant. The Chinese community may be a suitable population in which to test the effectiveness of specific immunoglobulin administration at birth in preventing the development of the HBsAg carrier state.


Dextran and intermittent pneumatic compression in prevention of postoperative deep vein thrombosis: multiunit trial. Seven general surgical units co-operated in a clinical trial of dextran 70 and pneumatic calf compression alone and in combination in the preventing of 125I-fibrinogen-detectable deep vein thrombosis in 305 patients. Both dextran  regimens were significantly more effective than pneumatic compression alone. Pulmonary embolism was diagnosed in 14 patients, but there was no significant difference in incidence among the three treatment groups. In patients receiving dextran there was no greater median operative blood loss but there was a significantly greater incidence of postoperative bleeding complications.


Effect of new dopamine-blocking agent (oxiperomide) on drug-induced dyskinesias in Parkinson's disease and spontaneous dyskinesias. Oxiperomide, a new dopamine-receptor antagonist, was found to decrease dyskinesias in patients with Parkinson's disease receiving levodopa or other dopamine agonists without necessarily increasing Parkinsonian symptoms. Oxiperomide also decreased spontaneous dyskinesias in those with tics and chorea and to a less extent in those with torsion dystonia, without necessarily causing Parkinsonism. These results provide evidence that more than one population of dopamine receptors exist in the extra pyramidal system, and encourage the search for selective dopamine antagonists.


Viral infections in travellers from tropical Africa. Examination of sera from 86 travellers to Britain from tropical Africa disclosed evidence of past infection with 10 identifiable viruses, of which the most important were O'nyong-nyong, dengue, chikungunya, and Ntaya. The findings indicate that infection with O'nyong-nyong may be acquired sporadically in Nigeria, Ghana, and Sierra Leone, where it has not previously been identified. Chikungunya infection had not been recorded in West Africa other than Nigeria and Senegal. Patients from Sierra Leone and contiguous Liberia had antibodies to this infection. An outbread of dengue fever in the Seychelles in early 1977 was confirmed. Ntaya virus, though known in Uganda, Cameroon, and Zaire, appears also to be transmitted in Kenya, Nigeria, and Zambia. Clinical studies indicated that chikungunya infection may present with alimentary features, possibly with jaundice. The clinical features of Ntaya infection may include kizarre neurological manifestations in addition to fever. The absence of Lassa antibodies among these travellers suggested that this infection is not a common hazard among such persons.


Assessment of patients with suspected viral haemorrhagic fever. We reviewed our two-year (1967-7) experience of patients who might have had an African-derived haemorrhagic fever: only two out of 46 suspects had such infections, and these were successfully contained. Malaria was the most frequent diagnosis in these patients recently returned from Africa, especially if malarial prophylaxis had been inadequate. Altogether 26% of patients had become ill before travelling to Britain. It is impossible to ensure absolute safety even with draconian measures, but the degree of isolation recommended (based on epidemiological factors that included return from Africa within the previous three weeks, visiting country districts, exposure to possible cases, or infected material and illness despite adequate malarial prophylaxis) has proved effective and acceptable.


Intravenous infusion of salbutamol in severe acute asthma. Out of 62 asthmatic patients admitted to hospital with an acute exacerbation of their disease, those whose symptoms had not sufficiently improved 15 minutes after an initial intensive regimen were randomly allocated to receive an intravenous infusion of either salbutamol 10 microgram/min (20 patients) or aminophylline 1 mg/min (19 patients). During the infusions, which lasted 36 hours, peak expiratory flow rates and spirometric values improved in both groups, but differences between the groups did not achieve statistical significance. Although salbutamol may be infused safely for a prolonged period to patients with acute asthma, it has no particular advantage over aminophylline. Furthermore, in patients who respond poorly to initial intensive treatment the subsequent infusion of a bronchodilator may not increase the rate of recovery from the rate that would occur naturally.


Spontaneous abortion and fetal abnormality in subsequent pregnancy. In a prospective survey neural tube defects and other congenital abnormalities were studied in the babies born to 510 mothers ascertained during pregnancy. The women were divided into two groups according to the outcome of their immediately preceding pregnancy. Those whose preceding pregnancy had resulted in a spontaneous abortion (256 women) formed the index cases; those in whom the outcome had been a normal baby (254 women) served as controls. There was a highly significant increased number of congenital abnormalities in the index cases. This may possibly be explained by the trophoblastic "rest" hypothesis and suggests that spontaneous abortions are more relevent to congenital abnormalities than has been thought.


Creamatocrit: simple clinical technique for estimating fat concentration and energy value of human milk. A simple micromethod has been devised for estimating the fat and energy content of human milk based on the centrifugation of milk in a haematocrit centrifuge. The percentage of cream, or "creamatocrit," is read from the haematocrit capillary tube and is linearly related to the fat and energy content. The technique, which is rapid and cheap, may be used in clinical practice, in research, and in epidemiological studies.


After-exercise thermography for predicting postoperative deep vein thrombosis. After-exercise thermography of the legs was carried out on 50 patients before undergoing major abdominal surgery (group 1) and on 59 patients before elective hip surgery (group 2). The incidence of postoperative deep vein thrombosis (DVT)--diagnosed by the 125I-fibrinogen uptake test in group 1 and phlebography in group 2--was significantly higher in patients whose after-exercise thermogram (AET) had been abnormal. Out of 19 patients in group 1 and 30 in group 2 with a normal AET, two and nine repsectively developed postoperative DVT. Among patients with a unilaterally abnormal AET the incidences were 12 out of 19 patients in group 1 and five out of nine in group 2. The incidences among patients with a bilaterally abnormal AET rose to 11 out of 12 patients in group 1 and 15 out of 20 in group 2. Preoperative after-exercise thermography is a simple, objective test that identifies patients at high risk of developing postoperative thromboembolic disease.


Chlamydia trachomatis as possible cause of peritonitis and perihepatitis in young women. Of 11 young women with acute peritonitis proved by laparoscopy, seven of whom also had perihepatitis, nine had serological evidence of recent infection with Chlamydia trachomatis; In five of these nine patients high antibody titres to chlamydiae were found without laboratory evidence of gonococcal infection, while the other four had evidence of simultaneous gonococcal infection. C trachomatis may play an important part in peritoneal inflammation previously attributed only to gonococci.


Contraceptive steroids and breast cancer. The prognosis and pathological findings in 44 patients with breast cancer who had taken contraceptive steroids during the year before diagnosis were compared with those in 44 controls matched for age and parity. No significant differences between the two groups were found in the histological features of the tumour or extent of axillary lymph-node disease. In patients with axillary node disease the recurrence rate in the controls was significantly higher than in the study group and more of the control patients had died. It is concluded that oral contraceptives have no untoward effect on the prognosis of breast cancer.


Self-poisoning: management of patients in Nottingham, 1976. Analysis of the management of a sample of patients with drug overdoses in Nottingham in 1976 showed that some 10% of the patients who arrived in the casualty department after an overdose were neither admitted nor seen by a psychiatrist. Of the patients who were admitted to medical wards for psychiatric evaluation, 31% were thought to need no further psychiatric action while the default-rate in those who were referred to a psychiatric outpatient clinic was 43%. Both these endpoints showed considerable variations among the 10 psychiatric teams, but of every 100 patients with drug overdose who arrived in the casualty department, 51 left hospital without continuing psychiatric or social action having been taken. As the recommendations of the Hill Committee are not being implemented we suggest that they should be critically re-examined and that the indication for, and value of, psychiatric intervention should be determined.


Tuberculosis among immigrants in Britain. Memorandum from the Joint Tuberculosis Committee. Tuberculosis is much commoner among immigrants to Britain than among the native-born. In 1971, 5% of the population were immigrants yet they accounted for 32% of tuberculosis cases. The notification rate among immigrants is falling in some areas but rising in others, and many immigrants are still arriving in Britain. Most immigrants arrive at London Airport, and as many as possible are x=rayed there with the resources available; Many cases escape detection, however, and it is therefore important that accurate information about all immigrants is sent to the medical officer for environmental health at their destination. New arrivals should then be sought out, tuberculin-tested, and positive reactors x-rayed. All those who are tuberculin-negative should be vaccinated with BCG whatever their age. Positive reactors should undergo annual radiography and be encouraged to report symptoms early. For both new and established immigrants with strongly positive tuberculin reactions chemoprophylaxis is suggested. All children of immigrants should be given BCG at birth and tuberculin-tested when they start school so that omissions can be rectified. Implementation of these recommendations could contribute considerably to the control of tuberculosis in Britain.


Prolongation and enhancement of serum methotrexate concentrations by probenecid. The disappearance of methotrexate (MTX) from the serum after an intravenous bolus injection and intravenous infusion was studied over 24 hours in eight and four patients respectively. Probenecid given at the same time as the bolus injection delayed the disappearance of MTX from the serum and resulted in enhanced concentrations throughout the 24 hours studied. At 24 hours the mean concentration was four times higher than in patients not given probenecid. Overall serum concentrations were even greater than those in patients who had received MTX by intravenous infusion. We suggest that smaller doses of MTX may be given and treatment costs thereby reduced if probenecid is given in addition.


Aluminium toxicity during regular haemodialysis. In the west of Scotland the incidence of dialysis encephalopathy has been confined to three geographical areas where the concentration of aluminium in the water supply is greatly increased owing to the addition of aluminium sulphate. Eight patients with encephalopathy who dialysed at home in these areas had greatly increased serum aluminium concentrations, and a significant correlation was found between serum aluminium concentrations and the concentrations of aluminium in the water supply. This study provides further evidence that the dialysis encephalopathy syndrome is due to aluminium intoxication, the major source of aluminium being the water supply from which dialysis fluid prepared.


Epidural analgesia improves postoperative nitrogen balance. Postoperative nitrogen balance was monitored in twelve patients undergoing hysterectomy under either epidural analgesia or general anaesthesia. The mean cumulative five-day nitrogen losses were significantly lower after epidural analgesia than after general anaesthesia. Nitrogen sparing presumably results from inhibiting the stress-induced release of catabolic hormones, since epidural analgesia abolished postoperative hyperglycaemia and increase in plasma cortisol concentrations. No adverse effects of inhibiting the stress response were observed. Neurogenic stimuli thus play a crucial part in the catabolic response to surgery. Inhibiting the endocrine metabolic response to trauma by neurogenic blockade may reduce the morbidity precipitated in high-risk patients by the catabolic response to surgery.


The Brighton resuscitation ambulances: review of 40 consecutive survivors of out-of-hospital cardiac arrest. In three years 40 patients were resuscitated by ambulancemen after out-of-hospital cardiac arrest and survived to be discharged. Twenty-six of these had had circulatory arrest before an ambulance arrived and a further three had developed ventricular fibrillation before they were moved. Thirty-two patients were alive at the time of review six months to three and a half years later. Resuscitation by ambulancemen can be effective for patients with unheralded sudden cardiac arrest as well as for patients with recent myocardial infarction. Survivors of out-of-hospital ventricular fibrillation may have a favourable long-term prognosis.


Randomised trial of a mobile coronary care unit for emergency calls. A randomised trial was conducted to assess the value of sending a mobile coronary care unit (MCCU) to all emergency calls other than those for children or for patients injured in road-traffic accidents or brawls. Over 15 months 6223 calls for emergency ambulances were considered for the study, but a routine ambulance had to be dispatched on 2583 occasions because the MCCU was not available. A group of 1664 patients was randomly allocated to transport by the MCCU and 1676 patients to routine transport. In these groups the prehospital mortality among patients with heart attacks was 45% and 47%, and no patient survived resuscitation attempts long enough to leave hospital. During the same period general practitioners sent 190 patients with heart attacks to hospital in routine ambulances and none of them died during the interval between the call for the ambulance and arrival at hospital. Although it may be worth equipping all emergency ambulances with a defibrillator, MCCUs as at present envisaged will not appreciably affect mortality from heart attacks.


Reversal of clofibrate-induced cholesterol oversaturation of bile with chenodeoxycholic acid. Giving clofibrate 2 g daily to seven patients significantly increased the biliary cholesterol concentration while the proportion of bile acids fell. Five patients on established clofibrate treatment were given 750 mg of chenodeoxycholic acid (CDCA) daily for one month. Biliary lipid analysis after the CDCA treatment showed a significant fall in the proportion of cholesterol and a rise in that of bile acids. The serum lipid concentrations, which had already been reduced by diet and clofibrate, showed a further significant reduction after the introduction of CDCA. This study suggests that CDCA may be usefully combined with clofibrate to reverse the tendency towards cholesterol saturation of bile and enhance the effect of lowering serum lipid concentrations.


Underlying immunopathology as a cause of adverse responses to two intravenous anaesthetic agents. A patient who had shown some evidence of immunological sensitivity underwent several operations under general anaesthesia for otitis media without ill effect. On his second exposure to Althesin, however, he suffered a severe reaction. Facial angioneurotic oedema was accompanied by peripheral vasodilatation and sweating, and C3 conversion was observed in his plasma. Subsequent anaesthetics produced no reactions until four years later, when thiopentone and suxamethonium were given. This reaction was much milder, but C3 conversion again occurred. Although the clinical signs indicated an anaphylactoid reaction, the laboratory findings suggested that this patient had an underlying immunopathological condition involving complement activation, which could be triggered by any intravenous agent that activated complement. The judgment that a reaction to a particular drug is anaphylactic cannot be made on the basis of clinical signs alone. Simple laboratory analysis will show whether the reaction is due to an underlying immunopathological condition that may be triggered by any of several drugs.


Seven-year follow-up of heroin addicts: drug use and outcome. A representative sample of 128 of the patients who in 1969 attended London drug dependence clinics and received daily prescriptions for heroin was personally followed up seven years later. The mean age of the patients at follow-up was 32.7 years, and a mean of 12.8 years had elapsed since they first admitted to using heroin. Follow-up was successful in 124 cases (97%). Fifty-two people (41%) had stopped attending the clinics, 6 (5%) were in prison, 55 (43%) were still attending the clinics, and 15 (12%) had died. Abstinence from opiates had been achieved by at least 40 people, 33 having abstained for two years or more. Abstinence did not seem to have been replaced by dependence on other drugs, including alcohol. Sixty-two people (48%) were still using opiates; only 7 (5%) did so without attending clinics and obtaining legal prescriptions.


Role of 24-hour ambulatory electrocardiographic monitoring in a general hospital. During 1976, 24-hour ambulatory electrocardiographic (ECG) monitoring was available to all physicians at this hospital, and 281 patients were investigated by 322 recordings. Cardiac arrhythmias requiring treatment were detected in 100 patients (36%). Some presented after symptoms such as faintness, giddiness, palpitations, collapse, or fits, but ominous arrhythmias were also found in asymptomatic patients. A demand pacemaker was implanted for episodic sinoatrial or atrioventricular conduction disorder in 30, while 70 patients (25%) required antiarrhythmic drug treatment for ventricular or atrial tachyarrhythmias. Facilities for ambulatory 24-hour ECG monitoring are necessary in any large hospital, and precise diagnosis in most of our patients studied could not have been achieved by any other investigation.


Diagnostic treatment and reporting criteria for gonorrhoea in sexually transmitted disease clinics in England and Wales. 2: treatment and reporting criteria. The current methods of treatment and reporting are described. The most common form of treatment for gonorrhoea in men and women was a single dose of oral ampicillin, usually 2 g. In proportionately more of the clinics treating women, treatment was given over several days. The wide use of ampicillin represents a marked change in treatment practice during the last decade. Procaine penicillin was the most commonly used parenteral preparation. The two dosages used most often for men were 1.2 and 2.4 megaunits. In women the commonest regimen was 2.4 megaunits and again there was a tendency for treatment to be given over several days. Epidemiology treatment was used widely and in one-third of clinics this occurred without confirmation that the patient was a true contact. Consultants used varying diagnoses on the quarterly returns for patients treated epidemiologically in whom the smears and/or cultures were negative. Most clinics classified these cases as 'other conditions requiring treatment' (D2) but as many as 19% of clinics designated these cases as being 'true' gonorrhoea. It is suggested that this results in an overestimate of the number of cases of 'real' gonorrhoea treated in England and Wales.


Chlamydial infection of the urethra in men. Chlamydia trachomatis was isolated from the uretha of 125 (52%) of 238 men with non-gonococcal urethritis (NGU). Repeat isolation attempts in 155 of these patients were successful in eight men in whom results had been negative on the initial visit, but they were unsuccessful in eight men who initially had had positive cultures. We must assume that with our present isolation techniques we are missing, at any single visit, at least 9% of chlamydial infections. C. trachomatis was also found in 32 (23%) of 139 men with gonorrhoea. Positive cultures were obtained from 15 (79%) of 19 men, who later developed post-gonococcal urethritis (PGU). Thiamphenicol, used for the treatment of gonorrhoea, was shown to have very little effect on C. trachomatis, which could still be recovered after treatment in 76% of the patients who initially had had a combined infection. The typing of 35 genital isolates by micro-immunofluorescence confirms the previously reported distribution of chlamydial serotypes. In this study a social profile is given of our patients with urethritis and a comparison is made of the duration of symptoms and the nature of discharge in men with gonococcal, chlamydial, and non-specific urethritis. We were able to show a clear difference in clinical symptoms in men with gonorrhoea and NGU, taken as a whole, but found only a slight difference between men with chlamydial and non-specific urethritis.


Circulating immune complexes in syphilitic nephropathy. A case report. A case of transient nephrotic syndrome caused by secondary syphilis is described. A renal biopsy was performed revealing subepithelial hump-like electron-dense deposits and fusion of epithelial foot-processes. Complement C1q-binding-activity and anticomplementarity were demonstrated in the blood, indicating the presence of circulating immune complexes. This strongly suggests that circulating immune complexes are significant in the immunopathogenesis of syphilitic nephropathy.


The antimicrobial susceptibility of Chlamydia trachomatis in cell culture. The action of 22 antimicrobial agents against the SA2f strain of Chlamydia trachomatis has been studied by the use of a simple cell culture technique. Tests for bactericidal activity were undertaken with some of the agents, and latency of infection was demonstrated. The susceptibilities of 10 clinical strains of C. trachomatis and of SA2f to oxytetracyline, erythromycin, and spectinomycin in cell culture were found to be identical.


Treatment and prognosis of non-specific genital infection. In a comparative trial minocycline was the best oral tetracycline compound for twice-daily administration in the treatment of non-specific urethritis. A review six months later showed that 29% of patients had needed further treatment, 35% of these more than one month after initial treatment and 12% between three and six months later. The history revealed no evidence of predisposition to non-specific urethritis among patients in whom relapse occurred. Multiple relapses were in the groups of patients who relapsed earliest. These cases proved more resistant to subsequent treatment, but all patients were eventually cured. The records of female contacts showed that 29% were symptomatic, 44% had an abnormal appearance of the cervix, but only 11% had inflammatory changes detected on cytological smear. A previous report was confirmed that there was no apparent benefit from the empirical treatment of contacts; possible reasons for this are given.


Current approaches to the diagnosis of herpes genitalis. The current methods of diagnosing and treating herpes genitalis in clinics for sexually transmitted diseases in England and Wales are reported. Virus cultures were used as a diagnostic test in some or all patients in nearly two-thirds of clinics. Darkground examinations were performed on all or selected patients in most clinics, but fewer than half the clinics performed them on three or more separate occasions. In over 80% of clinics attempts were made to see some or all contacts of patients with herpes. The treatments prescribed varied, the commonest being saline washes, idoxuridine, and oral antibiotics. Serological tests were repeated after the disappearance of the lesions in 90% of clinics, while in 60% of clinics women with herpes genitalis were advised to have cytological examination at regular intervals in future. The importance of excluding syphilis in patients presenting with genital ulceration, the most appropriate treatments for herpes, and the possible association between the disease and cervical carcinoma are discussed.


Evaluation of the early morning smear investigation. A retrospective study on early morning smears confirmed the value of this investigation for diagnosing urethritis in men. In 200 patients 108 new infections were diagnosed.


Tactile projections to granule cells in caudal vermis of the rat's cerebellum. We discovered a small tactile area in a single a folium of the uvula of the cauday vermis of the rat's cerebellum. Gentle mechanical stimulation of relatively small cutaneous receptive fields (RFs) activated multiple units in the granule cell (GC) layer in a portion of a single folium in rats anesthetized with sodium pentobarbital. The total size of this area on each side of the midline is about 1.5 mm2, yet micromapping within this tiny region using tungsten ball microelectrodes and a high puncture sampling density (about 75 punctures/mm2) revealed a highly differentiated pattern of cutaneous projections to the GC layer. All peripheral projections are ipsilateral; the two homologous areas from each side adjoining at the midline of folium 9a. The larger projection areas from cutaneous RFs are mostly from mystacial vibrissae and upper lip, but small projection sites from the remainder of the head, neck and forelimb also are present. The pattern of projections were patch-like, forming a fractured somatotopic pattern or mosaic, with some somatotopic and some nonsomatotopic features. Each RF activated units in a vertical column in the GC layer. This area has not been described in any mammal, and its functional role can now be studied.


Ipsilateral limb variation in cats during overground locomotion. The timing interval between the onset of knee extensor EMG (vastus lateralis) and the onset of the ipsilateral elbow flexor EMG (brachialis) was studied in adult cats during overground walking, trotting and galloping. Concurrent finding of the animals in locomotion was used to relate the electrical activity of the muscles to the physical events in a step cycle. The observed variability in the interval between the onset of knee extensor EMG and the onset of elbow flexor EMG lead to the conclusion that it is not appropriate to postulate a rigid neural coupling mechanism for the control and coordination of ipsilateral limbs in locomotion.


Intramembranous particles at the nodes of Ranvier of the cat spinal cord: a morphometric study. Size and distribution of intramembranous particles at nodes of Ranvier of the cat spinal cord were investigated by the freeze-etching technique and compared with those at the internodal axon. The particles are larger (up to 20 nm) at the nodal than at the internodal segment (up to 13 nm), and these large particles are more densely packed in the nodal (400 per sq micrometer) than in the internodal E (external) face (4 per sq micrometer). The nodal E face reveals a much denser overall population (1200--1300 per sq micrometer) of particles than the internodal E face (100--200 per sq micrometer), while at the P (protoplasmic) face the particle density is similar in nodal and internodal segments (1200--1600 per sq micrometer). It is suggested that the large nodal particles may be related to the mechanism of nerve excitation.


A radioautographic study of retinal projections in type I and type II lizards. The retinofugal projections of 5 species (Acanthodactylus boskianus, Scincus scincus, Tarentola mauritanica, Uromastix acanthinurus and Zonosaurus ornatus) belonging to 5 different families of Type I and Type II lizards have been examined by means of the radioautographic method. In the 5 species the retinal ganglion cells project to the contralateral hypothalamus (nucleus suprachiasmaticus), thalamus (nucleus geniculatus lateralis pars ventralis, nucleus geniculatus lateralis pars dorsalis), pretectum (nuclei lentiformis mesencephali, geniculatus pretectalis, postero-dorsalis griseus tectalis), tectum opticum (layer 2 to layer 6 of the stratum griseum et fibrosum superficiale) and tegmentum mesencephali (nucleus opticus tegmenti). Ipsilateral optic fibers were never observed in Uromastix acanthinurus, whereas an uncrossed quota was visible in both nucleus geniculatus lateralis pars dorsalis and nucleus postero-dorsalis in the other species. An ipsilateral retinotectal projection was observed only in Tarentola mauritanica. With the exception of the nucleus griseus tectalis the contralateral optic centers identified in this material have to a large extent been observed in other reptiles belonging to the different orders. The presence in reptiles of a general pattern of contralateral visual projections indicates that these were established very clearly in the course of evolution. Similarities become apparent when this plan is compared with that observed in birds. In marked contrast the ipsilateral component in reptiles is unstable and mutable in nature. This ipsilateral retinotectal projections do not appear to be a feature restricted to Type I lizards. On the other hand, the presence of this optic component cannot be linked solely to nocturnal habits.


Supraspinal regulation of spinal reflex discharge into cardiac sympathetic nerves. (1) In chloralose anaesthetized cats, reflex responses were recorded in inferior cardiac nerves following stimulation of intercostal nerves and hind limb afferent nerves. (2) In 80% of cats, a long latency reflex response alone was recorded, whereas, in the others, a short and long latency response was present to intercostal nerve stimulation. (3) In cats displaying only a long latency somatocardiac reflex response, damage to the ventral quadrant of the ipsilateral cervical spinal cord, through which runs a bulbospinal inhibitory pathway, resulted in the appearance of shorter latency reflexes to intercostal nerve stimulation. Lesions elsewhere in the cervical cord did not do this. (4) The characteristics of the early responses indicated that they were somatosympathetic reflexes and not dorsal root reflexes. (5) The early reflexes remained and the late reflex disappeared on subsequent complete transection of the spinal cord. The early reflexes were therefore spinal reflexes, and suppressed in the animal with cord intact. (6) Lesions at C4, which included a contralateral hemisection and a section of dorsal columns extending into the dorsal part of the lateral funiculus, abolished the inhibition of a sympathetic reflex that followed stimulation of some somatic afferent nerve fibres. These sections did not release the spinal reflex. Therefore, this reflex inhibition was not responsible for the suppression of the spinal somatosympathetic reflex. (7) The descending inhibitory influence on the segmental reflex pathway was not antagonized by strychnine, bicuculline or picrotoxin. (8) The possibility is discussed that the spinal reflex pathway into cardiac sympathetic nerves is tonically inhibited by a bulbospinal pathway originating from the classical depressor region of the ventromedial reticular formation.


The role of action reflexes in the damping of mechanical oscillations. Reflex responses measured during voluntary contraction of the muscle being stretched are known to differ markedly from reflex responses elicited from passive muscle. The term 'action tonic stretch reflex' or 'action TSR' has been used previously to describe a reflex response to continuous stretch, separated from voluntary activity by means of a cross-correlational and spectrographic analysis. In this paper it is proposed that the action TSR play a functional role during voluntary movement by damping the transient oscillations associated with the natural resonant frequencies of the limbs. It is suggested that oscillations excite an action TSR force response with phase lead ahead of muscle stretch. This force response can be resolved into two force components, one of which has a 90 degree phase lead ahead of muscle stretch and behaves like a viscous friction reaction force causing damping of oscillations. Three experiments which support this proposition are described. (1) Analog computer model stimulation studies of a muscle supporting a mass-spring load reveal that damping only occurs when the force response has a phase lead ahead of muscle stretch. When the force response has a phage lag behind muscle stretch, the system is unstable and the amplitude of oscillation increases with time. (2) It is demonstrated that when a mass-spring load is supported as rigidly as possible by the human arm, reaction forces from the arm damp and mass-spring oscillations more rapidly than when the mass-spring is rigidly supported. Electromyogram (EMG) recordings reveal that mass-spring oscillations excite action TSR responses with phase lead ahead of muscle stretch. (3) Recordings of elbow angle and biceps EMG during rapid forearm flexion or extension movements followed by sudden stops reveal critically damped oscillations in the elbow angle signal (i.e. no more than one or two small overshoots), which are accompanied by EMG action TSR responses with phase lead ahead of muscle stretch.


Development of the trochlear nerve: loss of axons during normal ontogen. Development of the trochlear nerve from day 11 of incubation through hatching was studied in white Peking duck embryos. Counts of fibers from the electron micrograph montages indicate that initially there is an abundant collateral sprouting which roughly coincides with the time of neuromuscular contacts, suggesting some sort of interaction between the developing nerve and the periphery. The maximum number of trochlear cells and fibers is present on day 12. Average cell and fiber counts on this day are 2325 and 47,386 respectively. Assuming all cells send their axons into the nerve and that all cell bodies are present within the trochlear nucleus, the ration of cells to fibers is 1:20. Average cell and fiber counts at hatching are 1338 and 1506 respectively. Thus, losses of approximately half the trochlear cells and of 97% of the fibers occur during normal development. Degenerating cells and fibers are first observed on day 13. Degeneration involves both the myelinated and the unmyelinated axons. The actual number of degenerating fibers which were observed, however, was very small compared to the number of fibers lost during development; thus, it is suggested that, in the majority of cases, fiber loss is perhaps via retraction of axon collaterals. In general, cell death slightly precedes axon loss, which suggests that the direction of the degeneration is from cell body to the axon. A cell/fiber ratio of approximately 1:1 is first observed on day 18 and remains so thereafter. Indirect evidence is discussed, suggesting that at least some cells which die during normal devleopment had sent their axon into the nerve prior to their death. Whether these axons make meaningful connections with the muscle is uncertain.


Morphological and biochemical studies on isolated molecular and granular layers from bovine cerebellum. Molecular layer, granular layer and white matter are dissected from bovine cerebellum under optical microscope and without freezing under conditions which preserve their main anatomical features. Polyacrylamide gel electrophoresis in sodium dodecyl sulphate of the isolated layers reveal that the P400 protein characteristic of the Purkinje cells is found in the isolated molecular layer and in the molecular layer free from Purkinje cell soma, but not in the granular layer or white matter. The histones (F1, F2A1,2, F2B, F3) are abundant in the granular layer and myelin proteins in the white matter. The DNA content per wet weight is 10 times greater in the isolated granular layer than in the other layers and the RNA content twice as great in the granular layer than in any other layer. The specific activity of acetylcholinesterase is 4 times greater in the granular layer than in the other layers. Homogenates of the isolated layers take up labeled amino-acids and the velocity of glutamate incorporation is 9 times greater in the molecular layer than in the granular layer, while GABA incorporation is about twice as great in the granular layer than in the molecular layer. Homogenates of isolated molecular layer are centrifuged on discontinuous Ficoll gradient after incubation with L[3H]glutamate and [14C]GABA. The analysis of the distribution of glutamate and GABA after centrifugation reveals that the particles which incorporate glutamate can be separated from those which take up GABA.


Light-evoked changes in extracellular potassium concentration in munpuppy retina. Light-evoked changes in extracellular potassium concentration ([K+]0) and field potentials were recorded simultaneously in response to a wide variety of stimuli and at various depths within the retina of Necturus. At both light onset and offset, small diameter flashed stimuli elicit a large increase in [K+]0 in the proximal retina. The depth profile of this K+ increase is nearly identical to that of the proximal negative response (PNR), and both responses exhibit similar behavior to a number of other stimulus parameters. This suggests that the same neurons which generate the PNR may be the source of the observed K+ flux. Large diameter flashed stimuli elicit a slow decrease in [K+]0 in the distal retina and a small increase proximally. The K+ increase occurs at a depth where the b-wave of the electroretinogram is positive going, and where its current source lies. Increasing background light intensity decreases [K+]0 in the distal retina, and generally increases [K+]0 proximally.


Functional characteristics of unmyelinated fibres in the hippocampal cortex. (1) In transverse hippocampal slices (350 micrometer thick), taken from guinea pigs initially anaesthetized with ether, intracortical afferent fibres were activated by small current pulses delivered through tungsten microelectrodes. Extracellular potentials were recorded from the zone of activated fibres in dendritic layers while intracellular recordings were made from the soma of CA1 pyramidal cells. (2) When recording was made from the same level as the stimulating cathode, the extracellular potential consisted of a diphasic deflection followed by a larger negative wave with a superimposed population spike. The negative wave corresponded to an intracellularly recorded EPSP, and is called an extracellular EPSP, whereas the initial diphasic deflection had no intracellular counterpart. (3) The initial diphasic deflection was linearly related to the size of both the intracellular and extracellular EPSP. It was not changed by removal of calcium ions from the bathing fluid, whereas all postsynaptic activity disappeared. The diphasic deflection was propagated along fibres lying parallel to the pyramidal layer with a velocity of 0.3 m/sec. It could follow short bursts of stimulation at 300 Hz. The absolute refractory period was 2.0 msec. (4) The initial diphasic deflection is interpreted as the compound action potential of the largely unmyelinated afferent fibres to the CA1 neurones.


Eye-head coordination in labyrinthine-defective human beings. (1) Eye-head coordination was studied in three human beings with absent labyrinthine function. Each subject adopted a unique pattern of adaptive responses to achieve optimal gaze stability. (2) One subject used saccades (even in darkness) to help stabilize gaze. In addition, during rotation of the body with the head stationary in darkness, he made slow and quick phases of nystagmus in the same direction. This subject apparently used quick phases to help stabilize gaze rather than to redirect the center of visual attention. (3) One subject, to help prevent gaze overshoot, showed a decrease in the saccadic amplitude-retinal error relationship selectively during active combined eye-head movements. (4) One subject showed a significant amount of preprogramming of compensatory slow phases independent of actual head motion. (5) In all subjects, the passively induced cervico-ocular reflex was moderately potentiated, accounting for about 25% of compensation for head motion during active target seeking. (6) In all subjects, 'effort of spatial localization', as shown by imagining targets in total darkness, increased the velocity of compensatory slow phases to near that of head movements during both active and passively induced head rotations. (7) In all subjects, gaze stability was enhanced during tracking of targets jumping in a predictable fashion. (8) The choice of strategies used by each subject may depend, in part, upon the latency of the cervico-ocular reflex during active head movements.


Retinotopic organization of the guinea pig's visual cortex. Under anaesthesia the right visual cortex of the guinea pig was investigated with 1.5 M potassium citrate-filled glass microelectrodes. Single unit and small unit cluster response showed an organized three-part representation of the contralateral visual field on the animal's visual cortex. The major central division (V1) had the representation of a nasotemporally elongated visual field. This visual field extended for about 110 degrees horizontally and for about 70 degrees vertically. The nasal visual field was represented laterally on the cortex and the lower visual field anteriorly. The visual field representation was not uniformly magnified in V1; the magnification of the nasal field was higher than the rest of the visual field. On either side of V1, the guinea pig's cortex had two additional visually responsive strips. The strip V2L, situated lateral to V1, had a condensed representation of about 40 degrees of the animal's nasal visual field and mirror-imaged the visual field representation of the adjacent V1. The strip V2M, situated medial to V1, had a similar representation of about 40 degrees of the animal's temporal visual field and mirror-imaged the visual field representation of the area V1 adjacent to it. A binocularly responsive zone of cortex was observed on either side of the boundary between the areas V1 and V2L, representing between 10 degrees and 15 degrees of the nasal visual field on each side of the boundary line. Investigation of the retinal ganglion cell distribution of the animal showed a nasotemporally oriented 'visual streak' with a high ganglion cell density per unit area of the retina, near the optic disc. Away from the 'visual streak' the density of the ganglion cells of the retina diminished progressively. The configuration of the 'visual streak' and the general pattern of the ganglion cell distribution in the rest of the retina coincided with the asymmetry in the magnification of representation of the animal's visual field on the cortex.


Studies on muscarinic acetylcholine receptors from mouse brain: characterization of the interaction with antagonists. The binding of tritium labeled N-methyl-4-piperidyl benzilate (4-NMPB) and scopolamine to the muscarinic receptor from mouse brain was investigated at 10, 25 and 37 degrees C. Approach to equilibrium experiments indicated that association involved a single population of binding sites. The formation of at least two types of ligand-receptor complexes had however to be assumed to explain the data obtained at 25 and 37 degrees C by equilibrium and dissociation experiments. In contradistinction, at 10 degrees C a single population of ligand-receptor complexes could be detected. The simplest model which fits the experimental findings consists of a fast binding step followed by a slow isomerization process of the receptor-ligand complex.


Evaluation of the effects of nerve growth factor and anti-nerve growth factor on the development of central catecholamine-containing neurons. Intracisternal NGF or anti-NGF has been found to produce no long-term major alterations in central norepinephrine (NE) or dopamine levels when administered to neonatal rats. While NGF and anti-NGF were found to produce significant changes in brain NE content within one week of treatment, changes in central NE were no longer detectable at 30 days of age. Modification of the growth response of the central adrenergic neurons following 6-OHDA treatment was also not affected by NGF or anti-NGF when evaluated 3 weeks after treatment. However, centrally administered anti-NGF did induce a loss of peripheral NE terminals, which was attributed to leakage of the anti-NGF from the central injection site.


Preoptic-hypothalamic control of LH and prolactin release in male rats under pentobarbital anesthesia: differential responses to electrical stimulation. In acute experiments under pentobarbital anesthesia, the brains of adult male rats were stimulated bilaterally with trains of monophasic pulses at different frequencies and current intensities through bipolar, concentric, stainless steel electrodes. Stimulation of the POA-SQ region at 3, 10 (200 muA) or 200 Hz (100 muA) increased plasma prolactin levels within 30 min of the onset of stimulation. Stimulus parameters fully effective when applied to the POA-SQ or ARC-MED. EM. regions were ineffective when applied to the ARC-VMH region. Maximal effects were obtained with 10 Hz (200 muA) stimuli applied to the POA-SQ region. LH levels were increased after stimulation of any of the three regions--POA-SQ, ARC-VMH or ARC-MED. EM. Conversely to the prolactin response, LH levels did not rise after 3 Hz stimulation of the POA-SQ region. In male rats under pentobarbital anesthesia, LH levels seemed to be affected maximally with a stimulus frequency rate of about 50 Hz applied to the POA-SQ region. The results suggest a potential physiological role of frequency discrimination in the functional segregation of LH and prolactin release controls.


Hyperthermia evoked by the intracerebral injection of morphine sulphate in the rat: the effect of restraint. Morphine sulphate (M) was microinjected intracerebrally into 26 sites in the free-moving and 11 sites in the restrained rat. The injections were made into the preoptic-anterior hypothalamic (POAH) region as core temperature (Tc) was measured. A marked increase in Tc was evoked from the free-moving rat following doses of M of 1 (n = 10); 10 (n = 19); 20 (n = 7); or 50 microgram (n = 6). On the other hand, no increase in Tc significantly above the control level was observed in the restrained rat following the intracerebral administration of M in doses of 10 (n = 8), 20 (n = 9), 50 (n = 10), or 70 microgram (n = 4). The control injection of the artificial cerebrospinal fluid (5-ion), used as the drug vehicle, caused a mild hyperthermia about 1.0 degrees C above the baseline level in both the free-moving and restrained rat. We conclude that morphine evokes a hyperthermia by its action on POAH neurons, but the M-induced hyperthermia can be attenuated by restraining the rat.


Effect of substantia nigra stimulation on identified neurons in the VL-VA thalamic complex: comparison between intact and chronically decorticated cats. The effects of substantia nigra (SN) stimulation on the activity of the nucleus ventralis lateralis of the thalamus (VL) have been studied. The VL cells were identified as relay or non-relay cells among the cerebellothalamocortical pathway on the basis of orthodromical activation from the cerebellum and antidromical activation from the cortex. Certain experiments were performed after wide pericruciate decortication in order to eliminate the response due to unavoidable activation of corticofugal fibers. These results show that nigrothalamic neurons exert an inhibitory effect on VL cells. This inhibition was observed on the relay as well as on non-relay cells and was strong enought to suppress the cerebellar monosynaptic excitatory input. Thus the SN can modulate the information running along the cerebellothalamocortical pathway. The topographic localization of inhibited cells suggests that the SN controls the activity of the thalamic neurons which interfere with axial and proximal musculature.


Tolerance to amphetamine's facilitation of self-stimulation responding: anatomical specificity. Further work on the phenomenon reported by Leith and Barrett, wherein tolerance was shown to develop to the well-known D-amphetamine-induced facilitation of self-stimulation, clearly indicates that the development of such tolerance is dependent on the location of the stimulating electrode. Thirty-seven Fisher or Harlan rats were trained to bar press for hypothalamic stimulation (60 Hz, AC). Following several sessions during which small doses of D-amphetamine were administered to demonstrate facilitation, the subjects were placed on a 4-day D-amphetamine regimen. During this time they were given three daily injections of continuously increasing doses of D-amphetamine (total 78 mg/kg). Subsequent tolerance was shown for electrodes stimulating dorsal or medial hypothalamic structures (H2 field of Forel, dorsal medial forebrain bundle, medial hypothalamic nuclei), but did not develop with ventral or lateral hypothalamic stimulation sites (fornix, ventral medial forebrain bundle).


Neuron specific protein (NSP) in neuroblastoma cells: relation to differentiation. The spectrum of enolase enzyme forms has been examined in several lines of neuroblastoma cells and compared to those present in whole brain. The neuron specific enolase (NSP) is greatly decreased in the cultured cells as judged by activity profiles and radioimmunoassay. The synthesis of neuronal enolase appears to be extensively depressed in these cells while the total enolase activity is not affected. The non-neuron form of enolase (NNE) apparently compensates for the lack of the neuronal forms in the cultured cells. The preponderance of NNE in cultured neurons suggests that this enzyme is present in immature neurons, and that neuroblastoma cells are not fully differentiated with respect to the enolase function. Dibutyryl cyclic adenosine monophosphate treatment does increase NSP levels in mouse neuroblastoma cells, but not to the levels expected for fully differentiated neurons. The results indicate that NSP is a molecular correlate of fully differentiated neurons.


Rapid decarboxylation of carbon-11 labelled DL-DOPA in the brain: a potential approach for external detection of nervous structures. The cerebral distribution of the positron-emitting agent [1-11C]beta-(3,4-dihydroxyphenyl)-D,L-alpha-alanine ([11C]DOPA) was studied after intravenous injection in rats pretreated with the peripheral decarboxylase inhibitor, carbidopa. Within 15 min of injection the accumulation of carbon-11 was almost twice as high in cortical areas and cerebellum as in the striatum and the brain stem. After destruction of catecholamine-containing nerve endings with 6-hydroxydopamine, the level of carbon-11 in the striatum was higher than in rats not treated with this neurotoxin. Pretreatment of rats with haloperidol or L-DOPA did not change the distribution pattern of carbon-11. Without pretreatment with carbidopa a uniform distribution of the label in the brain was observed. We suggest that [11C]DOPA is a potentially useful agent for external detection with positron imaging systems in patients and large animals of brain regions rich in the enzyme dopa-decarboxylase. (EC 4.1.1.26).


Release of dopamine evoked by electrical stimulation of the motor and visual areas of the cerebral cortex in both caudate nuclei and in the substantia nigra in the cat. The effects of unilateral stimulation of the cerebral motor cortex and of the visual cortical area on the activity of the nigrostriatal dopaminergic neurons were examined in halothane-anesthetized cats. For this purpose, one push-pull cannula was inserted in each caudate nuclei and another one in the substantia nigra ipsilateral to the stimulated side. In all cases, the release of [3H]dopamine ([3H]DA) continuously formed from L-[3,5-3H]tyrosine was estimated in superfusates. Unilateral electrical stimulation of the cerebral motor cortex (area 4) induced a long-lasting and similar activation of [3H]DA release in both caudate nuclei. The activation of [3H]DA release in the contralateral side was selectively abolished after acute transection of the rostral part of the corpus callosum. This transection also suppressed the flexion of the contralateral forelimb induced by the stimulation. The activation of [3H]DA release could be related to the stimulation of corticostriatal neurons which may interact directly or indirectly with dopaminergic terminals in both caudate nuclei. Unilateral electrical stimulation of the visual cortex (areas 18 and 19) markedly stimulated the release of [3H]DA in the ipsilateral caudate nucleus. A slight effect was seen in the contralateral structure 20 min after the stimulation. These results are consistent with the existence of a main ipsilateral pathway originating from the visual cortex and projecting directly to the striatum. Both types of electrical stimulation immediately activated the release of [3H]DA in the ipsilateral substantia nigra. These effects were still seen 20 min after the stimulations. The activation of the dendritic release of [3H]DA could be related to the stimulation of a corticonigral projection. These results further indicate that the nigrostriatal dopaminergic neurons may be involved in sensory motor integration.


Effect of electric organ discharge on ampullary receptors in a mormyrid. (1) Afferents from ampullary receptors were shown to be strongly affected by the electric organ discharge (EOD) in the mormyrid Gnathonemus petersii. (2) Over a broad range of resistivities (4-60 komegacm) the response to the EOD was similar to the response to a brief (50-200 microsec) outside positive pulse, i.e. an initial acceleration of the discharge rate followed by a deceleration. (3) Brief biphasic positive-negative or negative-positive pulses where both phases were of equal amplitude and duration had no effect on ampullary afferents. Each phase had an effect, however, when given in isolation. These results suggest that a DC component in the EOD may cause the response in the ampullary afferent. (4) The response of ampullary afferents decreased sharply as resistivity was lowered below 10komegacm. Responses to the EOD in mormyromast afferents also decreased. These effects were probably due to loading of the EOD at low resistivities and to a more rapid spatial decay of EOD voltage. (5) Responses of ampullary afferents to the EOD were much less affected by external non-conducting objects than were the responses of mormyromasts. These observations plus other considerations indicate that mormyromasts must still be held to play the major role in active electrolocation. Unresponsiveness of ampullary afferents to the EOD can not be taken as a reason for this, however.