Diagnosis and management of post-cholecystectomy symptoms: the place of endoscopy and retrograde choledochopancreatography. Endoscopic retrograde choledochopancreatography (ERCP) was employed in 52 patients symptomatic after cholecystectomy in whom barium meal studies and intravenous cholangiography had failed to yield a diagnosis. Cannulation of the papilla of Vater was carried out in 50 of the patients in a mean time of 10 min. Diagnostic information demonstrating a pathological lesion or a normal biliary and pancreatic ductal system was obtained by means of endoscopy and ERCP in 48 cases. There were no serious complications. A pathological lesion was demonstrated in all but one of the patients presenting with jaundice, cholangitis or pancreatitis but the diagnostic yield was not as high in patients with vague upper abdominal symptoms. Endoscopy and ERCP are the investigative procedures of first choice in complex post-cholecystectomy cases in whom intravenous cholangiography fails, gives incomplete information or suggests normality in the face of continuing symptoms or clinical evidence of residual biliary disease.


A case of myasthenia gravis with thyrotoxicosis treated by combined subtotal thyroidectomy and total thymectomy. Thyrotoxicosis occurring in conjunction with myasthenia gravis is rare. The usual treatment consists of medical control of the thyrotoxicosis, then thymectomy and later subtotal thyroidectomy. The case reported here concerns a 19-year-old girl who had surgical treatment for both lesions on the same occasion. With proper medical preparation, modern anaesthesia and respiratory care, the surgical treatment of both lesions can be accomplished in one stage.


Ultrasonic scanning of the thyroid gland as a guide to the treatment of the clinically solitary nodule. This study examines the diagnostic accuracy of ultrasonic scanning in the recognition of multinodular goitre in 87 patients referred for examination who were thought by the referring clinician to have a single nodule in the thyroid gland. Twenty-five were found to have multinodular glands, 23 of which were correctly identified by ultrasound. Of those who had truly solitary nodules, ultrasonic scanning enabled us to identify all 23 who had cystic lesions and 35 out of the 39 who had predominantly solid lesions. The clinical significance of these observations in the management of patients with so-called 'single nodules' is discussed.


Abnormalities of gastric emptying and pyloric reflux in uncomplicated hiatus hernia. We have measured the rate of gastric emptying of solid and liquid meals by an external scanning technique and have studied pyloric reflux by a radiological technique. Investigations were performed in patients with uncomplicated hiatal hernia, patients with uncomplicated duodenal ulcer and normal controls. There was a significant delay in the emptying of both solid and liquid meals in the patients with hiatal hernia compared with both the duodenal ulcer patients (solid meals P less than 0.01, liquid meals P less than 0.025) and with normal controls (solid meals P less than 0.05, liquid meals P less than 0.001). Duodenogastric reflux was observed in 35% of hiatal hernia patients compared with 24% of duodenal  ulcer patients and no incidence in the controls.


Partial hepatectomies with a hand-held laser knife: An experimental study. Fifteen mongrel dogs underwent a left lateral non-anatomical partial hepatectomy using a carbon dioxide laser, diathermy or a surgical scalpel. An original prototype of a compact hand-held laser was used and its effects were compared with those of the other two instruments. An improved dry cat surface was achieved by placing a rubber snare proximal to the planned incision. While no significant differences in the blood loss or in the operating time were found among the experimental groups, the laser beam sealed vessels of up to about 6 mm in diameter without any complementary suture ligatures, which were needed in the other groups. Histological studies revealed less tissue trauma in the sections performed by the laser and only slight secondary inflammatory reaction.


Closure of a loop colostomy by a modified Le Gac's operation. The results of closure of a loop colostomy presented by various authors are reviewed. It is suggested that postoperative faecal fistula is due most frequently to oedema and constriction at the site of bowel closure. Le Gac's method of closure is described. It comprises excision of the stoma and spur with side-to-side as well as end-to-end anastomosis, and it results in a wide lumen closure. A modified Le Gac's operation is described in which the mesocolic spur is not removed.


Pilonidal sinus: a 5-year appraisal of the Millar-Lord treatment. One hundred and two patients with a pilonidal sinus treated by minor excision had a life-table of 5-year freedom from recurrence of 89% provided that they attended a dressing clinic until the wound healed. With failure to attend the clinic, the recurrence freedom fell to 57% (P less than 0.004). Age, sex, acute abscess, previous excision, presence of hairs and the number of midline pits and lateral abscesses did not significantly influence the result. The method supersedes more extensive procedures, but should be tested against even less traumatic techniques.


A succesful repair of a recto-urethral fistula: a case report. A case report of a method of repair of a recto-urethral fistula is described. A combined synchronous abdominoperineal approach was used with the patient in the lithotomy-Trendelenburg position. The greater omentum was mobilized and interposed between the repaired rectum and the prostatic urethra. A review of the literature is presented.


A gravimetric plethysmograph and its evaluation in clinical use. A gravimetric plethysmograph, the technique of its use and its evaluation in vascular surgical practice are described. The instrument measures flow by the increase in leg weight (rather than volume) produced by an increase in blood content resulting from venous occlusion. The instrument was found to be convenient to use and satisfactory records were obtained in 88% of patients. Values for flow at rest and during reactive hyperaemia were clearly related to the presence of indications for surgical treatment and were similar to those reported by other workers. It is suggested that a peak hyperaemic flow of greater than 15 g 100 ml-1 min-1 may indicate that there are no indications for surgical treatment. The changes in hyperaemic flow values after treatment were clearly related to the symptomatic improvement resulting from it. It is concluded that the gravimetric plethysmograph is suitable for use in the assessment of patients with obliterative arterial disease of the legs.


Doppler ultrasound in the diagnosis of the popliteal artery entrapment syndrome. Doppler pulse recordings in a patient with asymptomatic popliteal entrapment were compared with those in 25 normal subjects. A drop in pulse amplitude and ankle systolic pressure produced by forcible leg extension and active foot plantar flexion distinguished the patient with the anomaly from the controls, in whom no change was noted during these manoeuvres. This simple, non-invasive test thus diagnosed a potentially limb-threatening congenital abnormality in an asymptomatic patient with equivocal arteriographic findings.


The incidence of malignancy in carotid body tumours. Twenty-three patients with 24 carotid body tumours are reviewed. A high incidence of malignancy (30%) was encountered. It is recommended that all carotid body tumours be removed unless there are contraindicating medical or technical reasons.


Postoperative depression of lymphocyte transformation response to microbial antigens. Cell mediated immunofunction, as expressed by total lymphocyte count, B and T cell count, in vitro blastogenic response to unspecific mitogens (phytohaemagglutinin and poke weed mitogen) and microbial antigens (Candida albicans, purified protein derivative, Staphylococcus aureus and Escherichia coli), was assessed in 8 otherwise normal patients undergoing elective, uncomplicated gastric surgery. The results showed a significant depression in all parameters on the first and/or third postoperative day, except for the blastogenic response to unspecific mitogens, which was unchanged throughout the study. Compared with the preoperative value, the total lymphocyte count decreased by 48% with a similar fall in both T and B cells. The blastogenic response to C. Albicans, purified protein derivative, Staph. aureus and E. coli decreased by 45, 42, 75 and 76% respectively. When measured on the seventh and ninth postoperatively days all parameters had returned to preoperative levels. Thus, even during clinically uncomplicated surgery, significant cell mediated immunodepression can be demonstrated by the blastogenic response of peripheral lymphocytes to common microbial antigens. The results suggest that this phenomenon may be secondary to the disappearance of specific reactive lymphocytes from the peripheral blood following surgical trauma.


A survey of protein nutrition in patients with inflammatory bowel disease--a rational basis for nutritional therapy. The incidence of protein malnutrition was studied in 74 unselected patients with inflammatory bowel disease who were in the following categories: ileostomy (16), remission (15), elective surgery (12), acute attack (12), urgent surgery (10) and post-surgical complications (9). Compared with a control group, the patients in the urgent surgery group had low values for plasma albumin transferrin, pre-albumin and haemoglobin and these values were even lower in the patients who developed a major complication after surgery. There was no evidence of protein malnutrition in the ileostomy patients or in those in whom the disease was in remission. Nutritional therapy is strongly indicated in patients who are admitted to hospital with a severe attack of colitis and in whom urgent surgery is probable.


Tumour stimulation by anti-oestrogens.

Tumour stimulation by anti-oestrogens. Two women who developed tumour progression while taking anti-oestrogens are described and some of the possible mechanisms for this action are discussed.


Lignocaine: its effects on wound healing. In the light of clinical observations that local anaesthetic impairs wound healing, the effect of lignocaine at various concentrations, with and without adrenaline, on the tensile strength of skin wounds in rats 3, 5 and 7 days after operation was studied. Lignocaine had an adverse effect on wound healing at 5 and 7 days, perhaps due partly to the destructive effect of the intra- and subcutaneous injection, but certainly due also to the lignocaine itself. Adrenaline potentiated this effect. It was concluded that it is better to use dilute solutions of lignocaine, preferably without adrenaline, for local anaesthesia.


Colectomy and ileorectal anastomosis for colitis: report on a personal series, with a critical review. In a consecutive series of 86 patients who required total colectomy for inflammatory bowel disease, 36 (43 per cent) had an ileorectal anastomosis. On review between 1 and 18 years after the operation, there were 25 patients who retained the anastomosis, all of whom were in good general health. Details of their clinical and sigmoidoscopic assessment and the histological grading of rectal biopsies are given. The results are compared with other published reports in a critical review of the present standing of ileorectal anastomosis.


Giant diverticula of the colon.

Giant diverticula of the colon. A case of a gas-filled intra-abdominal abscess cavity is reported. The literature is reviewed for similar cases and with reference to the cause and differential diagnosis of abdominal air cysts.


The value of ultrasonic B-mode scanning in the diagnosis of persistent jaundice. The use of ultrasonic B-mode scanning of the liver and biliary tract in patients with persistent jaundice is described. Sixty-seven consecutive jaundiced patients have been scanned. A correct diagnosis was obtained in 66 per cent, useful information in 26 per cent and in only 8 per cent was the information misleading or of no diagnostic value. In our opinion this simple and non-invasive technique is of great value in the definite diagnosis of persistent jaundice and should allow earlier surgery in the obstructive cases.


Occult rupture of the spleen.

Occult rupture of the spleen. Five cases of occult or 'spontaneous' rupture of the spleen are described. Pathological examination of the spleen showed changes of infectious mononucleosis in 2 cases, Hodgkin's disease in 1, amyloidosis in 1 and in the remaining spleen no underlying disease process was seen. All 5 cases survived, and evidence from the literature suggests that this may have been in some measure due to the fact that prompt surgical treatment followed a correct preoperative diagnosis. The importance of awareness of the condition, radiological investigation and peritoneal lavage in reaching the correct diagnostic conclusion is discussed.


Vascular injuries in the extremities in battle casualties. A serial of 51 wounded soldiers with 54 arterial and 28 venous injuries is presented. Interposition of autogenous vein grafts was performed in 30 arterial injuries. Lateral suture or patch arterioplasty was performed in 7 arteries. End-to-end anastomosis was possible in 8 cases. Primary vein repair was performed in 14 vein injuries. Lateral suture, patch plasty, end-to-end anastomosis and interposition composite vein grafts were used. A distal temporary arteriovenous fistula to increase the flow through venous interposition grafts was performed in 4 cases. Hyperbaric oxygen treatment was used in 7 cases in which successful arterial repair did not reverse ischaemia, and it prevented major amputations. Neurovascular injuries are not always an indication for primary amputation. Six such cases are discussed.


Abdominal aortic aneurysm: Perianeurysmal fibrosis and ureteric obstruction and deviation. Seven cases of ureteric obstruction and one case with bilateral medial ureteric deviation complicating inflammatory aneurysm of the aorta are reported. The value of routine preoperative pyelography in all patients with abdominal aortic aneurysm is emphasized. Diagnostic difficulties that may arise when these conditions coexist are discussed. Our experience suggests that these patients are best treated by both aneurysmectomy and ureterolysis and that long-term follow-up is advisable.


Knotted drainage tube: An unusual postoperative complication. Spontaneous knotting of a postoperative drainage tube is reported.


A complete suction system for operative surgery. A versatile suction system utilizing a hand-held suction head with on-off control is described. Interchangeable nozzles and guards adapt the sucker to work appropriately in most operative situations.


The pacemaker-twiddler's syndrome: another disadvantage of abdominal implantation of pulse generators. Breakage of a pacer lead due to the pacemaker-twiddler's syndrome (PTS) occurred in 4 of 62 survivors following epicardial-intramural pacer lead implantation with the pulse generator placed in each case in a subcostal left upper quadrant subcutaneous pocket. The abdominal pulse generator pocket appears to invite spontaneously occurring PTS, more so in a pregnant woman. The important predisposing factor to the development of PTS is an excessively spacious pulse generator pocket containing a pool of fluid. Addition of a few simple modifications to the technique of cardiac pacing would prevent the complication; these include implantation of the pulse generator in a plane deeper to the pectoral muscles, suspending the pulse generator from the clavicle and application of vacuum-suction drainage to the generator pocket in the initial phase of wound healing. In the presence of an optimally fitting pulse generator pocket, PTS should be rare with subclavicular subpectoral pulse generator implantation without active patient participation. The syndrome may not be as rare a cause of pacer lead malfunction as may appear from the relative paucity of reports in the literature.


Choledochoscopy in exploration of the common bile duct. The technique of operative fibreoptic choledochoscopy is described; the results are reported in 88 patients with gallstones requiring exploration of the common bile duct. There were no cases of retained calculi that were endoscopically undetected. Postoperative T-tube cholangiography was carried out in 81 cases and confirmed the findings of operative biliary endoscopy in all cases. Choledochoscopy is an accurate and safe operative procedure which can eliminate the problem of undetected residual calculi.


Serum ionized calcium in acute pancreatitis. Measurement of serum ionized calcium was performed daily for 7 days after admission in 8 consecutive patients with acute pancreatitis. The results support the findings of our previous study that the most common cause of the low serum calcium often found in patients with this disease is a low serum albumin; when correction of serum calcium is made for hypo-albuminanemia, most patients are found to be normocalcaemic. The occasional hypocalcaemia as shown by the 'corrected' serum calcium or by serum ionized calcium measurement is usually mild and transient, indicating that the normal homoeostatic mechanisms of the body can efficiently maintain the physiologically active fraction of the serum calcium within, or close to, the normal range. These findings explain the rarity of overt and subclinical tetany in acute pancreatitis. This study has shown that correction of serum calcium for albumin provides similar information to the direct measurement of serum ionized calcium. The value of 'apparent' hypocalcemia in assessing severity of acute pancreatitis requires reappraisal, while greater attention should be directed towards the investigation and management of hypoalbuminaemia in this disease.


The effect of experimental haemorrhagic shock on the bacterial content of thoracic duct lymph. The effect of haemorrhagic shock on the simultaneous appearance of enteric micro-organisms in the central lymph and the portal blood was studied in 30 dogs. Irreversible haemorrhagic shock results in portal bacteraemia but the lymph remains sterile. Thoracic duct drainage is harmful and hastens the onset of irreversibility.


A new interpretation of the insulin test validated and then compared with the Burge test. A prospective study of 40 patients undergoing proximal gastric vagotomy confirmed the validity of a new interpretation of the insulin test in the early postoperative period (Maybury et al., 1977). Of the 30 patients falling into the group expected to be free from recurrent ulceration (low risk group), none had developed symptoms suggestive of this condition, whilst of the 10 in the contrasting high risk group, 6 have already developed proved recurrences (mean follow-up period 26 months). A further group of 24 patients was studied by performing a peroperative Burge test for completeness of vagotomy and comparing these results with a postoperative insulin test. This study showed that the Burge test, properly performed, is a reliable test of the adequacy of vagotomy. The use of this test has led to a better understanding of the operative technique required to achieve the objective of an adequate vagotomy.


Adult intussusception in Glasgow 1968-74. A further review of adult intussusception in Glasgow between 1968 and 1974 is presented. A higher than expected incidence of idiopathic intussusception has been found both in this and in the earlier Glasgow series of Smith and Gillespie (1968)--44 per cent and 50 per cent respectively.


Primary vaginal stone following abdominoperineal excision of the rectum with total hysterectomy. This paper reports a case of primary vaginal calculus developing following abdominoperineal excision of the rectum with total hysterectomy. A review of the previous literature on primary vaginal calculus is included.


Should the indications for prenatal chromosome analysis be changed? Amniocentesis for chromosome analysis was performed in 1086 pergnant women, 739 of whom had an increased risk of giving birth to a child with chromosome abnormalities. Such abnormalities were found in almost identical proportions among the fetuses with an increased risk (1.2%) and among those with no increased risk (1.4%). Findings in several other studies seem to confirm that there is no significant difference between the risk groups in the proportion of abnormalities found. This suggests that our current risk groups may not be the right ones, but a much larger study is needed to confirm this.


Primary excision of brain abscess.

Primary excision of brain abscess. Sixteen consecutive patients with brain abscess, including two with multilocular and two with infratentorial abscesses, were treated by primary total excision of the abscess. The patients were followed for six months to three years. Only one patient died and there were no recurrences. Immediate primary excision is therefore the treatment of choice in brain abscess.


Why are children admitted to hospital?

Why are children admitted to hospital? The criteria for admitting children to hospital for medical care were examined in 399 consecutive, non-planned admissions to the Nottingham Children's Hospital between October 1975 and January 1976. Sixty-one per cent of the children were referred direct to the casualty department by their parents. Over 20% were admitted primarily for social reasons, and many of the remainder came from homes judged to be at a disadvantage. The hospital medical services for children should be aware of the needs of parents as well as of the needs of sick children in their catchment area.


Plasma androstenedione and oestrone levels in normal and osteoporotic postmenopausal women. Plasma androstenedione and oestrone concentrations were measured in 72 postmenopasual women. The women included some who had undergone oophorectomy, some with osteoporosis, and normal controls; they were matched for years since menopause. Both hormone concentrations were significantly reduced in the women with osteoporosis. The women who had undergone oophorectomy had hormone concentrations intermediate between the normal and osteoporotic values. Oestrogen deficiency secondary to low androstenedione levels is a major risk factor in postmenopausal osteoporosis, and may be caused by failure of ovarian stromal androgen secretion or some abnormality in the pituitary-adrenal axis.


Prolactin concentrations in ovulatory but infertile women: treatment with bromocriptine. We measured basal plasma prolactin concentrations (in samples obtained during the early follicular phase) in 25 normal (control) women and in a similar group of 40 patients with a long-standing history of infertility. The infertile patients were all ovulating regularly, and had been unsuccessfully treated with clomiphene and in some cases dydrogesterone and human menopausal gonadotrophin. Although none of the patients had plasma prolactin concentrations greater than 1000 muU/ml, 47.5% of the estimations were greater than 1 standard deviation (SD) above the mean established for our control group. This difference was highly significant (P less than 0.001). Treatment with various bromocriptine regimens effectively reduced prolactin concentrations to below normal in all cases, and 16 pregnancies followed-13 during bromocriptine treatment and three in the first post-treatment cycle. The cumulative conception rate was 63.4% after 10 months' treatment.


Effects of sputum on pulmonary function. The specific airways conductance (SGAW) of 23 patients with copious sputum production and airflow obstruction was measured before and after physiotherapy to determine the effect of bronchial secretions on pulmonary function. Chest physiotherapy to remove these secretions had the effect of reducing airflow obstruction, as measured by SGAW. These findings suggest that sputum has a detrimental effect on pulmonary function and that physiotherapy can reduce airways obstruction.


Rapid increases in plasma prostaglandin concentrations after vaginal examination and amniotomy. Peripheral plasma concentrations of 13,14-dihydro-15-keto prostaglandin F (PGFM) were measured in three groups of women after the 37th week of pregnancy. Samples were taken before and five minutes after (a) amniotomy, (b) vaginal examination with sweeping of the fetal membranes, or (c) vaginal examination without sweeping of the membranes. Each procedure significantly raised the circulating PGFM levels, although amniotomy and vaginal examination with membrane sweep were more potent stimuli than vaginal examination alone. These findings suggest that there is a considerable potential for rapid increases in prostaglandin production during late pregnancy and provide a possible explanation for the fact that amniotomy and vaginal examination with membrane sweep often initiate labour.


Association of serum lipids and obesity with cardiovascular mortality. Serum lipid concentrations, relative body weight, and smoking habits were assessed in a cohort of 1648 middle-aged Finnish men who were subsequently followed for seven years. Multivariate analysis showed that serum triglyceride and cholesterol concentrations and smoking were all independently associated with cardiovascular mortality. High serum triglyceride concentrations increased the risk of cardiovascular death only when they exceeded 1.7 mmol/l (150 mg/100 ml), but this occurred at all cholesterol and relative body weight levels. Obesity influenced death rates only in men with raised serum lipid levels, while smoking was associated with increased mortality when any combination of the other factors was present. Men who had raised triglyceride concentrations combined with smoking or obesity had the highest risk of cardiovascular death.


Observer variation in recording clinical data from women presenting with breast lesions. Report from the Yorkshire Breast Cancer Group. The degree of observer variation in recording 11 186 items of clinical data from 242 woman who presented complaining of a lump in the breast to a group of 10 surgeons was studied. Each women was interviewed and examined twice and the findings (of the two clinicians) compared. There was a wide range of variation among the observers. Variation in recording the presence or absence of axillary nodes was considerable (45%), as was that in sizing the primary lesion (55%). In 20% of cases the two assessments of primary lesion size differed by over 2 cm. In other respects the results were more encouraging; much variation could be eliminated by wording the proforma more clearly. Moreover, variation was not person-specific, so that these findings are probably reasonably representative. Any future trial of breast lesions should (a) design specific proformata, (b) define terminology, (c) make these definitions universally available, and (d) conduct observer variation studies before the start of the full trial.


Upper gastrointestinal endoscopy--a GP service. Since 1974 there has been an open endoscopy service available to general practitioners in the Bournemouth and Christchurch area. Patients are referred directly with a standard form. A retrospective comparison of requests for barium-meal examinations and for endoscopy by general practitioners showed that the reasons for referral were similar. Forty per cent of patients in each group showed no abnormality. Ulceration was found in 21.1% of patients who underwent endoscopy and 9.7% investigated by barium meal. Duodenitis or gastric erosions were found in a further 16% of endoscopies. More hiatus hernias and deformed duodenal caps were found at barium meal. Despite these differences the results of follow-up were similar.


Measuring the severity of injury.

Measuring the severity of injury. The injury severity score as a method for measuring the severity of injury has been found useful for epidemiological and metabolic research. Comparison with plasma cortisol concentrations confirmed that the method could distinguish between minor and moderate injuries. Before using the method one must decide on the need to weight the score for age. This is necessary when studying some relationships--for example, mortality and severity--but not others--for example, plasma cortisol concentration and severity.


Airway patency in fatal accidents.

Airway patency in fatal accidents. The state of the airway in patients who had fatal accidents over a five-year period was correlated with the severity of injury sustained. Necropsy of patients dying in hospital up to 72 hours after an accident showed that those with obstruction of the airway had less severe injuries than those in whome no such obstruction could be found. This suggests that airway obstruction contributed to their death. A similar distinction could not be shown for the patients who died before they reached hospital, indicating that airway management before arrival at hospital was probably satisfactory.


Increased plasma adrenaline concentrations in benign essential hypertension. Plasma adrenaline, noradrenaline, and dopamine concentrations and plasma renin activity were measured in the supine position and after standing for 10 minutes in 14 patients with sustained benign essential hypertension and in five patients with labile hypertension. Results were compared with values obtained in 11 normotensive control subjects. In controls plasma noradrenaline concentrations increased with age, while plasma adrenaline values tended to decrease with age. No significant difference in mean plasma noradrenaline was found between hypertensive and control subjects, but plasma noradrenaline seemed slightly increased in a proportion of hypertensive patients aged less than 50. Plasma adrenaline was considerably raised in both supine and standing positions in eight patients with sustained hypertension and in two with labile hypertension. Dopamine concentrations and plasma renin activity were similar in all groups studied. The finding of significantly raised plasma adrenaline concentrations in a large proportion of hypertensive patients supports the hypothesis that the activity of the sympathetic nervous system is increased in essential hypertension. Measurement of plasma adrenaline seems to be a more sensitive index of this activity than that of plasma noradrenaline.


Photochemotherapy in mycosis fungoides.

Photochemotherapy in mycosis fungoides. Six patients with mycosis fungoides were treated with methoxsalen and long-wave ultraviolet light. They were assessed clinically and histologically before and after treatment. All six patients showed clinical improvement. Histological clearing of both epidermis and dermis occurred in three patients, and epidermal clearing alone occurred in two. Photochemotherapy may have a place in the treatment of the early and intermediate stages of mycosis fungoides, and it may also be useful as an adjunct to other forms of treatment in the more advanced stages.


Diet and heart: a postscript.

Diet and heart: a postscript. During 1956-66, 337 healthy middle-aged men in London and south-east England participated in a seven-day individual weighed dietary survey. By the end of 1976, 45 of them had developed clinical coronary heart disease (CHD) which showed two main relationships with diet. Men with a high energy intake had a lower rate of disease than the rest, and, independently of this, so did men with a high intake of dietary fibre from cereals. Energy intake reflects physical activity, but the advantage of a diet high in cereal fibre cannot be explained; there was no evidence that the disease was associated with consumption of refined carbohydrates. Fewer cases of CHD developed among men with a relatively high ratio of polyunsaturated to saturated fatty acids in their diet, but the difference was not statistically significant.


Hands as route of transmission for Klebsiella species. Seventeen per cent of the staff of an intensive care ward were found to have Klebsiella spp contaminating their hands, and these strains could be related to serotypes infecting or colonising patients in the ward on the same day. We identified some simple ward procedures that resulted in contamination of nurses' hands with 100-1000 klebsiellae per hand. Klebsiellae survived on artifically inoculated hands for up to 150 minutes. Handwashing with chlorhexidine hand cleanser reliably gave 98-100% reduction in hand counts, and the introduction of routine handwashing by staff before moving from one patient to the next was associated with a significant and sustained reduction in the number of patients colonised or infected with Klebsiella spp. Staff clothing was occasionally contaminated, but ward air and dust rarely contained klebsiellae.


Plasma fenfluramine levels, weight loss, and side effects. Fifty women with refractory obesity received fenfluramine for 20 weeks. Every two weeks details of weight change, drug dose, degree of anorexia, and any side effects were recorded and plasma was obtained for fenfluramine and norfenfluramine measurements. Of the 41 patients available for final analysis 26 achieved a maximum plateau dose of 160 mg/day. Plasma fenfluramine concentrations did not correlate with the degree of anorexia or with the incidence of side effects other than the severity of dream disturbance. There was a highly significant relation between weight loss and plasma fenfluramine and norfenfluramine concentrations and also between weight loss and the presence of sustained anorexia. Women who achieved mean plateau concentrations over 200 ng/ml lost a mean 8.8 kg while those with concentrations less than 100 ng/ml lost a mean of only 2.1 kg. When fenfluramine is prescribed in refractory obesity the dose should be increased stepwise until either satisfactory weight loss is achieved or troublesome side effects appear.


High pressure paint gun injuries.

High pressure paint gun injuries. Despite their use for the past 20 years the dangers of injuries from high pressure paint guns are not widely known. Two cases treated incorrectly through ignorance in our casualty department resulted in amputation of digits. Paint solvents are far moe damaging than paint of grease injection. All cases should be treated urgently by an experienced surgeon as fairly extensive surgery may be needed.


Malaria in Nottingham children.

Malaria in Nottingham children. In five and a half years 16 children were admitted to hospital in Nottingham suffering from malaria. Thirteen cases were caused by Plasmodium vivax and two by P falciparum, and in one the type was not identified. All were children of immigrant parents, predominantly from Pakistan, although most were born in England but had been visiting Asia. Three children were ill on or soon after arrival, but in the others the onset of symptoms was delayed by up to nine months. All made an uneventful recovery, although two children with P vivax infections had a further relapse after chloroquine treatment only. The question "Where have you been?" should be put to all immigrant parents whose children have a febrile illness. Agencies who provide travel for Asian immigrant families returning home for a visit should be encouraged to provide instructions about malaria prophylaxis.


The National Poisons Information Service and hospital admissions for children--the experience in Wales of the Cardiff Centre. When inquiries to the Cardiff Centre of the National Poisons Information Service were compared with hospital admissions in the eight health authorities in Wales the findings suggested fewer admissions in the area within which the centre is situated and showed a more extensive use in that area than elsewhere. High inquiry rates were associated with high hospital admission rates when the eight areas were compared. If the service were delegated to area level a more complete community use would result.


Early assessment of severity of acute pancreatitis using peritoneal lavage. Diagnostic peritoneal lavage using one litre of isotonic saline was performed on 27 patients with acute pancreatitis as soon as possible after diagnosis. There were no complications. Severe attacks (defined retrosepctively according to the progress of the attack) were characterised by the presence of free peritoneal fluid and by dark-coloured and often opalescent return fluid. The concentrations of albumin, aspartate aminotransferase (SGOT) and total protein in the return fluid provided good discrimination between severe and mild attacks, and there were also significant differences in the concentrations of amylase, urea, calcium, potassium, bilirubin, alkaline phosphatase, and the white cell count. Lavage successfully predicted severe disease in five patients whose condtion had been clinically assessed as mild.


Transthoracic ventricular defibrillation in adults. A prospective study of the energy required for transthoracic ventricular defibrillation in adults showed that in 42 (81%) out of 52 episodes of ventricular fibrillation shocks of 100 watt-seconds (Ws) of stored energy were successful. Out of 233 episodes, 222 (95%) were converted by 200 W s shocks. Among patients in whom primary ventricular fibrillation occurred within one hour of the onset of acute myocardial infarction, 200 W s shocks were successful in 40 (98%) out of 41 episodes. When low-energy shocks failed, a stored energy of 400 W s invariably succeeded. The need for large and expensive defibrillators that store more than 400 W s and are less readily available is therefore questioned.


Effect of cigar smoking on carboxyhaemoglobin and plasma nicotine concentrations in primary pipe and cigar smokers and ex-cigarette smokers. Five ex-cigarette smokers and five primary pipe and cigar smokers each smoked a large cigar. Carboxyhaemoglobin (COHb) and plasma nicotine levels were measured. In the ex-cigarette smokers mean COHb rose from 2.9% to 9.6% and plasma nicotine from 79.0 nmol/l to 281 nmol/l (12.8-45.6 ng/ml). This response was similar to that of cigarette smokers smoking cigarettes, which indicated that the subjects had inhaled and absorbed significant amounts of nicotine. In the primary pipe and cigar smokers the mean COHb rose from 0.8% to 1.0% and the plasma nicotine from 21 nmol/l to 32 nmol/l (3.4-5.2 ng/ml), indicating neither significant inhalation nor significant nicotine absorption.Since ex-cigarette smokers do not seem to lose their habit of inhaling when they change to cigars, measures aimed at persuading smokers to switch to cigars will have little effect on their health. Pipe and cigar smokers who have never smoked cigarettes do not inhale, which probably accounts for their reduced incidence of coronary heart disease and lung cancer. But they also appear not to absorb nicotine, which suggests that nicotine is absorbed largely from the lung and that the buccal mucosa is unimportant. It also raises the interesting question of why primary pipe and cigar smokers do smoke.


Collaborative care of hypertensives, using a shared record. A shared hospital-GP record for control of hypertension was studied in a sample of 60 patients. Over 80% of patients brought the record to hospital duly completed. Two-thirds of GPs, and the hospital staff, assessed the record as a useful aid in the care of hypertensives. It is still employed enthusiastically, three years after its introduction.


Reticulocytopenia and "absence" of red cell autoantibodies in immune haemolytic anaemia. A raised reticulocyte count is common in patients with immune or autoimmune haemolytic anaemia, and the result of the direct antiglobulin test (DAGT) is usually positive because of IgG or IgG and complement components on the red cells. We report on three patients who had low reticulocyte counts when they were most anaemic, and in whom no red cell autoantibodies could be detected by the DAGT. We postulate that reticulocytes may be selectively destroyed if antibodies are directed against antigenic sites on these young red cells, thus giving rise to a population of cells whose antigenic sites are poorly expressed. This theory might explain the low reticulocyte counts and the "absence" of antibodies (as tested by the DAGT) in such patients. Radioisotopic studies with 51Cr and 59Fe may provide useful information on the rate and sites of red cell destruction.


Doxorubicin cardiotoxicity: possible role of digoxin in its prevention. Twenty-nine patients with gynaecological cancers who received over 400 mg of doxorubicin were monitored electrocardiographically to determine whether cardiac glycosides countered the adverse effects of high total doses of doxorubicin. Minor electrocardiographical changes were noted in five out of six patients who were not receiving a cardiac glycoside and four out of six who were receiving ouabain, and none of the 16 who were receiving digoxin. One other patient on digoxin stopped taking it and developed cardiomyopathy. One patient on ouabain also developed cardiomyopathy. So far nine patients on digoxin have received between 550 and 1000 mg/m2 of doxorubicin without ill effect. Cardiac glycosides are thought to prevent doxorubicin cardiomyopathy by competitively inhibiting doxorubicin at its receptor sites, but ouabain has a much shorter half life than doxorubicin and its metabolites and so is less effective than digoxin.


Non-invasive measurement of human fetal circulation using ultrasound: a new method. We combined two ultrasound techniques to develop a safe, non-invasive, transcutaneous method of observing the circulation in the umbilical arteries and vein in the fetus. The umbilical cord can be located by standard echo ultrasound procedures, and this information can be used to direct a Doppler ultrasound beam on to the vessels in the cord. The signals can be heard through audio headphones or recorded on a tape recorded and spectrum-analysed. The method was successful in each of 20 patients examined, whose pregnancies ranged from 12 to 40 weeks' gestational age, and was suitable for outpatient use. It should be useful in assessing such conditions as pre-eclampsia and intrauterine growth retardation.


Active management of labour: care of the fetus. A prospective study of 1000 consecutive primigravidae was conducted to assess the relevance of the colour of the liquor to the welfare of the child. The results showed that clear liquor early in labour virtually ensures the birth of a healthy infant, provided the duration of labour is limited and delivery is effected without trauma; and, conversely, that meconium--or no liquor--marks the fetus who may suffer death or brain damage during normal labour. Special techniques were reserved for the second group of cases.


Haemoperfusion with R-004 Amberlite resin for treating acute poisoning. Eleven patients who had taken overdoses of barbiturates, glutethimide, tricyclic antidepressants, and chloroquine were treated by resin haemoperfusion using an R-004 haemoperfusion cartridge containing XAD-4 resin. All but one patient showed rapid clinical recovery and the drugs were cleared rapidly from the plasma. There were few complications. Resin haemoperfusion is more effective than dialysis and other perfusion methods, especially in poisoning with tricyclic antidepressants. Although haemoperfusion is expensive, it greatly reduces the length of the patient's stay in an intensive care unit and hence is cost-effective.


Management of airway complications of burns in children. Children who have been exposed to smoke in a confined space or who have soot or burns, however minimal, on the face should be admitted to hospital. Respiratory distress may be delayed, but if it is progressive the patient should be curarised, intubated, and mechanically ventilated. Unless ventilation continues for 48 hours, followed by 24 hours' spontaneous respiration against a positive airway pressure, stridor and pulmonary oedema may recur. An endotracheal tube small enough to allow a leak between it and the oedematous mucosa must be passed to prevent laryngeal damage and subsequent subglottic stenosis. High humidity of inspired gases keeps secretions fluid and the endotracheal tube patent. A high oxygen concentration compensates for deficient oxygen uptake and transport caused by pulmonary lesions and the presence of poisonous compounds interfering with oxygen transport. Dexamethasone to minimise cerebral oedema and antibiotics to reduce the incidence of chest infections should be given.


Perceived noise in surgical wards and an intensive care area: an objective analysis. An investigation of noise levels in a hospital ward, a cubicle off the ward, and an intensive therapy unit (ITU) showed that the noise levels in all three areas were higher than internationally recommended levels at all times of day. Loud noises above 70 dB(A) were common in all areas but especially the ITU. The noise pollution levels reached annoying values during the day in the ward and cubicle and during both the day and the night in the ITU. Equipment and conversations among the staff were the main causes of noise in the ITU. These noisy environments are unlikely to help patients recover. Although measures designed to eliminate noisy surfaces will help, making staff aware of the noise they create and the effects it has may be much more effective in reducing noise pollution.


Cimetidine for duodenal ulceration in patients undergoing haemodialysis. Peptic ulcer is a common problem in advanced renal failure, but most drugs for ulcers are hazardous in this condition. In a small open study cimetidine was given to nine patients with acid hypersecretion and endoscopically diagnosed duodenal ulceration who were undergoing haemodialysis. The patients obtained good pain relief and suffered no serious side effects. Both basal and stimulated acid output fell considerably and the plasma gastrin response to food increased during treatment. Two patients with recurrent vomiting during haemodialysis had a striking response to cimetidine, which suggested that such vomiting may be acid-mediated in some patients. These preliminary results suggest that cimetidine may prove to be an advance in the management of peptic ulcer in uraemic patients.


Glutamate dehydrogenase: a reliable marker of liver cell necrosis in the alcoholic. The usefulness of blood enzyme determinations as markers of liver necrosis was tested in 100 alcoholics who underwent biopsy during clinical investigation. Mean values of glutamate dehydrogenase (GDH), serum aspartate and alanine transferase (SGOT and SGPT), ornithine carbamoyltransferase (OCT), and gamma-glutamyltranspeptidase (gamma-GTP) tended to rise with increasing liver cell necrosis, though values of SGOT, SGPT, OCT, and gamma-GTP showed considerable overlap between the 32 patients with histologically proved hepatitis and the 68 without. By contrast, GDH values showed virtually no overlap between patients with and without hepatitis, and a value of two and a half times the normal value discriminated between the two groups. Because of its easy determination and its reliable reflection of liver cell necrosis the GDH concentration should be estimated routinely in alcoholic patients.


Acute leukaemia after busulphan.

Acute leukaemia after busulphan. During a double-blind study of two years' cytotoxic chemotherapy with busulphan or cyclophosphamide in patients who had had resection of carcinoma of the bronchus the long-term effects of these two drugs were also studied. Four of the 243 patients treated with busulphan developed leukaemia compared with none of the 234 treated with cyclophosphamide and none of the 249 on placebo. None of these four patients received radiotherapy or other cytotoxic chemotherapy before leukaemia was diagnosed, and all four were among the 19 patients who developed pancytopenia while taking busulphan, five to eight years before leukaemia became clinically apparent. These findings suggest that busulphan is leukaemogenic, though its mode of action is uncertain.


Defective blood glucose counter-regulation in diabetics is a selective form of autonomic neuropathy. Administration of a low-dose insulin infusion to normal subjects results in a mild drop in blood glucose concentration (1.1 mmol/1 (20 mg/100 ml)) and the resetting of the basal glucose at the lower concentration. Clinical hypoglycaemia does not develop, and there is a significant release of glucagon, growth hormone, and cortisol. A similar infusion in insulin-requiring diabetics results in hypoglycaemia accompanied by a release of growth hormone and cortisol but no significant release of glucagon. Subsequently giving arginine to these patients results in a significant release of glucagon, indicating that the alpha cell is intact and can respond to local, direct stimulation. In one patient the defect in glucagon response to impending hypoglycaemia developed after two years' insulin treatment. This type of dissociated response' of the alpha cell has been reported in animals after denervation of the pancreas, and insulin-requiring diabetics may develop a selective form of autonomic neuropathy affecting the vagal control of glucagon release.


Psychological and social evaluation in cases of deliberate self-poisoning admitted to a general hospital. In a prospective clinical trial 312 cases of self-poisoning (276 patients) consecutively admitted to hospital were randomly allocated to medical teams or to psychiatrists for an initial psychiatric assessment and a decision as to "disposal." Junior doctors and nurses received some instruction in this work. Both groups of assessors asked for help from social workers when necessary. Once the medical teams had completed their assessments, psychiatrists provided most of the hospital treatment. Follow-up at one year showed no significant difference between the two groups of patients in the numbers who repeated their self-poisoning or self-injury (or both), or committed suicide. Provided junior doctors and nurses are taught to assess self-poisoned patients, we think medical teams can evaluate the suicidal risk and identify patients requiring psychiatric treatment or help from social workers, or both. Contrary to the Department of Health's recommendation that all cases of deliberate self-poisoning should be seen by psychiatrists, we have reached the conclusion that physicians should decide for each of their patients if specialist psychiatric advice is necessary.


Long-term prognosis of duodenal ulcer: follow-up study and survey of doctors' estimates. In 1976 we reviewed a randomly selected cohort of 227 patients with duodenal ulcer first diagnosed in 1963. The cohort comprised cases diagnosed in both hospitals and general practice. Fifty patients had died, 12 had emigrated, and 154 (93%) of the remaining patients were interviewed. Fifty-seven medically treated patients had no symptoms, 44 had mild symptoms, and 19 had more severe symptoms. The remaining 34 patients had been treated surgically. Cases diagnosed in hospital had a more severe prognosis than those diagnosed in general practice. A random sample of 65 general practitioners and 78 medical and surgical gastroenterologists tried to predict the results of this study. The range of the predictions was very wide showing that individual prognostic estimates were highly unreliable. The mean prediction by all doctors differed little from the actual result, suggesting that the collective experience of the medical profession is more reliable. The predictions of general practitioners, physicians, and surgeons showed small systematic differences, presumably reflecting the different types of patients they treat.


Comparison of metformin and chlorpropamide in non-obese, maturity-onset diabetics uncontrolled by diet. The clinical effectiveness of metformin was compared with that of chlorpropamide in closely similar groups of 216 non-obese patients recently diagnosed as cases of maturity-onset diabetes that could not be controlled by diet. The incidences of primary and secondary drug failures in each group and the numbers of patients satisfactorily maintained on each of the hypoglycaemic agents throughout the first year proved remarkably similar. In 61 of the successfully treated patients who were studied by crossover to the other drug and observed for a further year the mean blood glucose concentrations at the end of the year were roughly comparable, but the mean weight response was a small loss of 1.5 +/- 3.8 kg with metformin but a gain of 4.6 +/- 3.9 kg with chlorpropamide. Thus for non-obese, maturity-onset diabetics whose disease cannot be controlled by diet and who require oral treatment sulphonylureas and biguanides are equally effective, the choice depending on whether the patient is underweight and the severity of symptoms.


New classification of stroke: preliminary communication. We describe a new method of classifying stroke using a cumulative numbering system. The method is simple and more explicit than currently used classifications, and could be useful for different agencies looking after patients with stroke in hospital or at home.


What is the monetary value of a human life? The resources available to the health service are limited and so the amount the NHS can spend on saving human life is also limited. Rational allocation of resources requires a decision theory model, which in turn demands some monetary valuation of human life. Each of three approaches discussed--basing value on productive capacity, the NHS's implied values, or individuals' values--rests on an underlying set of non-monetary values. Choice of the underlying value will determine the method to be used in placing a monetary value on life. As the Health Service implicitly places certain values on life already, a means of making this valuation more rational and explicity can only improve the quality and quantity of health care.


Observations on syphilis in Addis Ababa. 2. Prevalence and natural history. Sera from various groups were tested for syphilis by cardiolipin, fluorescent treponemal antibody-absorbed (FTA-ABS), and treponemal haemagglutination (TPHA) tests. The proportion of positive results, 12.7%, obtained from an unselected urban population suggested that the prevalence of the disease had declined since 1953. The probable explanation is the widespread use of penicillin. Late manifestations of syphilis are much rarer in Ethiopia than would be predicted from the high incidence at the infectious stage and, if present, they affect the cardiovascular system. These findings confirm old observations. Llymphocytes from Ethiopians with early syphilis did not proliferate when cultured with Treponema pallidum in vitro, in contrast with cells from patients with cardiovascular syphilis. These findings differed from observations made previously on patients in England with early syphilis.


Nitroblue tetrazolium test in experimental syphilis. The reduction of nitroblue tetrazolium (NBT) by phagocytic leucocytes in peripheral blood has been examined in rabbits injected intratesticularly with Treponema pallidum, T. pallidum-free supernatant of orchitic testes, or normal rabbit testes supernatant. A significant (P less than 0.01) increase in NBT reduction was observed only in the infected animals.


Hepatitis in early syphilis. Report of three cases. Fifteen patients with early syphilis were seen between May 1974 and March 1975. These 15 patients comprised all the cases of early syphilis that were seen in Edinburgh during this period. Three of them were men of whom two were homosexual. Liver function tests in these three gave abnormal results.


Recent micturition does not affect the detection of urethral gonorrhoea. In 202 men with urethral gonorrhoea (176 symptomatic and 26 asymptomatic) who had modified Thayer-Martin cultures taken before and within five minutes after micturition there was complete agreement between results of the two cultures. Micturition did, however, temporarily eliminate the discharge in 100 (56.8%) and make interpretation of Gram-stained smears more laborious.


Short-term psychosomatic treatment of sexual problems. This is a review of 172 couples presenting with psychosexual problems. Ninety-four per cent of couples treated showed improvement after a mean time of 2.1 hours with the doctor. Older patients and those with longstanding problems showed lower rates of improvement. It is suggested that if such problems are treated it may help to reduce the rate of sexually transmitted diseases.


Diffuse brain damage of immediate impact type. Its relationship to 'primary brain-stem damage' in head injury. In a neuropathological analysis of 151 fatal non-missile head injuries, there were 19 cases with focal lesions in the dorsolateral quadrant of the brain-stem in the corpus callosum, and histological evidence of diffuse damage to white matter. Eight of these cases had not experienced a high intracranial pressure during life. All 19 cases had been rendered unconscious at the moment of impact and had remained so or in the persistent vegetative state until death. It is therefore concluded that diffuse damage to white matter may occur as a primary event at the moment of impact, that is, it is one type of immediate impact damage to the brain. It is also concluded that this type of damage is the pathological basis of 'primary brain-stem injury' since in no patient thought clinically to have sustained 'primary brain-stem injury' were abnormalities confined to the brain-stem. Since no patient with this type of brain damage recovered consciousness after injury, it is probable that diffuse damage to white matter is the most important single factor governing the outcome in a patient who sustains a non-missile head injury.


The effect of lesions of the sensorimotor cortex and the capsular pathways on servo responses from the human long thumb flexor. Lesions of the sensorimotor cortex, or of the capsular pathways beneath it, caused (with one exception out of 14 cases) diminution "r loss of the servo responses in the thumb, which are based on the long-latency stretch reflex. When not absent the long-latency stretch reflex tended to be late in onset. When absent it was often replaced by a large early reflex response at spinal latency. In general the results are consistent with the transcortical theory of the long-latency stretch reflex for the thumb, but, in detail, they indicate that the theory will require elaboration.


Acquisition of a motor skill after left-hemisphere damage. Specialization of function in the left hemisphere of man, as compared with the right, was studied with special reference to the nature of the impairments seen after left-hemisphere damage. Patients with unilateral lesions of the left or the right hemisphere were compared in the acquisition and subsequent performance of a manual skill requiring several hand movements. Patients with left-hemisphere damage were further subdivided into aphasic and non-aphasic groups. Patients with left-hemisphere damage were further subdivided into aphasic and non-aphasic groups. Patients with left-hemisphere damage, whether aphasic or not, were impaired in the acquisition of the task, relative to patients with right hemisphere damage, although aphasics were most severely impaired. Analysis of the errors made during acquisition indicated that perseverative errors and unique errors (unrelated movements) differentiated the left and right groups, but that sequencing errors did not. It was concluded that a major function of the left hemisphere is the control of changes in limb or articulatory posture, and that its complex verbal and praxic functions are derived from such control.


Functions of the centre section (trunk) of the corpus callosum in man. The case is reported of a patient in whom the middle sagittal third of the corpus callosum had been removed for the treatment of an underlying angioma. The special advantages of the case are that the patient is a young, relatively healthy person of normal IQ. The angioma had not interfered with interhemispheric transmission and the patient was described as neurologically normal before operation. After operation left-side neglect and extensive somatic disconnection were seen. A change in the balance between the hemispheres for handedness and ear superiority in dichotic listening was observed. The patient developed an aphasia after operation characterized by a simplification of language, the inavailability of complex ideas and emotional communication. He showed a disorder of memory--'autopragmatic amnesia'--in whice. The patient showed disorders of visuo-spatial transfer. These symptoms are thought to typify a syndrome of the centre trunk region of the corpus callosum, to follow as a direct function of the operation performed upon the callosum, and to illustrate the function of this region of the brain.


Visual acuity and contrast sensitivity in multiple sclerosis--hidden visual loss: an auxiliary diagnostic test. In 48 patients with multiple sclerosis sine-wave gratings were used to test visual sensitivity for coarse, medium, and fine detail rather than measuring visual acuity for fine detail only, as in conventional clinical tests. In 20/48 patients the test revealed a visual defect of neural origin, qualitatively different from that caused by refractive error. In 11 of these 20 patients, visual sensitivity to detail of medium coarseness was markedly degraded, even though sensitivity to both coarse and fine detail was unimpaired. In 3 of these 20 patients visual sensitivity to coarse detail was selectively degraded. These visual defects could not be detected by the Snellen test, yet the patient might experience visual problems in everyday life and also experience distorted visual perception. Possible neural bases for these visual impairments are discussed. Since 8 of the 14 patients with selective loss showed no clinical evidence of visual involvement, the test can aid the earlier diagnosis of multiple sclerosis.


The thoracic outlet syndrome.

The thoracic outlet syndrome. Thirty-one patients with thoracic outlet syndrome have been studied in detail in the neurological and vascular clinics at this hospital. The patients were classified on the basis of their presenting symptoms into four groups--predominantly vascular, neurological, combined vascular and neurological, and pain and paraesthesiae alone. The majority of patients had radiological abnormalities and all had structural lesions in the superior thoracic aperture seen at operation. All operations were carried out through a standard supraclavicular approach, enabling the compressive structures to be visualized. This would not have been the case had the commoner trans-axillary approach for first rib resection been followed and in fact none of the operations included removal of the first rib. The results of operation were evident in our patients with a marked relief in their vascular symptoms, their pain and paraesthesiae and a slight but definite improvement in muscle bulk and power.


Functional specificity of vocalizations elicited by electrical brain stimulation in the turkey (Meleagris gallopavo). All presently known naturally occurring call types, except those associated with dominance threat, were elicited with electrical brain stimulation in the turkey. Most vocalizations closely resembled contact and alarm cells. A concentration of sites for contact calls was in the dorsomedial thalamus and midbrain. Mechanical-sounding contact-type calls were elicited from sites in the central neostriatum caudale and paleostriatum primitivum. Vocalization specificity and latency indicate that the lateral mesencephalic grey may be an area of convergence of some efferent vocalization fibers. Anomalous vocalizations were elicited only in one site in the hyperstriatum ventrale. Singing was elicited reliably in the absence of any known key stimulus. Most of these vocalizations resembled the singing of nonstimulated turkeys in the natural situation. The major exception was that mesencephalic-grey-stimulation-elicited vocalizations were shorter in duration. Gobbling was elicited from two sites in sensory projection areas of the brain. Elicited gobbles were similar to natural calls except for the relative frequency of occurrence of certain syllables and the rapid habituation to brain stimulation.


Amphetamine and chick behavior. A role for monoamines in the causation of vocalizations and emotions. The effects of amphetamine (AMP) on the behaviour of domestic chicks were studied by methods of direct observation of behaviour. 7.5 mg/kg d-amphetamine sulphate injected into 5-day-old chicks characteristically facilitated vocalization-a period of peeps followed by short calls (twitters and short peeps), head shakes, forced locomotion and wing drooping; and decreased the duration of eye closure. AMP also increased the responsiveness of chicks to external stimuli. Bilateral lesions in the midbrain inhibited primarily the vocalizations but not the other behavioural changes produced by AMP. Evidence is presented to explain the neurochemical basis of the AMP-induced behaviour: namely, that peeping depends on 5-hydroxytryptamine-dependent mechanisms, which may also influence the postural changes, and head shakes, whereas short calls may be mediated by an interaction between dopaminergic and tryptaminergic mechanisms. It is suggested that the monoamines may also be involved in the attentional changes associated with the vocalizations.


Differential effects of morphine and D-amphetamine on self-stimulation from closely adjacent regions in rat midbrain. The effects of morphine were investigated on self-stimulation from numerous electrode placements in the area of the substantia nigra or in the ventral half of mesencephalic central gray matter. Before pharmacological testing, current intensity was reduced to yield stable, submaximal rates of self-stimulation. Rats were then injected daily with morphine for 10 days, and were tested three hours after injection. Between days 5 and 10 of treatment, many rats self-stimulated at more than 150% of baseline, but some others reduced self-stimulation to as little as 3% of baseline. Histological evaluation revealed that morphine facilitated self-stimulation when the electrode tip was located more than 0.3 mm from substantia nigra or more than 0.2 mm from the midline of central gray. In rats with electrode tips closer to substantia nigra or to the midline of central gray, morphine often reduced or failed to alter self-stimulation rates. The effects of a low dose of D-amphetamine (0.1 mg/kg) were investigated on electrode placements in the substantia nigra area. Placements close to the dorsal border of substantia nigra yielded less facilitation of self-stimulation by D-amphetamine than did placements located more dorsally or medially. Possible catecholaminergic substrates of these differential effects are discussed.


Lipoperoxidation in human and rat brain tissue: developmental and regional studies. Lipoperoxidation in human and rat brain was studied on the basis of formation in vitro of thiobarbituric acid positive (TBA) materials. In rats aged 1--540 days, the endogenous pools of reactive material were unchanged but on subsequent incubation of their homogenates the level of TBA-positive materials fell by 3 fold (fresh weight basis) and 5.4 fold (protein basis). In human brain, there was a distinct regional distribution of reactive materials in the endogenous pools with highest levels in the cerebellar vermis, and lower levels in thalamus, cortical regions, substantia nigra, caudate nucleus, pallidum, putamen, and hypothalamus. Only trace levels were detected in the pineal gland. On incubation all values rose 13--25 fold within 3 h at 37 degrees C except for cerebellar vermis which was increased 6 fold, and pineal gland 9 fold. Four TBA-positive materials were separated from rat brain by TLC, three of which were identical to malonyldialdehyde and its polymers. Lipoperoxidation in rat homogenates was inhibited 75--90% by sera from several different sources. The inhibitory properties were unaffected by dialysis and were not reproduced by addition of a large number of low and high mol. wt. components including vitamin E when added in concentrations equal to or exceeding that of native serum.


Ascorbic acid transport by a clonal line of pheochromocytoma cells. A clonal line of rat pheochromocytoma cells was used as a model of noradrenergic tissue to study ascorbic acid transport. These cells were used because, like sympathetic neurons, they synthesize large amounts of noradrenaline in the presence of ascorbate, they respond to nerve growth factor with the production of neurites and they release, store and take up catecholamines. In these cells, both with and without nerve growth factor (NGF) treatment, [14C]ascorbic acid was concentrated by a stereospecific saturable, energy dependent transport system that could be described by a Michaelis-Menten transport model. The Kt and Vmax for ascorbic acid were approximately 0.03 mM and 0.3 nmole per min per mg protein respectively for both untreated and NGF-treated cells. The ability of the cells to concentrate ascorbic acid was not due to intracellular binding. Cells untreated with NGF and loaded with [14C]ascorbic acid to a concentration of 5.6 nmoles per mg protein retained only 6% of the initial intracellular [14C]ascorbic acid after the 24 h in normal growth medium. Thus, although pheochromocytoma cells contain an ascorbate concentrating system, optimal production of noradrenaline requires ascorbate in the medium.


Energy utilization in the uptake of catecholamines by synaptic vesicles and adrenal chromaffin granules. Several inhibitors of energy metabolism decreased the ATP-stimulated uptake of catecholamines by isolated synaptic vesicles from rat brain and by chromaffin granules from bovine adrenal medulla. Catecholamine uptake was inhibited by dinitrophenol, S-13 and oleic acid, which are known to block active transport by dissipating trans-membrane proton gradients. Thus a proton gradient appears to be involved in catecholamine transport. Both catecholamine uptake and vesicle-associated Ca2+/Mg2+-ATPase were inhibited by dicyclohexylcarbodiimide and tributyltin, which had previously been shown to inhibit the Ca2+/Mg2+-ATPase of mitochondria. However, mitochondrial ATPase was not involved in catecholamine uptake as oligomycin and aurovertin, more specific inhibitors of mitochondrial ATPase, did not affect catecholamine uptake. It is suggested that ATP stimulates catecholamine uptake by serving as a substrate for the ATPase. Activity of this enzyme causes translocation of protons across the vesicle membrane establishing a trans-membrane proton gradient. The proton gradient drives the transport of catecholamines.


Involvement of complement in degeneration of sympathetic nerves after administration of antiserum to dopamine beta-hydroxylase. The involvement of complement in the degeneration of noradrenergic nerves in the guinea-pig iris produced by administration of antibody to dopamine beta-hydroxylase (DBH) in vivo was investigated histochemically. When 500 microliter of antiserum to DBH was injected systemically, no evidence of degeneration was observed in the iris although the noradrenergic supply of the myenteric plexus of the ileum degenerated within 2 days. However, injection of 20 microliter of complement (C) into the anterior chamber of one eye within 2 days of the systemic administration of anti-DBH produced a degeneration of 50--90% of noradrenergic terminals in the iris, the nerves of the iris of the contralateral uninjected eye being unaffected. Electron microscopy confirmed the presence of degenerating nerve terminals in the iris. The extent of degeneration produced by addition of C decreased when C was injected at increasing intervals after the antiserum. Intraocular injection of 5 microliter of anti-DBH together with 20 microliter of C caused a substantial degeneration of noradrenergic nerves in the iris. In contrast, intraocular injection of the Fab'2 fragment of anti-DBH (which did not bind C, but still bound DBH in vitro and in vivo) failed to cause degeneration in the presence of 20 microliter of C. The degeneration of guinea-pig sympathetic nerves caused by antibodies to DBH thus appears to be due to a complement mediated lysis of sympathetic axon membranes. The relative susceptibilities of the noradrenergic fibres in different tissues probably depend on the local concentrations of anti-DBH and C.


Metabolism of [3H]serotonin in the marine mollusc, Aplysia californica. The fate of serotonin was studied in several tissues of the marine mollusc, Aplysia californica. When isolated nervous tissue was bathed in [3H]serotonin, two radioactive derivatives were formed; both appeared to be sugar conjugates: the first, possibly of glucuronic acid, and the second, of a more complex sugar moiety. When [3H]serotonin was injected directly into cell bodies of identified neurons, both serotonergic and non-serotonergic, only the conjugate which behaved as the glucuronide was formed. [3H]Serotonin was also converted only to this substance during incubation with isolated heart, kidney and hemolymph. Metabolic activity of the blood resided within cellular elements. No evidence of oxidative deamination was found in any tissue. In contrast to serotonin, however, [3H]tryptamine was readily oxidized to indoleacetic acid by nervous tissue.


Penicillin effects on iontophoretic responses in Aplysia californica. The effect of penicillin on neurons of Aplysia californica was studied using drug concentrations which would be convulsant in mammalian nervous systems. Iontophoretic responses were elicited by the application of acetylcholine, dopamine, gamma-aminobutyric acid and serotonin. Low concentrations of penicillin (2 mM) consistently and reversibly reduced the chloride-dependent hyperpolarizing responses by approximately 70%, regardless of the transmitter required to evoke them. The short depolarizing responses which are sodium sensitive are slightly reduced by a much higher (10 mM) concentration. The extent of the reduction of the excitatory response varied with the transmitter. The slow sodium-dependent depolarizations and the slow potassium-dependent hyperpolarizations were unaffected by the concentrations of penicillin used. The possibility that the convulsant effect of penicillin is due to interference with membrane conductance to chloride is discussed.


Convergence of retinal inputs onto visual cortical cells: II. A study of the cells disynaptically excited from the lateral geniculate body. Spike discharges were recorded extracellularly from cells located in the superficial layer of cat's visual cortex. These cells were disynaptically excited and trisynaptically inhibited from the lateral geniculate cells. The vast majority of them responded to stationary and moving light stimuli. Their ON and OFF responses to a flash of light slit consisted of three components: (1) initial excitation, (2) depression and (3) later rebound. The three components were evoked from a broad area of the retinal receptive field. In one group of these cells, exploration of the receptive field with light slits of different lengths revealed a strong depressant zone at one or both ends of the excitatory receptive area, the characteristics property of 'hypercomplex' cell of Hubel and Wiesel. Another population of cells, however, did not show such length-specificity, and apparently correspond to 'complex' cell. In both groups of cells electrical stimulation at the excitatory receptive area produced a sequence of excitation, depression and later rebound, but only depression was evoked from the depressant zones. The latency of the excitation (6 msec) and the depression (7 msec) are in accordance with the view that the excitation is transmitted through disynaptic pathway and the depression through trisynaptic pathway after being mediated by the lateral geniculate cells.


The organization of reticulo-olivo-cerebellar circuits in the North American opossum. By employing the autoradiographic method we have determined that the inferior olivary nucleus receives input from the reticular formation of the midbrain, pons and, probably, the medulla. The remarkable thing about such connections is that they are not diffuse, but targeted in large part on restricted portions of the caudal acessory nuclei. From our previous studies it is clear that some of the olivary regions receiving reticular input also receive projections from the cerebral cortex, the spinal cord and the dorsal column nuclei. In addition, the HRP technique reveals that these same olivary regions relay to parts of the spinal cerebellum, i.e. to restricted zones of the anterior lobe (present study). Taken together these observations suggest that some reticulo-olivo-cerebellar connections provide indirect routes through which cortical and spinal information gains access to the spinal cerebellum. Such circuits have also been suggested by the physiological literature. Of particular interest, however, was our finding that several reticular areas of the midbrain and pons project to the portion of the medial acessory nucleus which relays in turn to auditory-visual areas of the cerebellar vermis (declive, folium and tuber). It would appear that at least some reticulo-olivo-cerebellar circuits are significant in the organization of motor responses to visual and/or auditory stimuli.


Visual function in goldfish with unilateral and bilateral tectal ablation. Following complete bilateral tectal ablation, the ability to detect light recovers in about three weeks. The non-tectal retinal connections which may mediate detection are about one log unit less sensitive than the retinotectal connections. At moderate illumination levels, tectumless fish do not react visually to objects. Tectumless fish integrate luminous flux over a very wide area (at least 25 degrees diameter) while the critical diameter for the normal in this experiment is smaller. Subcortical structures may mediate the interocular transfer of a brightness discrimination. The ipsilateral retinotectal projection following unilateral tectal removal is functional, with normal sensitivity to detection of light.


In vitro effects of chlorpromazine on microtubules and the Golgi complex in embryonic chick spinal ganglion cells: an electron microscopic study. Spinal ganglia from 11-day-old chick embryos were incubated in media containing chlorpromazine (CPZ), lidocaine or D-amphetamine and subsequently examined by transmission electron microscopy. CPZ and lidocaine both caused a structural modification of the neuroblasts similar to that induced by the microtubular-disrupting drugs colchicine and vinblastine. That is, there was a partial disappearance of cytoplasmic microtubules with a concomitant increase in the number of microfilaments and the dictyosomes of the Golgi complex changed, with the number of narrow cisternae decreasing and the number of associated vacuoles increasing. Moreover, the dictyosomes were more distinctly separated from each other than in control ganglia. D-Amphetamine did not give rise to any clear changes in either the microtubular system or the Golgi complex and, furthermore, opposed the colchicine-like effects of CPZ. On the basis of these results it is suggested that the subcellular mechanism of action of CPZ involves the cytoplasmic microtubular system and thus secondarily leads to structural and functional alterations in the Golgi complex, viz., in the case of nerve cells, a disturbance in the production and packaging of material destined for the axon terminals.


Aspartic acid and glutamic acid levels in the cochlear nucleus after auditory nerve lesion. Aspartic acid, glutamic acid and alanine were measured in the cochlear nucleus after lesioning the auditory nerve by cochlear ablation. Ultrastructural analysis of the cochlear nucleus showed that most primary auditory terminals were degenerating one day after cochlear ablation; the terminals were enlarged and the number of synaptic vesicles was reduced. Primary auditory terminals were virtually gone three days after cochlear ablation. Aspartic acid decreased after cochlear ablation in parallel with the morphological degeneration of the primary auditory terminals. The level of total aspartic acid in the cochlear nucleus had decreased more than 8% one day after cochlear ablation and more than 30% after two days, and remained at this level up to 28 days. Glutamic acid also decreased in the cochlear nucleus after cochlear ablation but not in parallel with the morphological degeneration of the primary auditory terminals. Following a slight increase one day after cochlear ablation, total glutamic acid decreased about 10% after two days and continued to decrease slowly through to day 28. Alanine dropped slowly after cochlear ablation and not in parallel with the degeneration of the primary terminals. Levels of other amino acids measured were unchanged or had increased two days after cochlear ablation. Aspartic acid and glutamic acid did not decrease in the superficial layers of the dorsal cochlear nucleus, an area receiving little or no primary innervation.


Two types of receptors for alpha-bungarotoxin in the synaptic layers of the pigeon retina. Pigeon retinae were analyzed for binding [125I]alpha-bungarotoxin (alphaBgt) by radioautographic and biochemical methods. Toxin binding, localized to the outer and inner plexiform layers (OPL and IPL), was inhibited by micromolar concentrations of native alphaBgt and D-tubocurarine and by 1 mM acetyl- and butyrylcholine in both synaptic layers. Nicotine, at comparable concentrations affected only the IPL. In vitro drug competition experiments showed that the pigeon retina contains two types of receptors for alphaBgt which differ in sensitivity to inhibition by nicotine by 4 orders of magnitued. The results suggest that: (1) the receptor for alphaBgt in the IPL is a nicotinic receptor, (2) the receptor for alphaBgt in the OPL may be involved in an unusual cholinergic system, and (3) ability to bind alphaBgt is not a sufficient criterion for identifying nicotinic-cholinergic receptors.


Are the dorsal noradrenergic bundle projections from the locus coeruleus important for neocortical or hippocampal activation? Three different methods were used to examine the importance of the dorsal noradrenergic bundle projections from the locus coeruleus (LC) in activation of the neocortex and hippocampus in freely moving rats. (1) After cerebral norepinephrine (NE) was depleted by systemic neonatal injections of 6-hydroxydopamine (6-OHDA) both atropine-resistant and atropine-sensitive forms of hippocampal rhythmical slow activity (RSA; theta) and neocortical low voltage fast activity (LVFA) remained intact. Compared to controls the adult rats treated with 6-OHDA in infancy reared less in a 24 h time sample of behavior and ran less in running wheels. (2) Brain dopamine and NE were also depleted by systemic injections of alpha-methyl-p-tyrosine. Following this treatment rats were very inactive behaviorally. However, normal activation of the hippocampus and neocortex was still present. (3) In normal rats, electrical stimulation of the LC was relatively ineffective, compared to stimulation of nucleus reticularis pontis caudalis, in producing behavioral changes (especially locomotion) or either atropine-resistant or atropine-sensitive hippocampal RSA or neocortical LVFA. It is concluded that the locus coeruleus is not important for cerebral activation, and that mechanisms for cerebral activation are probably diffusely represented in the reticular core. The data also show that when attempting to assess the effect of experimental manipulations on brain activity it is essential to control for the possible effects of changes in behavior.


The contribution of the contralateral labyrinth to second order vestibular neuronal activity in the cat. Vestibular brain stem units of the horizontal canal in the awake C1 transected cat were examined in acute experiments before and after the contralateral vestibular nerve was cut. The latter procedure resulted in an immediate increase in mean resting rate from 19 to 45 spikes/sec and greater spontaneous fluctuations in firing rate. Mean sensitivity to constant accelerations from 2 to 16 degrees/sec2 was significantly reduced. In the 4-6 degrees/sec2 range, for example, mean sensitivity fell from 5.7 +/- 3.2 spike/sec/deg/sec2 (range 0.7-13.6, n = 107) to 2.8 +/- 1.4 (range 0.2-5.5, n = 29). Mean sensitivity to 4-6 degrees/sec2 deceleration was reduced from about 4.5 to 3.0. On the other hand, time constants and the ratio of adapting to non-adapting units was unchanged. Removal of the midline cerebellum, including the vermis and fastigial nuclei in a portion of the animals, did not materially alter the above results. It is concluded that the contralateral labyrinth, acting via the vestibular brain stem commissural pathway, not only exerts a powerful effect on the resting activity of brain stem canal vestibular neurons, but also on their response to acceleration.


Development of the oculomotor nucleus, with special reference to the time of cell origin and cell death. The developmental pattern of the oculomotor nucleus from day 7 of incubation through two weeks after hatching was studied in white Peking duck embryos. The neuroblasts comprising the nucleus complete their last phase of DNA synthesis on days 4 and 5 and the anlage first appears on day 7. The various subnuclei become identifiable as distinct cell groups on day 8 or 9. There is a cell migration between the ventral-most portions of the two ventromedial nuclei on days 9 through 11, and as a result a well-developed oculomotor commissure is established between these two subnuclei. The maximum number of cells in the nucleus is present on day 11. There is a normally occurring overall loss of approximately 43% of the cells during ontogenesis. Cell death appears to be random, without any gradient, and virtually all of it occurs between days 11 and 15. Although the duration of cell death is essentially similar in all subnuclei, great variations exist in its magnitude. For example, there is a cell loss of approximately 61% in the accessory nucleus, 38% in the dorsolateral nucleus, 40% in the dorsomedial nucleus and 33% in the ventromedial nucleus. Cell loss in the oculomotor nucleus is compared with that observed in the other two eye-muscle nuclei.


The distribution of olfactory input in the opossum mediodorsal nucleus. Discharges of single cells in the thalamic mediodorsal nucleus (MD) of the opossum were recorded during electrical stimulation of the lateral olfactory tract. Responsive sites were histologically localized throughout the entire mediolateral extent of MD. In both rabbit and squirrel monkey responses are confined to the medial half of MD. Thus the lateral non-olfactory nuclear subdivision, common to both rabbit and squirrel monkey, was not found in the opossum. Firing patterns of cells were similar to those observed in rabbit and squirrel monkey. They commonly consisted of an early spike or burst of spikes, followed by a period of inactivity and then, in many cells, by a later period of response or of resumed spontaneous activity. The results indicate that olfactory input is characteristic of MD in a diverse sample of mammals but that topographic organization of the input is distinctly different in the opossum.


Binaural columns in the primary field (A1) of cat auditory cortex. Responses of single neurons and neuron clusters were studied at short intervals along penetrations into the high-frequency (4-25 kHz) representation of A1. The monaural and binaural sensitivities of neurons at best frequency were studied. With the exception of some neurons responsive only to binaural stimulation, the monaural responses of most were classified as contralateral dominant, ipsilateral dominant or equidominant. Binaural interactions of most neurons were classified as summation (binaural response size greater than the monaural response size) or suppression (dominant ear response size greater than the binaural response size). Most neurons arrayed in a column perpendicular to the cortical surface display the same aural dominance and binaural interaction. Summation columns occupy about two-thirds of the area sampled; suppression columns, about one-third. Within most suppression columns, the contralateral ear was dominant. Within summation columns, aural dominance varied. Summation columns appear to be composed of smaller columns differing in aural dominance. The sizes of binaural interaction columns vary considerably; some occupy several square millimeters of cortical surface. At least some binaural interaction columns occupy strips of cortex oriented orthogonal to isofrequency contours.


Dual excitatory inputs to caudate spiny neurons from substantia nigra stimulation. In the present set of experiments of two component excitatory postsynaptic potential (EPSP) (fast and slow) was recorded from caudate (Cd) neurons after substantia nigra (SN) stimulation in the alpha-chloralose anesthetized cat. Several unique properties of the fast response are demonstrated and used to determine certain functional properties of Cd neurons. The following conclusions have been drawn from these experiments. (1) A dual excitatory innervation pattern (fast and slow) exists to the Cd from SN stimulation. (2) The fast system is independent of the Cd efferent system. (3) Neurons receiving this dual input are spine laden neurons. (4) Dendritic inhibition is operating on these neurons and often has little or no direct influence on the observed soma membrane potential. The dendritic inhibition reduced test EPSP amplitude for several hundred milliseconds for all Cd afferents except for the fast SN input. Such a decoupling of the fast input from the inhibition may play an important role in Cd signal processing.


Amino acids in the synaptic vesicle fraction from calf brain: content, uptake and metabolism. A synaptic vesicle fraction was prepared from calf brain cortex, containing 10 identified amino acids and two unidentified ninhydrin-positive compounds, one of which is apparently a peptide. The most plentiful amino acids were taurine (1.8 nmol/g original tissue), glutamic acid (1.8), serine (0.9), aspartic acid (0.8) and GABA (0.8); the others identified were cysteic acid (or cysteinesulphinic acid), glutamine, alanine, glycine and lysine. The unknown peptide occurred in a high concentration (about 16 alanine equivalents/g), and contained mainly aspartic acid and serine. Cysteic acid (or cysteinesulphinic acid) also occurred in relatively high amounts, but its peak contained acid-labile impurities. The influx of [14C]glutamate into the vesicles took place by means of non-saturable migration, while two saturable systems having very similar properties were dominant only at low glutamate concentrations. Influx constants for these quantitatively low uptake systems were Km, 34 and 92 micrometer, and Vmax, 33 and 49 nmol/min/g obtained by v versus v/S plot. Almost the same values were also obtained by a 1/v versus 1/S plot. GAD and GABA-T activities in the vesicles were only 1/200th of those in the synaptosomes.


Stimulation and maintenance by nerve growth factor of phenylethanolamine-N-methyltransferase in superior cervical ganglia of adult rats. Treatment of newborn rats with nerve growth factor (NGF) results in a striking increase in phenylethanolamine-N-methyltransferase (PNMT) in the superior cervical ganglia. Between one and three weeks of age there is normally a 10-fold decrease in PNMT activity in ganglia of infant rats. NGF treatment maintains the PNMT in ganglia at levels 10-fold greater than in untreated controls, but the levels of enzyme in the ganglion show the same magnitude of decrease with age. Epinephrine levels are markedly increased in ganglia of NGF-treated rats younger than one week of age, but at older ages the levels of the catecholamine are only slightly greater than the controls. Dexamethasone is less effective than NGF in increasing the levels of PNMT in ganglia of infant rats and, unlike NGF, becomes ineffective by 44 days of age. These results suggest that there may be two types of PNMT-containing cells in ganglia of newborn rats.


Synaptosomal plasma membrane glycoproteins. II. Isolation of fucosyl-glycoproteins by affinity chromatography on the Ulex europeus lectin specific for L-fucose. After solubilization in sodium dodecyl sulphate, almost 90% of synaptosomal plasma membrane glycoproteins were separated from the bulk of synaptosomal plasma membrane proteins by sequential affinity chromatography on two immobilized lectins: concanavalin A and the Ulex europeus lectin specific for L-fucose. Four fractions were obtained and their sugar composition and electrophoretic patterns were determined. Fucosyl-glycoproteins contain more than 26% of protein and 85% of the protein-bound sugar of synaptosomal plasma membrane; hence they constitute a major class of glycoproteins in these membranes. The presence of some glucose in glycoproteins fractions obtained after affinity chromatography on the two lectins suggests that this sugar could be a structural component of some brain glycoproteins. Polyacrylamide gel electrophoresis revealed at least 28 major bands in fucosylglycoprotein fractions, and 11 in other fractions. Several of these major bands appear to contain more than one glycoprotein each. This heterogeneity appears to be mostly the result of the heterogeneity of the neuronal population in the central nervous system. Microheterogeneity of glycoprotein sugar chains and possible contamination of synaptosomal plasma membranes play, in our opinion, only a minor role.


Sodium nitroprusside-induced hypotension and renal blood flow. Hypotension produced by sodium nitroprusside during halothane anaesthesia in a series of experiments in dogs was accompanied by the maintenance of renal blood flow. Renal blood flow was maintained at levels of systemic pressure at which flow is customarily reduced in man and experimental animals. The significance of this observation is the possibility that sodium nitroprusside has a protective effect on the kidney, not only in states of deliberate hypotension, but in other low flow states where renal perfusion and function may be compromised.


Cyanide toxicity following nitroprusside induced hypotension. Several recently reported deaths following the use of sodium nitroprusside have been attributed to the accumulation of the nitroprusside metabolite, cyanide. In this study, brief nitroprusside infusions (mean = 36 minutes) were administered in currently recommended doses during intracranial surgery. The peak blood cyanide following the infusions was 65.2 +/- 17.5 microgram per cent (mean +/- SE) (n = 13). It occurred within 45 minutes after infusion. The highest cyanide level detected was 205 microgram per cent, which is within the range of reported lethal blood cyanide levels. Metabolic acidosis developed in the four patients with the highest blood cyanide levels (range 90-205 microgram per cent). This occurred between 45 and 180 minutes following the cyanide peak. Blood ATP levels were depressed in the same patients. These findings are indicative of disturbed aerobic metabolism. We conclude that there is evidence of cyanide toxicity when nitroprusside is infused into patients using currently recommended doses. We recommend that for short infusions the dose of sodium nitroprusside should not exceed 0.5 mg/kg.


Physostigmine reversal of postoperative somnolence. The effects of physostigmine on reversal of post-operative somnolence following general anaesthesia were evaluated in 187 patients. Significant reversal of anaesthetic-induced post-operative somnolence was observed in those patients receiving physostigmine when compared to a control group. These results suggest that general anaesthesia with halothane may be included in those situations where central nervous system depression may be reversed by administration of physostigmine. Cholinergic side-effects observed with physostigmine administration were minimal.


Effect of etomidate on intra-ocular pressure. Etomidate, a new short-acting non-barbiturate hypnotic, was administered to 40 patients between the ages of 12 years and 65 years. Intra-ocular pressure was measured before and after etomidate injection using a Schiotz tonometer. A significant reduction of intra-ocular pressure was found to follow etomidate injection in spite of the often associated myoclonic movements. The mechanism of reduction of intra-ocular pressure has not been determined in this study. It is suggested that etomidate will be a useful intravenous induction agent where elevation of intra-ocular pressure is undesirable.


The incidence of genetic disease and the impact on man of an altered mutation rate. In order to adequately assess the genetic risks to man of an altered mutation rate, it is necessary to know the naturally occurring frequency of mutation-maintained genetic ill-health and the burden that such defects impose. The relevant data that are available are largely inadequate to determine the incidence of genetic disease that is maintained by mutation, and measures of various aspects of the social and personal burdens due to hereditary ill-health are almost wholly lacking. It is suggested that the creation of individual and family histories, using large scale automatic record linkage and existing files of vital and ill-health records, may be a useful approach to these kinds of problems. Using such linked individual health histories, new data are presented that relate to measures of the burden due to childhood dominant and recessive diseases and congenital malformations.


The effect of mitomycin on the fertility and the induction of meiotic chromosome rearrangements in mice and their first generation progeny. The dose dependent effects of chronic application of Mitomycin C(MC) on the induction of chromosomal translocations in treated animals and F1 males and on their fertility have been examined. The C3H strain mice used in the present experiments were treated with MC during eight successive weeks in doses of 0.05 mg/kg and 0.1 mg/kg of body weight. 75 males were treated (25 males per dose and 25 males as controls). Immediately after the chronic treatment they were mated with normal females and were tested for their reproductive performance. The fertility of males was estimated from the number of pregnant females after one week of being together. After that all males were sacrificed and prepared for cytological analysis. No chromosomal translocations were found in diakinesis-metaphase I of meiosis. Data from the study of fertility showed that all treated males were fertile, but all females were not pregnant. The tests of all sterile, semisterile and fertile F1 males showed that F1 males could not be identified as heterozygous translocation carriers.