Risk factors for myocardial infarction in young women. Seventy-seven women discharged from hospital with a diagnosis of myocardial infarction and 207 control patients were investigated. All were under 45 years of age at the time of admission. Heavy cigarette smoking, reported treatment for pre-eclamptic toxaemia, and type II hyperlipoproteinaemia were found to be independent risk factors for myocardial infarction. Reported treatment for hypertension and diabetes are probably also independently associated with subsequent development of the condition, but the associations between myocardial infarction and reported treatment for obesity and psychiatric illness appear to be secondary. Previous publications have suggested that use of oral contraceptives is an independent risk factor. Examination of the effect of several factors combined, suggests that they act synergistically, the presence of three or more factors increasing the risk 128-fold.


The role of small bowel follow-through examination in the diagnosis of coeliac disease. A retrospective study of 105 barium follow-through examinations on 102 patients suspected of having malabsorption syndrome has been carried out to assess the usefulness of this technique in the diagnosis of coeliac disease. Comparison with histological and biochemical data has been made. Of the 34 examinations on 31 patients with a proven diagnosis of coeliac disease, 30 examinations showed both abnormal X-ray and biopsy findings, two examinations showed normal X-ray appearance but abnormal jejunal biopsy and two showed normal jejunal histology but abnormal X-ray findings. There were two cases with sensitivity, non-invasive nature, ease and cheapness of the technique, barium follow-through examination is suggested as the initial investigation in patients suspected of coeliac disease.


Azygography in the pre-treatment evaluation of oesophageal carcinoma. Azygography is a useful technique for the pre-operative detection of unresectability of oesophageal malignancies. Invarison of the azygos vein by oesophageal carcinoma occurs because of the anatomic proximity of the thoracic oesophagus and the azygos vein. Azygography may be performed by either intraosseous injection of a rib or by direct retrograde catheterization. Complete obstruction of the azygos vein indicates that an oesophageal carcinoma is unresectable if no other intrathoracic disease is evident.


The problem of discrimination in mammography. Arguments for using a biological test object. A specimen of breast tissue containing a carcinoma with multiple calcifications was used as a test object and examined by a range of mammographic techniques. The images were compared with a photograph of the actual specimen which was cleared and stained for calcium salts. A quantitative method of evaluating the discriminating ability of each technique is described and used to compare these images. Xeroradiography and Kodak Crystallex film clearly excelled other imaging methods. The value of using a biological test object is discussed.


Irradiation to the thyroid gland at cardiac catheterization and angiocardiography in children. Irradiation to the thyroid gland was measured during cardiac catheterization in 16 infants and 30 children aged 1 to 13 years. The doses from fluoroscopy, full-scale angiocardiography, and cineradiography were measured separately with thermoluminescent dosimeters and, in addition, the exposure-area product was assessed during fluoroscopy with a transparent ionization chamber. Median value of the absorbed dose to the thyroid from the complete heart investigation was 370 mrad in infants and 260 mrad in children. The highest values and also the greatest range in dosage were observed in infants. The quotient of the thyroid-absorbed dose divided by the integral dose or the dose per exposed film area was also highest in infants, due to anatomical conditions. The absorbed dose to the thyroid during heart catheterization comes almost exclusively from scattered radiation. By appropriate examination technique this dose can be kept within acceptable limits.


Tolerance of rodent tails to necrosis after "daily" fractionated X rays or D-T neutrons. The rat tail has been used as a model system to study the necrosis of an organized tissue following fractionated doses of collimated D-T neutrons or 290 kV X rays. RBE values for tail tolerance - 10 per cent of tails necrosing after the early skin reactions - rise from about 1-7 (single doses) to about 3-1 (16 fractions in 22 days). Neutron tolerance doses are almost independent of fractionation from 2 to 16 fractions. The tissues at risk are shown to be rather hypoxic. Early skin reaction levels can be used to predict the fraction of tails that will necrose. Early peak reactions for a given fraction of necrotic tails were slightly higher for neutrons than for X rays, and this difference was consistent for all the dose fractionation schedules employed.


Effects of fractionated irradiation on mouse lung and a phenomenon of slow repair. The LD/50 between 40 and 180 days after irradiation of the thorax has been taken as a measure of lung damage in mice. The method has been used to derive the relationship between total dose, number of fractions (N) and overall treatment time (T). For X rays the results fit an Ellis type of relationship, i.e. total dose alphaN0-25 T0-07. This only applies for more than 8 fractions, below which N0-39 becomes a good fit to the results. For neutrons, the best fit is total dose alphaT0-07. Various possible explanations for the T factor are discussed, but for lung damage we attribute it to a slow repair process which possibly may only be observed in slowly proliferating tissues. Slow repair is about 100 times less rapid than Elkind-type of repair of sublethal damage and whereas Elkind repair is greatly reduced for irradiation with fast neutrons, relative to X rays, slow repair is not.


Modification of the radiocurability of a syngeneic murine squamous carcinoma by its site of growth, by electron-affinic drugs, and by ICRF 159. A series of TCD50 experiments using a spontaneously arising, syngeneically transplated, murine squamous carcinoma is reported. Tumours implanted intradermally and irradiated while they remained superficial had a small but nonetheless cure-limiting hypoxic fraction of cells (TCD50 3,324-4,257 rad). The hypoxic fraction increased dramatically when these tumours invaded the subcutaneous tissues, or when tumours were implanted subcutaneously (TCD50 greater than 5,544 rad). Pre-treatment of mice with the electron-affinic drug Ro-07-0582 at a dose of 1 mg/g i.p. 20-30 minutes before irradiation effectively eliminated the hypoxic element from superficaial tumours (TCD50 1.862 rad). The same drug at a dose of 0-25 mg/g reduced the TCD50 for superficial tumours by a factor of 1-87 (3,986-2,134 rad), while another electron affinic drug, metronidazole, given at a dose of 0-25 mg/g reduced the TCD50 by a factor of 1-28 (4,257-3,337 rad). Treatment of mice with the drug ICRF 159, 30 mug/g daily from the time of tumour cell injection until the day of irradiation, reduced the TCD50 in unclamped tumours by less than 1-19. However, a commensurate reduction of TCD50 in clamped tumours suggested that improved tumour vascularization could not explain fully the drug's "radiosensitizing" action. The unique single radiation dose curability of most human skin cancers is discussed in the light of the experimental results, and the possible clinical implication of an increase in hypoxic fraction with tumour invasion is raised.


An after loading colpostat (using standard source tubes). An afterloading system for the treatment of gynaecological patients is described. It uses a rigid tandem to which afterloading colpostats are attached. The catheters for afterloading the colpostats are flexible thus minimizing patient discomfort. A constant 90 deg. alignment of source tubes between the uterine tandem and colpostats is achieved.


Multiple superficial gastric erosions due to Crohn's disease of the stomach. Radiologic and endoscopic diagnosis. A case of Crohn's disease involving the stomach and duodenum is presented. The patient had a four-and-a-half year history of ankylosing spondylitis. Double contrast radiography of the stomach and duodenum showed multiple superficial gastric erosions and a duodenal ulcer. There were typical changes of Crohn's disease in the terminal ileum. At endoscopy, numerous superficial erosions were seen in the stomach and duodenum and biopsies of the stomach showed granulomatous inflammation, consistent with Crohn's disease. These lesions are similar to those seen in the colon in the early stages of granulomatous colitis and it is likely that this represents the early stage of Crohn's disease in the stomach. With increasing application of double-contrast radiography and endoscopy, these lesions may be found more frequently.


The surgical management of tuberculous lower ureteric stricture. 25 years' experience of the open surgical management of the lower ureteric stricture is reviewed. An extravesical anti-reflux tunnel procedure has been found to be simple and effective. There is still a place for the Boari procedure or psoas hitch, particularly in the management of a long stricture of when gross thickening of the ureter makes the formation of a tunnel of effective length impracticable.


Traumatic avulsion of the ureter with obstruction, pseudocyst formation and hypertension. A further case of traumatic avulsion of the upper ureter is described; it was complicated by hypertension and treated by removal of the pseudocyst. Delay in diagnosis should not be a contraindication to reconstructive surgery which should always be attempted if the kidney is functioning. The possibility of renal artery ischaemia should be considered when hypertension develops in the presence of a pseduocyst.


Influence of vesico-ureteral reflux on the response to treatment of urinary tract infections in female children. 3 groups of female children, comprising a total of 169 patients, were followed through successive episodes of urinary tract infection with respect to recurrence of infection. Group A consisted of 66 patients with no evidence of vesico-ureteral reflux. Group B comprised 42 patients with demonstrated vesico-ureteral reflux. The infections in these patients were treated with medical therapy alone and the reflux was not corrected. Group C consisted of 61 children who had surgical correction of vesico-ureteral reflux. While Groups B and C were not strictly comparable, the data indicate that there was no demonstrable difference in the rate of urinary tract infection among the 3 groups. Following short-term specific antibacterial therapy of a new infection, about 20% of children in each group were "cured", i.e., had no further infections during the 12 months or more that they were subsequently followed by the authors. Patients with less severe grades of reflux treated by medication alone (Group B) experienced no greater rate of reinfection than those children presenting with infections in the absence of vesico-ureteral reflux. In those children whose infections could not be adequately controlled by antimicrobial therapy, and those patients with severe (Grade III) reflux, surgery was performed to eliminate the vesico-ureteral reflux. The data also reinforced the concept that correction of reflux does not eliminate the need for constant vigilance and proper treatment of recurrent infections even after successful surgery has been carried out.


Percutaneous suprapubic cystostomy after spinal cord injury. The results of treatment of urinary bladder paralysis with small calibre (9 Charriere) suprapubic drainage in 41 male patients are described. It was found that suprapubic drainage could be maintained for an average of 8 weeks and that the urine in 43% of patients remained sterile for an average of 7 weeks. This technique merits further trial, both in the paraplegic patient and in normal patients requiring catheterisation because of obstruction of the lower urinary tract.


Asymptomatic phaeochromocytoma of the bladder co-existing with carcinoma. A case of asymptomatic phaeochromocytoma occurring in co-existence with a transitional cell carcinoma of the urinary bladder is reported and the significant characteristics discussed.


Male epispadias: surgical repairs of urethropenile deformity. A surgical technique for the repair of complete epispadias, with emphasis on correction of the urethropenile deformity and attempt to restore normal anatomic relations has been presented. The epispadiac orifice is dissected and followed proximally to beyond the bladder neck, then brought out perineally between the bifurcated crura. The penis is denuded from its skin, then embedded in the scrotum, except for the glans penis which protrudes from the midscrotum. Penile skin is folded into a tube to be used later for urethral reconstruction. Excellent cosmetic and functional results are consistently obtained by this multi-stage technique.


An unusual case of right and left testicular arteries arching over the left renal vein. An unusual case in which both testicular arteries arched over the left renal vein is described. A developmental explanation for the unusual vascular pattern is given. The possible importance of this and similar anomalies in the causation of varicocoele and orthostatic proteinuria is discussed.


A.I.D.--a review of 200 cases.

A.I.D.--a review of 200 cases. 2OO consecutive cases of couples referred for A.I.D. are reviewed. The reasons for referral are given and the technique and donors are discussed. It is estimated that about 85% of women who receive donor insemination will achieve pregnancy if they presevere. Infertility factors are common in women who present for donor insemination and this usually takes the form of ovarian follicular deficiency, probably with non-ovulation. It is suggested that a biphasic basal temperature record or a secretory endometrium in the luteal phase are unreliable tests for ovulation.


Ascorbic acid levels in stored blood and in patients undergoing surgery after blood transfusion. Blood was obtained from 11 healthy voluteers, mixed with two standard types of anticoagulant used in blood transfusion centres and stored for 21-28 days at 4 degrees C. Leucocyte ascorbic acid (LAA) fell to deficient levels after 7 days in all cases. There were no corresponding changes in plasma ascorbic acid (PAA) levels. LAA and PAA were measured before, during and after surgery in 5 control patients who underwent definitive operations for benign peptic ulceration and in 4 patients under-going surgery for bleeding peptic ulceration. The average amount of blood administered to the latter group was 10 units. There was a fall in LAA and PAA in both groups of patients after operation. This fall had returned to normal by 7 days in the controls, but the LAA remained at a deficient level at 7 days in the patients who had bled. Deficient ascorbic acid in stored blood may contribute to low leucocyte ascorbic acid levels in patients after blood transfusion and may contribute to the increased complication rate when surgery is undertaken in these patients.


Bronchopleural fistula: a review of 86 cases. A review of all the bronchopleural fistulas which developed following pulmonary resection in the Department of Cardio-Vascular and Thoracic Surgery of The London Hospital between 1953 and 1973 is presented. During this period 3150 pulmonary resections were performed for various conditions and 86 fistulas occurred, an incidence of 2-7 per cent. The aetiology, diagnosis and treatment of these fistulas are discussed.


Postgastrectomy afferent loop obstruction due to efferent loop herniation simulating acute pancreatitis. A case of afferent loop obstruction due to efferent loop retro-anastomatic herniation following a Polya gastrectomy is presented. The clinical picture closely mimicked that of acute pancreatitis. The difficulty in diagnosis in this situation is discussed and the importance of operative techniques in its prevention emphasized.


Multivariate analysis of clinical and operative findings associated with bilary sepsis. A cluster analysis of 17 preoperative and 10 operative variables has been undertaken from a prospective study of 181 patients undergoing operations on the biliary tract in order to identify those with organisms in the bile who would therefore benefit from prophylactic antibiotic cover. The analysis defined populations of high risk (45 patients) and low risk (136 patients) in which the incidence of infected bile was 67 and 19 per cent respectively (P less than 0-001). Eight variables were more common in the high risk than in the low risk group (P less than 0-001). These "high risk factors" were: jaundice at operation, recent rigoors, emergency operation or one within 4 weeks of an emergency admission, age over 70 years, previous biliary operation, common duct obstruction and stones in the bile duct. In 67 patients where one or more "high risk factors" was present, the bile contained organisms in 37 (53 percent); when 4 "high risk factors" occurred in the same patient (16 cases) biliary organisms were isolated in 14(87 per cent). We conclude that the presence of one or more "high risk factors" indicates a patient in whom prophylactic antibiotics would be advised during an operation on the biliary tract.


Colonic lymphoma complicating ulcerative colitis. Colonic lymphoma is a rare complication of ulcerative colitis. Two cases are described in patients who had had ulcerative colitis for 12 and 22 years respectively. Both patients presented with a recent change in their symptoms, which had become increasingly severe and which had not remitted with customary treatment for ulcerative colitis. Physical and haematological examinations revealed no evidence of generalized lymphoma, though barium enema studies indicated the sites of the lymphomatous lesions superimposed on chronic ulcerative colitis which were confirmed at operation and biopsy.


Anorectal function after major resections of the sacrum with bilateral or unilateral sacrifice of sacral nerves. The anorectal function in 3 patients with bilateral and 4 patients with unilateral well-defined loss of sacral nerves after radical tumour excision was studied by clinical examination and by simultaneous registration of the following variables: volume and pressure in the rectum, pressure in the internal anal sphincter area and myoelectrical activity in the external anal sphincter. The patients with bilateral loss of sacral nerves had serious impairment of function. Constipation was their only safeguard against incontinence. The preservation of the first and second sacral nerves bilaterally was not sufficient for discrimination between different qualities of rectal contents passing the anal canal. The sensation of rectal distension was also impaired. The reflex pattern of the internal anal sphincter was, however, intact. The external anal sphincter displayed a weak spontaneous myoelectrical activity in the patients who had at least one second sacral nerve intact, and a weak increase of the activity could be induced voluntarily. The normal transient increase of myoelectrical discharge from the external anal sphincter in response to rectal distension could not, however, be elicited. In patients with total unilateral loss of the sacral nerves no significant impairment of anorectal function was noted. Total one-sided denervation implied deficient sensibility of the anal canal unilaterally, but no disturbance of sphincter function as judged from the reflex response of the internal and external anal sphincters to rectal distension.


A study of perineal wound healing after abdominoperineal resection. A comparative study of 53 cases has revealed that a technique of complete primary closure of the perineal wound after abdominoperineal resection of the rectum and anal canal appears to be a superior, more rational approach than other orthodox techniques. (It is unsuitable for any case contaminated with pus or faeces during operation.) Redivac apparatus used through a separate route for continuous drainage from the sacral cavity has made the postoperative care easier for nurses and surgeons and this period more comfortable for the patient. It provides a simple method compared with other suction apparatus used for the same purpose. Of the 53 cases, 12 were operated on using a traditional technique involving the closure of the perineal wound around a tube drain connected to an underwater seal, while in the remaining 41 the approach described here was used. Primary healing of the perineal wound with the later approach was obtained in about 88 per cent. With the other technique the figures were 34 and 66 per cent respectively for early healing within 3 weeks and delayed healing between 3-8 weeks. Primary healing of the perineal wound reduces the total stay in hospital and the morbidity.


Altered viscosity and yield stress in patients with abdominal malignancy: relationship to deep vein thrombosis. Twenty-eight patients undergoing laparotomy were studied. Blood viscosity at both high and low rates of shear and a yield stress index were measured preoperatively and correlated with the incidence of post-operative deep vein thrombosis (DVT). There was a correlation between a raised index of yield stress and the incidence of DVT. Patients with cancer had a very high incidence of postoperative DVT and a high index of yield stress.


"Hitch-hike" grafts for limb salvage in peripheral arterial disease. A technique of arterial reconstruction suitable for patients with extensive arterial occlusions and for previous failed arterial surgery is described. The "hitch-hike" graft consists of a proximal limb of 6-mm velour Dacron prosthesis and a distal limb of autogenous vein. The intermediate prosthesis-to-vein anastomosis is made into an endarterectomized segment of upper popliteal artery. The results in the first 16 limbs are described. Eleven grafts are functioning from 2 to 14 months after operation and 5 of these have functioned for more than 1 year. The advantages of the technique are: long arterial occlusions may be bridged; autogenous vein is used to cross the knee joint; good measured blood flows may be demonstrated at operation; acceptable patency rates may be obtained up to 1 year.


Simple mastectomy and pectoral node biopsy. Evidence is presented to support the view that biopsy of the pectoral and axillary tail nodes obtained at simple (total) mastectomy gives a reliable estimate of axillary node status. The technique is described.


The relationship between thermographic findings and size and depth of tumour in carcinoma of the breast. Fifty thermograms of histologically proved breast carcinomas have been analysed without knowledge of the clinical or mammographic findings. Thermographic asymmetry between the breasts was found in 76 percent of the patients, but in only 64 per cent of the patients was the correct side indicated. Poor correlations has also been found between the thermographic findings and the size of a tumour and its distance from the skin.


Mortality of oesophagal surgery in the elderly. The operative mortality in pulmonary surgery was found to be four times higher in patients aged above 70 compared with those below 65. A similar study has been carried out in patients undergoing oesophageal surgery. A corresponding increase in operative mortality with advancing age was not found in this group. Anastomotic leakage remains the most common cause of operative mortality, the incidence of which is no higher in the elderly, though they are more liable to general complications. The overall mortality figures are comparable. The surgical approach to carcinoma of the oesophagus must be radical, and advanced age should not be a reason for withholding surgery.


The effect of posture on the emptying of the intrathoracic vagotomized stomach. Ten patients were studied at periods ranging from 6 months to 25 years after oesophagogastrostomy and gastric drainage. Gastric emptying studies and overnight gastric aspirates in both the supine and erect positions were carried out. Evidence was found in these patients of increased duodenogastric reflux and poor gastric emptying in the supine posture. All of the patients had gastritis, and some had gastric mucosal ulceration. These findings have led to the conclusion that in the supine posture the combination of duodenogastric reflux and poor gastric emptying leads to gastric mucosal damage.


The distribution and early morphology of the chronic gastric mucosal reaction. The distribution of the chronic gastric mucosal reaction (CGMR) that resulted from the exposure of the mucosa to refluxing duodenal contents did not suggest that one area of the stomach was more susceptible than another. The earliest histological appearances of established CGMR as seen 3 months after surgery were epithelial proliferation and pseudy-pyloric metaplasia.


Is the lesser curvature an area especially susceptible to injury by duodenal contents? The lesser curvature does not appear to be an area of increased susceptibility to injury. The fact that this is the usual area for the development of chronic gastric ulceration could in part be explained by reflux of duodenal contents along the lesser curvature.


The role of the pyloric antrum and Hofmeister value in the development of the chronic gastric mucosal reaction. A limited chronic gastric mucosal reaction (CGMR) develops when duodenal contents enter the stomach with an intact pyloric antrum. However, after antrectomy the same stimulus leads to a widespread CGMR. The pyloric antrum, therefore, seems to influence the development of the CGMR. A Hofmeister valve included in a Polya gastrectomy does not prevent the development of the VGMR, presumably because reflux is not prevented.


Extragastric gastrinoma or G-cell hyperplasia of the antrum? The preoperative diagnosis in a case of hypergastrinaemia. A patient is described with recurrent peptic ulceration, evidence of hypersecretion of gastric acid and excess circulating gastrin. The preoperative differentiation between extragastric "gastrinoma" and G-cell hyperplasia of the pyloric antrum as a source for the hypergastrinaemia can be made by immunofluorescent staining of an antral biopsy for "gastrin cells", and by measuring the response of the gastric antrum to an amino acid meal or secretion infusion stimulus. The site of excessive gastrin production determines the nature of the surgery required. A classification of recurrent peptic ulceration types is suggested.


The effect of metramide on the prolonged serum gastrin response to feeding observed in patients with duodenal ulcer. The response of serum gastrin to a meal has been studied in 11 normal subjects and 16 patients with duodenal ulceration. The mean serum gastrin concentration rises after a meal to similar peak values in both normal subjects and duodenal ulcer patients, and fall to basal values with 3 hours in normal subjects. In duodenal ulcer patients the peak concentration is sustained throughout the 3 hour test period, and this response is not affected by the administration of Metiamide. It is concluded that the control of gastrin release is defective in duodenal ulceration, and this may be due to a failure of the antral pH feedback mechanism. Gastrin may be a primary pathogenetic factor in duodenal ulceration.


Cancer of the stomach: a review of 854 patients. A review is presented of 854 patients suffering from cancer of the stomach who attended St Bartholomew's Hospital between 1948 and 1962. The presentations and methods of investigations showed little change over the 15-year period, which is similar to other large series. The symptoms of anaemia and indigestion appear to be paramount in making an early diagnosis, and negative barium meal studies should not be accepted when these two symptoms are present. There are indications that early laporotomy and a more aggressive surgical approach may increase the 5-year survival rate.


Drug therapy for postragotomy gastric stasis. An unusual but well-recognized complication of truncal vagotomy with a drainage procedure is severe gastric stasis (atony). In 6 patients presenting with this problem drug therapy was initiated after mechanical obstruction of the gastric outlet was excluded by radiology. Bethanechol chloride was successful in stimulating gastric peristalsis in all the patients, with consequent improvement of symptoms in 5 out of the 6 subjects. Metoclopramide alone was of no value in starting peristalsis but of pssible benefit once gastric motility had begun.


The relationship of plasma glucagon to the hyperglycaemia and hyperinsulinaemia of surgical operation. In a controlled metabolic study of 42 patients undergoing abdominal surgery a significant increase in basal values of immunoreactive glucagon (IRG) was found 24 hours postoperatively. No correlation between the onset and duration of hyperglycaemia and the increase of IRG was observed. No increase in immunoreactive insulin (IRI) was seen during operation, but there was a rise 24 hours postoperatively. The infusion of arginine was accompanied by a rise in IRG both pre-and postoperatively, but despite the high values obtained there was no accompanying further increase in basal plasma glucose in the postoperative situation. The pre- and postoperative IRI responses were similar. Our evidence suggests that glucagon is not a primary mediator of the stress response, or of the hyperglycaemia of surgical operation in these patients.


A conrolled trial of glucagon in experimental pancreatitis. This study was designed to assess the value of glucagon infusion in pigs with experimental pancreatitis. The condition was induced by injection of bile into the pancreatic duct directly after intravenous injection of secretion. Macroscopic haemorrpagic pancreatitis ensued immediately, and was accompanied by a rise in the serum amylase of five to ten times. An experimental group of 15 pigs was given glucagon by continous infusion for 18 hours beginning 18 hours after induction of pancreatitis. A control group was given intravenous saline. Fourteen of the 15 treated animals survived for 1 week and 3 died within 2 weeks, after which the remaining animals were sacrificed. Ten of the 15 controls died within the first week. Serum amylase levels in both groups began to decline when infusion was commenced, but levels in the treated group were significantly lower than in the controls. Autopsy showed prominent peripancreatic granulation tissue in the treated animals, a significant incidence of pericarditis in both groups and pancreatic pseudocysts in 3 controls and 1 treated animal. These results suggest that glucagon effectively reduced the mortality in pigs with experimental pancreatitis and that a controlled clinical trial of treatment is justified.


Ischaemic necrosis of the gallbladder following hepatic artery embolism. A case of ischaemic necrosis of the gallbladder due to hepatic artery embolism diagnosed at operation and treated successfully by cholecystectomy and embolectomy is presented. The clinical and biochemical features are described, together with a short review of the literature.


Peicystogastrostomy: internal drainage in the treatment of certain hydatid cysts of the liver. The effectiveness and simplicity of drainage of hydatid cysts of the liver into the digestive tract are demonstrated. A new technique, pericystogastrostomy, is described.


Cholecystostomy.

Cholecystostomy. The role of cholecystostomy in the sugical treatment of gallstones has been considered. In a consecutive series of 558 patients who underwent surgery for gallstones, 30 (5-4 per cent) had cholecystostomy alone and a further 17 (3-1 per cent) cholecystostomy combined with exploration of the bile ducts. Cholecystostomy was done because cholecystectomy was technically very hazardous in 15 patients. In the remaining patients cholecystostomy was preferred to cholecystectomy because o f the poor general condition of the patient or the presence of pancreatitis. Of the 47 patients submitted to cholecystostomy, 2(4-2 per cent) died postoeratively and 4(8-4 percent) subsequently underwent cholecystectomy. Of 24 patients who were available for long term follow-up, only 1 patient had pain which was definitely considered to be due to gallstones, although 3 other patients also had abdominal pain, while 7 patients showed radiological evidience of gallstones. It is contended that cholecystostomy has a small but definite part to play in the immediate surgical treatment of gallstones and that the long term results of the operation are sufficiently good to justify its use in selected patients.


Intraperitoneal rupture ofhydronephrotic kidney. Two cases of intraperitoneal rupture of hydronephrotic kidney are presented. The possibility of making a preoperative diagnosis and the type of management are discussed.


Follow-up study of left suprarenal to inferior mesenteric venous shunt for advanced breast cancer. Major endocrine ablation therapy was carried out in 133 patients with advanced breast cancer. Of 40 patients undergoing left suprarenal to inferior mesenteric venous shunt with bilateral oophorectomy and right adrenalectomy, 16 cases (40 per cent) had an objective response. The mean postoperative survival of the patients with a positive response, those showing some response and those who failed to respond was 35-8, 26-5 and 8-8 months respectively. Thus, the results of the present procedure are comparable to those of adrenalectomy. No replacement therapy with corticoids was necessary. An increase in the response rate and extension of the survival time can be expected with the addition of postoperative long term maintenance therapy with chemotherapeutic agents and androgens.


The haematological hazards of autotransfusion. Fourteen heparinized dogs were autotransfused from 1-5 to 6 times calculated blood volume. Five animals retransfused 12 litres from an intraperitoneal bleed had marked decreases in all cellular elements, haematuria and a large (82 percent) drop in fibrinogen. All these animals died within 12 hours and post-mortem examination revealed evidence of disseminated intravascular coagulopathy. The dogs in which a smaller volume (3-6 litres) was recycled showed similar, but less devastating, changes. Haematocrit and platelet count dropped by a half and fibrinogen by 20 per cent. A leucocytosis of about 30 000/mm3 occurred within 24 hours. Autotransfusion of salvaged blood which was not allowed extravascular tissue contact significantly lessened these adverse effects. We conclude that the risk of cellular destruction and defibrination in large volume intra-operative autotransfusion is significant and must be weighed against its potential benefits in each case, and that red cell and platelet damage results primarily from extravascular tissue contact and is therefore unavoidable.


Changes of smoking habits and cough in men smoking cigarettes with 30% NSM tobacco substitute. The effects of smoking cigarettes with 30% of the tobacco replaced by NSM tobacco substitute, which lowered their tar and nicotine delivery, were studied by comparing them with the effects of conventional cigarettes in a controlled crossover trial lasting 20 months. Chest symptoms, cigarette consumption, and forced expiratory volume in one second (FEV1) were measured each month. Two-hundred men began the trial and 159 completed it. The test cigarettes were acceptable to all but one of the men. In a subsample of 35 men estimates of nicotine intake were obtained from monthly analyses of cigarette stubs. On changing from NSM to control cigarettes six of the 17 men, who were accustomed to low nicotine, kept their nicotine intake down by some change in smoking habit. Before the crossover and this change in smoking habit the men smoking NSM cigarettes had a small but significant reduction of cough. Cigarettes containing 30% NSM and delivering only 1 mg of nicotine are likely to be acceptable to smokers and may reduce coughing. Further trials are needed to confirm these findings and establish what long-term effects such cigarettes may have on smokers' health.


Low-tar medium-nicotine cigarettes: a new approach to safer smoking. The logic of expecting people who cannot stop smoking to switch to cigarettes that have hardly any nicotine is questionable. Tar and nicotine yields of cigarettes available in Britain today correlate 0-93, and further reduction of tar intake is limited by the reluctance of smokers to tolerate similar reductions in nicotine. A new approach would be to aim at lowering tar yields of cigarettes from the present average of 18 mg to around 6 mg but maintaining nicotine yields at around 1-0 to 1-2 mg, which would be acceptable to most smokers. This approach requires that emphasis be placed on tar: nicotine ratios as well as on the absolute yields. These ratios for brands on sale in Britain today average 14-2 and range from 9-6 to 20-8. They provide an additional guide for comparing the relative harmfulness of different brands. For example, 35% of cigarette smokers in Britain smoke either Embassy Filter or Players No 6 Filter; by changing to John Player Carlton King Size they could reduce their tar intake by more than 20% without having to suffer any nicotine deprivation.


Ultrasonic monitoring of fetal respiratory movement. Ultrasonic monitoring of fetal respiratory movement including velocity measurements is described. Both proximal and distal walls of the fetal chest are imaged simultaneously. The time-position mode clearly defines fetal respiratory movement and rejects artefacts.


Carpal tunnel syndrome, humeral epicondylitis, and the cervical spine: a study of clinical and dimensional relations. Forty-three patients with idiopathic carpal tunnel syndrome, confirmed by nerve conduction studies and treated by surgery, were compared clinically and radiologically with 43 age- and sex-matched control patients. Patients with carpal tunnel syndrome had a significantly greater prevalence of lateral humeral epicondylitis (tennis elbow) (33%) than controls (7%). Randomised reading of the cervical spine radiographs in ignorance of the groups to which they belonged showed no significant difference in the prevalence of either intervertebral disc degeneration or intraforaminal osteophyte protruion using conventional grading methods. Measurement of the minimum anteroposterior diameter of the cervical spinal canal, the anteroposterior diameters of the cervical vertebral bodies, and the ratio of intervertebral disc height to adjacent vertebral body height in the cervical spine, however, showed a consistent trend to smaller measurements in the carpal tunnel group. Differences were significant at several vertebral levels in each of these dimensions. The narrowing of the intervertebral discs relative to the vertebral bodies in patients with carpal tunnel syndrome may indicate connective tissue changes, which might also occur in the common extensor origin at the elbow or in the contents of the carpal tunnel.


Management of psychiatric problems in a Kenyan mission hospital. Many psychiatric conditions are found in the rural general hospital in Kenya and are recognisable and manageable along standard Western lines. An essential element in management is the training of the nursing staff. The psychiatric patient should be actively managed and can benefit from the unsophisticated treatment possible at the mission hospital.


Breast-feeding protects against respiratory syncytial virus infections. Eight out of 115 infants admitted to hospital with respiratory syncytial (RS) virus infection had been breast-fed compared with 46 out of 167 controls; this difference was statistically significant. Twenty-one specimens of human colostrum were examined, and all contained RS virus neutralising activity. Specific IgA and IgG were detected in 18 specimens, whereas IgM was detected in none. The titre of IgA antibody was usually higher and correlated more closely to the titre of neutralising activity than that of IgG. Infants inhale milk feeds and regurgitate them through the nose, and the IgA collecting in the respiratory tract might protect against severe respiratory infection. Alternatively, if severe RS virus illness is a sign of hypersensitivity to the virus breast-feeding might protect the infant from an early sensitising infection.


Lymphocyte cytotoxicity for kidney cells in renal tubular acidosis of autoimmune liver disease. Sensitisation to a renal tubular antigen, Tamm-Horsfall glycoprotein, has been shown to be common in patients with renal tubular acidosis complicating autoimmune liver disease, and it has been suggested that this immune reaction, by damaging renal tubular cells, might be responsible for the acidification defect. The lymphocytes from 10 out of 13 patients with chronic active hepatitis or primary biliary cirrhosis and an associated renal tubular acidosis were shown to be cytotoxic for a kidney cell line known to secrete Tamm-Horsfall glycoprotein. The cytotoxic reaction was blocked by this antigen, but not by two other proteins, indicating that sensitisation to the renal glycoprotein was the likely cause of the target cell damage. Significant reduction in cytotoxicity after the addition of aggregated IgG suggested that the reaction was of the antibody-dependent cell-mediated type. These results, together with the finding of antigenic material in the surface membrane of liver cells that cross reacts immunologically with Tamm-Horsfall glycoprotein, provide an explanation for the association between chronic liver disease and renal tubular dysfunction.


Oral contraceptive use in older women and fatal myocardial infarction. A previous study of women who had died from myocardial infarction and of a control group of women matched with them for age suggested a fivefold increase in the risk of death from myocardial infarction among users of oral contraceptive aged 40-44 years compared with women not using such preparations. Only a small proportion of women in the infarction and control groups had used oral contraceptives, however, so the margin of error was wide. We therefore investigated a further 54 women in this age group who died from myocardial infarction and compared their oral contraceptive histories with those of age-matched, living controls. Combination of the findings from the present investigation with the previous results have enabled a revised estimate of a threefold increase in risk to be made. Although this risk estimate is similar to that previously shown for a younger age group, the total mortality attributable to complications associated with the use of oral contraceptives remained considerably greater among women over the age of 40.


First electrocardiogram in recent myocardial infarction. The admission electrocardiogram (ECG) was studied in 898 patients admitted to a coronary care unit over two years. The diagnosis made from this tracing was compared with that made at the end of the patient's stay. About half the cases of recent myocardial infarct were diagnosed from the admission ECG, but accuracy rose to 83% with serial ECG's in the unit. The ECG is important but not entirely reliable in the early detection of acute myocardial infarction, which should be largely a clinical diagnosis.


The elderly in a coronary unit.

The elderly in a coronary unit. The clinical features of myocardial infarction were compared in 104 patients over the age of 70 and 399 younger patients admitted to a coronary care unit. Absence of an age bar at 70 years has increased the number of admission to the unit by 24%, and the number of patients with proved infarcts by 26%. Severe complications are more common and mortality is doubled in the elderly. Although immediate management of primary ventricular fibrillation is as successful in older as in younger patients, treatment of the elderly with less dramatic conditions is less successful. The elderly survivors tend to spend longer in the coronary unit and subsequently in the general medical ward.


Value of renal biopsy in acute intrinsic renal failure. Eighty-four patients presented with acute renal failure and features suggesting a diagnosis of intrinsic renal disease other than "acute reversible renal failure." Renal biopsy proved valuable in establishing the diagnosis, in indicating the reversibility of the lesion, and in helping to decide on treatment.


Cost of management of patients with haemophilia. The cost of managing 114 adult haemophiliacs in the west of Scotland was assessed for the period 1 March 1971 to 28 February 1974. Altogether 23 of them (20%) accounted for 80% of the resources used. The cost of hospital treatment of these patients during the period was compared with the predicted cost of home treatment, given the availability of freeze-dried factor VIII concentrate in sufficient amounts. We calculate that adequate on-demand home treatment would cost only 16% more than the present treatment, which is substantially less efficient.


Mountain sickness, retinal haemorrhages, and acclimatisation on Mount Everest in 1975. During the 1975 British Everest Expedition, which made the first ascent of the south-west face, observations were made in relation to mountain sickness and the appearance of retinal changes. Two Sherpas with cerebral oedema and one Briton with pulmonary oedema were treated. Retinal haemorrhages occurred in four out of six Britons who were newcomers to altitudes over 6000 m (19 685 ft) but in only two out of 14 Britons who had previously visited these altitudes. Intraocular pressures during ascent to 6000 m were within normal limits. The relevance of the ocular findings to acclimatisation in previous years was examined, the results supporting the hypothesis of a "carry-over" effect from previous visits to high altitude.


Postoperative hypoglycaemia in small children. Six of 57 children under 4 years old became hypoglycaemic during postoperative recovery from various surgical procedures. Fluids either by mouth or intravenously did not always prevent this. Children at risk could not be predicted on the basis of age or weight-for-age. Small children should be fed as soon as practicable after operations, preferably with milk.


Completeness of statutory notification for acute bacterial meningitis. Several different sources of data, including statutory notifications, were used to identify cases of acute bacterial meningitis in childhood in a defined population. Only half the cases of meningococcal meningitis and less than one quarter of ofther types of bacterial meningitis had been notified. Notified cases differed from the remainder with respect to causative organism, age, outcome, and type of hospital of admission. Thus notifications are an unreliable measure of incidence for this disease, and studies of infectious disease based on notified cases alone should be interpreted with considerable reserve. It is suggested that infectious-disease surveillance should be both clinical and microbiological and that data from different sources need to co-ordinated. The reason for reporting each disease (or organism) should be specified and and reviewed periodically.


A general practitioner in an ophthalmology accident and emergency department. After a short period of intensive training, a general practitioner successfully replaced a senior house officer (SHO) in the accident and emergency department of an eye hospital on one morning a week for a year. An unbiased observer compared the performance of the general practitioner after one year with that of a full-time SHO who had had 17 months' experience; their performances were about equal. Although a sessional general practitioner costs about 28% more than an SHO, the real cost is much less because undue length of service as an SHO or change to another specialty (because of the SHO surplus) delays achievement of a permanent grade. Continuity is a great advantage of the general practitioner. Replacement of some SHOs by general practitioners would reduce the surplus of SHOs with poor promotion prospects. The commonest diagnoses were Meibomian cysts (18%), corneal foreign bodies (20%), corneal abrasions (12%), and conjunctivitis (8%).


Emergency medical care.

Emergency medical care. A survey carried out over five periods between 1973 and 1975 to study the mode of referral of emergency medical patients to a district general hospital showed that, out of a total of 2511 patients, 51% referred themselves, 40-8% were referred by general practitioners, and only 4-7% by doctors employed by the emergency treatment service. Of the 1720 patients admitted to the medical wards, 50-9% were referred by general practitioners and 37-3% were self-referred while the corresponding figures for the 791 not admitted were 19% and 80-7% respectively. Two-thirds of the self-referred patients came from their own homes, usually by ambulance ordered by a "999" emergency call. The figures were similar in each of the five periods.


[Pathways and ascending vestibular projections emanating from primary nuclei: radioautographic study (author's transl)]. A study of the pathways and ascending vestibular projections was carried out in the cat after unilateral injection of tritiated leucine into the rostral vestibular complex. Radioautographic analysis revealed a gradual decline in the density of labeling as ascending fibers were found to progress towards more rostral relays. The pathways and projections were very compact in the oculomotor nuclei, became less intense in the Cajal and Darkschewitsch nuclei, and thinned out considerably until they reached a transitional zone in the thalamus between the ventrobasal and ventrolateral complexes. These results confirm established and previous findings in this laboratory obtained by neurophysiological and neurohistological examination procedures. They provide the first anatomical evidence concerning the existence of vestibulothalamic projections and pathways.


GM2 ganglioside in fetal Tay-Sachs disease brain cultures: a model system for the disease. Cultured cells derived from Tay-Sachs disease (TSD) fetal cerebellum were shown to accumulate GM2 ganglioside when compared with control cultures. In contrast, fibroblasts derived from TSD fetal lung do not contain GM2. GM2 was identified by thin-layer chromatography (TLC) and confirmed by gas-liquid chromatography (GLC). Unlike fetal TSD brain, the cell cultures established from fetal TSD brain have high concentrations of globoside and GD3 and little or no asialo GM2(GA2). The GM2 and related glycosphingolipids in these cultured cells contain a high percentage of C24:0 and C24:1 fatty acids. In spite of these differences, this TSD cell strain is unique in that it accumulates GM2, and can therefore serve as a useful in vitro model for the study of TSD.


Neurochemical aspects of the ontogenesis of GABAnergic neurons in the rat brain. Examination of various biochemical characteristics of the GABAnergic nervous system in the rat brain was made between 15 days of gestation and adulthood. At birth, the concentration of GABA in whole brain and most regions is approximately 50% of adult levels, whereas the medulla-pons has achieved adult levels by this time. Compared to GABA levels, there is a marked lag in the development of the activity of glutamic acid decarboxylase in all areas studied; however, the activity of the enzyme increases in a linear fashion from birth to adulthood. The development of the uptake of GABA into particulate fractions prepared from whole brain and regions differs markedly from that of GABA and glutamic acid decarboxylase, with uptake near adult levels by birth, peaking considerably above that of the adult between one to two weeks after birth and then declining toward adult activity by 4 weeks after birth. Examination of the kinetics of GABA uptake into resuspended P2 fractions demonstrates that the developmental changes in the uptake reflects differences in the Vmax whereas the Kt remains constant; Studies on the development of the apparent postsynaptic receptor for GABA reveals that in all regions binding is approximately 25% of adult up to 8 days after birth, at which time it increases dramatically, approximating adult levels by 4 weeks after birth. The rise in the density of the apparent postsynaptic GABA receptor after 8 days postpartum correlates best with the increase in the activity of glutamic acid decarboxylase, a presynaptic marker.


[Postnatal maturation of vestibular nuclei in the cat: histological study by the Golgi-Cox method (author's transl)]. Postnatal maturation of vestibular nuclei in the cat was studied from both the qualitative and quantitative points of view, following impregnation of the sections by the Golgi-Cox method. Three principal data arise from our results. (1) The different vestibular neurones undergo significant growth during the first two weeks of extra-uterine life: during this time, the progressive disappearance of dendritic growth cones and filopodia, an increase in area and volume of the perikarya as well as that of dendritic fields are remarkable; the smallest neurones completing their maturation before the largest. (2) Average sized neurones of the superior vestibular nucleus show a significant increase in the number of dendritic spines between birth and the age of 3 days. (3) On the 12th day, a decrease in the number of dendritic spines is noted. This decrease is accompagnied by a modification in spine density along the dendrites.


Binding of alpha-bungarotoxin to chick sympathetic ganglia: properties of the receptor and its rate of appearance during developement. Studies were carried out on the binding of [125I]alpha-bungarotoxin (alphaBT) to membrane fragments of chick sympathetic ganglia. Specific binding of toxin was saturable with a KD of 1.1 nM. The rates of association and dissociation of the toxin from ganglionic membranes were 4.3 X 10(4) M-1 sec-1 and 4.6 X 10(-5) sec-1 (t 1/2 = 4.2 h). respectively. Binding was inhibited (by up to 95%) by low concentrations of nicotinic, but not by a muscarinic cholinergic ligand. The properties of the ganglionic binding site for alphaBT were consistent with its being a nicotinic acetylcholine receptor. The development of toxin receptors in chick ganglia was also studied. From days 7 to 11 in ovo, few receptors were present; from days 12 to 20 in ovo, there was a 10-fold increase in receptor number per ganglion; from hatching to maturity, the receptor number per ganglion slowly increased and reached a maximum of 14 fmoles. The ontogeny of receptors for alphaBT in sympathetic ganglia appears to correlate with the cytological maturation and innervation of the principal neurons.


The head extractions, brain and pituitary uptake and metabolism of progesterone and 5alpha-dihydroprogesterone in anesthetized, female rabbits. Three days after ovariectomy adult female rabbits were injected intramuscularly with either 2 mug estradiol/kg b.w., 0.5 mg progesterone/kg b.w., 2 mug estradiol plus 0.5 mg progesterone/kg b.w., or oil vehicle daily for 5 days. On the sixth day the animals were anesthetized and given a continuous infusion of [14C]progesterone and [3H]5alpha-pregnane-3,20-dione (5alpha-DHP) for 4 h via the femoral vein. Head extractions, calculated from the difference in blood concentrations of radioactive steriods between the femoral artery and jugular vein, were in the range of 60-75% for both progesterone and 5alpha-DHP and were unaffected by the hormone treatments. Nine brain areas and the pituitary were analyzed for [14C]progesterone, [3H]5alpha-DHP and [14C]-5alpha-DHP. Generally, the brain and pituitary retention and distribution of [14C]progesterone and [3H]5alpha-DHP and the brain and pituitary metabolism of [14C]progesterone were unaffected by hormone treatments. In the cerebellum, progesterone treatment increased [14C]progesterone retention as compared to oil treatment. All tissues contained 2-7 times more [14C]progesterone than arterial blood concentrations. [3H]5alpha-DHP tissue: arterial blood concentrations ratios were much lower ranging from 0.9 to 1.78. [14C]progesterone and [3H]5alpha-DHP showed similar brain distribution with highest concentrations in the pons, pons reticulum and midbrain reticulum. All tissues converted progesterone to 5alpha-DHP, but only the cerebellum contained more [14C]5alpha-DHP than [14C]progesterone.


Inhibitory potentials produced in cortical cells by stimulation of the lateral hypothalamus in rabbits. (1) Intracellular potentials were recorded from pyramidal tract (PT) and non-pyramidal tract (non-PT) cells of the frontal cortex in urethane-anesthetized rabbits and the effects of electrical stimulation of the lateral hypothalamus (LH) were examined on the ipsilateral side. (2) Latencies of antidromic spikes of PT cells evoked by stimulation of the medullary pyramidal tract (PYR) had a unimodal distribution with the mean at 4.0 msec. The mean conduction velocity of the pyramidal tract fibers was 10.5 m/sec. (3) Prolonged IPSPs were produced in PT and non-PT cells by single shock stimulation of LH (LH-IPSP). They were significantly longer lasting than those produced by PYR stimulation (PYR-IPSP). (4) The latencies of LH-IPSPs ranged from 1.7 to 25.0 msec and were divided into two groups. The latencies of PYR-IPSPs had a unimodal distribution ranging from 2.5 to 30 msec. (5) In a few non-PT cells, a sequence of brief depolarization and prolonged hyperpolarization occurred in response to LH stimulation. (6) In some non-PT cells, EPSPs which occasionally resulted in spike discharges were observed after LH stimulation. However, no excitation of PT cells was observed by LH stimulation.


Reticular suppression of flash-evoked IPSPs in visual cortex neurons. In a majority of visual cortex (VC) neurons recorded intracellularly in chronically implanted rabbits, light flashes evoked responses consisting of protracted IPSPs (duration 160-200 msec) followed in some cases by a rebound. Inhibition of spontaneous activity through high frequency reticular stimulation (MRF) or through presentations of non-visual arousing stimuli, was not associated with strong hyperpolarization of the cell membrane. Reticular stimulation evoking both activation and inhibition of spontaneous neuronal activity elicited attenuation or complete elimination elimination (disinhibition) of flash-evoked protracted IPSPs and of the postinhibitory rebounds. Rhythmic neuronal discharges elicited by stimulation of the visual pathway was also reduced during reticular activation, due to attenuation of the IPSP-rebound sequence.


Catecholamines released from cerebral cortex in the cat; decrease during sensory stimulation. In an attempt to determine the functional role of catecholamine (CA) nerve terminals in cerebral cortex the release of endogenous norepinephrine (NE) and dopamine (DA) into superfusates from visual and somatosensory cortex of the cat have been measured by a sensitive radiometric enzymatic assay based on the methylation of CA by catechol-O-methyltransferase (COMT) in the presence of a [3H]-methyl donor and followed by resolution of 3H derivatives through a series of organic extractions. In the flaxedilized animal maintained under local anaesthesia with artificial respiration the concentration of CA measured in 30-min superfusates was fairly constant in a given experiment under basal conditions without sensory stimulation, but varied widely from one experiment to another. Variations in NE were often independent of those for DA. For visual cortex the average basal release of NE in experiments was 20.09 +/- 3.64 pg/min/sq.cm while the average for DA was 34.01 +/- 7.62 pg/min/sq.cm. In all experiments intermittent visual stimulation (15/sec) produced a significant reduction in release rate averaging about 42% for NE and 64% for DA in visual cortex. The reduction was relatively non-specific since visual or somatic sensory stimulation produced a decrease in release from both visual and somatic sensory cortical areas. Since it has been shown that there is a relatively non-specific increase in acetylcholine (ACh) release from sensory cortex during stimulation, it is proposed that ACh may regulate CA release at presynaptic CA terminals in the cortex as it does in the periphery. A marked increase in CA release observed on perfusing with nicotine or atropine is consistent with this hypothesis.


The morphology of identified neurons in the abdominal ganglion of Aplysia californica. The morphology of identified neurons and of one multiaction interneuron (L10) of the abdominal ganglion of Aplysia has been studied using cobalt chloride, injected intracellularly. Cells with little synaptic input, R3-R14, had a relatively poorly developed dendritic tree, whereas the dendrite tree of cells L7 and L10, with extensive synaptic input, was highly complex. Cells L1-L6 and the RB cell cluster were found to have intermediate complexity of synaptic inputs and dendritic morphology. Within cell clusters, individual cells were often morphologically distinct. Identified cells have both invariant and variant axonal branches. Variant axons often project down other than their customary nerve trunks or are supernumerary. Three features of neuropil architecture were encountered. (1) When cells from the same cluster send their axons down the same nerve the axons often run in fascicles. (2) Although an identified cell's dendritic geometry varies from preparation to preparation, its dendrites always occupy approximately the same position in the neuropil. (3) The postsynaptic follower cells of L10 send their main axons through the axonal arborization of L10.


A radioautographic analysis in the light and electron microscope of identified Aplysia neurons and their processes after intrasomatic injection of L-(3H)fucose. We have studied radioautographically the distribution and fate of 3H-glycoproteins within the single identified neurons L10 and R12 of Aplysia californica after intrasomatic pressure injection of [3H]fucose. Silver grains were localized to intracytoplasmic membranes in both cell body and axon 3 h after injection of the cholinergic neuron L10. Grains also appear at this time over presumptive synapses. In the cell body the Golgi apparatus was labeled, as were vesicles, multivesicular bodies, pigment granules, smooth endoplasmic reticulum, mitochondria and peroxisomes. The Golgi apparatus is the most intensely labelled organelle (relative specific activity 9,5). Over 50% of the silver grains are associated with the Golgi apparatus and with vesicles. In the axons, vesicles were labeled most intensely, having a relative specific activity of 40.4 (% silver grains/% area), an intensity 10 times that of similar appearing somatic vesicles, and 4.5--10 times that of other organelles (multivesicular bodies, mitochondria, smooth endoplasmic reticulum) in the axon. At least 32% of the silver grains are associated with vesicles. It appears that the biosynthetic machinery of these neurons is heavily involved in the production of vesicle membrane destined for transport along axons and to terminals. The preponderant labeling of vesicles in the axon parallels the rapid and perferential transport of glycoprotein components described by Ambron et al. and may indicate that specific glycoprotein molecules can be identified as components of these vesicles. After injection of the cholinergic neuron R2 transport of radioactivity was restricted to the axonal tree of the injected neuron. After injection of L10, one other neuron was invariably labeled. By varying the conditions of injection, as many as 5 other neuron cell bodies could be labeled. These are located in the position of cells known to be electrically coupled to L10, and they probably became labeled by transneuronal movement of fucose across electrotonic junctions. Since restriction of label to the injected neuron is easily determined in each experiment, this technique makes possible the identification of chemical and perhaps electrical synapses of identified cells with optimal preservation of fine structure.


Brain stem reticular units: synaptic responses to stimulation within the ascending reticular pathways. When the ascending reticular axonal system is stimulated, the responses of distal structures (e.g., the cerebral cortex) appear to outlast the stimulus; these longlasting effects could reflect the intrinsic nature of the distal structure, or the response could reflect an interaction among the reticular cells which tends to prolong the effects of stimulation. To examine the latter hypothesis, single units with ascending axons (projecting units) were recorded in the cat rostral rhombencephalon in acute experiments conducted under halothane-nitrous oxide anesthesia. Stimulation of areas to or through which axons of reticular neurons projected (midbrain tegmentum and lower tectum, medial thalamus, and basal forebrain) produced a consistent and specific response which was elicited only from these areas: suppression of spontaneous activity which was typically elicited from several areas having ascending axons. One-half of these responses were accompanied by a short latency-single spike synaptic excitation. Stimulating areas more than 1.0 mm from the ascending trajectory never  produced this response, whereas the number of responses was directly related to the number of projecting axons identified in any one experiment from a given site. Thus, the predominant effect of stimulating within the ascending axonal trajectory was suppression of spontaneous activity in the projecting units, not an 'en cascade' activation of these units; on the contrary, the only type of excitation encountered was a single, short latency spike. Therefore, any effects of stimulation within the ascending reticular pathway which appear to outlast the stimulus (as previously described in the literature) cannot be ascribed to a reverberating (excitatory) circuit among projecting units. A possible source of the synaptic responses of projecting units is a retrograde activation of collaterals interconnecting the reticular cells. If such interaction exists, it is specifically distributed among cells with ascending axons, as the responses were only observed in a very few units not identified by antidromic excitation; however, other evidence is adduced to support the belief that these few units were projecting units whose axons were beyond the reach of the stimulating electrodes. Futhermore, the axons may be bundled such that units with axons nearest that of a given projecting unit give rise to the most extensive synaptic interactions; the activation of these nearby axons suppresses spontaneous activity, while axons farther away have a greater possibility of being excitatory in nature. Should such a medium for interaction exist, reticular collateral interactions might be seen to exist specifically for the purpose of decreasing the activity of cells destined for similar rostral target structures.


Intracellular study of synaptic events related to phase-locking  responses of cat cochlear nucleus cells to low frequency tones. In this study intracellular recording techniques were used to study the synaptic events related to phase-locking of cochlear nucleus cells to low frequency stimuli. A variable degree of phase-locking was noted even with units of the same low characteristic frequency. With low frequency phase-locking units an excitatory postsynaptic potential (EPSP) occurred in response to each period of the frequency stimulus, but the probability of an action potential occurring decreased as the frequency of the stimulus was raised. Complex units were described which phase-locked at lower frequencies of stimulation but did not at higher frequencies where the temporal pattern of firing to tone burst stimulation changed as well. Results are discussed as they relate to  the frequency following response recorded with gross electrodes in the lower auditory pathway and the relationship to frequency coding in the auditory pathway.


Immunoelectrophoretic determination of brain-specific antigens in bulk-prepared neuronal and glial cells. The relative amounts of brain-specific antigens, S-100, glial fibrillary acidic protein (GFA), 14.3.2, synaptin C1, D1, D2 and D3 were determined by crossed immunoelectrophoresis in bulk-prepared neuronal, glial and synaptosomal fractions from 35-day-old rat brains. Little enrichment was ontained for any antigen in the neuronal perikaryal fraction. The glial fraction showed a 3.5-fold enrichment in GFA but had levels similar to whole brain with respect to S-100. Synaptosomes were somewhat enriched in the synaptin C1 protein, but did not differ markedly from whole brain with respect to the most antigens. The extent  of cross-contamination in the various fractions could be judged only tentatively, partly due to differences in extractability of the proteins.


The effect of trauma on the activity of central noradrenergic neurones. Changes in the concentration of the main noradrenaline metabolite in rat brain, 4-hydroxy-3-methoxy-phenylethyleneglycol sulphate (MOPEG-SO4) have been studied during and after injury by limb ischaemia. In the hypothalamus the MOPEG-SO4 concentration rose in about 30 min to a new plateau level which was maintained during a 4 h period of bilateral hind-limb ischaemia and then rose further when the circulation to the limbs was restored. After about 2 h hind-limb ischaemia the concentration in the hind-brain, particularly in the caudal half, rose progressively and this rise continued when the tourniquets were removed after 4 h. Limb ischaemia did not affect the MOPEG-SO4 concentration in the cerebellum but the concentration rose in the cerebrospinal fluid. Attempts to study the production of MOPEG-SO4 in more detail by inhibiting its transport from the brain with probenecid were not helpful and reasons are given for thinking that probenecid is not a useful tool for this type of  investigation. The results are considered to provide further evidence that trauma activates ascending and descending pathways which arise from the noradrenergic nerve cells in the hind-brain.


Release of exqenous glycine in the pigeon optic tectum during stimulation of a midbrain nucleus. A pathway having an affinity for glycine has been investigated in the pigeon optic lobe; it originates in the nucleus isthmi pars parvocellularis (Ipc) and terminates in the tectum, In an attempt to obtain evidence that glycine plays a role as a transmitter in this system, the effect of electrical stimulation on release of labeled substances previously injected in the tectum was tested. By perfusing the upper strata of the optic tectum with a push-pull cannula the release of radioactive glycine was shown to be markedly increased by electrical stimulation of Ipc, but not by stimulation of other sites. Ipc stimulation did not affect the efflux of exogenous leucine or urea, whereas a GABA release was observed. With K+ (40 mM) stimulation all amino acids tested were released. It is suggested that the Ipc neuron terminals in the tectum take up glycine and release it upon stimulation of the Ipc nucleus.


Developmental changes in brain glycoproteins. During the postnatal development of rat brain there are large increases in the concentration of brain glycoproteins. Between 1 and 30 days the greatest changes (70-100%) take place in the levels of glycoprotein mannose, galactose and glucosamine, accompanied by smaller increases (35-55%) in sialic acid and fucose. By 30 days of age levels of brain glycoproteins are within 5% of the adult values. Analyses of the molecular size and composition of glycopeptides prepared from brains of 1- and 30-day-old rats lead to the conclusion that during postnatal brain development there is a preferential synthesis of a distinct population of glycoproteins containing oligosaccharides consisting predominantly of glucosamine, mannose and galactose. These oligosaccharides therefore have a large 'core' segment and a relative deficiency of the characteristically terminal sugars, fucose and sialic acid. In very young rat brain there are also large amounts of a metabolically stable form of glycogen or limit dextrin which accompanies the glycopeptides through the usual methods involved in their preparation from brain glycoproteins. The concentration of this glucose polymer decreases by 93% within 30 days after birth, but its presence even in adult brain is a likely explanation for the numerous reports of small amounts of glucose in brain glycopeptides and glycoproteins.


Laminar patterns of geniculocortical projection in the cat. The cortical afferents from individual laminae of the dorsal lateral geniculate nucleus (LGN) were studied using both light and electron microscope autoradiography. In area 17, the A geniculate laminae (A and A1) had two main bands of projection, one extending from the bottom of IVc to the deepest cells in layer III, and one in layer VI. The C geniculate laminae projected in two dense bands to the upper and lower borders of layer IV, thus bracketing the A laminae projection, though with some overlap. In addition, the C laminae projected to the superficial half of layer I, which the A laminae did not. Conversely, while the A laminae projected to layer VI, the C laminae did not. The two sets of laminae also showed differences in the areas to which they projected. The A geniculate laminae projected to areas 17 and 18, whereas the C geniculate laminae had a more extensive projection, including areas 17, 18, 19 and other areas on the suprasylvian gyrus. The laminar organization of the projection to area 18 was similar to that found in area 17. At the electron microscopic level the geniculate terminals were found to make Gray's type 1 synapses, for the most part onto dendritic spines. Labeled terminals were found in all the projection bands seen in the light microscope. The implications of these findings on the connectivity of cells in layer IV are discussed. The presence of labeled terminals in layer VI, which contains the cells of origin of the corticogeniculate pathway, suggests that the recurrent loop to the LGN is mediated monosynaptically. Finally, the afferents from each geniculate lamina were found to be segregated into patches, about 500 mum wide, which probably form the anatomical basis for ocular dominance columns.


The binding properties and regional ontogeny of receptors for alpha-bungarotoxin in chick brain. The subcellular distribution, binding kinetics, pharmacologic properties and regional ontogeny of binding sites for alpha-[125I]bungarotoxins (alpha-[125I]BT) were studied in preparations of chick brain. Almost 95% of the specific binding was found in a 20,000 X g pellet. Two binding components were found, one with high (half-saturation at 1.5 X 10(-9) M) and another with low affinity for the toxin. The rate constants of association and dissociation of the toxin for the high-affinity site were found to be 3.5 X 10(4) M-1 - sec-1 and 3.8 X 10(-5) sec-1 (tau1/2 = 5.1 h, respectively). These data yielded a K alpha value of 1.1 X 10(-9) M. Nicotinic, but not muscarinic ligands were potent inhibitors of toxin binding at the high-affinity site. Thus, as in muscle, the binding site for toxin in chick brain appears to have the properties of a nicotinic acetylcholine (ACh) receptor. The ontogeny of the alpha-BT/ACh receptor was studied using homogenates of both whole brain and of discrete brain regions. In brain stem, optic lobe and cerebellum specific binding reached maximum levels in ovo and then decreased by maturity to values of 10,22 and 4.5 fmoles/mg protein, respectively. In contrast, whole brain and cerebral hemispheres reached plateau levels in ovo of 17 and 10 fmoles/mg protein, respectively. Major increases in total receptor number per region appeared in ovo between days 12 and 19 in brain stem and cerebellum, days 12 and 15 in optic lobes, and days 15 and 19 in hemispheres. The hemispheres were the only region to show a continued increase in total binding after hatching (3-fold increase by maturity). These findings are interpreted with respect to the development of chick brain and a model is suggested for the relationship between receptor ontogeny and neuronal differentiation and maturation.


Action of amino acids and convulsants on cerebellar spontaneous action potentials in vitro: effects of deprivation of C1-, K+ of Na+. (1) The inhibition of spontaneous action potentials in guinea pig cerebellar cortex slices by GABA, glycine, taurine and beta-alanine is maintained when C1- in the superfusion medium is almost completely replaced by NO3- or I-('permeant' anion), but the inhibition decreases in magnitude with repeated application of the amino acid. Replacement of C1- by sulfate or isethionate ('impermeant' anion) causes a conversion of inhibition by these amino acids to excitation. The initial excitation which is sometimes seen with these inhibitory amino acids in high C1- media is abolished when C1- is replaced by either permeant or impermeant anions. (2) Reduction of K+ in the medium causes an increase of inhibition by the inhibitory amino acids in the presence of high C1- and reduction of excitation when C1- is replaced by impermeant anion. (3) Excitation by GABA in impermeant anion (low C1-) media  is unaffected by reduction of Na+ in the media by 50% but excitations by glycine, taurine, beta-alanine and L-glutamate are greatly reduced. (4). Excitation by GABA in impermeant anion (low C1-) media is abolished by picrotoxin and bicuculline which both suppress inhibition by GABA in a high C1- medium. Strychnine suppresses the effects of glycine, taurine and beta-alanine in either a low or high C1- medium. Bicuculline blocks the inhibitory effect of these three amino acids in a high C1- medium but does not affect their excitatory effects in a low C1- medium. (5) These results are consistent with the hypothesis that the inhibitory amino acids, GABA, glycine, taurine and beta-alanine, cause inhibition via increase of C1- (and perhaps K+) permeability and that glycine, taurine and beta-alanine also interact with strychnine-sensitive receptors mediating (perhaps indirectly) increased permeability to Na+ and, therefore, excitation in low C1- media.


Effects of reciprocal forebrain transplantation on motility and hatching in chick and duck embryos. Effects of reciprocal forebrain transplantation on the embryonic motility and the hatching behavior in the chick and the duck embryos were studied. The forebrains were transplanted before the establishment of circulation. The grafted tissue formed the telencephalon, diencephalon, eyes, upper beak and part of the cranium. Data indicate that the size of the forebrain has no significant influence on the early embryonic motility (Type I and II) in the chick and the duck embryos. The initiation and maintenance of the pre-hatching behavior (Type III motility) does not reside in the forebrain. The final stage of hatching (climax) on the other hand may be controlled by the forebrain.


Evidence for the existence of a raphe projection to the substantia nigra in rat. The effect of electrical stimulation of the median raphe nucleus on the activity of spontaneously firing single neurones in the substantia nigra and mesencephalic reticular formation (MRF) has been investigated in urethane anaesthetized rats. Depression of activity was the predominant effect observed although this was sometimes accompanied by periods of excitation. Some neurones were only excited. The latency of inhibition of substantia nigra neurones was constant whereas that of MRF neurones was more variable. Microiontophoretically applied 5-hydroxy-tryptamine (5-HT) and dopamine (DA) produced mainly inhibition of neuronal activity, but excitation and biphasic effects were also seen. There was a good correlation between the direction of neuronal responses in the substantia nigra to median raphe stimulation and to the effects of 5-HT but not DA. Discrete electrolytic lesions of the median raphe nucleus were followed by a decrease in 5-HT but not GABA concentrations in the substantia nigra. In addition striatal 5-HT, GABA and NA concentrations were unchanged whereas striatal DA was increased. These observations strongly suggest that the substantia nigra receives a direct inhibitory input from the median raphe nucleus and this pathway uses a 5-HT-like neurotransmitter. This pathway probably contributes to the regulation of nigrostriatal dopaminergic transmission.


Attenuation of self-stimulation from substantia nigra but not dorsal tegmental noradrenergic bundle by lesions of sulcal prefrontal cortex. Rats that self-stimulated from electrodes implanted in either the substantia nigra pars compacta (SNC) or the dorsal tegmental noradrenergic bundle (DTB) received bilateral electrolytic lesions of the prefrontal cortex dorsal to the rhinal sulcus. Immediately after the lesions, animals with SNC electrodes (n = 9) showed significant and permanent reductions in self-stimulation rates. The average reduction in the SNC group was 67% of prelesion bar-pressing scores. In contrast, rats with DTB electrodes (n = 11) were not significantly affected by similar sulcal lesions. Subsequent examination of the brains for prograde degeneration using procedure I of Fink and Heimer 11 revealed a descending system of sulcal efferents that was very dense in the region of the SNC but only scattered in the area of the DTB. The close relation between the effects of sulcal lesions on self-stimulation and the resultant density of degeneration as a function of stimulation site is discussed in terms of the contribution of prefrontal cortex to self-stimulation in general, and of the implications for the catecholamine hypothesis of self-stimulation in particular.


Evidence that self-stimulation of the region of the locus coeruleus in rats does not depend upon noradrenergic projections to telencephalon. Rats with intracranial self-stimulation (ICSS) electrodes in the locus coeruleus and adjacent pontine tegmental structures received stereotaxically placed bilateral injections of 6-hydroxydopamine (4 mug/2 mul) into the mesencephalic trajectory of the dorsal tegmental noradrenergic bundle. The consequent depletions of norepinephrine in the cerebral cortices and hippocampi (96.7%) did not result in significant changes in ICSS. Thus, diencephalic and telencephalic noradrenergic projections of the locus coeruleus do not appear to be critical for the occurrence of ICSS from that nucleus or its surrounding region. Nor do these projections appear to be crucially involved in the enhancement of this ICSS by D-amphetamine. Rats in this study showed two-fold increases in responding following injections of D-amphetamine sulfate (0.5 mg/kg) both before and after the lesions of the dorsal tegmental bundle. These results suggest that the ascending projections of the locus coeruleus are not critically involved in ICSS of the dorsal pontine tegmentum.


Sensory and reflex responses to tooth pulp stimulation in man. Experiments have been carried out to investigate whether all tooth pulp afferent nerves are capable of producing pain. Monopolar and bipolar stimuli were applied to teeth in human subjects and sensory thresholds determined. EMGs were recorded from the masseter and the anterior digastric muscles. With stimuli up to three times the sensory threshold, no response could be detected in the digastric but at, or just above, the sensory threshold, inhibitory effects were produced in masseter muscle. The latency of the muscle response with bipolar stimulation was 18-22 msec. There was no evidence of stimulus spread to nerves outside the teeth. Bipolar and monopolar stimulation both produced the same sensation but this was not described as painful. It is concluded that some pulpal afferent nerves may not be capable of producing pain, and that the sensory and reflex responses at threshold were probably produced by the same fibres.


Neurite outgrowth from explanted Xenopus retina:  an effect of prior optic nerve section. Experimental conditions are described for the in vitro study of explanted eyes from embryos of Xenopus laevis and of retinas from older larvae. When eyes are explanted from embryos of stages 25-34, a rapid outgrowth of fibroblast-like and pigment cells is observed, upon which a neuritic outgrowth is eventually superimposed. Outgrowth from the retina of later stage tadpoles (50-54) is not seen until about a week following explantation and resembles the mixed cell outgrowth observed in whole eye explants from early stage embryos. If, however, the optic nerve of an older tadpole is cut 7 days prior to explantation, a purely neuritic outgrowth is seen from the previously denervated retina  within 1-3 days.


Axon regeneration following a lesion of the carotid nerve: electrophysiological and ultrastructural observations. Carotid nerves of the cat were crushed and allowed to regenerate in order to study the properties of regerating fibers and the role of carotid body parenchymal cells (glomus or type I, and sustentacular or type II) in the transduction of chemosensory activity. Such activity is reinitiated 6 days after the nerves are crushed close (1-2 mm) to the carotid body. The process of recovery is delayed when a crush is made at successively greater distances (5-6 and 10-12 mm) from the carotid body. Ultrastructural studies show that the  reappearance of nerve endings on the glomus-sustentacular cell complex coincides in time with the onset of chemosensory activity. The  regenerated nerve endings increase in size and number and appear normal by 48 days. Some barosensory activity can be elicited 6 days after a nerve crush close to the carotid sinus, but rhythmic barosensory discharges  only occur after the 21st  day when myelinated axons  reappear in the carotid sinus adventitia. Results suggest that recovery of chemosensory function depends on the reestablishment of apposition between regenerating carotid nerve fibers and parenchymal cells of the carotid body.


Visual cortical neurons influenced by the oculomotor input: characterization of their receptive field properties. A class of cells in cat visual cortex (area 17 and 18) had a tight correlation with spontaneous and electrically evoked PGO waves under reserpine. They tended to have high maintained activity and a large receptive field which was preferentially excited by fast moving slits. They were also direction selective and influenced through both eyes. For these cells, the selectivity for visual stimuli was dramatically altered in the presence of PGO waves induced by pontine stimulation. They were complex cells. A second class of cortical cells showed a moderate correlation with spontaneous PGO waves. Visually evoked activity of these cells was either excited or inhibited  by evoked PGO waves in response to pontine stimulation. A third class of cells, the majority, did not seem to have any correlation with PGO waves. The second and third classes of cells could be either one of the 3 main categories of visual cortical cells, predominantly simple cells in area 17 and complex cells in area 18. The present study provided further support to a previous proposal that PGO waves in the visual cortex, as neural correlates of saccadic eye movements, modulate specifically the ongoing activity of a selective type of cortical cell. A type of complex cell in the deeper layers is supposed to integrate visual and oculomotor inputs. It is hypothesized that the consequence of oculomotor inputs to the visual cortex is specified by the type of cells which receive oculomotor inputs, rather than by the nature of the inputs themselves.


Studies on cellular toxicity of bilirubin: effect on brain glycolysis in the young rat. (1) The levels of glycolytic intermediates in the brain tissue of  15-day-old homozygous and heterozygous Gunn rats were determined with or without novobiocin treatment in vivo, and the inhibitory effects of bilirubin on the glycolytic activity and the key glycolytic enzyme activities were investigated in vitro. (2) the pattern of glycolytic intermediate levels in the non-treated homozygotes compared with those in the non-treated heterozygotes  showed a significant increase of G6P and F6P,  and  decrease of GAP plus DAP. Enhancement of bilirubin concentration in the brain tissue of homozygotes by novobiocin treatment brought about a significant decrease of FDP, 3PG, Pyr and Lac, and a slight increase of G6P compared with the respective values on the treated heterozygotes. (3) the overall glycolytic activity with 2mM glucose as a substrate was significantly inhibited in vitro by 100 muM bilirubin at 3-4, 20 and 600muM NAD concentration, whereas with 0.15 mM glucose the inhibition was observed only at a concentration of 3-4muM NAD. The inhibitory effect of bilirubin (120-140 muM) on lactate formation with FDP as a substrate was also found at three different NAD concentrations. And the marked inhibition of PFK activity by bilirubin was observed at physiological concentrations of ATP  and F6P. (4) The present findings suggest that reduced rates of glycolysis might be involved in bilirubin encephalopathy.


Studies on the control of myelinogenesis. II. Evidence for neuronal regulation of myelin production. Tritiated thymidine has been used as a nuclear marker to trace the origin of Schwann cells, sited in the distal stump of a severed unmyelinated nerve, which are able to elaborate myelin around axons regenerating from an anastomosed proximal stump of a severed myelinated nerve. Two types of cross-anastomosis experiments were performed in young, adult rats: (1) the proximal stump of a myelinated sternohyoid nerve was labeled (5 mCi/kg body weight) selectively over a 4-day period of predetermined maximal thymidine uptake and two days later, after flushing the animal repeatedly with cold thymidine, the unmyelinated cervical sympathetic trunk was transected and its unlabeled  distal stump linked to the proximal stump of the labeled sternohyoid nerve; (2) the distal stump of an unmyelinated cervical sympathetic trunk was labeled selectively over a 5-day period of predetermined maximal uptake and two days later, after flushing with cold thymidine, the myelinated sternohyoid  nerve was severed and its unlabeled  proximal stump linked to  the labeled  distal stump of the cervical sympathetic trunk. The fate of the labeled cells in each type of anastomosis was determined 3 weeks later by autoradiography and liquid scintillation spectrometry. In the first type, a small amount of label had migrated from proximal stumps but labeled Schwann cells were not found in successfully anastomosed distal stumps. In the second type, labeled Schwann cells were seen in the cervical sympathetic trunk in association with myelinated and non-myelinated axons regenerating from the sternohyoid nerve. These data suggest that the presence or absence of myelin formation by a Schwann cell is controlled by some property of the axon with which it is associated. Putative mechanisms underlying neuronal control of myelinogenesis are discussed.


Morphological evidence of alteration in myelinstructure with maturation. The periodicity of the myelin sheath in glutaraldehyde carbohydrazide (GACH) embedded tissues from three 10-day-old and two 43-day-old mice was investigated with the electron microscope. The mean repeat period and number of repeats per fiber was measured in 31-89 fibers in the trapezoid bodies, olfactory tract and sciatic nerves. The mean period of the myelin sheaths in both the peripheral and the central nervous systems of the 10-day-old mice (15.1 +/- 0.07 nm (S.E.M.) and 13.4 +/- 0.09 nm respectively) are smaller (rho less than 0.001) than those of the adult mice (15.9 +/- 0.08 nm and 14.7 +/- 0.06 nm respectively). These differences may be related to the known differences in chemical composition of immature and mature myelin.


Effects of subfornical organ extracts of salt-water balance in the rat. The subfornical organ (SFO) is regarded as a neurosecretory structure but no information is available on the nature or biological effects of the secretory products(s). Supernatants of water homogenates of rat SFO were lyophilized and reconsittuted in artificial cerebrospinal fluid (CSF). Intracerebroventricular (IVT), but not subcutaneous, administration of this material to rats produced diuresis, natriuresis and kaliuresis in the following 8 h daylight period. During the overnight cycle, consummatory behavior and excretion of sodium and potassium were reduced. Similar responses were obtained after IVT administration of cerebellar cortex (CB) or large amounts of plasma. SFO, CB and cerebral cortex (CC) were incubated in potassium-enriched CSF to enhance release of secretory products. Urine volume was increased 8 h after IVT injection of SFO media; in the overnight cycle, food consumption, absolute urinary sodium and potassium, and [Na+-a1 were reduced. These effects were not produced by IVT injection of CC or CB media, or equal amounts of plasma proteins. Additional experiments demonstrated that choroid plexi and SFO effects were similar and that the active SFO material was dialyzable and thermal stable. These data suggest that SFO contains a water-soluble substance which is released into a posassium-enriched medium. The material is heat stable, has a relatively low molecular weight, and alters salt-water balance after injection into ventricular cerebrospinal fluid.


Regional concentrations of noradrenaline and dopamine in rat brain. The concentrations of noradrenaline and lopamine of 92 brain regions have been measured by a radiometric method which enabled discrimination between noradrenaline and adrenaline. Almost all brain regions investigated contained both noradrenaline and lopamine in measurable amount. However, both catecholamines appeared to be unevenly distributed. Very high dopamine concentrations were measured in the olfactory tubercle, the nucleus accumbens, the caudate nucleus and the rostral part of the medial forebrain bundle; the globus pallidus, the nucleus tractus diagonalis and the nucleus septalis lateralis were also very rich in dopamine. Outside the telencephalon the dopamine concentrations were rather low, except in the median eminence and the area tegmentalis ventralis (Tsai), an area corresponding to the A10 region. High noradrenaline concentrations were measured in most hypothalamic nuclei. Relatively high concentrations of this catecholamine were also measured in several mesencephalic (the ventral part of the central gray, the nucleus raphe dorsalis and the nucleus cuneiformis) and pontine (the locus coeruleus and the nuclei parabrachiales) regions. The highest noradrenaline concentrations in the medulla oblongata were observed in the A2 region and the nucleus commissuralis, which contained at least twice as much noradrenaline as did the more rostral part of the nucleus tractus solitarii.


Some effects of undernutrition on synaptic development -- a quantitative ultrastructural study. The development of synaptic junctions in rat occipital cortex has been studied at 7 and 20 days postnatal in control and undernourished animals. In addition, adult control cortex has been compared with cortex derived from animals undernourished until 35 days postnatal and then nutritionally rehabilitated. Emphasis has been placed on material stained with phosphotungstic acid (E-PTA technique) although osmicated material has been examined. The body weights of the undernourished animals were lower than those of their age-matched controls, the deficit at 20 days being 55%. The number of synaptic junctions per unit area of the molecular layer was lower in the undernourished animals at 7 and 20 days, the most prominent deficit being at 20 days. In an attempt to detect ultrastructural correlates of undernutrition, E-PTA stained synaptic junctions were divided into 5 types (A-E), based upon their presynaptic characteristics are reflecting varying degrees of maturity. During normal development the immature synaptic types, particularly type E, are predominant, giving way to the more mature types (A-C) as development proceeds. Undernutrition however, appears to disrupt this developmental sequence, with a higher than normal percentage of immature synaptic types present at the age studied. Nutritional rehabilitation rectifies the imbalance to a degree, the adult rehabilitated pattern resembling the 20-day control pattern. Preliminary examination of the 20-day osmicated material confirmed the deficit of synapses per area of tissue in the undernourished cortex. It  also revealed decreases in the number of vesicles per terminal unit area and in the internal area of the synaptic vesicles in the undernourished tissue.


The fine structure of the axons and growth cones of the human fetal cerebral cortex. The fine structure of axon cylinders and growth cones has been examined in serial sections through the marginal zone of the human cerebral cortex from 10 to 22 weeks of gestation. Neurotubules, mitochondria, agranular reticulum, coated vesicles, and synaptic vesicles both of the translucent and dense core variety are found throughout the axon cylinders. At periodic intervals along the axons, bulged-out regions display accumulations of either synaptic vesicles or transversely oriented neurotubules. Prominent, growth cone varicosities are encountered at the distal segment of the axon cylinders. In these, mitochondria, channels of both tubular and dilated agranular reticulum, dense core vesicles, and multivesicular bodies lie in a finely filamentous matrix. Processes characterized by their content of either agranular reticulum and synaptic vesicles or a finely filamentous meshwork are infrequently continuous with these varicosities. Dense membrane thickenings are associated with some varicosities and their processes. The ultrastructural features of the human fetal growth cones have been compared to growth cones previously described in other mammalian and submammalian species.