The value of measuring intravascular platelet aggregates in the prediction of postoperative pulmonary dysfunction. A modified Swank screen filter technique was used to investigate, first, whether intravascular platelet aggregates (IPA) could be detected in patients immediately after surgery and then, the relationship between IPA levels and postoperative pulmonary function. The test, as modified, achieved an excellent reproducibility (r = 0.95) and a close correlation with the number of aggregates identified in samples of femoral vein blood by subsequent scanning electron microscopy (r = 0.93). In 20 patients IPA levels were measured 30 min and 3 h after surgery and pulmonary function (arterial PO2, physiological dead space and alveolar/arterial PO2 gradient) was evaluated preoperatively and on days 1 and 7 postoperatively. Patients with elevated IPA levels suffered a greater mean fall in arterial PO2 at 7 days (1.8 kPa) than did patients with normal IPA levels (0.6 kPa) (P less than 0.05). This was explained by a marked increase in the pulmonary arteriovenous shunt as indicated by the alveolar/arterial PO2 gradient (2.3 kPa v. 0.4 kPa, P less than 0.01). Those patients with increased pulmonary shunting and arterial hypoxia 1 week after surgery also had a greater fall in the platelet count on the first postoperative day. The screen filtration technique is a reproducible test which measures IPA accurately and may be used to predict pulmonary function 1 week later. This suggests that treatment to inhibit IPA may reduce postoperative pulmonary dysfunction.


Regulation of enterokinase synthesis in animal and human small intestine by luminal signals: its implication in upper gastrointestinal surgery. Enterokinase is an enzyme produced by the mucosa of the small intestine. Its sole function is to activate trypsinogen to trypsin. In animals and man the duodenum and proximal jejunum have high levels of activity whereas the remaining small bowel has minimal levels. A reproducible assay was developed for measuring mucosal enterokinase activity applicable to operative and endoscopic biopsies. Anaesthetic and operative techniques were developed for small intestinal resections in guinea-pigs to ensure their long term survival. Transposition of high-enterokinase-secreting segments of guinea-pig small intestine to low-enterokinase regions and vice versa showed no alteration of enterokinase activity in the transposed segments. Similarly, resection of the enterokinase region in five proximal pancreaticoduodenectomy operations in man revealed no induction of enterokinase in the remaining jejunum at endoscopy 6 months later. Isolation of high-enterokinase-secreting segments of small bowel from their luminal continuity by fashioning of Thiry--Vella fistulas led to a decay of enterokinase activity to minimal levels within 12--16 h. Perfusion of these fistulas with trypsin and sodium, or chymotrypsin and sodium, prevented this decay. If the enterokinase was allowed to decay over 24 h its activity could be restored to 80 per cent of its normal level by perfusion for 24 h with trypsin and sodium. Trypsin and sodium acti in combination on an enterocyte membrane receptor to stimulate enterokinase synthesis.


Plasma exchange and Raynaud's phenomenon--its assessment by Doppler ultrasound velocimetry. In a group of 47 patients with Raynaud's phenomenon, Doppler ultrasound velocimetry was used to establish the severity of the disease by detecting the patency of the digital arteries. In conjunction with small digital occlusion cuffs, digital artery systolic pressure was measured on either side of the finger. A significant variation in systolic pressure was detected in each finger, and on each side of individual fingers. A more sensitive index of the severity of the disease was noted when the digital systolic pressure was compared to the brachial systolic pressure. Plasma exchange, a potent method of lowering whole blood viscosity and plasma fibrinogen, was used to treat 18 of these patients. There was a significant improvement in digital vessel patency at both 21 degrees C and 13 degrees C after plasma exchange. Both the digital artery systolic pressure and the pressure index improved significantly after treatment.


Long term results of autogenous vein bypass grafts in femoropopliteal arterial occlusion. The results of 329 consecutive autogenous vein grafts carried out between January 1962 and June 1973 have been reviewed. The 5- and 10-year mortality rates were 14.6 per cent and 18.7 per cent respectively. The corresponding patency rates were 70 per cent at 5 years and 34 per cent at 10 years, the lowest patency (27.8 per cent) occurring in below-knee anastomoses with grafts of 5 mm or less in diameter. As other have noted, the state of the popliteal--tibial run-off vessels had a considerable influence on long term patency rates. In severely ischaemic limbs, the limb salvage rate following this operation was 77 per cent. An analysis of symptoms, associated disease and complications is presented and discussed. No valid conclusions could be made regarding the effect of lumbar sympathectomy and postoperative anticoagulants on long term patency. This review has confirmed the findings of earlier studies that a satisfactory 5-year patency rate and a gratifying limb salvage rate can be achieved with an extremely low operative mortality rate of 0.37 per cent. Despite the presence of widespread atherosclerotic arterial disease, the 5-year mortality rate is 14.6 per cent, indicating that an attempt at reconstructive surgery is usually well worth while.


Lesser curve superficial seromyotomy--an operation for chronic duodenal ulcer. Lesser curve superficial seromyotomy has been investigated in the dog and in man. The anatomical basis for the operation, which produces an easily performed denervation of the parietal cell mass, is discussed. Acid studies in the dog confirmed that the operation was capable of producing secretory inhibition in keeping with vagotomy of the parietal cell area. A consecutive series of 25 patients with chronic duodenal ulcer has been treated by lesser curve myotomy without a drainage procedure. The operation has the advantages of being easily performed and the risk of damage to the nerve of Latarjet or of ischaemic necrosis of the lesser curvature is obviated. In 20 insulin tests performed within the first month postoperatively all patients have been negative within the first 75 min and there were 4 late positive responses. Early clinical results have been encouraging, there has been no dumping or diarrhoea and all patients are well. It is suggested that further investigation of lesser curve myotomy is warranted.


Antibiotic-associated colitis--a review of 66 cases. We have reviewed 66 cases of antibiotic-associated colitis since March 1975, which have been associated with a 27 per cent mortality. We believe antibiotics may predispose patients to this condition which is caused by a toxin produced by Clostridium difficile. Although the disease is rare, it is more common than previously reported. The presentation, methods of diagnosis and treatment are discussed.


Anorectal Crohn's disease.

Anorectal Crohn's disease. Four hundred and twenty-three patients with Crohn's disease have been reviewed, 48 of whom had isolated anorectal involvement--an incidence of 11.4 per cent. These patients were compared with 48 randomly selected and sex-matched cases who presented with isolated ileocolic disease. The age of the anorectal patients (53.6 +/- 18 years) was greater than that of the controls (34.2 +/- 12 years). The duration of follow-up was 6.0 +/- 4 years and 12.6 +/- 8 years respectively. Rectal bleeding, diarrhoea and perianal disease were more common in the anorectal group. Twenty-two patients (46 per cent) with anorectal disease and 40 (83 per cent) in the ileocolic group underwent definitive surgery. There were 4 (18 per cent) postoperative deaths in the anorectal group and none among the controls. The incidence of recurrence was lower among the anorectal patients (21 per cent) compared with the ileocolic group (40 per cent). However, the estimated probability of recurrence, based on the duration of follow-up, the number of deaths during follow-up and the actual incidence of recurrence, is similar in both groups.


Bone scanning: its lack of value in the follow-up of patients with breast cancer. Three hundred and fifty-four women with primary operable breast cancer had a bone scan performed within 6 weeks of a simple mastectomy. Eight (2.3 per cent) were positive, but 7 of these patients had radiological evidence of bony metastases. Follow-up bone scans 1 year postoperatively on 278 patients showed only 12 (4.3 per cent) positive, and of these, 9 had other radiological evidence of metastatic disease. At 2 years postoperatively there were 13 (9.2 per cent) positive bone scans amongst 141 patients. Only 2 of these 13 had no other evidence of metastases. Although a bone scan is a useful investigation in patients with bone pain, there is no place for routine bone scanning in either the staging or follow-up of women with operable breast cancer.


Adjuvant cytotoxic liver perfusion for colorectal cancer. Colorectal liver metastases develop by malignant cells entering the portal venous circulation. A randomized prospective clinical trial was commenced in 1975 to assess the value of adjuvant umbilical vein cytotoxic perfusion (with 5-fluorouracil) following colorectal resection. One hundred and fifty-four patients without macroscopic liver secondaries have so far entered the trial. The mean age, sex, site and stage of the disease were similar in the control and perfusion groups and there was no statistically significant difference in postoperative complications or hospital stay (17.1 +/- 7.9 days control, 15.8 +/- 7.4 days perfusion group). So far, 23 deaths have occurred in the control group (20 due to recurrent disease) and 7 in the perfusion group (5 due to recurrent disease). Liver metastases were present in 13 control patients and 2 perfusion patients. These results show an encouraging trend and suggest that adjuvant cytotoxic liver perfusion may reduce the development of colorectal liver metastases and hence improve the subsequent prognosis.


Anticoagulant activity and operative blood loss after intrapulmonary heparin. The safety and efficacy of heparin given by the intrapulmonary route are further assessed in this study. A single dose of heparin (2000 units/kg) was given by intratracheal instillation in dogs and measurements of plasma heparin concentration, whole blood clotting time and partial thromboplastin time made at intervals for 48 h. These values rose progressively and in parallel for 7 h and remained elevated for 48 h. A series of operations was performed on dogs within 3 h of a single dose of intrapulmonary heparin (1500 units/kg). Operations involving minimal dissection (small bowel resection) and extensive dissection (resection of muscle) were performed in two separate groups. Within each group the animals were randomly given heparin or saline. In the limited dissection group there were no differences in operative blood loss, wound healing, or sequential haemoglobin and haematocrit measurements. In the group subjected to muscle resection there was increased postoperative wound drainage and a slightly greater fall in haemoglobin and haematocrit in those given heparin. It is concluded that heparin is absorbed from the lung causing significant changes in coagulation parameters. Even with the relatively high dose of 1500 units/kg, operations were performed with minimal hazard. Intrapulmonary heparin may have important clinical applications after further investigation.


The distribution, size and density of the apocrine glands in hidradenitis suppuritiva. The distribution, size and density of the apocrine glands in hidradenitis suppuritiva as compared with those in axillary hyperhidrosis and normal controls have been studied. There are no significant differences in the size or density of the apocrine glands in hidradenitis suppuritiva as compared with normal controls. The apocrine glands in axillary hyperhidrosis are significantly larger than those in axillary hidradenitis and in normal controls. A simple method that can be used to demonstrate the distribution of the apocrine glands preoperatively is described. This has proved useful in delineating the area which it is necessary to excise to obtain complete apocrine gland excision in the diseased area. The apocrine gland-containing skin in the diseased region does not always correspond exactly to the hair-bearing area in that region.


Continent anal ileostomy with mucosal proctectomy: a bloodless technique using a surgical ultrasonic aspirator in dogs. At present, mucosal proctectomy with ileo-anal anastomosis is a difficult, time-consuming operation involving much blood loss, often associated with impaired postoperative continence. A new operation has been devised in our department in which a surgical ultrasonic aspiratory, the CUSATM System (Cavitron Corporation) was used to fragment directly and strip bloodlessly mucosa from the rectal wall in 20 dogs as part of a simple ileo-anal sleeve anastomosis. All dogs were closely followed for up to 10 months. The only operative mortality occurred in the first dog where the upper rectum sloughed because the superior haemorrhoidal artery was divided. Preoperative weight was regained within the first 2 months. Initially stools were loose and frequent. Within 2 weeks the daily stool count was 5-6 with gradual thickening to semisolid consistency by 6 weeks. Finally 3-4 normal stools were passed daily. Postoperatively, all dogs remained contingent.


Modulation of the immune response and control of tumour spread by a new synthetic compound. A small molecular weight biofunctional polymer, NED 137, has been investigated for its anti-neoplastic effect. Through its effect on the immune system, particularly the induction of B cell differentiation to antibody producing cells, this synthetic compound can retard tumour growth and prevent the development of distant metastases. Reactivity to tumour developed following administration of the NED 137. No toxicity has been observed. The polymer NED 137 is now being tested in phase I and phase II clinical trials.


The effect of epidural analgesia on postoperative sodium balance. The effect of a high epidural blockade on postoperative sodium (Na) retention has been studied in 8 patients undergoing cholecystectomy, with a further 8 patients, who received conventional anaesthesia and analgesia, acting as a control group. Preoperatively, all the patients received 90 mmol of Na per day and were in Na balance at the start of operation; this intake was continued for 48 h after the operation by intravenous infusion, and the epidural blockade was maintained with regular supplements of bupivacaine throughout. In addition to urine Na excretion and blood pressure changes, plasma levels of aldosterone, cortisol, renin activity and glucose were measured at appropriate intervals. The Na retention in both the epidural and control groups was the same (139 mmol and 135 mmol respectively at 48 h), but there were significant differences in the measurements of all the other factors. It is concluded that the epidural was providing effective blockade, but that the factors which cause Na retention were not affected by the epidural blockade. These results are at variance with another study of the effect of epidural blockade on postoperative Na retention (Bevan, 1971), and the possible reasons for this are discussed.


Perinatal mortality by birth order within cohorts based on sibship size. Cross-sectional surveys of perinatal mortality show a U-shaped curve when plotted against parity, implying that fourth and subsequent babies are at increased risk. Our study of a large, population-based longitudinal data set shows that this result is an artefact and that perinatal mortality falls with increasing parity. Within cohorts of mothers based on attained sibship size the perinatal mortality decreases with increasing parity and increases with sibship size. These associations, which are not noticeably affected by maternal age, ssem in part to operate through an association between parity, sibship size, and birth weight. This analysis shows the importance of using longitudinal data in analysing such relations.


Is appendicitis familial?

Is appendicitis familial? A family history of appendicectomy was sought in two groups of children admitted to Llandough Hospital over sixteen months. The study group consisted of 29 children with histologically confirmed acute appendicitis, while the control group consisted of 29 children admitted for reasons unrelated to abdominal pain. A history of appendicectomy was elicited in first-degree relatives--that is, siblings and parents of 20 of the children in the study group and of four of the controls--a statistically significant difference. The results obtained from this study suggest that a familial predisposition to appendicitis exists.


Obstetric anaesthetic and analgesic services in Wales. A survey of obstetric anaesthetic services in Wales covering 21 major units in which over 31 000 deliveries take place annually showed inadequacies in staffing at consultant and resident anaesthetist level. At least 20 additional consultant sessions were required to meet the recommendations of the Association of Anaesthetists of Great Britain and Ireland. If patients' requests for epidural analgesia are to be met some reorganisation and centralisation of facilities is needed.


Effects of bromocriptine on pituitary tumour size. In a prospective study designed to assess the influence of bromocriptine on pituitary tumour size 12 patients with pituitary tumours, eight of whom had suprasellar extensions, were treated for three months with 20 mg of bromocriptine daily after a gradual increase to this dose. The group comprised eight women and four men, five with prolactin-secreting adenomas, four with acromegaly, two with functionless adenomas, and one with Nelson's syndrome. All five patients with prolactin-secreting adenomas showed a reduction in pituitary tumour size as assessed by computerised tomography and metrizamide cisternography accompanied by a fall in prolactin concentrations and clinical and biochemical improvement in their hypopituitarism. One patient in this group had a visual-field defect before treatment, and this resolved. There was no radiological evidence of reduction in tumour size in the remaining seven patients, though this might refect the fairly short duration of treatment, particularly in view of the ancillary evidence of clinical, biochemical, and visual-field improvement in some of the patients. These results emphasise the potential value of bromocriptine in treating patients with large prolactinomas or recurrences of such tumours after previous chiasmal decompression and conventional external megavoltage irradiation on the pituitary.


Operations for hernia and varicose veins in a day-bed unit. Over eight years (1970-8) 1055 patients underwent operations for hernia or "major" varicose veins in a day-bed unit. Here, 608 were discharged home on the day of operation, 262 were transferred to a convalescent hospital for 48 hours, and 161 were retained in the acute ward as part of a controlled trial. Special emphasis was placed on selection and preadmission screening. Failure of planning was uncommon in that only 2.5% were detained in hospital and 1% had to be readmitted. About one-quarter of the patients had complications but these were generally trivial and were satisfactorily treated by the community nursing sisters or general practitioners, or both. Analysis of the total operations for hernia or varicose veins in the unit over the past 19 years shows that, whereas formerly all patients with these conditions were admitted to the main surgical ward, nowadays almost all are managed either by day care or in a five-day ward.


Work of a day-bed unit 1972-8.

Work of a day-bed unit 1972-8. From 1972 to 1978 inclusive 32 311 patients were managed in a 24-bedded day-bed unit in a district general hospital. The principal specialties using this were urology, gastroenterology, general surgery, gynaecology, haematology, orthopaedics, and radiology. Patient selection, a high standard of secretarial work, and good liaison with general practitioners, the community nursing service, and the ambulance service are most important. Day care forms a large, important, and increasing part of the work of the hospital, and without it many of the specialties would be unable to cope with the demand, and their waiting lists would lengthen continuously.


Value of emergency toxicological investigations in differential diagnosis of coma. Out of 208 cases of coma of unknown aetiology referred to the poisons unit of this hospital during 1978 for emergency toxicological investigations, 108 were found to be due to self-poisoning medical conditions, mainly neurological, accounted for coma in 90 patients; the cause was not ascertained in the remaining 10 cases. More than one preparation had been ingested by 58 (54%) of the poisoned patients, although barbiturates were the drugs most commonly encountered in the severe cases. Toxicological investigations should be considered in the differential diagnosis of coma when history, physical examination, and emergency biochemical measurements yield little diagnostic information.


Retrograde spread of hydrocortisone containing foam given intrarectally in ulcerative colitis. A method is described of estimating retrograde spread through the colon of a 10% hydrocortisone acetate foam by labelling the foam with technetium-99m sulphur colloid and observing spread after intrarectal administration by serial gamma-camera pictures. The recommended 51 ml dose of foam reached the mid-sigmoid colon in all of the nine patients who had active ulcerative colitis. Furthermore, in seven the foam reached the proximal sigmoid colon. Foam spread less extensively in five patients with quiescent disease than in those with active disease. Increasing the volume of enema to 50 ml did not improve retrograde spread through the colon. These results suggest that 10% hydrocortisone foam may be useful in treating patients with distal ulcerative colitis that is not necessarily limited to the rectum.


Inflammatory bowel disease in the West Indies. Inflammatory bowel disease is generally assumed to be rare among negroes and Indians. Over 10 years 34 cases of ulcerative colitis and 14 cases of Crohn's disease were seen in one medical and one surgical unit in Port-of-Spain, Trinidad. Twenty-six patients were Negroes, 18 were Indians, three were of mixed race, and one was Caucasian. In many of these patients the disease was extensive and several of those with Crohn's disease suffered severe complications. The assumption that inflammatory bowel disease is rare among West Indians of African and Indian origin therefore seems to be wrong.


Finger clubbing in inflammatory bowel disease: its prevalence and pathogenesis. Finger clubbing, measured objectively by using the hyponychial angle, was present in 75 out of 200 (38%) patients with Crohn's disease, 15 out of 103 (15%) with ulcerative colitis, and two out of 24 (8%) with proctitis. In Crohn's disease and ulcerative colitis the hyponychial angle was significantly correlated with both disease activity and the extent of fibrosis in the resected specimens from 47 surgically treated patients. The prevalence of finger clubbing in patients with macroscopic disease within the area of the gut innervated by the vagus nerve was significantly higher than that in patients in whom the disease was confined to the distal colon and rectum. Finger clubbing in patients with Crohn's disease tended to regress after resection of macroscopic disease. It is concluded that finger clubbing is significantly commoner in Crohn's disease than ulcerative colitis. The focal stimuli for finger clubbing include mucosal inflammatory change and fibrosis mediated by the vagus and possibly other autonomic pathways acting as the afferent arc of a finger-clubbing reflex.


Head injuries in three Scottish neurosurgical units. Scottish head injury management study. The organisation of care for patients with head injuries in Scotland was investigated by studying retrospectively 785 patients admitted in 1974 and 1975 to neurosurgical units in Glasgow, Aberdeen, and Dundee. The reasons for the injuries and the patients' clinical conditions were similar in each unit. The referral practices at the hospitals containing the units were compared and found to be different from that of the unit in Edinburgh. It is concluded that patients in the Glasgow, Aberdeen, and Dundee units, which operate a similar policy for head-injured patients, are in general similar. Transferring to a neurosurgical unit only selected patients rather than all patients with head injuries is safe practice only if policies are agreed with primary surgeons and patients can be transferred without delay.


Development of a cushion to prevent ischial pressure sores. A study was carried out jointly by nursing staff and technologists in an attempt to develop a cushion based on scientific principles and measurement that might prevent pressure sores. At each stage in the development clinical trials were carried out, and using the results of these together with the opinions of medical staff and patients who used the cushion the design was suitably modified. Over four years a seat was evolved that was simple to construct and fulfilled the clinical requirements for a wide range of patients while providing maximum relief of high-pressure points. The design was subsequently taken up commercially.


Haemostatic variables associated with diabetes and its complications. To study the possible role of an "increased thrombotic tendency" in the vascular complications of diabetes several tests of haemostatic function were carried out on 91 men and 63 women with diabetes aged 35-54 years and the results compared with findings in 686 men and 393 women of the same age in the Northwick Park Heart Study. Mean values for factors VII and X, fibrinogen, and platelet adhesiveness were higher in the diabetics, but mean fibrinolytic activity and whole blood platelet counts were lower. Antithrombin III values were also higher in the diabetics, which may have constituted a protective response to other changes favouring the onset of vascular disease. Diabetics with retinopathy had higher factor VII and antithrombin III values, and those with proteinuria had higher values for factor VII, fibrinogen, and platelet adhesiveness than those without these complications. These findings suggest a potentially important association between a thrombogenic tendency and vascular disease in diabetes. Nevertheless, prospective data are needed to clarify whether the haemostatic abnormalities precede the onset of clinically manifest vascular complications or are a consequence of them.


Penis captivus--did it occur?

Penis captivus--did it occur? The symptom of penis captivus during sexual intercourse has had a largely hearsay existence in medical history, and rumour has embellished the drama of its occurrence. It is not entirely mythical, however. It seems to have been a symptom of great rarity in former times and to have vanished perhaps completely in this century.


Use of CB hamsters in the study of Treponema pertenue. The CB/Ss LAK strain of inbred hamster was used as a model for studies of infection with Treponema pertenue and of acquired resistance to it. When infected, this strain developed cutaneous lesions which lasted for six to seven months, even in the presence of peak titres of antitreponemal antibody. The rate of appearance and resolution of these lesions varied with the size of the inoculum. The infected hamsters' inguinal lymph nodes increased significantly in weight and teemed with treponemes for several weeks. Animals infected for eight or 10 weeks obtained quick resolution of their lesions by treatment with penicillin and were thereafter resistant to reinfection.


Vaginal oxytetracycline concentrations.

Vaginal oxytetracycline concentrations. Although tetracycline preparations are widely used in departments of genitourinary medicine, or sexually transmitted diseases clinics, little is known of the concentrations of these preparations in genital secretions. For this reason a microbiological method was used for estimating oxytetracycline concentrations in vaginal secretions. These concentrations varied from 0.6 to 6.5 microgram/ml in 19 women who had had sexual contact with a man with non-specific urethritis and who were taking oxytetracycline dihydrate 250 mg four times daily. They were well in excess of the minimum inhibitory concentration of oxytetracycline (0.2 microgram/ml) for the strains of Chlamydia trachomatis isolated from the patients with positive culture results. Thus, oxytetracycline 250 mg four times daily appears to be a satisfactory regimen for the treatment of chlamydial genital infection in women.


Sexual transmission of hepatitis B surface antigen. Infection of husbands by HBsAg carrier-state wives. The husbands of 68 hepatitis B surface antigen (HBsAg) carrier-state wives were tested for the presence of hepatitis B surface antibody (HBsAb) and antigen (HBsAg) to assess possible transmission of HBsAg. Eight (11.8%) of the 68 husbands gave negative results for HBsAg and 22 (32.4%) positive results for HBsAb. Furthermore, eight (26.7%) of 30 husbands with presumed HBsAg transmission from their wives developed acute viral hepatitis after marriage, and e antigen (eAg) was detected in the serum from all eight wives. Although HbsAg was not detected in specimens of sputum and cervical mucus of carrier-state women by reverse passive haemagglutination, it was detected in the vaginal discharge of women during days 1--6 of the menstrual cycle at a rate ranging from 20--60%. Thus, sexual transmission of HBsAg seems to occur, particularly if sexual contact takes place during or immediately after menstruation.


The asymmetric lateralization of tactile extinction in patients with unilateral cerebral dysfunction. Two hundred and thirty-four patients with unilateral cerebral pathology and 175 control subjects were examined with a sensitive test for tactile extinction. Damage to the right hemisphere was associated with extinction slightly (but not significantly) more often than damage to the left hemisphere; the asymmetry may be due to selective exclusion of aphasics with damage to the left hemisphere. Extinction of the left side of the body, however, was significantly more common than of the right side; this asymmetry could not be accounted for by exclusion of untestable aphasics, but was a consequence of frequent ipsilateral (left side) extinction among the group with damage to the left hemisphere while the group with damage to the right hemisphere extinguished the contralateral (left) side almost exclusively. Although the hemispheres as a whole did not differ in their association with extinction, lesions in the right parietal lobe were significantly more effective in producing extinction than lesions in the left; in both cases the contralateral side of the body was affected. By contrast, lesions in the left frontal lobe were moderately but not significantly more effective in producing extinction than right frontal damage; in almost all these cases the left side of the body was affected, regardless of which frontal lobe was damaged. A relationship between extinction and pathology in the vicinity of the anterior callosum, as determined from CT scan and angiography, was found among the frontal cases. We propose an anatomical model to explain tactile extinction and its asymetric characteristics in the human. During the extinction tests a response mechanism in the left (speech) hemisphere bases its perceptual output on the relative strengths of two simultaneous sensory inputs. Damage at any point in the channel from the periphery to the response mechanism weakens one signal in comparison to the other, resulting in a response bias favouring the stronger stimulus. Tactile information from the left hand, after reaching the somatosensory zone in the right hemisphere, is transmitted to the left hemisphere by a diffuse, widespread network including the frontal lobes and the anterior callosum. This anatomical arrangement renders left-hand information more vulnerable to chance lesions than right-hand information, which has direct access to the response mechanism via a more compact projection system.


Infantile neuroaxonal dystrophy.

Infantile neuroaxonal dystrophy. Eight cases of late infantile neuroaxonal dystrophy are reported. In all cases, the diagnosis was made during life on the basis of the clinical picture and course, the results of neurophysiological studies and the finding of typical spheroids in cortical or peripheral (skin and conjunctival) biopsies. A review of 76 previously published cases revealed that 42 displayed a stereotyped clinical picture identical to that exhibited by our 8 patients. The most important clinical features, as they emerge from the study of these 50 cases, are those of a progressive disorder starting at the end of the first or beginning of the second year of life, progressive motor and mental deterioration bilateral pyramidal tract signs, marked hypotonia and early visual disturbances without epileptic seizures. The presence of high voltage, fast rhythms in the EEG and signs of denervation of an anterior horn-cell type at EMG, with normal nerve conduction velocities, is frequent additional evidence in favour of infantile neuroaxonal dystrophy. The finding of spheroid bodies in axonal endings seems to be constant and is necessary for an in vivo diagnosis. Spheroids can be found in peripheral tissues, for example, skin and conjunctiva, and cortical biopsy is no longer required. The spheroids, however, are not specific and both clinical and pathological features are necessary to establish a firm diagnosis. Since infantile neuroaxonal dystrophy is a recessively inherited disorder its recognition is imperative even though the nosology of the disease remains uncertain.


Quantitative studies of saccadic and pursuit eye movements in multiple sclerosis. Ocular movements were studied in 108 patients with established or suspected multiple sclerosis using an on-line computer-based electro-oculographic technique. In one group of patients peak eye movement velocities alone were measured during horizontal refixation saccades. In a second group saccade reaction times and accuracies were measured in addition to velocities, while in a subgroup a quantitative analysis of horizontal pursuit eye movements was also carried out. With the saccade velocity test abnormalities were present in 44 per cent of cases studied and were subclinical in 18 per cent. Abnormalities were found in 57 per cent of cases in whom the detailed saccade analysis was performed, including 48 per cent of patients with clinically normal eye movements. Saccade reaction time and accuracy were more sensitive parameters than saccade velocity, and the highest yield of abnormalities was obtained when all three were taken into consideration. Abnormalities of pursuit movements were found in 71 per cent of cases studied and were frequently subclinical. Abnormalities of saccadic and pursuit movements were not always present together in the same patient, and the overall yield of abnormalities was higher when the results of both types of study were taken into account. The yield of abnormalities with the eye movement studies was somewhat lower than with the pattern-reversal VEP in the clinically definite multiple sclerosis group, but was higher in patients in the other categories. Subclinical abnormalities of eye movement were found in a significant number of patients with normal VEPs. The finding of such an abnormality in patients with spinal cord syndromes allowed reclassification of 14 patients to a category with a higher degree of diagnostic certainty. It is concluded that quantitative electro-oculography is a valuable adjunct to the clinical evaluation of eye movements and has an important role in the investigation of patients suspected of multiple sclerosis.


The contribution of the 'second' visual system to directed visual attention in man. The visual functions of a patient suffering from a brain lesion incorporating the left n. pulvinar was examined in order to assess the contribution of this structure to human vision. With the exception of the following abnormalities visual functions were normal. First, there was a decrease in the critical flicker frequency in the periphery (but not in the parafoveal region) of the right visual hemifield, that is, that contralateral to the pulvinar lesion. However, the second and most striking characteristic was--as shown by presenting visual stimuli bilaterally and simultaneously-a 'neglect' for the periphery of this contralateral visual half-field. This 'neglect' was a function of (a) position in the visual field (eccentricity), (b) stimulus properties (size and luminance), (c) temporal properties (length of presentation and interstimulus interval). In addition to this reduced capacity to detect stimuli appearing in the periphery of the right visual hemifield, there was also prolonged latency of visually evoked saccadic eye movements and a paucity of spontaneous eye movements directed towards the right visual hemifield. These results are interpreted in terms of a contribution of the n. pulvinar to the detection of light stimuli presented in the periphery of the visual field, and support the view that the tectopulvinar extrastriate visual pathway plays an important role in the control of visual attention.


Cardio-inhibitory mechanism in the gigantocellular reticular nucleus of the medulla oblongata. A cardio-inhibitory mechanism was localized in the ventral part of the medullary gigantocellular reticular nucleus (GRN) in chloralose--urethane anesthetized cats. Stimulation of this mechanism produced an average 58.9% reduction of the heart rate (calculated from 55 responsive points having more than 40% reduction) associated mostly with hypotension, or no change or occasionally a slight increase of the arterial blood pressure. Midcollicular decerebration did not affect this bradycardia. The bradycardia following GRN stimulation of either side by a pair of symmetrically placed electrodes was reduced slightly but equally by: (1) sectioning either side of the vagus nerve; (2) hemisection at a level 4 mm rostral of the obex on either side; or (3) partial destruction of the dorsal motor (DM) and solitary (SN) nuclei on either side. Additional section of the vagus nerve on the opposite side completely abolished the bradycardiac response. Besides, the GRN bradycardia was also slightly but equally attenuated by making a midline bisection in a length extending from 10 to 4 mm rostral of the obex. Additional section of the vagus nerve on either side abolished completely only the bradycardia following electrical stimulation of the GRN on the same side, while that following electrical stimulation of the GRN on the opposite side remained unaffected. On the other hand, the GRN bradycardia was not affected by simply making a caudal midline bisection in a length extending from 3 or 4 mm rostral to 2 mm caudal of the obex. The results suggest: (1) the ventral part of the GRN is a cardio-inhibitory mechanism independent of the higher center; (2) the efferent pathway descends both ipsilaterally and contralaterally and makes synaptic relay in the areas of DM and/or SN and finally exits via the vagus nerves; (3) the fibers decussate rostral to the level 4 mm rostral of the obex; and (4) both ipsilateral and contralateral descending fibers appeared to exert the same degree of suppressive influence in the heart rate.


Morphometrical synaptology of Clarke cells and of distal dendrites in the nucleus dorsalis: an electron microscopic study in the cat. The fine structural synaptology of large Clarke cells in L3 has been investigated from a morphometrical point of view in both normal and adult cats which received horseradish peroxidase (HRP) injections in the cerebellum. This marking method made it possible to distinguish small or distal dendrites of large Clarke cells from those of interneurons and the marginal cells of Clarke's column. A total of 1036 boutons was observed on the perikarya of 21 large Clarke cells; 81.9% (848/1036) were small-sized boutons, the cross-sectional areas of which ranged between 0.3 and 2.9 sq. micrometer, while 18.1% (186/1036) were giant boutons ranging between 3.0 and 8.0 sq. micrometer. From 1075 boutons on 17 primary dendrites of Clarke cells, 72.4% (778/1075) were small-sized boutons and 27.6% (297/1075) were giant boutons. From 1679 boutons contacting 366 distal or small HRP-labeled dendrites, 89.9% (1507/1679) were small boutons and 10.1% were giant boutons. The giant boutons were more frequently located on the proximal dendrites than on the cell bodies or small distal dendrites of Clarke cells. The proportion of S- and F-type boutons was different in 3 parts of large Clarke cells. F-type boutons were more frequent on soma (55.0% 570/1036) and primary dendrites (59.4%, 635/1075). S-type boutons outnumbered the F-type on small or distal dendrites (62.6%, 1952/1679). The S/F ratio seemed to increase from the cell body toward the distal dendrites. The results suggest that Clarke cells receive predominantly small S-type boutons since the total receptive area of the dendrites is supposed to exceed that of the cell body.


The organization of projections to selected points of somatosensory cortex from the cat ventrobasal complex. The organization of neurons in the cat ventrobasal complex (VB) which project to somatosensory cortex (SI) was investigated by the use of the retrograde transport of the enzyme horseradish peroxidase (HRP). Two histochemical procedures were used to visualize retrogradely transported HRP. Injections of HRP in electrophysiologically characterized points of SI cortex labeled distinctive zones of neurons in VB ipsilateral to the injections. Injections placed in the forelimb or hindlimb cortical areas labeled laminar-like aggregates of neurons have long axis corresponded to the long axis of VB. Injections of the SI trigeminal representation resulted in very compact aggregates of HRP positive neurons which were less clearly laminar. The density of projection from VB to various portions of SI paralleled the general innervation density of the peripheral skin. Injections of the cortical vibrissal, face and forepaw representations labeled a greater number of neurons in VB per unit area of cortex injected than did injections of the hindpaw or trunk representations. For a given somatotopic area, the number of labeled neurons in VB increased linearly as the area of the cortical HRP injection increased. Differences in the sensitivity of each histochemical procedure and the relationship of differing sensitivities to the observed results are also discussed.


Tonic stretch reflexes in lip, tongue and jaw muscles. Despite considerable speculation it remains unclear as to whether stretch reflexes perform a functional role in speech articulator muscles. Recent research, however, has shown that long loop stretch reflex mechanisms are brought into play during voluntary contraction of limb muscles and a functional role in oscillatory damping has been suggested. It was decided, therefore, to use a method and a technique of analysis similar to that used in limb muscles to search for tonic stretch reflex (TSR) responses in lip, tongue and jaw muscles during sustained voluntary contraction. The term 'action TSR' is used to differentiate stretch reflex responses measured from voluntary activity from those measured at rest. Simultaneous electromyogram (EMG) recordings were taken from the lip, tongue and jaw musculature in normal, stutterer and cerebral spastic subjects. Subjects were instructed to hold the appropriate articulator in a fixed position while the experiment applied an irregular, continuously changing, stretching force. The stretch and EMG signals were analyzed using a cross correlation and spectral analysis technique. This provided a sensitive means of detecting any EMG fluctuations which covaried with applied stretch and might therefore be classified as reflex. No suggestion of such action TSR responses could be found in lip or tongue muscles of any of the subjects tested, including the cerebral spastic subjects with dysarthric speech. It is therefore concluded that action TSR mechanisms are not operative in control of lip and tongue muscles in man. Furthermore, dysarthric speech in cerebral spasticity cannot be attributed to exaggerated tone of lip and tongue muscles resulting from hypersensitivity of TSR mechanisms. In contrast, clear action TSR responses were demonstrable in jaw closing muscles while in jaw opening muscles, small amplitude responses were detected but were not substantial in comparison with background activity. Since the action TSR is present in jaw and limb muscles, but absent in lip and tongue muscles, the suggestion of a functional role of this reflex in damping mechanical oscillations associated with inertial loads is further supported.


Immunologic similarities between the hypothalamic alpha-bungarotoxin receptor and the Torpedo californica nicotinic cholinergic receptor. The solubilized rat central nervous system (hypothalamic) nicotinic cholinergic receptor and the Torpedo nicotinic cholinergic receptors are immunologically similar and show greater than 60% immunologic cross-reactivity using a double-antibody technique. Antibodies to the Electrophorus and Torpedo receptors also decrease the rate of alpha-bungarotoxin binding to these membraneous receptors. It is concluded that the Torpedo and hypothalamic nicotinic receptors are immunologically similar and that receptor binding sites for alpha-bungarotoxin and antibodies are physically close. These studies indicate that alpha-bungarotoxin can be used to study the nicotinic cholinergic receptor of the rat hypothalamus.


Grafting of additional periphery reduces embryonic loss of neurons. Effects of increased peripheral field of innervation on the magnitude of the spontaneously occurring embryonic cell death in the chick trochlear and isthmo-optic nuclei were examined. Grafting of an additional optic primordium and the surrounding mesoderm (which forms extraocular muscles) was performed at stage 11 (HH stage series). The grafted tissue is innervated by the appropriate neuron pool as revealed by the retrograde axonal flow of HRP. Cell counts of the trochlear nucleus on day 19 indicate a mean increase of 37% (range 19--62%) in the number of cells on the experimental side (contralateral to the graft) as compared to the ipsilateral control nucleus of the same embryos. Cell counts of the isthmo-optic nucleus on day 19 show an average increase of 35% (range 27--41%) on the experimental (contralateral) side over the ipsilateral control side. This increase in cell survival is not due to a stimulatory effect of grafting on cellular proliferation as revealed by the cell counts of trochlear and isthmo-optic nuclei on day 9 and 11 respectively. Thus, the increased cell survival is attributed solely to the reduction in the magnitude of the embryonic cell death. Whether this reduction in embryonic cell death is due to increased number of synaptic sites or increased amounts of trophic substances remains uncertain.


Effects of baroreceptor activation on spontaneous activity in the sweat glands and nictitating membrane of the cat. (1) In chloralose-anesthetized cats, elevation of carotid sinus pressure caused blood pressure, sweat gland potentials and nictitating membrane tension to decrease. (2) The onset and recovery of the sweat gland and nictitating membrane responses usually preceded the respective phases of the blood pressure (depressor) response; the latencies of the sweat gland and nictitating membrane responses agreed with the latencies predicted for neural reflex pathways. (3) The sweat gland and nictitating membrane responses were evoked less consistently than the depressor response. (4) In experiments where only the sweat gland potentials and blood pressure were studied: (a) the sinus pressure threshold for inhibition of sweat gland activity was similar to the threshold for the depressor response; (b) cutting the sinus nerves, or blocking the efferent neural activity to the sweat glands, eliminated the effects of sinus pressure elevation on the sweat gland potentials; (c) with carotid sinus pressure held constant, decreases in blood pressure, produced by stimulating the peripheral end of the vagus nerve, did not affect the sweat gland potentials. (5) These results indicate that baroreceptors can reflexly modulate activity in sympathetic neurons whose target organs are not fundamentally involved in blood pressure regulation.


Staggerer chimeras: intrinsic nature of Purkinje cell defects and implications for normal cerebellar development. The site of gene action of the Staggerer mutation of mice was investigated with Staggerer in equilibrium or formed from wild-type chimeras. Homozygous Staggerer mice show severe locomotor difficulties due to cerebellar abnormalities which include degeneration of virtually all granule cells and cytological defects in Purkinje cells. Although the locomotor deficits of the mutant were not present in the chimeras, the presence of Staggerer cells affected cerebellar structure. The size and the extent of foliation of the chimeric cerebella were intermediate between wile-type and homozygous Staggerer. A normally proportioned granule cell layer was present. Using beta-glucuronidase as an independent determinant of a cell's genotype, it was found that the genotypically Staggerer medium-to-large neurons expressed all of the light microscopic defects observable in these cells in the homozygous mutant. These defects include: (1) smaller size; (2) usually ectopic location; and (3) regional variation in the cytological appearance of the perikaryon. By contrast, all Purkinje cells which were genotypically wild-type appeared normal in size, in location and in their cytological appearance. Their density, however, was much reduced from wild-type. The effects of the Staggerer mutation on the granule, stellate and basket cells could not be directly assessed as the glucuronidase marker is not suitable for use with these cells. The Staggerer gene thus acts directly on Purkinje cells rather than via extracellular environmental changes. The findings are discussed in terms of their implications for normal cerebellar development.


The effect of depolarizing potassium concentrations on the efflux of GABA from rat dorsal medulla in vivo and from slices and synaptosomes. The efflux of [3H]GABA from the dorsal surface of adult rat medulla overlying the dorsal column nuclei (DCN) was found not be influenced by increasing the concentration of potassium in the superfusing solution to 40 mequiv. Similarly, raised potassium was found not to influence the efflux from slices of the dorsal region of the caudal medulla containing the dorsal column nuclei. This lack of effect of raised potassium is not thought to be due to lack of GABAergic terminals in this region because there is good pharmacological evidence for their presence and bacause both electrical stimulation and 100 microM veratridine increased the efflux of [3H]GABA from such slices. Also, 40 mequiv potassium was found to increase the efflux of both endogenous and [3H]GABA from crude synaptosome preparations of this region without influencing the efflux of [14C]sucrose or [3H]leucine. This release of [3H]GABA was calcium-dependent, and was similar whether produced by 20, 40 of 60 mequiv potassium and occurred whether eos or AOAA was used to inhibit GABA metabolism. Release from synaptosomes could also be induced with 100 microM veratridine. Raised potassium was additionally found to prevent the increased efflux from slices produced by electrical stimulation and to increase the efflux from slices prepared from the brains of rats 14 days old. It is suggested that the astrocytic swelling produced by raised potassium concentration restricts the diffusion of GABA away from depolarized terminals.


Denervation supersensitivity to serotonin in rat forebrain: single cell studies. To investigate the development of denervation supersensitivity to serotonin (5-hydroxytryptamine, 5-HT) in the amygdala (AMYG) and the ventral lateral geniculate nucleus (vLGN), single cell recordings, microiontophoretic, histochemical and biochemical techniques were used in the present study. 5-HT projections to the vLGN and the AMYG were destroyed by 5,7-dihydroxytryptamine (5,7-DHT, a relatively selective toxin for 5-HT neurons) injected directly into the lateral ventricle or the ascending 5-HT pathway in the ventromedial tegmentum area. Enhanced responsiveness of cells to the inhibitory effect of microiontophoretically applied 5-HT (ionto-5-HT) began to develop within 24 h and approached a maximum 7 days after 5,7-DHT pretreatment. In general, the time courses for the reduction in both the density of 5-HT fluorescent varicosities and synaptosomal 5-HT uptake activity paralleled the time course for the development of denervation supersensitivity to 5-HT. During the first 2 days after 5,7-DHT, the enhanced sensitivity was selective for 5-HT; responses to D-lysergic acid diethylamide (LSD), norepinephrine (NE) and gamma-aminobutyric acid (GABA) were unchanged. Seven or more days after 5,7-DHT there was a marked increase of the responsiveness of neurons in the vLGN and the AMYG to both 5-HT and LSD (a 5-HT agonist which is not a substrate for the high affinity 5-HT uptake system). At these later times, the responsiveness of cells in the AMYG to NE and to a lesser extent GABA was also increased. In contrast to the marked supersensitivity seen after 5,7-DHT induced denervation, chronic administration of parachlorophenylalanine, a 5-HT synthesis inhibitor, failed to induce 5-HT supersensitivity.


Pharmacologic independence of subfornical organ receptors mediating drinking. In rats with chronically implanted cannulae in the subfornical organ (SFO), the relationship between cholinergic- and angiotensin (AII)-induced drinking was investigated pharmacologically. All substances were injected via SFO cannulae which did not rupture ventricular ependyma. Pretreatment with low doses of the muscarinic antagonist atropine abolished carbachol-induced drinking, while nicotinic antagonists had no effect. Nonetheless, pretreatment with much larger doses of atropine had no effect on AII-induced drinking. Similarly, relatively small doses of the AII antagonist, saralasin, blocked AII-induced drinking, yet a much larger dose of saralasin had no effect on carbachol-induced drinking. The receptors mediating cholinergic- and AII-induced drinking therefore cannot be in series and must be in parallel. A hypothesis is proposed to account for this independence and for the significance of the SFO cholinergic innervation.


Pharmacological characterization of adrenal paraneurons: substance P and somatostatin as inhibitory modulators of the nicotinic response. A pharmacological study was made of the effects of various muscarinic and nicotinic agonists and their antagonists on the release of [3H]noradrenaline ([3H]NA) from cultures of isolated bovine adrenal medullary cells. A study was also made of the effects of substance P and somatostatin on the release of [3H]NA evoked by nicotinic agonists. By 2 days in culture these adrenal 'paraneurons' had developed long varicose processes with growth cones and generally resembled noradrenergic neurons in culture. In the present study, adrenal paraneurons were incubated with [3H]NA which was taken up and stored in reserpine-sensitive sites. Exposure of the cultures to acetylcholine (ACh) resulted in release of [3H]NA into the external medium. High concentrations of K+ (56 mM) also evoked release of [3H]NA. The release of [3H]NA induced by ACh or K+ (56 mM) was Ca2+-dependent. Pharmacological studies with nicotinic (ACh, nicotine) and muscarinic (methacholine, pilocarpine) agonists and their antagonists (mecamylasmine, d-tubocurarine, hexamethonium; and atropine, scopolamine, respectively) showed that the adrenal paraneurons contained only nicotinic receptors. Substance P produced a dose-dependent inhibition of ACh (5 x 10(-5) M) stimulated [3H]NA release in the range of 10(-8) to 5 x 10(-5) M with an ID50 of 10(-6) M. A similar inhibition of NA release by substance P was obtained when nicotine (K X 10(-6) M) was used as the agonist, but not when K+ (50 MM) was used to depolarize the cells. Substance P (10-10) to 5 x 10(-5) M) by itself did not have a significant effect on the basal release rate of [3H]NA from these cells. Somatostatin at relatively high concentrations (10(-6)-10(-3) M; ID50 2 x 10(-5) M) inhibited the release induced by ACh, but not by K+ (56 mM). The present results provide the first direct evidence at a cellular level that substance P and somatostatin act as inhibitory modulators of the nicotinic ACh response, and support a role for these peptides as inhibitory neuromodulators at nicotinic receptor sites in the nervous system.


Effect of thiamine deficiency on brain serotonin turnover. Serotonin turnover has been investigated in regional brain areas of rats made thiamine deficient by pyrithiamine (PT). Following intracisternal injection of [14C]5-hydroxytryptamine ([14C]5-HT), a marked increase in the accumulation of [14C]5-hydroxyindoleacetic acid ([14C]5-HIAA) was found in the medulla-pons, hypothalamus and cerebral cortex. [14C]5-HT levels were normal in all of the brain areas except the cerebral cortex which had an increase of 58%. The ratio of [14C]5-HIAA/[14C]5-HT was significantly increased in every brain region of PT-treated rats except the cerebral cortex. Part of this increase in [14C]5-HIAA was shown to be due to impairment of active transport of this 5-HT metabolite out of the brain. However, increased 5-HT synthesis in the cerebellum, hypothalamus, striatum, hippocampus and cerebral cortex was demonstrated by measurement of 5-HT accumulation after inhibition of brain monoamine oxidase. PT-induced increase in endogenous 5-HIAA in the medulla-pons occurred simultaneously with the onset of neurological signs and both parameters were reversible by thiamine administration. These results suggest that acute thiamine deficiency, induced by PT, both increases brain 5-HT synthesis and impairs 5-HIAA efflux from the brain. There is a close correlation between neurological manifestations and changes in brain 5-HT metabolism in acute thiamine deficiency.


Brain catecholamines during development of DOCA-salt hypertension in rats. The activity of the adrenaline-forming enzyme, phenylethanolamine-N-methyltransferase (PNMT) and the levels of the catecholamines dopamine, noradrenaline and adrenaline were determined during the development of the DOCA-salt hypertension in selective areas of the rat brain stem and hypothalamus. Increases in PNMT activity were restricted to the A1 area and locus coeruleus after 2 weeks of DOCA-salt treatment and were extended to the A2 area after 9 weeks of treatment. Adrenaline concentrations were higher in these areas only after 9 weeks of treatment. Noradrenaline levels did not change, except in the nucleus tractus commissuralis. Dopamine levels were unchanged at all times and in all structures studied. These results implicate brain stem adrenaline neurons in the central response which occurs during the DOCA-salt experimental hypertension.


Cerebral metabolic and circulatory changes in the rat during sustained seizures induced by DL-homocysteine. Sustained, generalized seizure activity was induced in anaesthetized (70% N2O), paralyzed and artifically ventilated rats by i.p. DL-homocysteine thiolactone in a dose of 11 mmol/kg. Epileptic discharges in the EEG were accompanied by marked perturbation of tissue metabolites. There was a fall in phosphocreatine concentration to 40% of control but only moderate changes in adenine nucleotides, a marked rise in lactate concentration, and a pronounced increase in the lactate/pyruvate ratio. Excessive amounts of dihydroxyacetone phosphate (and glyceraldehyde phosphate) accumulated, indicating that depletion of NAD+ occurred. There was marked accumulation of ammonia, glutamine and alanine, and reduction in glutamate and aspartate concentrations. Administration of a subconvulsive dose of homocysteine (7.5 mmol/kg) gave rise to changes in ammonia and amino acids, qualitatively similar to those occurring during seizures. It is concluded that although changes in the metabolites of the energy reserve were mainly caused by the induced seizures, those affecting amino acid concentrations were significantly influenced by accumulation of ammonia, secondary to metabolism of injected homocysteine. Cerebral blood flow (CBF) and oxygen utilization (CMRO2) were measured during sustained seizures. CMRO2 rose to 150% of control, with a corresponding increase in CBF.


Supraspinal influences on nociceptive flexion reflex and pain sensation in man. The sensation of pain and the nociceptive flexion reflex of the biceps femoris muscle (RIII, Bi) elicited by electrical stimulation of the ipsilateral sural nerve were studied in human during 4 conditions: (1) a mental task; (2) a stress; (3) during noxious stimulation of the contralateral ulnar nerve; (4) after an intense noxious stimulation of the sural nerve itself. An inhibition of both pain sensation and RIII, Bi was observed in (1), while a facilitation of these parameters was noted in (2). In contrast, no change in RIII, Bi occurred in (3) while the pain sensation was inhibited. In (4), just after the noxious stimulation, there was a marked facilitation of RIII, Bi associated with increased pain sensation. However, 10--12 sec later, the pain sensation returned to its control values, while the RIII, Bi reflex was still facilitated. The latter recovered to its control values 28--30 sec later. These results show the possibility of a dissociation between afferent ascending nociceptive messages and nociceptive motor activity (in 3 and 4). They suggest that supraspinal descending influences can act differently on spinal dorsal horn neurons in the case of pain ascending volleys, and in the case of spinal nociceptive motor activity.


Dopamine metabolism, spiperone binding and adenylate cyclase activity in the adult rat hippocampus after ingrowth of dopaminergic neurones from embryonic implants. The growth of dopamine (DA) neurones of rat embryonic mesencephalic brain tissue implanted close to the anterior part of the hippocampus of adult rats was studied by measuring the levels of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the host hippocampus. The hippocampal levels of DA and DOPAC reached maximal values 6 months after transplantation. The neuroleptic drug haloperidol evoked an increase in the levels of DOPAC. No evidence was found for the induction of DA-sensitive adenylate cyclase activity or of binding sites of [3H]spiperone. These results indicate that there is a substantial ingrowth of transplanted DA neurones into the host hippocampus, but no evidence was found for the development of functional contacts between the embryonic DA neurons and the host tissue.


Perinatal development of the endorphin- and enkephalin-containing systems in the rat brain. Radioimmunoassay and microdissection procedures were used to study the perinatal development of the endorphin- and enkephalin-containing systems in the rat brain. In contrast to values reported on adult rat, endorphin levels are much higher than enkephalin levels on embryonic day 16. The highest endorphin values are found in the diencephalon, midline telencephalon and medulla-midbrain regions. Perinatally, enkephalin content increases at a faster rate than endorphin in all brain regions, producing a marked drop of the endorphin/enkephalin ratios. Between postnatal days 6 and 25, both endorphin and enkephalin levels increase, approaching their adult distribution pattern. No correlation was found between regional distributions or rates of increase of endorphin and enkephalin in any of these developmental stages, suggesting that the two peptide systems develop independently from each other.


Motorneuronal control of locomotion in Aplysia. We have carried out a combined behavioral and cellular analysis of escape locomotion in Aplysia. Using videotape recording we obtained a detailed description of the coordinated movements of the different regions of the foot and body during locomotion. Alternating waves of extension and longitudinal contraction begin at the head and propagate caudally through each pedal segment at a constant rate. Cobalt backfill of pedal nerves indicated that certain regions of the pedal ganglia were likely to contain motor neurons for the foot and body wall musculature. We examined these areas using intracellular techniques and identified three unique cells and three regional classes of neurons having clear motor effects on the foot and body wall. We also found that locomotion is driven by a central program. The basic locomotor pattern of the identified motor neurons and regional classes of motor neurons persists even after the circumesophageal ganglia have been isolated from the periphery. The motor neurons are not synaptically interconnected; patterned bursting during locomotor activity is produced by cyclic synaptic input. Because the locomotor system has large neurons favorable for cellular analysis and because locomotion is characterized by features of both stereotypy and flexibility, Aplysia promises to be useful for investigating the mechanisms underlying both the generation and modulation of a central program.


Involvement of catecholamines in eliciting LH peaks in 15-day-old female rats: effects of treatment with prolactin. In the serum of 15-day-old female rats, treated either with alpha-methyl-p-tyrosine (alpha-MPT) or saline, serum LH levels were determined. From the brains of all animals the medial preoptic areas (MPO) and the anterior and posterior mediobasal hypothalami (AMBH and PMBH) were punched out and stored frozen in perchloric acid. In the punches of those animals with very high or basal LH levels catecholamine concentrations were measured radioenzymatically and on the basis of the degree of catecholamine depletion after alpha-MPT the turnover rates of dopamine (DA) and norepinephrine (NE) were calculated. NE turnover in the MPO was significantly higher in the animals with high LH levels as compared to those with low LH values. In the PMBH an inverse correlation between LH levels and NE turnover rates could be demonstrated. NE turnover in the AMBH, and DA turnover in all 3 structures did not correlate with serum LH levels. Serum FSH and prolactin levels were higher in the animals with high LH levels. These changes are similar to those observed in adult proestrous rats and it is concluded that the LH peaks in 15-day-old animals reflect a positive feedback action of estradiol. In a second experiment prolactin was administered to determine if it could prevent the occurrence of these LH peaks. Ovine prolactin (2 X 0.5 micrograms/g body weight) injected from day 8--15 suppressed serum LH levels to almost undetectable values. Catecholamine turnover measurements in these animals revealed increased DA turnover in the MPO, AMBH and PMBH, whereas NE turnover was not affected. These results indicate that DA turnover of the incertohypothalamic and of the tuberoinfundibular DA neurons is accelerated by prolactin and that an increased DA turnover in one of these systems is responsible for inhibition of LH release.


Alteration of catecholamine uptake in cerebral cortex from rats fed a saturated fat diet. The transport of [3H]norepinephrine into chopped cerebral cortex of neonates was changed by feeding pregnant rats with semisynthetic diets enriched in saturated fat (coconut oil) as compared to polyunsaturated fat (sunflower oil). There was a significant decrease in the uptake of norepinephrine in neonates from dams fed coconut oil compared to neonatal pups from animals fed sunflower oil. Differences were observed on days 7, 11, 24, and 37 but not in adults which had been maintained on the diet since birth. Kinetic analysis of norepinephrine uptake on day 7 neonates demonstrated a 5-fold increase in Km and a 2-fold increase in Vmax for the coconut oil fed group as compared to control or the sunflower oil fed rats. [3H]Dopamine uptake kinetics revealed no significant difference in day 7 neonates but a doubling of the Km and Vmax in day 37 rats and in adults fed coconut oil. Lipid analysis of cerebral cortex synaptosome membrane fractions revealed significant differences in the fatty acyl composition of the phospholipid. The results indicate that the norepinephrine and dopamine transport systems can be differentially affected by dietary lipid composition in the developing rat. It is suggested that the changes may be due to alterations in membrane fluidity in the local environment of the transport system.


Synthesis of lecithin (phosphatidylcholine) from phosphatidylethanolamine in bovine brain. Choline molecules are needed for the synthesis of acetylcholine and phospholipids in the mammalian brain. An enzymatic activity capable of forming lecithin (phosphatidylcholine) from the step-by-step methylation of phosphatidylethanolamine is identified in the bovine brain. This enzyme(s), phosphatidylethanolamine-N-methyltransferase (EC 2.1.1.17), is localized in the synaptosomal fraction of bovine caudate nucleus, uses S-adenosylmethionine as the methyl donor (apparent Km = 20 micrometers), and has a Vmax of 50--60 pmol/mg protein X h (i.e. about 1% of that found in rat liver). The brain may be able to meet some of its choline requirements by de novo synthesis.


Incorporation of intrastriatally injected[3H]fucose into electrophoretically separated synaptosomal glycoproteins. I. Turnover and molecular weight estimations. The radioactivity profiles of electrophoresed neostriatal P2 fraction glycoproteins were examined at a series of times (2.5, 3 and 4 h; 1, 5 and 10 days) following intracranial injections of [3H]fucose into the neostriatum. Ten major fucosylglycoprotein peaks were discerned in these profiles and certain aspects of their metabolism were characterized. The half-life of fucosylglycoproteins in the P2 fraction was estimated to be 9.7 days. The half-lives of the individual glycoprotein peaks ranged from 4.9 to 17.9 days. The apparent molecular weights of the glycoprotein peaks obtained by our procedures ranged from 32,000 to 180,000 daltons. One peak (peak VIII) incorporated radioactivity primarily at short intervals following the injection. The time course of [3H] fucose incorporation into this peak suggests involvement in the transport, activation and/or incorporation of fucose in brain. Since intracranial injections of [3H]fucose are incorporated into proteins in the cell body, synaptosomal fractions from caudate neurons alone are labeled by this technique. This may be useful in separating pre- and postsynaptic glycoprotein biochemistry. Finally, we tentatively propose that the glycoprotein peaks observed in neostriatum may be identical to previously isolated glycoproteins of known function or subcellular location.


The incorporation of intrastriatally injected [3H]fucose into electrophoretically separated synaptosomal glycoproteins. II. The influence of passive avoidance training. Following intrastriatal injections of [3H]L-fucose, male albino rats served as (a) trained subjects in a step-down passive avoidance task, (b) stress controls receiving inescapable shock or (c) handled controls. At a series of time points after treatment the animals were sacrificed and the P2 fraction of the injected neostriatum was isolated. This tissue was electrophoresed on SDS-polyacrylamide gels and radioactivity profiles were constructed from 1 mm gel slices. The profiles of trained subjects were compared to shocked and handled control subjects from the same time point group. No differences in total [3H]fucose incorporation into neostriatal glycoproteins were detected as a result of the behavioral treatment used, nor was an incorporation into the majority of electrophoresed peaks altered. Three radioactive gel peaks were significantly altered as a function of experience. At the one day time point, trained  subjects exhibited a significant increase in the tritium content of a 70,000 dalton fucosyl-glycoprotein peak. At the 5 day time point, increased label was detected in a 180,000 dalton peak in both trained and shocked subjects, while a significant increase in a 140,000 dalton peak was observed only in trained animals. The relation of the present findings to perviously reported training related differences in glycoprotein metabolism are discussed.


Thickness and composition of nonrespiratory bronchiolar walls in normal and emphysematous lungs with some functional implications. The thickness and composition of the walls of nonrespiratory bronchioles were quantitatively assessed in groups of normal and emphysematous lungs. In both the groups there was a gradual increase in the thickness of the walls of nonrespiratory bronchiles with increasing caliber, but this change was not proportionate. Smaller bronchioles possessed thicker walls in both the groups. Bronchioles of comparable internal diameter were also found to be slightly thicker than normal in emphysematous specimens at all levels of caliber. Through a system of schematic models, it was shown that the relatively thicker walls of smaller bronchiles in normal and emphysematous lungs would enhance airflow in the proper direction both during expiration and inspiration. The slightly thicker walls of bronchioles in emphysema would result in their closure at substantially higher lung volumes than would occur with the somewhat thinner walled bronchioles of corresponding diameters in normal lungs. Although such thickening might only be focal in emphysema, this would interfere with expiratory airflow and result in air-trapping. This investigation failed to demonstrate differences in the composition in the walls of nonrespiratory bronchioles of normal and emphysematous lungs.


Measurements of total and intrabronchial resistances in normal and diseased isolated lungs. Postmortem studies of the total lung airways resistance (Rt), the central airways resistance (Rc), and the peripheral airways resistance (Rp) had been performed on normal lungs, on lungs with emphysema and lungs from patients with chronic obstructive pulmonary disease (COPD). In the normal lung a significant relationship between age and Rt was found. A decrease between 20 and 40 yr of age resulted from a decrease of Rp whereas an increase of Rt above the age of 40 was related to an increase in Rp. In the lungs with emphysema and obstruction Rp was increased especially. By variations of the breathing frequency and the lung volume (% of vital capacity) it could be detected that a remarkable effect upon Rt was caused by Rp. In general we found that even in normal lungs Rp is much higher than previously thought.


The role of fibrosis in the small airways in centrilobular emphysema. Small non-respiratory bronchi of lungs of patients suffering from slight and severe centrilobular emphysema of city dwellers and from focal dust emphysema, has been studied, by means of serial sections assessing the importance of the connective tissue proliferation in relation to the cross-sectional morphology of the bronchus, its diameter and longitudinal profile. Camera lucida drawings of parietal muscle and reconstructions of the bronchial wall and lumen were done. A positive relationship between the amount of the connective tissue proliferation, the severity of emphysema and the changes in the parameters indicated was found. The repercussion of fibrosis in the small airways disease of centrilobular emphysema, can be summarized as follows: the production of areas of localized stenosis, the contribution to the development of bronchiolar deformities, the obliteration of some airways and the alteration of bronchial muscle. It can be concluded, therefore, that the fibrosis, as second main cause of small airways obstruction, has a more wide repercussion on the bronchiolar structure than that of alveolar loss, and that it can probably affects not only the "static" characteristics of the bronchial wall, but also their "dynamic" behaviour by means of disorganization of the muscle.


Epidemiology of chronic non specific respiratory disease and the smoking-control program in young people. In an epidemiological study in the Kolin-District, Czechoslovakia, the percentage of cigarette-smokers was 57% of the male inhabitants aged 15 years and over, and 14% of the females of the same age group. The greatest proportion of cigarette smokers was in the age-group 25-34 years. The prevalence of chronic bronchitis was 13% of all males aged 15 years and over, and 4% of all females. An association of chronic bronchitis with age and smoking habits was found, in both sexes. In another study in the Prague-District No. 7 the smoking habits of male adolescents were related to their socio-economic status. Conclusions of epidemiological studies are important for the formulation and accomplishment of smoking-control program in young people. Health education should encourage school-children and adolescents by methods corresponding to their age to participate actively in the formation of a healthy style of their life.


Bronchial provocation tests in etiologic diagnosis of asthma. Several methods of bronchial challenging have been described in literature. The comparison of the results obtained in different departments is, of course, very difficult. The Authors have been interested in the standardization of inhalation challenge techniques and they present in this work their method and the results obtained. The standardized method has a good specificity, because of the agreement between B.P.T. and other diagnostic tests. The bronchial reaction generally developes after the exposition to low doses of allergen extract, and this confirms the specificity of the method. Its precision, depending on the standardization of allergen extract activity by RAST and of inhalation procedures, is good. The reproducibility is of 100 per cent. The safety is high (rare untword reactions). this standardized method of bronchial challenging is useful in etiologic diagnosis of asthma.


Complement, IgE- and IgG4-antibodies in the diagnosis of atopic diseases. Haemolytic complement (C) in human sera is readily consumed by most of the common inhalant allergens. The reactivity of C among individual sera differs considerably and is a characteristic parameter for the condition of atopy. The phenomenon is not mediated by specific IgE or IgG4 antibodies. Whereas in groups of patilues (by RAST) are negative in about 50 percent of the cases, this is not so with regard to C-reactivity. In somes cases, especially in allergy to guinea pigs, correlation with the clinical history is better with IgG4 than with IgE antibodies. In other allergies, there is a close correlation between Ige and IgG4 antibodoes.


Cardiovascular signs of acute hypoxaemia and hypercarbia during enflurane and halothane anaesthesia in man. We investigated the impact of enflurane and halothane (1.1 MAC) on heart rate and blood pressure responses to experimental hypoxaemia (PETo2 6.0 kPa [45 torr]) and small increments in PCO2 (1.3--1.6 KPa [10--12 torr]). The results reaffirm that circulatory signs of mild hypercarbia are vitually abolished by these anaesthetics. The important new observation is that signs of acute moderate hypoxaemia are also markedly depressed. Although potential modifying factors such as surgical stimulation were not evaluated, this study indicates that human subjects anaesthetized with enflurane or halothane lack reliable cardiovascular signs of acute hypoxaemia.


A randomized evaluation of the reversal of ketamine by physostigmine. One hundred and eleven patients undergoing ketamine anaesthesia for therapeutic abortion were studied in a double-blind trial of the reversal of ketamine by physostigmine administered postoperatively. The results demonstrate that physostigmine does not shorten recovery time or reduce the occurrence of ketamine emergence phenomena such as hallucinations, restlessness and dreams. In fact, the recovery course was prolonged in patients given physostigmine immediately upon termination of anaesthesia as compared with controls. By contrast, when physostigmine was given 30 minutes after the last dose of ketamine, the recovery was not prolonged as compared with that of the placebo-treated controls. These findings suggest some synergism between the effects of ketamine and physostigmine and should discourage the use of physostigmine as a ketamine antidote.


[Delay of retinal fluorescence as a death criterion]. Retinal fluoroscopy with measurement of the arm to retina circulation time can be used to evaluate the blood supply to the brain. When the brain tissue suffers from ischaemia as a result of circulatory failure, the arm to retina circulation time will be prolonged. Sixteen patients in deep coma resulting from serious cerebral disease were examined to verify cerebral ischaemia. The results of retinal fluoroscopy and cerebral angiography agreed. We find that retinal fluoroscopy is a simple and reliable method that can be used to detect brain death in comatose patients treated by automatic ventilation. We conclude that the main cerebral circulation can be regarded as occluded if the retinal fluorescence does not appear within 25 seconds after antecubital intravenous injection of fluoresceine. We suggest that the arm to retina circulation time exceeding 25 seconds may be used as a criterion of death.


Nitrous oxide levels in operating room air with various gas flows. Monitoring of nitrous oxide concentrations in operating rooms disclosed some leaks that had hitherto been unrecognized. Because nitrous oxide concentrations reported before 1967 had been obtained for the most part with high flows of the gas and without information concerning room air exchange, measurements were made of nitrous oxide levels during operations with an infra-red analyzer. after correction of leaks. Measurements were made at six sites in the operating-room suite, with and without scavenging. Flows that varied 0.1 to 2.5 litres of nitrous oxide were used in rooms that had 20 changes per hour of fresh air. Without scavenging, the highest time-weighted average value inhaled by any of the personnel (anaesthetists) was 31 ppm, when flow of 500 ml of nitrous oxide per minute were employed. The lowest reported deleterious concentration (unconfirmed) is 50 ppm. Lower flows produced lower values. With good scavenging, using flows as high as 2.51/min of nitrous oxide, the highest average value (anaesthetist) was 7.2 ppm. A short discussion is given concerning reasons for using low flows, including the cost of wasting agents and pollution of the entire atmosphere.


Successful use of dantrolene sodium in human malignant hyperthermia syndrome: a case report. We present a case of malignant hyperthermia in which successful management included the intravenous use of dantrolene sodium. A subsequent operation under spinal anaesthesia with oral dantrolene prophylaxis did not lead to development of malignant hyperthermia. Since this syndrome is rare during regional anaesthesia, the role of prophylactic oral dantrolene in preventing the redevelopment of malignant hyperthermia in our patient is open to question.


Anaesthetic considerations in idiopathic orthostatic hypotension and the Shy-Drager syndrome. Orthostatic hypotension due to autonomic failure may occur secondary to systemic disease states (notably diabetes) or as a disease entity in its own right with a variable degree of neurological involvement that has resulted in a confused classification. The diagnosis, classification and treatment of these latter forms of orthostatic hypotension is reviewed. The pathology is in the central and efferent autonomic pathway, resulting in a disordered baro-receptor reflex, postural hypotension, abnormal responses to tilting and the Valsalva manoeuvre, an inappropriately fixed heart rate and other autonomic features. Anaesthesia may be associated with profound hypotension and some of the signs of anaesthesia may be absent. The response to cardiac depressant drugs and reduction of circulating blood volume may be exaggerated due to absence of compensatory mechanisms. The response to vasoactive agents is unpredictable. The importance of preoperative evaluation, monitoring during operation and the careful selection of anaesthetic agents and techniques is discussed.


Smoking and gastric juice volume in outpatients. The volumes and pH of gastric juice in 26 outpatients presenting for dental surgery were measured by simple aspiration through a nasogastric tube introduced after the induction of anaesthesia. The average volume in these patients who were non-smokers was 9 ml and in those patients who had smoked on the day of the operation was 19 ml. Four of the smokers had more than 25 ml of gastric juice with a pH of 2.0 or less. It is suggested that out-patients who smoke would benefit from prophylaxis such as oral antacids or metoclopramide before anaesthesia.


Studies on isocitrate lyase isolated from Lupinus cotyledons. Isocitrate lyase (threo-DS-isocitrate glyoxylate-lyase, EC 4.1.3.1) was isolated from cotyledons of Lupinus seedlings, purified 100-fold with respect to its initial specific activity and characterized (Km, pH optimum, Mg2+ requirement, sulfhydryl inhibitors, and synthase activity). The final purified preparation consisted of two homogeneous protein bands clearly separated by electrophoresis on polyacrylamide gel and chromatography on Sephadex G 200. Reducing agents are necessary for the maintenance of enzyme activity. The most effective reducing agent studied was 1,4-dithioerythreitol. The effect of several metabolites (oxalate, malonate, phosphoenolpyruvate, succinate, malate, tartrate, gluconate-6-phosphate, sorbose, sorbitol, and inositol) on the activity of purified preparations was tested. Oxalate proved to be the strongest inhibitor, seconded closely by phosphoenolpyruvate. The spectral characteristics of the purified enzyme are as follows: ultraviolet peak at 280 nm and fluorescence peak at 340 nm. The solid state infrared spectrum of the enzyme (lyophilized) showed that the enzyme was mostly in the alpha-helix conformation with very slight random orientation.


Action of galactose oxidase on galactolipids. Exposure of galactose-containing glycosphingolipids and certain glycoproteins to galactose oxidase followed by treatment with sodium borotritide has been used to label specifically the terminal galactose and N-acetylgalactosamine moieties of these glycoconjugates. This labelling procedure was shown to be ineffective with a lipid isolated from rat testis, 1-O-palmityl-2-O-palmitoyl-3 beta-galactosyl-glycerol, under conditions which resulted in excellent labelling of galactosyl-ceramide. Monogalactosyldiacylglycerol was also poorly labelled by this procedure. It was shown that neither 1-O-palmityl-2-O-palmitoyl-3 beta-(3'-sulfogalactosyl)-glycerol nor sulfogalactosyl-ceramide ("classical sulfatide") was labelled by this procedure indicating that sulfate substitution of the galactose inhibits the action of galactose oxidase. The labelling of galactosyl-ceramide was not inhibited in the presence of the galactoglycerolipid, sulfogalactoglycerolipid, or sulfatide. The property of the lipid aglycone responsible for inhibiting galactose oxidase action remains to be determined.


The effects of alcohols on the structure of human glycophorin. The effects of alcohols on human glycophorin were monitored by circular dichroism, solvent perturbation of absorption spectra, fluorescence of 8-anilino-1-naphthalene sulfonate, and sedimentation equilibrium in the ultracentrifuge. Both ethanol and 2-chloroethanol gradually increase the alpha helix in glycophorin and its sialic acid free counterpart. The same alcohols do not cause a cooperative transition in the structure of the polypeptide chain of glycophorin. Other alcohols also increase the alpha-helix content of glycophorin. Binding of ANS to glycophorin is abolished at relatively low alcohol concentrations. Ethanol at 60% (v/v) reduces the molecular weight ratio of glycophorin and at the same time increases the exposure of tyrosine residues to solvent. These observations indicate a complex mechanism of interaction of weakly protic solvents with this stable membrane protein.


Dopamine-4-O-sulfate: a possible precursor of free norepinephrine. Incubation of dopamine-4-O-sulfate with purified bovine dopamine-beta-hydroxylase led to the formation of free norepinephrine. The production of free norepinephrine was completely inhibited in the presence of 5.6 mM of fusaric acid, an inhibitor of dopamine-beta-hydroxylase. No sulfatase activity was detected in the incubation medium. The reaction of dopamine-4-O-sulfate with dopamine-beta-hydroxylase followed Michaelis-Menten kinetics, showing an apparent Km of 2.6 mM.


Wheat embryo ribonucleates. XIV. Mass isolation of mRNA from wheat germ and comparison of its translational capacity with that of mRNA from imbibing wheat embryos. Commercially milled wheat germ is shown to be a convenient source material for facile recovery of mass (milligram) quantities of highly purified poly(A)-rich RNA. This poly(A)-rich RNA is efficiently translated in a nuclease-treated extract of rabbit reticulocytes. By sucrose density gradient fractionation of bulk poly(A)-rich RNA from wheat germ, it has been possible to show that there is a direct relationship between the molecular weights of the polypeptide products of cell-free synthesis and the molecular weights of the wheat mRNA molecules which program their synthesis. As assessed by SDS -- polyacrylamide gel electrophoresis, the same array of polypeptides is synthesized when nuclease-treated reticulocyte extract is programmed by poly(A)-rich RNA from either commercially supplied or laboratory-prepared wheat embryos. Significantly, there are gross quantitative if not qualitative differences between the translational capacities of poly(A)-rich RNA from dry and imbibing wheat embryos, and the possible importance of these differences for interpreting a changing pattern of polypeptide synthesis in imbibing wheat embryos is the subject of a brief discussion.


Nonspecific inhibition of dehydrogenases by folates: an artifact. The previous reports of inhibition of alcohol dehydrogenase and lactate dehydrogenase by the vitamin folic acid and its analogues are in error. The high absorbance of solutions containing folate causes distortion of the measurements of reaction velocities, leading to apparent inhibitions. When cuvettes of sufficiently short optical path length are used, no inhibition by folate can be observed. Similarly, the reported inhibition of ribonuclease by folate is an artifact. Glutamate dehydrogenase and dihydropterin reductase actually are inhibited by folate. The reported nonspecific inhibitions of over a dozen enzymes by folate, though, must be regarded as erroneous.


Some effects of superior laryngeal nerve stimulation on sympathetic preganglionic neuron firing. Repetitive electrical stimulation of afferent fibers in the superior laryngeal nerve (SLN) evoked depressant or excitatory effects on sympathetic preganglionic neurons of the cervical trunk in Nembutal-anesthetized, paralyzed, artifically ventilated cats. The depressant effect, which consisted of suppression of the inspiration-synchronous discharge of units with such firing pattern, was obtained at low strength and frequency of stimulation (e.g. 600 mV, 30 Hz) and was absent at end-tidal CO2 values below threshold for phrenic nerve activity. The  excitatory effect required higher intensity and frequency of stimulation and was CO2 independent. The depressant effect on sympathetic preganglionic neurons with inspiratory firing pattern seemed a replica of the inspiration-inhibitory effect observed on phrenic motoneurons. Hence, it could be attributed to the known inhibition by the SLN of central inspiratory activity, if it is assumed that this is a common driver for phrenic motoneurons and some sympathetic preganglionic neurons. The excitatory effect, on the other hand, appears to be due to connections of SLN afferents with sympathetic preganglionic neurons, independent of the respiratory center.


Nonparticipation of extracellular glutathione in renal transport of dibasic amino acids. Microinjections of L-[14C]arginine (2.9 mM) and L-[14C]ornithine (3.4 mM) were made into renal proximal tubules of rats in the presence of methionine sulfoximine (MSO) (10, 20 mM), ATP (10 mM), and MgCl2 (20 mM) together. Absorption of both labelled amino acids dropped, respectively, by 31.1 and 49.1% compared with control microinjections. The MSO alone or ATP plus MgCl2 had no effect. These data suggest that the inhibition by MSO plus ATP plus MgCl2 is not due to direct competition between MSO and dibasic amino acids but rather to suppression of the renewal of intracellular glutathione. Such an effect is discussed in comparison with cycloleucine inhibition of dibasic amino acid transport. Addition of exogenous glutathione to microinjectates die not reverse either type of inhibition. This study shows that while intracellular glutathione may affect amino acid transport, extracellular glutathione has no effect.


Glucose oxidation in fresh guinea pig cornea. The rate of glucose oxidation of fresh corneas of guinea pigs at different ages has been determined. Full-thickness corneal discs, 4 mm in diameter, were incubated in radioactive glucose solution. The quantity of the released CO2 was expressed in terms of the corneal discs, their dry weights, and DNA and protein contents. The rate of glucose metabolized to CO2 per hour was about 300 pmol/microgram DNA for guinea pigs weighing approximately 800 g. Glucose oxidation decreased as the age of the animals increased. Our results compared well with those obtained in other species. We therefore feel that the guinea pig should be a suitable model for research on the metabolism of corneas.


Unusual particle trajectories and structural arrangements in myelinated nerve fibers. Others have reported that axonally transported particles, which usually travel in a direction roughly parallel to the axis of the nerve fiber, may suddenly shift sideways as though changing tracks. Examples of this rare type of movement are shown for particles undergoing transport in myelinated axons of Xenopus laevis. An examination of the structure of axons from Xenopus showed that some microtubules, neurofilaments, and elements of endoplasmic reticulum may also exhibit marked deviations from the axial direction. It is concluded that it is not necessary to propose any mechanism for changing tracks in order to explain the particle motion.


Use of the overturn end point in goldfish to measure the interaction of diazepam and ethanol and the effects of the binding of diazepam to bovine serum albumin. Over the ranges 2.8 X 10(-5) to 8.78 X 10(-5) M diazepam and 4.85 X 10(-2) to 1.22 X 10(-1) M ethanol, addition of the effects of these agents on the overturn end point in goldfish was observed. The addition of bovine serum albumin (1.56 X 10(-5) M) to aqueous solutions of diazepam modifies the diazepam effect by reducing the "free" drug concentrations.


The stiffness of slow-twitch muscle lags behind twitch tension: implications for contractile mechanisms and behavior. Small, square stretches were applied during contractions of soleus and plantaris muscles in the cat to measure muscle stiffness. The stiffness of the slow-twitch soleus muscle (but not of the fast plantaris muscle) reaches a maximum after the peak in twitch tension. Since the number of active bonds should be maximum before the peak in tension, we suggest that many bonds are in the rigor state during the falling phase of the twitch. The stiffness of the bonds in this state may be useful for prolonging the twitch in slow-twitch muscles and for maintaining a posture.


Hepatic glycogen formation by direct uptake of glucose following oral glucose loading in man. The extent of direct uptake of glucose into hepatic glycogen following oral glucose loading in man is determined by mobilizing newly formed glycogen with a glucagon infusion in the immediately postabsorptive period. The amount of glucose flushed from liver glycogen is measured by using "out-of-steady-state" tracer turnover techniques. Following a 93 +/- 1 g load of glucose, at most 7.7 +/- 1 g of ingested glucose is recovered from glycogen. If the unlabelled glucose pool is taken into account, at most 10 g of available glucose can be said to be taken up directly into hepatic glycogen during the absorption of the glucose load.


Calcium ion stimulated endogenous protein kinase catalyzed phosphorylation of peripheral nerve myelin proteins. Myelin isolated from the rat peripheral nervous system (sciatic nerve and cauda equina) contained Mg2+-dependent protein kinase that phosphorylated myelin polypeptides. Ca2+, in micromolar concentrations, markedly stimulated phosphorylation (half-maximal stimulation at 5 microM (free) Ca2+) but at higher concentrations (greater than 100 microM Ca2+) it caused inhibition. In the presence of Triton X-100, phosphorylation (+/-Ca2+) of myelin was increased and Ca2+ caused up to a 10-fold increase in phosphorylation. Among the myelin polypeptides, P0 (Mr, 28 000), a major glycoprotein, accounted for nearly 60% of the total phosphate incorporated into the myelin and Ca2+ markedly promoted phosphorylation of P0. Phosphorylation of other myelin polypeptides, P2 (Mr, 16 000), Y (Mr, 26 000), and P1 (Mr, 20 000), and the Ca2+-stimulatory effect on phosphorylation of these were also evident. Cyclic AMP (or other cyclic nucleotides) failed to show any significant stimulatory effect on myelin phosphorylation.


The rates and patterns of survivorship and disease in a university dairy herd. The rates and patterns of disease occurrence and survivorship were determined over a six year period in a university operated dairy herd. Of the ten diseases selected for study, clinical mastitis occurred most frequently with an incidence rate of 10.1% and displaced abomasum occurred least frequently with an incidence rate of 4.4%. The occurrence of all disease except those of the ovary was associated with the age of the cow. Mastitis, pneumonia and cystic graafian follicles tended to reoccur in the same cow after the initial occurrence. The average culling rate was 25.6% and the median number of years cows survived in the herd was 3.4 years. Methods for calculating the various rates and survivorship are described and their interpretation discussed.