Platelet MAO activity and evoked potentials in the identification of subjects biologically at risk for psychiatric disorders.

Individuals potentially at risk for psychiatric disorders were identified by screening 375 college student volunteers for low platelet monoamine oxidase (MAO) activity levels. The lower and upper 10% in MAO activity were administered a personal and family history interview, psychological tests and average evoked response (AER) electroencephalographic procedures. Results indicated that low MAO males and females were socially more active, had more psychiatric contact, and had relatives who were psychiatrically more disturbed than high MAO subjects. Low MAO males had more convictions, experimented more with illegal drugs and had elevated scores on the MMPI. AER criteria further defined a high risk group of low MAO-AER augmenters which had more suicides among their relatives and higher scores on the schizophrenia scale of the MMPI.


A new depression scale designed to be sensitive to change.

The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample. Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change. The inner-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.


Clinical response and tricyclic plasma levels during treatment with clomipramine.

Fifty depressed in-patients at two psychiatric units, one in Italy the other in England, were treated with clomipramine, either orally, or intravenously and orally. A comparison of clinical response with plasma levels of clomipramine and its metabolite, desmethylclomipramine, showed clear relationships especially in the case of desmethylclomipramine. In the intravenously-treated group this was linear, in the orally-treated group it was curvilinear. Plasma levels of desmethylclomipramine and administered clomipramine correlate highly. These findings, together with the fact that significant clinical improvement was observed in only 55% of the patients, suggest that titration of the administered dose to obtain more effective plasma levels of the metabolite might improve the clinical response to the drug in some patients.


Psychiatric morbidity and pregnancy: a controlled study of 263 semi-rural Ugandan women.

Two hundred and sixty three pregnant Ugandan women and 89 non-pregnant, non-puerperal women were interviewed using a semi-structured psychiatric questionnaire. Comparison of psychiatric morbidity between the control group and matched pregnant women showed an increased frequency of psychiatric morbidity in pregnant women. Separated pregnant women were particularly at risk. No association was found between antenatal psychiatric morbidity and age, gravidity, number of co-wives or the duration of the pregnancy.


A comparative study of parents of emotionally disturbed and normal children.

Parents of fifty children attending a child guidance clinic (clinic parents) were studied and compared with the parents of non-referred children matched on relevant parameters (control parents). The clinic parents differed significantly from the control parents on certain variables: presence of psychiatric morbidity in clinic mothers, disciplinary techniques used, attitude towards their own children and the marital relationship. There were no significant differences between the parents of the two groups in their attitudes towards their own parents. Alcoholism and sociopathy were not common among clinic fathers.


A method for monitoring the treatment of schizophrenics in the community.

A trial was carried out over twelve months of a method for monitoring the care of a large number of schizophrenic patients in the community. The method has been demonstrated to be practical in use, economical of resources and potentially relevant to a number of chronic disorders.


Use of hospital services by chronic schizophrenics in the community.

A sample of chronic schizophrenic patients from an urban community, living outside hospital, were reassessed on the Present State Examination one year after a first examination. During this time their use of psychiatric hospital services was recorded. One hundred and two patients had satisfactory interviews on both occasions. These could be divided into Heavy, Medium and Light users of services, the numbers being 8, 14 and 63 respectively, while 17 only saw their general practitioners or had no treatment. A ranking of the sample in terms of severity showed no correlation with use of these services; second PSE scores were not significantly different from the first. Heavy and Medium users of hospital services were in contact with Social Services to a significantly greater extent than other patients.


Prediction of successful rehabilitation by nurse rating scale.

The predictive value of the NOSIE, a ward behaviour rating scale, was investigated in a group of long-stay patients. After a follow-up period of 3 1/2 years, it was found that all NOSIE scales differentiated continuing in-patients from those discharged. Regression analysis showed that age and florid psychoticism carried most predictive weight. These findings and the value of reliable rating scales for rehabilitation purposes are discussed.


The effect of some incentives on the work performance of psychiatric patients at a rehabilitation workshop.

Five experimental incentive conditions were compared with a control condition in terms of their effect on work performance. Each of the six groups studied had a standard four-week baseline period (Block 1) consisting of an attendance payment, followed by a four-week experimental period (Block 2). Whereas all patients in the Control and Feedback groups produced less during Block 2, only two patients in the remaining four groups failed to improve. An analysis of variance indicated that Social Reinforcement, Piece Rate, Piece Rate plus Social Reinforcement, and Pay Increase plus Social Reinforcement were significantly superior to the Control and Feedback conditions.


Gains, losses and lateral differences in the hearing of schizophrenic patients.

Schizophrenic patients, whether newly admitted to hospital or institutionalized, exhibited ear differences in absolute threshold. Right ear thresholds were superior to left ear thresholds especially at frequencies above 2 kHz, but deteriorated in the course of the day or as a result of repeated testing. These effects were attributed to the dynamics of left hemisphere processes which in schizophrenia appear susceptible to inhibition and fatigue, effects that may be endocrine related. Relative to control subjects institutionalized schizophrenic patients showed superior hearing below 1 kHz and inferior hearing above 2 kHz.


Progressive changes in energy cost during a three-hour race-walk exercise.

Twenty experienced race-walkers were exercised in a controlled routine walking at 11.6 km/hr continuously for 3 hr, alternately on a treadmill and a cinder track. Analyses of expired air samples taken at 30 min intervals were used to calculate average R.Q. and energy expenditure. R.Q. was found to decrease progressively from 0.92 to 0.66 in the 3 hr and remained at this level 30 min later. The mean energy cost rose from 46.2 to 55.4 kJ/min or 24.7 to 29.7 kJ/min.m2. The results indicate that this group probably experienced an elevation of aerobic activity as they utilized progressively more fat to satisfy metabolic demands and that R.Q. may be a good indicator for determining recovery after severe long duration exercise.


Human endurance--mind or muscle?

Two investigations have been carried out. The first studied the effects of autonomic blockade on the cardiovascular response to a step test, a 50% maximum isometric grip test and a Valsalva manoeuvre: the step test was of 5 minutes duration and the other two for as long as possible. beta adrenergic blockade by propanolol diminished the blood pressure and pulse rate response to both the step test and isometric grip. The pulse rate response to the step test was also affected by cholinergic blockade with atropine. The response to the Valsalva test showed a cholinergic blockade effect of pulse rate alone and a blood pressure response alone on alpha adrenergic blockade by phenoxybenzamine. The second studied psychological stressing on physical and mental ability. A potential 'punishment' situation increased the blood pressure and pulse rate response to isometric grip while decreasing the time for which it could be maintained. A potential 'reward' situation increased both the maximum grip and the time for which 50% grip could be maintained. It is concluded that psychological factors can affect performance dependant on whether the situation is perceived as one of 'reward' or 'punishment'. A factor in the mediation of the adverse response is an inappropriate response of the autonomic nervous system.


Chronic overuse injuries of the piso-triquetral joint in racquet game players.

Three squash racquets and one badminton player presented with pain in the base of the hypothenar eminence, due to minor degrees of subluxation of the pisiform bone. Two of them also showed chondromalacia of the articular cartilage of the pisotriquetral joint. All four patients were relieved by excision of the pisiform bone and had returned to their normal daily and sporting activities within three months of their operation.


Cognitive aspects of performance.

The study of cognitive structures and processes in the control of skilled performance is considered and reviewed with special reference to a proposed hierarchical system incorporating levels of motor integration. Cognitive styles and dispositions of general behaviour are suggested as factors which may determine performance levels. The relative importance of these personal factors and stronger personality traits in accounting for variance in performance is considered in the light of a critique of the current interactional controversy.


Exercise prescription--North American experience.

The principles of exercise prescription are reviewed with respect to North American experience. The required regimen must be safe, therapeutically effective, and ensure a high rate of compliance. Precautions to increase the safety of exercise are discussed. Cardiac emergencies are sufficiently rare events (less than 1 in 200,000 hours even in post-coronary classes) that the need for immediate medical supervision of a well-designed programme can be questioned. The prime determinant of the response to training is the intensity of effort relative to the individual's initial fitness. Post-coronary patients often have a great potential for training due to their previous inactivity, but this will not be realised if the prescribed exercise is of insufficient intensity. Exercise programmes are plagued by a high 'drop-out' rate; 50% of normal middle-aged volunteers are lost in 6 months, and even with post-coronary programmes losses can be 60--70% over 4 years. Simple suggestions are made for improving compliance with the required exercise prescription.


The radiological diagnosis of polyps in the presence of diverticular disease.

The double contrast barium enemas in 20 patients with endoscopically proven polyps within a segment of diverticular disease have been reviewed. Ninety per cent of the polyps were detected. The increased density sign and negative shadow filling defect proved valuable in their detection. Antispasmodics are advised to distend the sigmoid and allow double contrast views to be obtained. With severe diverticular changes it may be impossible to exclude a polyp, and if the patient complains of rectal bleeding, endoscopy is indicated.


Magnification renal arteriography.

Magnification selective renal arteriograms were performed on 24 patients, 12 of whom were hypertensive, and compared with non-magnification arteriograms by two observers independently. The magnification angiograms were performed on a Siemens Microfocus Bi 125/3/50 RG tube with a 0.1 mm focal spot. Of the 24 patients examined, information crucial to the diagnosis was found only on the magnification films in three patients (12.5%). Extra information compared with the nonmagnification films was found in the magnification films in 12 patients (50%). No additional information was discovered in the remaining nine patients (37.5%). The magnification angiograms enabled the interlobular vessels to be visualized--this was not possible on the non-magnification films. Against the additional information gained must be weighed the disadvantages of magnification arteriography which include increased radiation dose and lengthening of procedure time plus additional injections of contrast. In conclusion, there is a place for magnification renal arteriography and the advantages seem to outweigh the disadvantages.


Angiography in leiomyosarcoma of the inferior vena cava--report of two cases.

Two patients with leiomyosarcoma of the suprarenal inferior vena cava are presented. In one case the tumour was misinterpreted as intrahepatic at angiography. In the second case an extrahepatic location was suggested after repeated angiography. The diagnosis should be borne in mind when a large hypovascular mass appears to be located centrally in the liver at coeliac angiography and when ultrasound examination has revealed its solid nature.


Ultrasound in the evaluation and diagnosis of jaundice.

Our experience in the evaluation and diagnosis of jaundice by ultrasound in a consecutive series of patients examined in the past year is reported. A final diagnosis is available in 49 patients with obstructive jaundice and 41 patients with nonobstructive jaundice. The accuracy of separation into these two groups is 97% in this series. We would like to stress the value of ultrasound as a complete investigation in many jaundiced patients. In this series a full diagnosis of the cause of jaundice was achieved in 58% of patients.


Grey-scale ultrasonic characteristics of carcinoma of the pancreas.

Fifty-five sonograms were performed on 25 cases of surgically and histologically proven carcinoma of the pancreas. The sonographic appearances of the tumour were determined. A diffuse echogenic pattern with irregular margin was the most common appearance. Displacement and indentation of the inferior vena cava and superior mesenteric vessels, greatly assist in localizing the tumour to the pancreas. A reliable prediction of tumour size and resectability cannot be determined by sonography alone. Sonography is helpful in assessing the response of unresectable pancreatic carcinoma to therapy. A more sonolucent appearance of the tumour occurs following chemotherapy.


Radionuclide venography in the management of proximal venous occlusion. A comparison with X-ray contrast venography.

Ascending contrast venography often fails to show the proximal venous system when there is co-existing occlusion of femoral or iliac veins. Retrograde and pertrochanteric venography both have severe limitations in terms of invasiveness and reliability. Radionuclide venography (RNV) is suggested as a less invasive alternative. 100 patients were investigated by both RNV and X-ray contrast venography (XRV). There was a 72% overall correlation between two methods of investigation. The proximal definition of XRV was limited in those cases with femoral obstruction. RNV, however gave progressively better views as imaging became more proximal and this was accentuated in the presence of femoral or iliac occlusion. RNV is simple and easy to perform and less invasive than XRV. The definition at calf level is such that it cannot at this stage replace XRV as the standard diagnostic procedure. However, in patients with proximal occlusions it gives more reliable information than that obtainable by ascending contrast venography.


Induced thermal resistance in the mouse ear.

The mouse ear (pinna) was used to investigate the effect of two hyperthermic treatments. Heating was by immersion in hot water at 43.5 degrees C. A single treatment of about 50 minutes was required to cause necrosis in 50% of the ears heated. When heat treatment was given in two equal fractions the total heating time had to be increased if the interval between fractions was greater than four hours. By 24 hours a total treatment of about 100 minutes was required, indicating almost complete recovery from the first heating. Priming treatments at 43.5 degrees C induced thermal resistance to a second heat treatment at 43.5 degrees C. Maximum resistance was observed one day after a 20 minute priming and two days after a 40 minute priming, when the heating time had to be increased to 120 minutes, an increase by a factor of 2.4. Shorter priming treatments induced less resistance, the minimum heating time to produce an effect being two minutes. In all cases the effect decreased during the next four to five days. These results indicate that the reduced response of tissues to fractionated hyperthermia is due both to the repair of sublethal heat damage and induction of thermal resistance.


The effect of prior heat treatment on the thermal enhancement of radiation damage in the mouse ear.

The effects of prior heat treatment on the skin reaction produced by a subsequent treatment with combined heat and X-rays were investigated in the mouse ear. Ears were heated by immersion in hot water. The priming heat treatment was always 43.5 degrees C for 40 minutes. Its effect was transient, beginning between 24 and 48 hours after the priming treatment and reaching a maximum at 48 to 96 hours when there was a reduction in the skin response to combined heat and X rays, i.e. it caused a reduction in the thermal enhancement ratio (TER). The effect was lost by 192 hours. At 96 hours after the priming treatment the TER for 30 minutes at 42.5 degrees C or at 43.5 degrees C was reduced by a value equivalent to decreasing the temperature by about 0.4 degrees C. This was equivalent to increasing the heating at 43.5 degrees C required to produce a given enhancement of radiation damage by a factor of 1.4 relative to that required without prior heating. The effect was smaller than induced resistance to damage caused by severe heat treatment alone (i.e. necrosis) and it occurred later. These differences support the concept that two separate mechanisms underlie direct heat necrosis and thermal enhancement of radiation damage.


Measurement of regional cerebral blood volume using the EMI 1010 scanner.

Regional cerebral blood volume (rCBV) was measured in 14 patients with normal CT scans. An EMI CT 1010 scanner was used in combination with a computer subtraction technique. The mean CBV in the cortex was 5.0 ml/100 ml of tissue and 2.2 in the white matter. Regional differences were not significant and no difference was found between the right and left hemispheres.


Ultrasound diagnosis and treatment of gall-bladder fossa collections following biliary tract surgery.

Three patients are presented with sterile or septic subhepatic fluid collections after biliary tract surgery. In each patient, the common clinical presentation was fever and ultrasound was primarily responsible for demonstrating its source. In one patient, percutaneous aspiration of the abscess under ultrasonic guidance obviated the need for any further treatment. We conclude.that ultrasound is an effective method for investigating suspected fluid collections after biliary tract surgery. Aspiration of the lesion under ultrasonic guidance is a safe means for confirmation of the diagnosis and may be therapeutic as well.


Radiosensitizing effect of misonidazole in fractionated gamma-ray treatment of a human malignant melanoma grown in athymic nude mice.

The effect of the hypoxic cell radiosensitizer 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 animals. The tumours were exposed daily to 3.75 Gy (375 rad) over four consecutive days, to a total dose of 15.0 Gy. Misonidazole in doses of 500 mg/kg bodyweight was administered intraperitoneally in the mice 45 minutes before each irradiation. The time necessary for the tumours to regrow to their original sizes was compared with that of tumours treated with four daily fractions of 3.75, 4.50 and 5.25 Gy without sensitizer. The enhancement ratio of misonidazole was found to be 1.05.


Castleman's disease. Angiofollicular benign lymph-node hyperplasia. Radiological features in the differential diagnosis of vascular tumours of the pelvis.

An unusual case of benign lymph-node hyperplasia (Castleman) in the pelvis is reported and its clinical, histological and radiographic characteristics discussed. The angiographic appearances in this situation have to our knowledge not been described before in the literature. The angiographic features are not diagnostic, being mimicked by a wide variety of vascular tumours in the pelvis. The benign nature of the condition is stressed. BLH should be considered in the differential diagnosis of vascular tumours in the pelvis.


The management of suspected tumours of the colon: the role of colonoscopy in general surgery.

The role of colonoscopy in the management of 100 cases of suspected large bowel tumour is described. Forty out of 47 patients with an equivocal barium enema examination were satisfactorily examined and the possibility of a tumour being present was either confirmed or refuted. Examination of 30 patients with otherwise unexplained blood loss from the bowel revealed the cause in 50 per cent of them. Twenty-nine patients had pedunculated polyps which were snared and removed, thus avoiding laparotomy and colotomy. The problem of distinguishing tumours from other lesions or retained faeces by radiology arises most often in the sigmoid colon. This segment is easily examined using a short flexible endoscope. General surgeons taking up colonoscopy will find a 1-m single-channel instrument convenient to use and capable of reaching approximately 90 per cent of colonic tumours that require further investigation or endoscopic resection. Facilities for the examination of the whole colon should be available in established endoscopy units.


Cancer of the large bowel in a defined population: Canterbury, New Zealand, 1970--4.

A total of 1024 new cases of cancer of the large bowel occurred in Canterbury, New Zealand (population 400,796), in the 5 years 1970--4. Of these, 992 were diagnosed before death and are reviewed in this paper. The high incidence of this disease in New Zealanders of European origin is illustrated. A significant difference in site distribution of primary tumours between the sexes was found, with a female preponderance of cancer of the proximal colon gradually changing to a male preponderance of cancer of the rectum. In all, 61.5 per cent of the patients had lymph node metastases or advanced disease at the time of diagnosis or treatment. Largely as a consequence of this, only 65 per cent were able to have potentially curative treatment. The estimated crude 5-year survival rate of the whole group was 32.7 per cent (relative rate 42.8 per cent) and the crude 5-year survival rate after potentially curative surgery was 48.4 per cent (relative rate 62.4 per cent). The results are compared with those of other authors. They emphasize the generally unsatisfactory outcome of treatment.


Extra-intracranial revascularization.

Twenty-four extra-intracranial revascularization procedures were undertaken in 23 patients with occlusion of the ipsilateral internal carotid artery. The superficial temporal artery was anastomosed to a cortical branch of the middle cerebral artery in 23 cases and a vein graft inserted between the external carotid artery and the cortical vessel in 1, a microsurgical technique being used. Twenty-one patients were suffering from transient ischaemic attacks (TIAs) and 2 had developing strokes. Nineteen patients had radiologically demonstrated bilateral disease of the carotid vessels, 9 having undergone contralateral carotid artery surgery before the intracranial procedure. No improvement was noted in the 2 patients with developing strokes; one patient developed a stroke contralateral to the intracranial procedure 24 h postoperatively, this being accompanied by occlusion of the anastomoses, and one patient had progression of the stroke syndrome following occlusion of the intracranial vein graft. All other patients have shown a reduction of abolition of TIAs over a follow-up period of 24 months. These findings suggest that intracranial revascularization is of value in patients with total internal carotid artery occlusion and continuing TIAs.


Deep vein thrombosis after total hip replacement: a clinical and phlebographic study.

Two hundred and forty-seven phlebograms (113 bilateral and 21 unilateral) were performed in 134 patients 10--14 days after total hip replacement. Fifty-eight per cent of the patients were found to have deep vein thrombosis. The patients with DVT were significantly older than patients without DVT, but there was no difference regarding sex, type of hip prosthesis, side of operation or day of mobilization. No difference was found in the duration of operation and anaesthesia, the operative haemorrhage and the amount of bank blood transfused in patients with and without DVT. Fifty per cent of the thrombi were confined to the calf veins. Ninety-seven per cent of these thrombi were asymptomatic and were as frequent on the operated as on the non-operated side. The remaining 50 per cent of the thrombi engaged the thigh with or without simultaneous calf vein involvement. These thrombi produced symptoms in 23 per cent of the cases and were significantly more common on the operated than on the non-operated side. It is concluded that DVT after hip replacement can be of two different types: thrombosis caused by stasis and the general effects of trauma and thrombosis caused by local factors involving the thigh veins of the operated leg.


Ambulatory calf volume plethysmography in the assessment of venous insufficiency.

Ambulatory calf volume plethysmography has been used to study venous insufficiency in 50 lower limbs. The results demonstrate that it is possible to determine the presence of venous insufficiency and differentiate between normal limbs, limbs with superficial venous insufficiency only, limbs with deep venous insufficiency and limbs with deep venous insufficiency and occlusion by determining the ambulatory volume change and maximum venous outflow or venous volume.


Axillary vein entrapment.

This paper describes a patient with right axillary vein obstruction resulting from compression of the vein due to anomalous muscle tissue extending from the latissimus dorsi muscle across the neurovascular bundle to the pectoralis major muscle. This 'axillopectoral muscle' causing entrapment of the axillary vein has been described in only a few cases. These previous reports are discussed, with special reference to the symptoms and phlebographic findings. The obstruction and the symptoms caused by it are intermittent; the phlebographic features are characteristic.


Partial and complete atrophy affecting hepatic segments and lobes.

Thirty-four patients with atrophic lesions of liver segments or lobes are described. The primary diagnoses included alcoholic liver disease, various forms of cirrhosis, hydatid disease, tumours and sclerosing cholangitis. Seventeen patients had complete atrophy of the segment or lobe and the other 17 patients had partial atrophy (i.e. a reduction of at least 50 per cent in the size of the affected area). Complete atrophy affected the left lobe more frequently than the right. The condition is important, first, because it is more common than is generally recognized, and second, because it may create considerable diagnostic and therapeutic problems.


The treatment of major liver trauma by primary packing with transfer of the patient for definitive treatment.

Four patients are reported in whom massive haemorrhage from severe hepatic trauma was managed initially by conservative surgery and packing. The patients were then transferred by ambulance to Addenbrooke's Hospital where further treatment involved elective surgery and removal of packs. All 4 patients were discharged from hospital and have made full recoveries. It is felt that the management of liver trauma should be to do the minimum that is necessary to staunch bleeding, by suture, arterial ligation, lobectomy, resectional debridement or simply by packing. This allows the patient's haemodynamic state to be restored to normal before further surgery is attempted.


Postoperative hypophosphataemia.

The possible mechanisms of postoperative hypophosphataemia were studied in women undergoing uncomplicated cholecystectomy. Six patients were allocated to each of three groups. Group I received no intravenous fluids, group II received dextrose/saline solution alone and group III received dextrose/saline solution with phosphorus supplementation. The serum concentration of inorganic phosphorus fell in all three groups, the greatest fall being in the group receiving dextrose/saline solution. However, the lowest level reached (0.82 mmol/l) was within the normal range for our laboratory. Concentrations of red blood cell adenosine triphosphate and 2,3-diphosphoglycerate showed similar changes. The operations were not associated with a large catabolic response nor with an increase in urinary phosphorus excretion. The postoperative reduction in serum concentration of inorganic phosphorus appeared to be due mainly to haemodilution. There is no indication for routine phosphorus supplementation following uncomplicated elective surgery.


Chronic abdominal pain: a surgical or psychiatric symptom?

A prospective investigation of chronic, non-specific abdominal pain in 20 patients is reported. The cause was found to be psychiatric in 8 (40 per cent), while a surgical cause was found in only 3 (15 per cent). Four had irritable colon (20 per cent) and no diagnosis was made in 5 (25 per cent). It is suggested that such pain is more often a psychiatric than a surgical symptom and therefore a psychiatric consultation should be a routine part of the investigation.


Interstitial emphysema of the stomach.

A case of interstitial emphysema of the stomach is reported and the possible aetiological factors involved are discussed.


Hospital resuscitation from ventricular fibrillation in Brighton.

The overall results over three and a half years of the treatment of ventricular fibrillation secondary to ischaemic heart disease in the Royal Sussex County Hospital were reviewed. Records of all patients who were brought to hospital by resuscitation ambulances or who were admitted to the coronary care unit from any source were analysed. Eighty-seven of the 174 patients (50%) who developed ventricular fibrillation were discharged. The survivors included 13 out of 61 patients (21%) in whom fibrillation was secondary to cardiogenic shock or severe left ventricular failure. The presence of resuscitation equipment and nursing staff trained to use it in the general wards and emergency areas ensured a uniformly high success rate throughout the hospital, similar to that achieved in the coronary care unit. Prompt defibrillation in the general wards and the accident and emergency department may improve overall survival.


Current required for ventricular defibrillation.

The mean current required for ventricular defibrillation was measured and found to be 0.35 +/- SE 0.03 A/kg body weight, which is about one-third of that predicted from animal experiments. There was no apparent correlation between the current required and body weight (r = -0.007 +/- SE 0.213). There is no evidence of need for defibrillators storing more than 400 J.


Evaluation of ultra-short dialysis.

A study was carried out to compare the effects of three dialysis regimens of different durations. Nineteen patients dialysed over 1975--7 for an average of only 11.2 hours per week were compared with nine dialysed for 24 hours per week (1974--6) and 10 dialysed for 27 hours (1971--3). Clinical, biochemical, and haematological results showed that the short dialysis regimen was as effective as the longer regimens, except that patients had to take a phosphate binder regularly, and that it was considerably cheaper. Short dialysis has social and economic benefits, since patients have more free time and more patients can be treated with the same number of staff and dialysis stations. As in many areas there is a shortage of places for patients needing dialysis, a short regimen is recommended.


Sodium retention and hypertension with short dialysis.

Exchangeable sodium was measured in 26 patients undergoing dialysis with a modestly shortened schedule of 14.8 hours weekly and related to blood-pressure control. The group was compared with 27 patients studied in 1969 during twice-weekly dialysis totalling 22 hours, and with 18 patients studied in 1973 during dialysis of 18--21 hours weekly in three sessions. Exchangeable sodium was significantly increased with short dialysis compared with the other schedules and, although mean blood pressure was not significantly increased, significantly more patients required antihypertensive treatment than in either 1969 or 1973. A trend towards more frequent resort to bilateral nephrectomy than in 1973 did not reach significance. Problems of hypertension and the side effects of its treatment, both medical and surgical, should be weighed against the social and economic advantages of short dialysis in deciding on the ideal schedule.


Diagnosis and management of brain death.

Finland was the first country in which brain death was legally accepted. Since 1975, 37 cases of brain death had been recorded in a university hospital in Finland, and these were reviewed. The cause for brain death was intracranial bleeding in 32 cases, other cerebrovascular disorder in two, and intracranial neoplasm in three. In 21 brain death was diagnosed clinically. In 16 cases confirmatory investigations (electroencephalography, cerebral angiography) were needed. After brain death had been established artificial support was withdrawn in 15 patients and organ transplantation was carried out in 10. In 12 patients, however, diagnosis of brain death did not influence management, though the heart stopped beating on average 25 hours after diagnosis. The Finnish criteria for brain death seem to be reliable and suitable for routine use.


Prescription for a better British diet.

A new approach to establishing an upper or prescriptive level of recommended intakes of nutrients was devised for use in Britain. It was based on present food supplies in the UK, and the following measures were proposed to improve the national diet: moderate reductions in intakes of fat, sugar, meat, and alcohol; increased intakes of cereals, potatoes, and other vegetables and fruit; while intakes of milk and eggs and fish, pulses, and nuts were to remain unchanged. The proportions of food energy derived from protein would be increased, despite reduced meat consumption. Nutrient content of the diet may be expressed in terms of food groups or as nutrient concentrations per energy unit, which is particularly applicable to planning or prescribing diets for individuals or small groups. The suggested changes in the national diet are large enough to be meaningful, yet would not disrupt agricultural or trade policies if implemented over the next decade. Furthermore, the methods used to assess the recommended intakes of nutrients are flexible enough to be used both for planning and prescribing diets and for evaluating results of dietary surveys or histories.


Hypopituitarism in normal-pressure hydrocephalus.

Hypothalamic hypopituitarism has been associated with the intermittent intracranial hypertension of "normal-pressure" hydrocephalus. Six patients with this condition were studied endocrinologically; five showed evidence of hypothalamohypophyseal insufficiency, and, though only one needed treatment, all needed continued assessment of their endocrine state during follow-up. Thus, hypothalamohypophyseal dysfunction is more common than might be expected. Tests of anterior pituitary function should be preformed before surgical intervention, as such dysfunction may adversely affect survival and the response to ventricular shunting.


Comparison of black and white patients attending hypertension clinics in England.

Reports suggest that hypertension and death due to hypertensive disease are commoner among black than among white people. One hundred and thirty-five black patients attending hypertension clinics at three English hospitals were compared with age-, sex-, and clinicmatched white patients. The black women had higher blood pressures and weighed more than the white women, but there were no differences between the men. The black patients had not increased risk from family, obstetric, or smoking history. Proteinuria and nocturia were more common in black patients while urinary infections were less common. Heart size and left ventricular voltage were greater in black patients. Haemoglobin and plasma cholesterol and triglyceride concentrations were smaller and serum globulin concentration greater in black patients. No difference in response to treatment, attributable to race, was observed during the period of clinic attendance, which averaged 1.7 years. There was a slightly greater rate of default among black men during the first year of attendance.


Outbreak of trichinosis near Paris.

A localised outbreak of trichinosis occurred in January 1976 in the southern suburbs of Paris. A total fo 125 cases was recorded including 30 children. The prominent symptoms were oedema of the face or eyelids, fever, and myalgia; diarrhoea was unusual and constipation common. An increased blood eosinophil count and raised serum concentrations of muscular enzymes strongly indicated trichinosis. This diagnosis was confirmed later immunologically. The parasite was found in only three out of 32 muscle biopsy specimens but this investigation was made relatively early in the disease. No deaths occurred. In all cases clinical recovery was fast and serum antibody titres were maximum during the first month and decreased slowly. The disease was milder and the recovery faster in children than adults. Epidemiological study suggested that horse meat was responsible for the infection, though no meat could be examined.


Randomised trial of two-drug and four-drug maintenance chemotherapy in advanced or recurrent Hodgkin's disease. Medical Research Council's working party on lymphomas.

Between 1970 and 1975, 108 patients who presented with advanced or recurrent Hodgkin's disease and were free of disease after six courses of chemotherapy with mustine, vinblastine, procarbazine, and prednisone (MVPP) were allocated at random to one of two regiments of maintenance treatment: either intermittent treatment with vinblastine and procarbazine or intermittent treatment with MVPP. After a median follow-up period of nearly five years there was no significant difference between the two groups in either the rate of relapse or death rate. Six of the 55 patients given the two-drug regimen died compared with 10 of the 53 given the four-drug regimen. The four-drug required hospital attendance and was less agreeable than the two-drug regimen. The efficacy of maintenance chemotherapy with the two-drug regimen was no less than that with the four-drug regimen, but the two-drug regimen had several practical advantages.


Vision screening of adolescents and their use of glasses.

Vision screening was performed in over 11 000 16-year-olds who were taking part in the National Child Development Study. For distance vision 75% had normal acuity, 9% a minor defect, and 16% a more severe unilateral or bilateral defect. For near vision 85% had normal vision, 8% a minor defect, and 7% a unilateral or bilateral defect. Few children (62) with normal distant vision had defects in near vision, though many more (607) had both poor distant vision and poor near vision. Vision defects were more common in girls than in boys and occurred more often in adolescents from non-manual than manual families. Athough 18% of children had been prescribed glasses for current use, a third did not have their glasses available at the examination: 27% of the children prescribed glasses had normal unaided distant visual acuity or only a minor defect, and they constituted 42% of those who were not wearing their glasses. Further investigation is needed into the criteria on which glasses are prescribed for children and into the reasons for which they are not worn.


Indomethacin increases plasma lithium.

The effects of indomethacin on plasma lithium concentrations and renal lithium clearance were investigated in three psychiatric patients and four normal volunteers. After steady-state plasma lithium concentrations had been reached, the subjects received indomethacin placebo for three to seven days, indomethacin (50 mg thrice daily) for seven days, and placebo again for three to seven days. Indomethacin increased plasma lithium concentrations by 59% in the psychiatric patients and 30% in the volunteers. Renal lithium clearance was reduced by indomethacin by 31% in the group as a whole, and prostaglandin synthesis, determined by measuring the major metabolite of PGE2 with mass spectrometry, was reduced by 55%. These results show that indomethacin reduces renal lithium clearance to an extent which may be clinically important. They also suggest that the renal clearance may be affected by a prostaglandin-dependent mechanism, possibly located in the distal tubule.


Failure of cerebral autoregulation as a cause of brain dysfunction in the elderly.

Cerebral blood flow in relation to change in arterial pressure was measured in 11 elderly patients with postural hypotension. Seven patients with symptoms showed bilateral or unilateral failure of cerebral autoregulation, while the four asymptomatic patients did not. Variations in cerebral autoregulation would explain why some elderly people with minor falls of systemic arterial pressure develop clinical signs of cerebral ischaemia whereas others with greater falls in blood pressure remain asymptomatic. Elderly patients with impaired autoregulation may be at risk of brain damage from minor falls in blood pressure.


Indications for electric convulsion therapy and its use by senior psychiatrists.

A survey by questionnaire of all senior psychiatrists in the Wessex Region showed that they considered depressive psychosis to be the major indication for electric convulsion therapy (ECT). A good clinical response was thought to be predicted by the presence of psychomotor retardation, depressive delusions, depressed mood, early morning wakening, diurnal variation, loss of appetite, and agitation. ECT was judged to be extremely useful for treating mania and acute undifferentiated, catatonic, and paranoid schizophrenia; of some use in hypochondriasis; but of little value or contraindicated when there was severe, depersonalisation, or hysterical symptoms. Only 40% of the psychiatrists favoured unilateral ECT, and the variation in electrode placements used by different psychiatrists was surprising. Eighty per cent of the respondents used courses averaging six to eight treatments given over two or three weeks. Results obtained in this study, based on clinical judgment, differed from research findings, which emphasises the need for further study of this important treatment.


Campylobacter enteritis associated with consumption of unpasteurised milk.

In October and November 1978 two outbreaks of enteritis occurred in the north of England. Symptoms lasted two to over eight days but in no case necessitated admission to hospital. Faecal specimens from most of the patients were found to contain thermophilic Campylobacter sp. Inquiry disclosed that all patients had consumed unpasteurised milk from local farms. Examination of rectal swabs from the cattle concerned and milk socks yielded strains of Campylobacter sp indistinguishable from those isolated from the patients. It was therefore concluded that, since campylobacters are not known to be excreted in milk, faecal contamination of the milk had probably occurred and had led to these outbreaks. Evidence suggests that thermophilic Campylobacter sp is an occasional contaminant of milk. So long as unpasteurised milk continues to be distributed further outbreaks will probably occur.


Pressure on the tracheal mucosa from cuffed tubes.

During cuffed intubation, damage to the trachea is least likely when the lateral wall pressure exerted by the cuff does not exceed the mean capillary perfusion pressure of the mucosa. A study was carried out of eight different types of endotracheal tubes. At the seal point the traditional red rubber tube and the armoured latex and Softway tubes exerted pressures above the mean systemic arterial pressure. Although the Portex and Mallinckrodt tubes exerted pressures close to the mean capillary perfusion pressure, much higher pressures resulted if they were overinflated. The Lanz tube, however, with its over-pressure safety balloon, maintained a lateral wall pressure below the mean capillary perfusion pressure even when inflated considerably beyond the seal point. Endotracheal cuffs are often overinflated in clinical practice. Since cuff-induced tracheal damage is most influenced by the lateral wall pressure, these results suggest that the use of Lanz-type tubes should be mandatory in intensive care units or when a cuffed tracheostomy tube is required and they should also be considered for use in more routine anaesthetic practice.


Urinary tract infections treated with single dose of short-acting sulphonamide.

In a prospective study 29 patients with urinary tract infections caused by sulphonamide-sensitive organisms were treated with a single oral dose of the short-acting sulphonamide sulphafurazole. Twenty-seven (93%) of the 29 patients--and possibly all 29--were cured of their infections. There was no difference in the recurrence rates after single-dose treatment and treatment for 10 days or more. Six out of eight strains of Escherichia coli causing early recurrences were sensitive to sulphonamides. These results suggest that uncomplicated infections may safely and successfully be treated by a single oral dose of a short-acting sulphonamide.


Severe hypernatraemia in adults.

In a prospective study of abnormalities of plasma sodium concentration carried out over one year 20 patients were identified who had a concentration exceeding 154 mmol(mEq)/1. Of these, eight patients had diabetes mellitus, eight had primary intracranial disorder, and four had become dehydrated. Five of the eight diabetics presented with hyperosmolar, non-ketotic precoma, and in all eight hypernatraemia developed despite treatment with hypotonic (0.45%) saline. There was a good correlation (r = -0.93) between the rates of change of plasma sodium and blood glucose concentrations, and thus a rise in plasma sodium concentration appeared to be a consequence of the treatment. In the early phase of treatment urinary sodium loss was extremely low despite a brisk diuresis, the infused sodium then predisposing the patients to hypernatraemia. All of the eight patients with intracranial disorders showed evidence of abnormal production of the antidiuretic hormone, six having frank diabetes insipidus. Severe hypernatraemia in this group was associated with a high mortality, fluid balance being difficult to maintain. Two of the four patients who had become dehydrated had had a recent gastrointestinal haemorrhage. In these patients infusion of 0.9% saline contributed to the hypernatraemia since urinary sodium loss was low. Severe hypernatraemia in adults is uncommon, but in established cases plasma and urinary biochemical indices should be measured frequently. Monitoring of the central venous pressure is usually necessary, and patients are best managed in an intensive care unit.


Fibromuscular dysplasia of the renal arteries.

Two cases of severe fibromuscular dysplasia of the renal arteries are described in which the diagnosis was made 12 and 11 years after renal angiography had shown the arteries to be normal. The discovery of hypertension preceded the diagnosis by two and 11 years respectively, and in one case hypertension was present at the time of the normal renal angiogram. The report suggests that fibromuscular dysplasia of the renal arteries is acquired and may not be present from birth. The importance of regular review in cases of severe hypertension is emphasised.


Extended role for general practitioners in obstetrics? A medical audit.

A study was designed to evaluate provision of services, process of medical care, and outcome in four general-practitioner obstetric units in isolated areas (Berwick, Whitby, Guernsey, and Brecon). All units were equipped to induce labour; to perform instrumental vaginal delivery and selected breech deliveries; and to remove placentas manually. All had some fetal monitoring equipment. Caesarean sections could not be performed at Berwick and Whitby. Proportions of normal deliveries during 1976-7 varied from 75% to 93%. Perinatal mortality was acceptably low, as were transfer rates for neonates and mothers in labour. With specialist help and particular attention to training and broadening local doctors' experience of abnormal obstetrics, such units should be able to provide an excellent obstetric service.


Obstetric history of diabetics: its relevance to the aetiology of diabetes.

The birth weights of infants born to patients with insulin-dependent diabetes (IDD) and insulin-independent diabetes (IID) before the disease was diagnosed were compared. An appreciable excess of infants above the 90th centile for weight was found, the proportions being 27% of infants born to mothers with IDD and 30% of those born to mothers with IID. These findings suggest that many patients with both types of diabetes have a prolonged period of metabolic abnormality before overt symptoms of diabetes arise and that the apparent acute onset of the disease in patients who are insulin dependent is illusory.


Evidential value of the hospital record in clinical decision making.

A simulated retrospective exercise in the diagnosis and management of 53 readmissions to a gastrointestinal unit was undertaken by two consultants. Diagnosis of the illness at readmission was made on evidence sought from a referee, who also supplied, on request, items of relevant evidence from the past medical record. Patient management was agreed from these sources. For each item of evidence the evidential weight, the irrecoverability, and the expected benefit accruing to the patient of its availability was calculated. It was concluded that the evidence worth recording in the event of subsequent hospital admission could be largely specified for each diagnosis and each operation. It would be brief and could be numerically coded.


Biochemical testing for acute medical emergencies in four district general hospitals.

Comparable samples of 200 medical emergency admissions in four district general hospitals showed a threefold difference in the mean number of biochemical test values provided per patient, nearly all of which were obtained from blood specimens. Hospitals had consistently high or low mean numbers of values per patient for specific tests and clinical presentations and whether first or repeat tests were considered. Only 30 out of 188 different test types were reported at all four hospitals. Clinicians and chemical pathologists might benefit from regular expert advice on the most discriminating use of test information in cases with various clinical presentations.


Assessment of tine tuberculin test.

Mantoux (10 tuberculin units) and tine tuberculin tests were performed in 190 subjects and the results recorded at 48, 72, and 96 hours. Altogether 1010 readings were recorded. Of these, 555 (55%) were Mantoux-test positive and 525 (52%) tine-test positive. While the tine test is marginally less sensitive, its advantages are simplicity and ease and speed of application. It thus provides a useful screening test for eliciting tuberculin sensitivity.


Incidence and outcome of symptomatic urinary tract infection in children.

The incidence of symptomatic urinary tract infection in 2879 children aged under 15 years was studied over 18 months in a single general practice. Infection was diagnosed if bacterial counts in three consecutive samples exceeded 100,000/ml. The incidence of urinary tract infection was 1.7 per 1000 boys at risk per year and 3.1 per 1000 girls. These values are lower than those of comparable studies, possibly because of the stricter diagnostic criterion used in the study. Urinary pus cell counts were also carried out and sometimes found to be misleading. Of the 14 children found to have an infection, three had a radiological abnormality. Five of the children had a recurrence of infection within the first two years, and one an asymptomatic bacteriuria seven years after diagnosis. Only six out of 34 children presenting with dysuria had infected urine, and an association was discovered between abacterial dysuria (or the urethral syndrome) in the remainder and a concurrent upper respiratory tract infection. All children should undergo radiological investigation after their first confirmed infection. Diagnosis and management could be improved by providing all general practitioners with a semiquantitative method of urine culture such as the dip slide.


Accuracy of diagnostic content of hospital activity analysis in infectious diseases.

Hospital activity analysis (HAA) was used to identify 2151 patients in whom the diagnostic code fell within the infectious disease categories of the International Classification of Disease. The clinical notes of these patients were examined by a doctor and in 414 (19.2%) the diagnostic coding was incorrect. Diarrhoea and viral infections were miscoded most often. The possibility of inaccuracy must be considered when HAA aggregated data are used for planning purposes. Accuracy could be improved if clinicians routinely completed the diagnostic sections of the HAA form.


Management of maternal phenylketonuria: an emerging clinical problem.

The children of untreated phenylketonuric women have a significantly higher mortality and morbidity than average. The success of neonatal screening for phenylketonuria (PKU) means that an increasing number of healthy intelligent women with PKU are reaching childbearing age and will create a new therapeutic problem for physicians and obstetricians in the next decade. This unit managed six mothers with PKU and treated three of them with diets throughout four pregnancies. The treatment and outcome was assessed in relation to those in other reported cases. Although treatment was beneficial in the four pregnancies studied directly, in all the reported cases the outcome of treatment varied considerably and was not clearly related to any one factor such as onset of treatment or the type of PKU. It is therefore not possible to give confident advice about the management of such cases. Since the number of women at risk will reach a peak in 10 years' time there is an immediate need for a well-planned prospective study of this problem.


Evaluation of one-visit endoscopic clinic for patients with dyspepsia.

An evaluation was made of the feasibility of an instant upper-gastrointestinal endoscopy clinic for patients referred to hospital for the investigation of dyspepsia. A total of 200 patients underwent endoscopy using a small-diameter endoscope with only topical pharyngeal anaesthesia but no premedication or sedation. The procedure was successful in 187 of the patients. Its acceptability was high for both patients and doctors. The average duration of the hospital visit was 45 minutes. Instant endoscopy with a small-diameter endoscope provides a convenient and fast primary diagnostic service for patients with dyspepsia.


Hospital antibiotic policy in a health district.

A hospital antibiotic policy is described in which only a few antibiotics were used over a two-year period. Six antibiotics--namely, ampicillin, cloxacillin, cephradine, penicillin, erythromycin, and oxytetracycline--accounted for 98% of the antibiotics consumed. Gentamicin was not used topically. Apart from high levels of resistance to ampicillin in Staphylococcus aureus (80%), the Enterobacteriaceae (37%), and Bacteroides (83%), antibiotic resistance was not a problem and no major epidemics of cross-infection occurred. With this policy antibiotic consumption declined and the total true cost of the antibiotics fell from 16 361 pounds in 1976 to 10 448 pounds in 1978.


Comparison of central nervous system malformations in spontaneous absortions in Northern Ireland and south-east England.

A study of 1140 pregnancies ending in spontaneous abortion disclosed a central nervous system (CNS) malformation in 4.9% of all complete conceptuses. Life-table analysis suggested that the incidence of CNS malformations is 16/1000 at the beginning of the eighth week of gestation. It was also estimated that only one-fifth of these infants are born alive, 41% being aborted spontaneously and 38% stillborn. A hypothesis that differences in the incidence of CNS malformations result from area differences in the mortality rate of malformed embryos and fetuses was examined by comparing the findings in Northern Ireland, an area of high incidence, with those in south-east England, an area of low incidence. In Northern Ireland 4.6% of complete conceptuses had a CNS malformation compared with 3.0% in south-east England, but the difference was not statistically significant. There is no evidence that in Northern Ireland a lower mortality rate among malformed fetuses and embryos is responsible for the high incidence of malformation at birth. The geographical variation of CNS malformations in the United Kingdom still awaits explanation.


Continuing mortality and morbidity from smallpox vaccination.

Three cases of cross-infection after smallpox vaccination are described, in two of which the outcome was fatal. Probably all occurred because simple precautions were not observed at the time of vaccination--for example, exclusion of contraindications and warnings about risks. If those countries still requiring evidence of vaccination for entry were to abolish this rule, however, the risk of cross-infection could be eliminated. Vaccinating a person with contraindications is justified only when exposure to smallpox has occurred.


Intensive care in tetanus: management, complications, and mortality in 100 cases.

One hundred cases of tetanus were treated in the intensive care unit of Leeds General Infirmary during during 1961--1977. In 90 patients disease was severe enough to require paralysis and artificial ventilation; a further three needed tracheostomy but not paralysis; and in seven the condition was mild, requiring sedation only. Ten patients died, but all deaths were attributable to complications of treatment rather than to the disease itself and were theoretically avoidable. No evidence of permanent neurological damage from tetanus was found. In 65 patients a wound was the source of infection, most of which were minor, often receiving no medical attention. In five patients the source was probably varicose ulcers of the leg. Such patients, if lacking immunity, are at risk, particularly when farming or gardening. Only two patients had received a full course of tetanus toxoid, in one case eight years and in the other three years before injury; neither received a booster dose at the time of injury and in the second tetanus was mild. Of the 35 patients who did seek medical attention at the time of wounding, 21 received prophylactic antibiotics and 25 tetanus toxoid, but none received equine or human antitetanus serum. Early resort to tracheostomy and paralysis in severe tetanus resulted in a favourable mortality of 10% in the series. To implement such a policy full intensive-care facilities, with a trained nurse to care for each patient, must be available at all times.


Therapeutic effect of oral doxycycline on syphilis.

Fifty-one patients with syphilis were treated with oral doxycycline. A course of the antibiotic treatment consisted of 200 mg of doxycycline daily in two divided doses for 28 days. The courses were repeated three to four times a year with an interval of several months. Quantitative Venereal Disease Research Laboratory (VDRL), Wassermann reaction (WR), and Treponema pallidum haemagglutination assay (TPHA) tests were performed monthly to evaluate the therapeutic effect of doxycycline treatment. The response rate was 100% for primary, 90% for early, 68% for late, and 90% for congenital syphilis in adults. No notable side effects were encountered except for epigastric fullness in one patient, which did not require the treatment to be discontinued. No abnormalities were detected in the results of laboratory tests.


Vaccination for herpes simplex genitalis.

Type-specific vaccines containing heat-inactivated herpes simplex hominis virus type 1 or 2 have been developed for the treatment of herpes simplex genitalis. When patients with recurrent herpes genitalis were treated with the type 2 vaccine the clinical course of the disease improved and the eruption-free interval was extended. In severe cases, especially in permanent genital herpes, the concurrent administration of vaccine and immunoglobulin concentrates improved the clinical course of the disease. Antibody titres and the in-vitro stimulation of lymphocytes with phytohaemagglutinin or herpes simplex hominis virus antigens remained constant during administration of the vaccine.


Therapeutic aspects of herpes genitalis. A short review.

The treatment of manifestations of infection by herpes simplex hominis virus must be aimed at both the local eruptions and the mechanism of recurrence. Recently, some success has been achieved with the use of vaccines and other agents to stimulate a cell-mediated immunity in patients with recurrent herpes infection.


Epidemiology of gonorrhoea and syphilis in South Australia (1966--77).

Data from the annual general report of the Venereal Disease Control Centre (VDCC) in a state with a population of approximately 1 250 000 people (in 1977), of whom about 1 100 000 live within 25 miles of the centre of Adelaide, the capital city, are presented.


Epidemiological importance of concealed nongonococcal urethritis.

Of the 229 806 new male patients attending venereal disease clinics in England in 1976, 31.9% had recognisable non-specific genital infection (NSGI), which was easily the most common diagnostic category of the sexually transmitted diseases (STDs) and one which had increased more markedly than all the others in the previous 25 years. Many more cases of nongonococcal urethritis (NGU) are concealed under the diagnosis of gonorrhoea, as is clear from the high incidence of post-gonococcal infection following treatment with penicillin. From 44% to 56% of male patients with gonorrhoea can also have non-specific genital infection during the same year. A practical treatment schedule for gonorrhoea which is also effective against simultaneously acquired non-gonococcal urethritis would be of great value.


Attenuated yaws in Surinam.

Results of a pilot survey in the central, northern region of Surinam indicate that yaws is prevalent (hypoendemic) in this part of the country. No classical symptoms of yaws were seen. The observed lesions were scanty or solitary, dry papillomatous, or macular and scaly, which fits into the clinical picture of attenuated endemic treponematosis.


Myelin protein composition in the rat spinal cord in culture and in vivo: a developmental comparison.

Biochemical characterization of the development of myelin in vitro was extended to an analysis of myelin protein composition in cultures of explanted foetal rat spinal cord. Myelin fractions were isolated from pooled explants after 12-30 days in vitro and, for comparison, from the spinal cords of rats of equivalent developmental ages. Electron microscopic examination of the culture myelin fractions revealed the presence of multilamellar myelin fragments and some single membranes. All fractions were analyzed using a micro-polyacrylamide gel electrophoresis technique. Qualitatively similar protein profiles were observed for myelin isolated from either cultures or from spinal cords. Fractions from cultures contained a greater proportion of high molecular weight proteins than those from spinal cords, although with respect to the 'major' myelin proteins, a quantitatively similar developmental pattern was observed both in vivo and in vitro.


Rapid loss of nicotine-cholinergic receptor binding activity in the deafferented avian optic lobe.

The levels of alpha-bungarotoxin (alpha-BuTX) sensitive receptor sites were investigated in the optic lobe after optic deafferentation in the neonatal and adult chicken. Within two days a 30% loss of alpha-BuTX binding sites per optic lobe is observed in the neonatal chick after enucleation. The results are similar with the adult chicken in experiments where the receptor binding activity is measured in the optic lobe and in the optic tectum after enucleation. The possibility that acetylcholine is a neurotransmitter in the vertebrate retinotectal pathway is discussed.


Response properties of units in the lateral geniculate nucleus of the domestic chick (Gallus domesticus).

One hundred and four visual units of the (ventral) lateral geniculate nucleus (GL) of chicks (Gallus domesticus) were studied with extracellular microelectrodes. Most were extremely responsive to moving targets even at low speeds (0.1 degrees/sec). They were classified as follows. (1) movement-sensitive units with uniform, restricted receptive fields (47%). (2) Movement-sensitive units with small receptive fields possessing regions responding to differing modes of stimulation ('center-periphery units'). (3) Movement-sensitive neurons with uniform, wide receptive fields, larger than 75 degrees x 65 degrees (15%). (4) Movement-insensitive cells, responsive only to illumination changes (7%). (5) Units with indeterminate receptive fields, a poor visual response or a poor response to movement (14%). The firing of neurons in classes I-III was mostly an accurate function of target speed; half of them also provided accurate monitoring of the beginning, course and termination of target movement (tonic units). In view of the above, the high proportion of directionally selective cells (31%) and the large size of many of its receptive fields, the GL is considered as a candidate structure for optomotor integration but the evidence is otherwise scant. There is, however, an apparent contribution to its unit properties from both retinal ganglion cells and neurons from different tectal layers. Whatever its role, it is unlikely to be the functional homologue to the mammalian ventral lateral geniculate as the unit properties of two structures differ substantially.


Enhancement of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of anticonvulsant action.

Murine spinal cord neurons grown in dissociated cell culture were used to study the effects of barbiturate (phenobarbital, mephobarbital) and benzodiazepine (diazepam, chlordiazepoxide( anticonvulsants on amino acid responses. Both types of anticonvulsant augmented GABA-mediated postsynaptic inhibition without augmenting beta-alanine or glycine-mediated postsynaptic inhibition. Barbiturates, but not benzodiazepines, antagonized glutamate-mediated postsynaptic excitation. Augmentation of GABA-mediated inhibition by the anticonvulsants should contribute to their anticonvulsant action; antagonism of glutamate-mediated excitation by barbiturates should also contribute to their anticonvulsant action and could be at least in part responsible for their sedative actions.


Differential effects of veratridine and potassium depolarization on neuronal and glial GABA release.

The effect of veratridine and potassium depolarization on the release of [3H]GABA from neural tissues in which GABA uptake is neuronal (cerebrocortical slices and frog retina) or glial (rat retina, spinal and sympathetic ganglia) was studied. The 'neuronal' but not the 'glial' release of [3H]GABA was greatly increased by KC1 (25 mM) and veratridine (10 microM). The 'neuronal' release of [3H]GABA evoked with KC1 was calcium dependent but the small potassium induced increase in 'glial' release were not reduced in the absence of calcium ions even when additional Mg2+ was included in the medium. Surprisingly, the veratridine induced release of [3H]GABA from cortical slices was greatly potentiated in calcium free medium although the release of [3H]noradrenaline produced by veratridine was calcium dependent. Because of the insensitivity of the glial GABA release mechanism to potassium depolarization, it is concluded that release of endogenous GABA from glial pools in response to physiological increases in extracellular potassium is unlikely to be important.


Intercellular junctions and the development of the blood-brain barrier in Manduca sexta.

In early embryonic development of the tobacco horn moth no blood-brain barrier is present, as shown by the unimpeded entry of exogenous tracers into the nervous system. However, later on, just before hatching, lanthanum and horseradish peroxidase (HRP) are unable to move inwardly beyond the level of the perineurium, which is the morphological site of the blood--brain barrier in the adult moth, as well as in other insects. Freeze-fracture studies indicate that in the early embryo, 10 nm particles are scattered about in the perineurial membrane PF, either as separate entities or as short linear arrays. By hatching or just before, however, the 10 nm particles have become aligned into lengthy linear aggregates as PF ridges with EF grooves. These would appear to be the simple, arthropod-form of tight junction, and are presumed to be the basis of the perineurial blood-brain barrier. At about the same time, gap junctional elements appear both between adjacent perineurial cells and between glial cells. In both cell types, the gap junctions form from free 13 nm EF particles which gradually become aligned or clumped into strands and aggregates which ultimately coalesce to form first irregular masses and then the macular plaques typical of mature gap junctions. Many of the latter stages are coincident with the hatching of a motile larvae, so that the perineurial and glial cells are by this stage coupled via the channels of the gap junctional particles. They are therefore able to undergo both ionic and metabolic exchange and cooperation during larval life, in addition to being able to respond to hormonal substances in an integrated way. During the 5 larval instars more gap junctions form as the perineurial layer grows thicker. These junctions become more regular in outline and their particles more tightly packed; these larval structures are compared with junctions found in the adult which tend to be more extensive but otherwise similar. Since no septate junctions are apparent during Manduca embryonic or larval life when the blood-brain barrier forms, nor in adults, the results of this report support the contention that it is the tight junctions rather than septate ones which form the basis of permeability barriers in this, and probably other, arthropod systems.


An 125I-labeled binding probe for the muscarinic cholinergic receptor.

We describe the synthesis and characterization of [125I]3-quinuclidinyl-(3-iodo-4-hydroxy-benzilate), a binding probe for the muscarinic cholinergic receptor of high specific radioactivity. The binding isotherm of this 125I-labeled compound to a rat synaptic plasma membrane-enriched fraction consists of two components: a 'specific' component which is saturable and closely fits hyperbolic binding to a single class of sites as evaluated by Scatchard analysis (Kd = 1.5 to 3 nM), and a linear component which may be measured directly by preincubating membranes in 0.1 microM 3-quinuclidinyl-benzilate, the most potent muscarinic antagonist known. The specific binding of [3-3H]3-quinuclidinyl-benzilate and [125I]3-quinuclidinyl-(3-iodo-4-hydroxy-benzilate) to rat brain subcellular fractions is parallel in myelin, synaptic plasma membrane and mitochondrial fractions with a 3--4-fold enrichment observed in synaptic plasma membrane over crude mitochondrial fractions. The concentrations of muscarinic antagonists required to block [125I]3-quinuclidinyl-(3-iodo-4-hydroxy-benzilate) binding parallel that reported for tritiated binding probes and are consistent with physiological measurements of their dissociation constants. Because of the high specific radioactivity of [125I]3-quinuclidinyl-(3-iodo-4-hydroxy-benzilate), this iodinated binding probe should prove useful in assaying low levels of muscarinic receptor in tissue culture and other biological sources.


Characterization of the calcium-induced disruption of neurofilaments in rat peripheral nerve.

Transverse frozen sections of desheathed rat peripheral nerve were incubated in media of different composition prior to fixation and processing for electron microscopic examination. Neurofilaments remained intact when these tissues were incubated in calcium-free media. A loss of neurofilaments and their replacement by granular debris occurred in myelinated and unmyelinated fibers following incubation in media containing 2 mM calcium. The calcium-mediated disruption of neurofilaments was inhibited by preincubation or incubation with 1 mM p-chloromercuribenzoate (PCMB). The inhibition by preincubation with PCMB could be partially reversed by subsequent preincubation with 10 mM dithioerythritol (DTE). Calcium-mediated breakdown of neurofilaments did not occur after prolonged preincubation in calcium-free media, a finding which suggested that neurofilament disruption was dependent upon a tissue factor which could be lost or inactivated in frozen-sectioned nerve tissues. The findings of the present study provide morphological evidence that neurofilament disruption in mammalian peripheral nerve is mediated by a calcium-activated, PCMB-sensitive enzyme in the axoplasm of myelinated and unmyelinated nerve fibers.


An autoradiographic study of the chick brain after imprinting.

On the first day after hatching domestic chicks were exposed to an imprinting stimulus, a horizontal yellow slit of light moving upwards in a window and presented at a rate of 4 slits/sec. Chicks were exposed for either 45 min (undertrained) or 180 min (overtrained) on the first day of hatching (60 or 240 min in the case of 1 pair). On the second day all birds were exposed for a further 63 min. Twenty birds were matched in pairs and each chick received 1.1 muCi [14C]uracil/g body weight injected into the heart region before exposure on day 2. At 150 min after the injection the chicks were decapitated and serial coronal sections of their brains cut; alternate pairs of sections were prepared for autoradiography. The optical density for a number of major anatomical regions was measured. The measurements for each region were averaged over congruent to 0.6 mm 'slabs' of brain and expressed as a percentage of the mean of all measurements for that brain. Standardized mean optical density was significantly greater in undertrained chicks than in overtrained chicks in a part of the medial region of hyperstriatum ventrale (MHV) which extended across two adjacent slabs. The slabs were slightly posterior to the mid-point between anterior and posterior poles of the brain. In the next two, adjacent, anterior slabs the variances for MHV were significantly greater in undertrained chicks than in overtrained chicks. There were no other significant differences between brain regions. Taken together with previous studies these results suggest that the intermediate and medial part of hyperstriatum ventrale is intimately linked with the imprinting process.


Morphology of dissociated hippocampal cultures from fetal mice.

Dissociated hippocampal cultures from fetal mice (13--18 days gestational age) can be maintained for up to two months in culture. Cells grow as either isolated neurons or in small neuronal aggregates. Neurons remain small with a soma diameter of 15--20 micrometer even in mature cultures and develop extensively branched processes during the first two weeks in culture. After this time, processes become more difficult to visualize with phase-contrast optics because of a tendency to grow within the underlying non-neuronal cells. However, the presence of processes has been proved by silver-staining which demonstrates an organizational complexity ranging from a loosely reticulated neuropil to fascicles containing many fibers. More detailed study of individual neuronal morphology was carried out in cells filled with the fluorescent dye, Lucifer Yellow CH, in conjunction with the intracellular recording of synaptic and action potentials from dye-containing micropipettes. Dye-filled cells show a well-developed branching morphology. Process specializations include spines, beading, and basket-like endings. Processes tend to emanate from one side of the soma, either originating at the cell body or from a single trunk. Commonly there are 2--4 orders of branching, but up to 6 orders can occur (counted centrifugally from the soma). Electron microscopy revealed synapses distributed predominantly on dendrites with a smaller number on somata. Dendritic spines are present and are contacted principally by asymmetric synaptic junctions. Symmetric synapses are relatively more common on somata and proximal dendrites.


Electrophysiology of dissociated hippocampal cultures from fetal mice.

Action potentials, postsynaptic potentials (PSPs) and burst potentials have been recorded intracellularly from over 200 neurons in hippocampal cell cultures prepared from fetal mice of 13-18 days gestational age. Repetitively firing action potentials are elicited by intracellular electrical stimulation and often are preceded by stereotyped prepotentials which probably are generated on processes remote from the cell body. In some cells, action potentials are succeeded by long duration depolarizing afterpotentials (0.3--2 sec) with additional superimposed action potentials. Postburst afterhyperpolarization can last up to 2.5 sec. Action potentials are short (0.6--1.2 msec) with peak rates of rise from 64 to 267 V/sec (mean 139 +/- 13 V/sec, 24 cells) and corresponding rates of fall from 21 to 133 V/sec (mean 70 +/- 7 V/sec, 24 cells). Following single action potentials, the afterhyperpolarization is usually less than 10 msec. Inhibitory PSPs occur frequently (up to 70% incidence), have reversal potentials of--30 to--40 mV, and can be evoked in synaptically coupled cell pairs. Excitatory PSPs can initiate prepotentials and action potentials, suggesting dendritic and somatic loci respectively. Neural networks exhibit a broad range of electrophysiologic phenomenology including reciprocal innervation, multiple innervation and synchronous bursting among a widespread population of neurons.


Morphology of catecholamine-containing amacrine cells in the cat's retina, as seen in retinal whole mounts.

The morphology of catecholaminergic cells of the cat's retina was studied by fluorescence microscopy of retinal whole mounts. Although varied in soma shape, these cells seem to represent a single group of cells with an average soma diameter of 14.5 micrometer in freeze-dried material. The fluorescent terminals of these cells formed a striking two-dimensional pattern: a significant portion of them appeared to be arranged in rings located at the boundary of the inner plexiform and inner nuclear layers. The mean diameter of these rings was 9.7 micrometer and their pattern appeared to extend unbroken across the retina. It was, in general, not possible to observe the connection between these rings and fluorescent somas, except when a ring was in a juxtasomatic position. It is suggested that the postsynaptic somas within these rings are either of other amacrines or of interplexiform cells. Using the Golgi-Colonnier technique on retinal whole mounts, an attempt was made to identify the cell type which resembles the catecholaminergic cell in its size, location and morphology. The suggested cell type appears to be among the largest amacrine cells, (mean soma size of 11.5 micrometer in Golgi material) with a considerable dendritic network at the border of the inner plexiform and inner nuclear layers, although there are branches reaching as far as the middle of the inner plexiform layer.


Regional differences in the timing of synapse elimination in skeletal muscles of the neonatal rabbit.

The time course of disappearance of polyneuronal innervation during development was studied electrophysiologically in skeletal muscles of the rabbit. There were differences of up to a week in the estimated time of onset of synapse elimination in various muscles, with a tendency for the process to begin earlier in muscles situated more anteriorly in the body. There were also differences among muscles in the peak rate of synapse loss during maturation, but these differences do not appear to be related to position in the body or to contractile properties of the muscle.


Electrophysiological studies on the neural networks among estrogen and progesterone effective brain areas on lordosis behavior of the rat.

The present study was performed in an attempt to elucidate the possible neural networks and their functional modification by progesterone among estrogen and progesterone effective brain areas for lordosis behavior of the rat. Single and multiple unit activities were recorded in the medial preoptic area (MPO), dorsomedial thalamic nucleus (MD), interpeduncular nucleus (IP) and ventral part of midbrain reticular formation (MRF), and single or train pulse stimulation was applied to the MPI, MD, IP, MRF, caudate-putamen (CP), habenular nucleus (HB), dorsal hippocampus (HPC), medial and lateral septum (m- and 1-SEPT) and lateral amygdala (1-AMYG). Unit activity was recorded under urethane anesthesia in ovariectomized rats pretreated with estrogen or with estrogen and progesterone. MPO units showed facilitatory responses to stimulation in the MRF, HB and 1-SEPT, and inhibitory responses to stimulation in the MD, HPC, m-SEPT and 1-AMYG in ovariectomized estrogen-primed rats. CP stimulation inhibited the MD unit activity. Stimulation in the IP had no effect on the MPO or MD units, while the IP units were affected by stimulation in the MPO, MD, CP and HB. MRF unit was accelerated by the MD and CP and inhibited by the MPO stimulation. In the ovariectomized, estrogen and progesterone-treated rat, the MPO unit responses to the MRF and MD stimulation, and the MD unit responses to the MRF and CP stimulation were different from those in the rat with only estrogen treatment. In addition, in the ovariectomized estrogen-primed rat, local application of progesterone to the MD prevented the inhibitory effect of the MD on the MPO unit. Progesterone, when given to the stimulated brain area, accelerated the MPO unit which was activated by the MRF stimulation, and inhibited the MD neuron which was inhibited by the CP stimulation. Multiple unit recordings showed similar results. Moreover, multi-unit activity in the HB and IP was elevated following a systemic progesterone application. On the basis of these results, the possible neural networks in the brain which participate in the lordosis control mechanisms are discussed.


Influences of pituitary-adrenal hormones on kindling.

The kindling process represents a progressively augmenting electrical and behavioral response to brain stimulation, that has been proposed as a model for the development of epileptogenesis. The first experiment examined the effects of hypophysectomy on the kindling process. The effects of hypophysectomy were found to be dependent on the number of days between hypophysectomy and the beginning of kindling. The kindling rate was slowed, compared to intact controls, when hypophysectomy was performed less than 2 weeks prior to the first kindling stimulation. However, if more than 4 weeks and passed since hypophysectomy, the kindling rate was faster than that of intact controls. The second experiment tested the influence of systemic administration of cortisone (10 mg/animal), upon kindling of control and hypophysectomized animals. Cortisone was found to reverse the kindling deficit of hypophysectomized animals at less than 2 weeks and to slow kindling of intact controls, but to have no effect on hypophysectomized animals at more than 4 weeks (at this dose). These results are interpreted as indicating that pituitary-adrenal hormones have profound influences on the kindling process, but it is unclear whether the influence is upon brain excitability or more directly upon modification of synaptic function.


Aging and unusual catecholamine-containing structures in the mouse brain.

Brains of C57BL/6J mice, aged 4, 8 and 20--29 months, were examined by the Falck-Hillarp histochemical fluorescence technique. Numerous large, intensely fluorescent green to yellow-green spots (LIFS) were observed in the brains of senescent mice. LIFS were generally round to ovoid in shape and ranged in size from about 10 micrometer to about 30 micrometer. Histochemical and pharmacological procedures and spectral analysis indicated that the formaldehyde-induced fluorescence of the LIFS was due to the presence of catecholamines (CA) rather than aging pigment. Their distribution in the brain suggests an association with nerve axons or terminals rather than cell bodies. The number of LIFS in the hypothalamus increased progressively during aging. It is proposed that LIFS may represent age-related, unusual CA accumulation in enlargements proximal to axonal or terminal portions undergoing spontaneous degeneration.


Effects of transecting lateral neural connections of the medial preoptic area on maternal behavior in the rat: nest building, pup retrieval and prolactin secretion.

In lactating female rats bilateral parasagittal cuts transecting the dorsolateral neural connections of the medial preoptic area (MPOA) abolished nest building and retrieving components of maternal behavior, while crouching and nursing were unaffected. While few animals with these cuts were suckled when presented with pups the prolactin secretion response was undiminished when suckling did occur. Whereas previous studies have demonstrated that extensive surgical separation of the medial preoptic area-anterior hypothalamic continuum from the lateral preoptic area-lateral hypothalamus disrupts all aspects of maternal behavior, the present study has determined more specifically the zone of fibers essential for the active components of maternal behavior, i.e., nest building and retrieving. These fibers appear to enter/leave MPO dorsolaterally beneath the crossing of the anterior commissure in the region of the bed nucleus of the stria terminalis. These neural connections are not the same as those that regulate prolactin secretion in the lactating rat.


Operant conditioning of vertical eye movements without visual feedback in the midpontine pretrigeminal cat.

An operant conditioning of vertical eye movements was achieved in the midpontine pretrigeminal cat in total darkness by contingent reinforcement of spontaneous eye movements with lateral hypothalamic (LHT) reward stimulation, when each movement (upward direction was chosen in this experiment) exceeded a preset amplitude. However, the response rates in the dark were lower than those in the light and the time to reach the peak response rate was much longer. Recording of evoked potentials to optic chiasma (OC) stimulation revealed enhancement of late components of the visual cortex (VC) and superior colliculus (SC) responses in relation to eye movements. Sequential records of the averaged evoked responses associated with eye movements indicated that the amplitudes of the late components of the VC and SC waves gradually increased in the course of establishment of the operant conditioning, and decreased gradually during extinction. In a yoked control test, increase in amplitudes of the late components was much less significant during non-contingent reinforcement given independently of the eye movements. These results suggest that 'corollary discharge' may play a critical role as a cue in acquisition of the operant conditioning of vertical eye movements when visual feedback is absent in total darkness.


The relationship of Schwann cell migration in vitro to injury, using normal, Wobbler, and dystrophic mice.

A quantitative in vitro study of the cellular outgrowth from mouse sciatic nerve explants has been carried out using both normal untreated nerves and nerves taken at various times after the in vivo application of trauma. The results obtained have been compared with the results for outgrowth from sciatic nerve of two neurological mutants: 'the Wobbler mouse' and the 'ReJ 129 Dystrophic mouse'. It has been shown that the in vitro response to peripheral injury does reflect the activity known to occur in vivo. Outgrowth from explants of mutant mouse nerves, although differing from normal has been found to be less profuse than that occurring after mechanical nerve injury.


Computer separation of unitary spikes from whole-nerve recordings.

A practical and efficient off-line computer technique is described for automatically separating unitary waveforms from multiunit whole-nerve spike train data with no a priori knowledge about the number of units or their waveforms. The procedure requires two recording eletrodes which provide 3 measures on each putative unit: (1) peak-to-peak amplitude on the proximal channel, (2) amplitude on the distal channel, and (3) temporal offset (depends on conduction velocity) between proximal and distal spikes. On the basis of these 3 measurements, individual unitary spikes are automatically separated into clusters according to empirically-determined limits of variability. The results of the program are displayed in 3-D plots of the 3 measures on each unitary spike and in plots of superimposed waveforms from each cluster. These plots can be used to interactively correct clustering errors. The procedure is illustrated with a 1-min segment of spike train data recorded in vivo from the siphon nerve of a freely-behaving Aplysia. We routinely obtain about 10 relatively well-isolated units in such segments. By utilizing the average waveforms and conduction velocities for individual clusters, it may eventually be possible to separate unitary spikes from compound waveforms resulting from simultaneous of two or more units.


Participation of brain catecholaminergic neurons in a self-sustained circadian oscillation of plasma corticosterone in the rat.

Circadian rhythms of locomotor activity and plasma corticosterone were determined simultaneously in individual rats which were injected intraventricularly with 6-hydroxydopamine (6-OHDA), a specific depletor of catecholamines. In light-dark cycles (LD), 6-OHDA-treated rats showed essentially normal circadian rhythms of both functions. In 200 lux continuous light (LL) the locomotor activity in the drug-treated rats ran freely with a period slightly longer than 24 h: free-running parameters (mesor, amplitude and period) of the locomotor activity were the same as those control rats. The circadian rhythm of plasma corticosterone in control rats also ran freely in LL, resulting in a reversal of their phase after 12 days exposure to LL. However, the rhythm disappeared in 6-OHDA-treated rats under LL: instead in these rats 3--4 episodes of secretion were obsered over a 24 h period. These results suggest a difference in the biochemical background between the regulatory mechanism of circadian rhythm of locomotor actitivity and that of plasma corticosterone. It is also apparent that brain catecholaminergic components are indispensable for the circadian rhythm of plasma corticosterone to freerun normally in LL, but are dispensable in LD. A plausible model consisting of two oscillators is proposed to explain these findings.


Conformation of exocyclic amino groups in purines and pyrimidines: crystal structure and conformation of 1-methyl-N4-hydroxycytosine hydrochloride.

The hydrochloride salt of 1-methyl-N4-hydroxycytosine crystallizes in the triclinic space group P1 with cell dimensions: a = 8.232(1), b = 9.293(1), c = 5.416(1) A (1 A = 0.1 nm); alpha = 91.95(1), beta = 91.72(2), gamma = 71.56(1) degrees (SE in parentheses). The structure was solved by direct methods and refined to R = 3.7% for 1514 reflections. Despite the absence of an intramolecular hydrogen bond in the solid state, the N4-hydroxy substituent is syn to the ring N(3). This conformation, which probably prevails also in the neutral form, is of relevance to the mechanism of attack of cytosine by hydroxylamine, known to involve predominantly the cytosine cation, as well as to the mechanism of hydroxylamine mutagenesis. Such conformational aspects are also relevant to other phenomena, including translation and restriction.


Products of mitochondrial protein synthesis in Tetrahymena.

The products of mitochondrial protein synthesis have been investigated in Tetrahymena after labelling with [35S]methionine in the presence of cycloheximide. The labelled proteins were analyzed by sodium dodecyl sulfate slab polyacrylamide gel electrophoresis. We have identified 13 electrophoretically discrete bands as well as 4 other bands with a more variable occurrence. These proteins ranged in apparent molecular weight from 8100 to 57,500. The cycloheximide-resistant incorporation could be blocked with chloramphenicol. The mitochondrial proteins appeared to be in a disaggregated state and were stable to agents such as trichloroacetic acid (hot or cold) and chloroform-methanol. The pattern of proteins was similar following labelling times ranging from 30 min to 3 h.


Isolation and translation in vitro of poly(A)+RNA from the free-living nematode Panagrellus silusiae.

Polysomal RNA was isolated from the free-living nematode Panagrellus silusiae. Passage of this RNA through a cellulose column resulted in the fractionation of the input RNA into poly(A)-RNA (ca. 97.5% of the total) and poly(A)+ RNA (ca. 2.5% of the total). RNase digestion, followed by polyacrylamide gel electrophoresis, revealed that the poly(A)+ RNA contained poly(A) tracts that ranged from 75 to 104 nucleotides in length with a mean value of about 90 residues. There was no evidence of poly(A) sequences in the poly(A)- RNA fraction. Poly(A)+ RNA gave a 25- to 50-fold stimulation (over background) of amino acid incorporation in the wheat germ cell-free protein-synthesizing system. At least 26 proteins were evident after electrophoresis in cylindrical sodium dodecyl sulfate-polyacrylamide gels. Poly(A)-RNA was capable of stimulating protein synthesis in vitro with about five discrete proteins being produced. In summary, the properties of mRNA from a simple organism such as P. silusiae are very similar to those of more complex eukaryotes.


Characteristics of glutamine metabolism by rat kidney tubules: a carbon and nitrogen balance.

The metabolism of glutamine by a suspension of rat kidney tubules was studied in vitro. The influence of duration of incubation, glutamine concentration, and metabolic state of the donor animals was investigated. The relative importance of glucose synthesis, amino acid production, and oxidation to CO2 was estimated by drawing a complete balance of the nitrogens and the carbon chains of the extracted glutamine. It was found that the initial (first 15 min) rate of glutamine utilization was significantly greater than the subsequent rate due to an initial, but transient, extracellular accumulation of glutamate. This phenomenon was suppressed when a small amount of glutamate was added to the incubation medium. Glucose production constitutes the major fate for glutamine metabolism. No net oxidation of glutamine could be detected with 1 mM glutamine during the first 30 min. However, glutamine oxidation becomes significant after prolonged incubation (16% at 120 min). The metabolic fate of glutamine differs when 5 or 10 mM are presented to the tubules, glutamate production and oxidation to CO2 becoming more important. Metabolic acidosis or a 48-h fast increases glutamine extraction and enhances its utilization glucose synthesis while they depress glutamate accumulation and oxidation to CO2. Metabolic alkalosis has the opposite effect. It is concluded that the metabolism of glutamine in vitro is dependent on the conditions of the study. Furthermore, total oxidation to CO2 is not a major fate for glutamine metabolism at physiological concentration and is not enhanced by acidosis in the rat kidney in vitro.


Inhibition of carboxypeptidase A catalyzed peptide hydrolysis by 3-phenylpropanoate at activating and nonactivating substrate concentrations.

The carboxypeptidase A catalyzed hydrolyses of five structurally related dipeptide substrates in the presence of the inhibitor 3-phenylpropanoate have been studied. At nonactivating substrate concentrations, 3-phenylpropanoate is a mixed inhibitor of carbobenzoxyglycyl-L-phenylalanine hydrolysis and a noncompetitive inhibitor of the hydrolyses of benzoylglycyl-L-phenylalanine, cinnamoylglycyl-L-phenylalanine, hydrocinnamoylglycyl-L-phenylalanine, and acetylglycyl-L-phenylalanine. When carbobenzoxyglycyl-L-phenylalanine and benzoylglycyl-L-phenylalanine exhibit substrate activation, inhibition by 3-phenylpropanoate is mixed but appears to be mostly competitive. Proposed here is a site for the binding of 3-phenylpropanoate along with a kinetic mechanism consistent with these data.