The outcome of adolescent school phobia. A hundred-and-twenty-five school phobic youngsters had been treated in a psychiatric in-patient unit for young adolescents of secondary school age over a seven-year period; a hundred of them were reviewed on average three years after discharge. About a third of cases were found to have improved little; they had persistent severe symptoms of emotional disturbance and continuing social impairment. Another third had improved appreciably and were affected by neurotic symptoms rather than social impairment. The remaining third had improved substantially or completely. School attendance difficulties had remained in about half of all cases. Subsequent difficulties in going to work were less pronounced. The best predictor of outcome was clinical state on discharge. High intelligence also emerged as a significant predictor of poor outcome. Five girls and a boy had already developed severe and persistent agoraphobic difficulties when reviewed. It was found that severe school phobia in early adolescence resembled adult affective disorders in some clinical features and in outcome.


School phobia in the children of agoraphobic women. As part of a survey of agoraphobic women in the general population, it was found that school phobia occurred in their children to a greater extent than would be expected. The average incidence in children aged 11 to 15 was 14 per cent. The women with school phobic children had had school phobia themselves to an undue extent.


Carcinoma of the renal pelvis: an analysis of the diagnostic problems in 23 cases. A series of 23 patients with carcinoma of the renal pelvis is presented. The different presentations are described and discussed, and the difficulties in establishing a preoperative diagnosis are considered. There were 3 squamous cell carcinomas in the series, all of them associated with renal stone and urinary tract infection.


Unoperated ruptured abdominal aortic aneurysms: a retrospective clinicopathological study over a 10-year period. A series is described of 41 cases of unoperated ruptured abdominal aortic aneurysm in 9894 consecutive autopsies performed in two large general hospitals in Glasgow between 1964 and 1974. The preceding clinical presentations are discussed. These show the difficulaties in diagnosing the condition correctly and quickly and the liability to confusion with other intra-abdominal conditions. The correct diagnosis was established before death in only 11 cases, it was suspected in 6 cases and was completely missed in 24 cases. Pathologically, all the cases were atheromatous and measured more than 5 cm in diameter, and the most common site of rupture was through the lateral wall. Resection would appear to have been technically possible without undue difficulties in the majority of the cases. An analysis of all the findings indicates the necessity for greater clinical awareness of this condition and its variable mode of presentation. Only in this way will early diagnosis and safer surgical intervention be possible.


A combined synchronous technique for the McKeown three-phase oesophagectomy. A combined synchronous technique is described for the McKeown three-phase oesophagectomy; it reduces operative time and allows a safer mobilization of the stomach into the neck.


Repair of epigastric incisional hernia.

Repair of epigastric incisional hernia. A 4-18 year follow-up of a series of epigastric incisional hernia repairs by a method using lateral relieving incisions of the anterior sheath of the rectus is presented. The practicality of operating through the repaired abdomen is shown. The possibility of performing this method of repair at the end of an operation through an existing incisional hernia is mentioned. The recurrence rate was less than 20 per cent.


The relationship between alcohol and head injury and its effect on the conscious level. The incidence of head injury has risen in recent years and now accounts for almost one-third of acute male surgical admissions to the Western Infirmary, Glasgow. A prospective study has established that in Glasgow alcohol is a major associated factor, 62% of males and 27% of females having detectable levels in the blood (greater than 5 mg/100 ml); in these patients the mean level was 193 mg/100 ml in men and 165 mg/100 ml in women. The alcohol level was significantly higher in patients who had had 'a fall under the influence', or had been the victims of an assault, than in those involved in traffic or other accidents. This suggests that alcohol may be an important contributroy cause of head injuries in this city. Depression of the conscious level occurred at blood alcohol levels aroung 200 mg/100 ml, but a significant number of patients in coma had a serious head injury.


Gallstone obstruction and perforation of the duodenal bulb. A case of gallstone ileus is presented in which the stone became impacted in the first part of the duodenum and then caused perforation at the site of impaction. This is only the second published British case of gallstone impaction at this site. Perforation of the duodenum by a gallstone has not previously been recorded. The clinical and radiological features of this case are discussed.


Decreased trypsin and bile acids in ileal fistula drainage during the administration of a chemically defined liquid elemental diet. Ten patients with a well-established ileostomy were studied in a metabolic ward and alterations in ileostomy contents of trypsin and bile acids were measured during the ingestion of an elemental diet. After a 4-day control study the patients were given an elemental diet as the sole nutritional source for a 10-day period. For the last 3 days of the study an additional 2 litres of water were consumed with the elemental diet. The mean daily faecal output for the group during the control period was 578 +/- 300 ml, and during administration of the elemental diet the fistula output fell to 418 +/- 190 ml (P less than 0-02) and there was a fall in the concentration of sodium in the ileal fluid (104-7 +/- 22 mEq/l to 80-2 +/- 25 mEq/l, P less than 0-01). For the group as a whole there was a fall in the concentration of trypsin (0-671 +/- 0-53 i.u./ml to 0-554 +/- 0-56 i.u./ml, P less than 0-025) and bile acids (0-911 +/- 0-56 mmol/ml to 0-662 +/- 0-53 mmol/ml, P less than 0-005) in the ileal excreta. Althoug the concentration of amylase in the ileal fluid rose, the total output was not altered. Oral administration of an additional 2 litres of water did not later the concentration of trypsin or bile acids in the ileal fluid. It is concluded that elemental diet ingestion produces changes in ileal fistula output which are of benefit to the patient with an enterocutaneous fistula. Output from the fistula of fluid and electrolyte is less and the corrosive nature of the discharge is reduced.


Assessment of the results of surgery for varicose veins. Fifty-six patients undergoing primary surgery for unilateral varicose veins by a standardized Trendelenburg procedure were reviewed postoperatively by a panel of three observers. Agreement between the observers was high in assessing symptomatic response (up to 98%), but only moderate in evaluation of any visual changes in affected legs (60%). Moreover, intr-observer agreement comparing symptomatic response and visual impression was very low (30-4%). It is suggested that inter-series comparisons should be made solely upon the response of specific symptoms to treatment.


Self-retaining chest drainage tubes.

Self-retaining chest drainage tubes. A self-retaining chest drainage tube together with a special introducing trocar and cannula is described. The tube has been designed to overcome the disadvantages of existing conventional chest drainage tubes.


The value of the leucocyte count in the diagnosis of acute appendicitis. Total and differential leucocyte counts were performed on 175 patients with a provisional diagnosis of acute appendicitis. Ninety-six per cent of patients with acute appendicitis had either an abnormal total or differential leucocyte count. Four of 24 patients operated on with a normal leucocyte count had acute appendicitis. It is concluded that leucocytosis of above 10 000/mm3 or a differential in excess of 75% neutrophils supports the clinical diagnosis of acute appendicitis and that routine estimation of the leucocyte count is a useful investigation. While a normal leucocyte count does not exclude even a perforated appendicitis, such a count should prompt further review of the diagnosis, especially in the presence of an atypical history or minimal physical signs.


An unusual case of growing fracture of the skull in childhood. A case of growing fracture of the skull with an unusually large traumatic meningocele in a child is presented.


Hip pain as a presenting symptom of acetabular metastasis. Three case histories are presented in which each patient developed pain in the hip which was caused by an acetabular metastasis. Resection of an adenocarcinoma of the colon had been performed previously and in only 1 patient were radiographic changes or abnormal gamma-scan pictures obtained.


Diverticular disease: three studies. Part I--Relation to other disorders and fibre intake. The fibre intake of 40 patients with diverticular disease was compared with that of 80 age- and sex-matched controls. The daily crude-fibre intake of the patients was significantly lower than that of the controls, and the incidence of haemorrhoids, varicose veins, hiatus hernia, gall stones, and abdominal hernias was significantly higher than in the control group. These findings suggest that a fibre-depleted diet may be a causative factor in diverticular disease and several other conditions.


Diverticular disease: three studies. Part III - Metabolic effect of bran in patients with diverticular disease. Patients with diverticular disease were given about 24 g bran daily for at least six months. After treatment the oral glucose tolerance curve fell, faecal fat excretion increased, the serum lipoprotein pattern was altered, urinary calcium excretion was reduced, and the serum folate level fell. These changes were not considered to contraindicate the use of bran in the treatment of diverticular disease.


Thyroid disease and sebaceous function.

Thyroid disease and sebaceous function. Sebum excretion rates (SER) were measured before and after treatment in patients with hypothyroidism and thyrotoxicosis. The mean SER in the former was significantly less than that in normal controls but there was no correlation between SER and the severity of the disease as indicated by serum thyroid-stimulating hormone levels. After treatment with L-thyroxine the SER increased but remained subnormal. By contrast the SER was not increased in patients with thyrotoxicosis and it was unaffected by treatment. The human sebaceous gland seems to respond to thyroid hormone mainly in the hypothyroid range.


Vertebral artery occlusion and oral contraceptives. If vertebral artery occlusion occurs in degenerative arterial disease it is almost invariably left-sided, but in vertebral artery deficiency syndromes associated with oral contraceptives a striking preponderance of right-sided involvement has been shown. This observation adds support to the view that causes other than changes in the wall of the vessel at the site of occlusion must be sought as an explanation of the occlusion.


Extrinsic allergic alveolitis in Scottish maltworkers. In a survey of respiratory disease in the Scottish malting industry 5.2% of employees were found to have symptoms of extrinsic allergic alveolitis. In most cases the disease was mild and not associated with any serious respiratory disability. It was significantly less common where modern mechanical methods of malting were used. Mycological and serological studies suggested that it was usually caused by a type 3 allergic reaction to Aspergillus clavatus.


Epidermal architecture, growth, and metabolism in acromegaly. Epidermal architecture, replication, and anabolic activity were studied in six patients with acromegaly. Patients with acromegaly had significant larger viable epidermal cells than controls. The rates of incorporation of tritiated thymidine, proline, and histidine into skin slices in vitro was also significantly increased in acromegalic patients. The mean autoradiographic labelling indices after intracutaneous injection of triated thymidine were 8.4% in the acromegalic patients and 5.1% in the control group. None of the changes observed could be closely correlated with levels of serum growth hormone.


Pseudomonas aeruginosa in hospital pharmacies. The environments of hospital pharmacies and the preparations made in these pharmacies were examined for Pseudomonas aeruginosa. This organism was widely distributed in the pharmacies and was isolated from 9% of preparations. In 11 instances strains of Ps aeruginosa from the preparations bore a close resemblance to strains previously found in the pharmacy environments.


Renal disease in rheumatoid arthritis.

Renal disease in rheumatoid arthritis. N-Acetyl-beta-D-glucosaminidase (NAG) is a sensitive indicator of renal damage. When the urinary NAG levels of 60 patients with rheumatoid arthritis (RA) were measured a highly significant difference was detected between the mean urinary NAG excretion of the patients with RA (341 +/- 294-92 nmol h-1 mg creatinine-1) and that of 60 matched controls (67-53 +/- 16-93 nmol h-1 mg creatinine-1). In 10 patients studied no correlation could be shown between the urinary NAG levels and levels in either serum or synovial fluid. A significant positive correlation was noted between urinary NAG excretion and disease activity as estimated by the Lansbury activity index, the Ritchie articular index, and the haemaglobin level. An abnormally raised urinary NAG excretion was detected in eight out of 20 previously untreated patients with RA, which suggested that the rheumatoid process may affect renal function.


Detection of deep vein thrombosis by Doppler angiography. A new technique, ultrasonic Doppler angiography, was used to examine the deep veins in 50 legs of 40 patients in which deep vein thrombosis was suspected. The results were compared with those of venography. The ultrasound method detected 30 out of 32 venographically confirmed thrombi and showed 17 out of 18 venographically proved normal deep veins. It was equally effective in detecting partial as well as totally occluding thrombi.


Hormonal assessment before and after vasectomy. Animal experiments have suggested that vasectomy may disturb the endocrine function of the testis. To explore this possibility in man blood was obtained from 277 men who had undergone vasectomy up to six years earlier or who were about to undergo the operation. Mean plasma testosterone concentrations seemed to be slightly higher in those who had undergone vasectomy than in the preoperative group, although this difference was not statistically significant. There was no significant difference between these two groups in the concentrations of luteinising hormone, follicle-stimulating hormone, prolactin, or oestradiol.


The retroverted gravid uterus and its effect on the outcome of pregnancy. Among 1954 pregnant women who booked before the end of the 14th week of gestation the uterus was retroverted in 220 (11.2%). The incidence of bleeding in early pregnancy and spontaneous abortion was significantly higher in the retroverted group. Only three patients (1.4%) with a retroverted gravid uterus developed acute retention of urine. Patients with retroverted uteri did not have a higher incidence of previous infertility, nor any increase in the incidence of common obstetric abnormalities.


Lysozymuria in diabetes.

Lysozymuria in diabetes. A reversible lysozymuria indicative of proximal tubular damage to the kidney was found in three out of five patients with diabetic ketosis, and a persistent lysozymuria was found in many patients with diabetic nephropathy. There was no relation between lysozymuria and the degree of proteinuria, and lysozymuria was not due to urinary tract infection. The degree of lysozymuria could be used to assess the severity of diabetic nephropathy.


Public attitudes towards kidney transplantation. A representative sample of 500 members of the public was interviewed about kidney transplantation. The survey showed that despite widespread awareness of the need for kidney donors only 4.4% of the respondents had completed a donor card. The small percentage holding kidney donor cards appears to reflect a failure to inform and motivate the general public. There was no evidence of any widespread objection to the procedures involved in obtaining cadaver kidneys, but there was strong objection to the introduction by law of an "opting out" system. The findings suggest how the numbers of potential donors could be increased without changing the law as regards consent to donation.


Randomised controlled trial of computer-held medical records in hypertensive patients. A total of 278 hypertensive patients in three clinics were randomly allocated to have their medical records held in a computer system (136) or on standard hospital notes (142). For the computer system the doctor completed a structured input form, and the information on symptoms, physical findings, and diagnoses was more complete than that in the standard notes. This resulted in certain symptoms and risk factors being recognised more often when the computer system was used. The hypertension clinics' routines were not disrupted by the introduction of a computer-held system, and follow-up consultation times were not affected by the type of records kept, although the first consultation took eight minutes longer when computer documents were completed. The patients remained in the trial for one year and clinical management was assessed from blood pressure control, drop-out rates, and the frequency of performing investigations. These estimates of management showed no significant difference between the two groups, but the attempt to tailor the computer system to help management made the system acceptable to the doctors using it. The computer system continues to be used and is providing data for research into hypertension.


Comparative double-blind study of cephalexin and co-trimoxazole in urinary tract infections. Treatment with cephalexin 1 g twiec daily and cotrimoxazole 2 tablets twice daily was compared in a double-blind, randomised study of 100 women with urinary tract infections. CO-trimoxazole gave a significantly higher cure rate compared with cephalexin two and six weeks after the one-week course of treatment. The higher failure rate with cephalexin was not related to the age of the patient, presentation, pyelographic appearances, or type of organism in the initial infection. Among the failures all but one of the organisms were sensitive to cephalexin. With the dosage regimen and duration of treatment used in this study cotrimoxazole appears to be superior to cephalexin in the management of acute urinary infections.


Recurrent haematuria: role of renal biopsy and investigative morbidity. The usefulness of renal biopsy in investigating unexplained haematuria was assessed by a study of 33 adults referred consecutively with this syndrome. Unequivocal abnormalities were seen on light microscopy or immunofluorescence in 31 of the 33 specimens of renal tissue examined. In 18 patients deposits of IgA were present in the mesangium. Loin pain occurred in only two of the 18 patients with mesangial IgA deposits, compared with 11 of the 15 patients without these deposits. Seven of the nine women in this series had had loin pain compared with only six of the 24 men. Thus a woman with loin pain and haematuria was not likely to have mesangial IgA nephropathy but this was found in 14 of the 18 men with unexplained painless haematuria. Failure to appreciate the role of renal biopsy in the investigation of unexplained haematuria may result in unnecessary radiology, considerable morbidity, and even in unjustified nephrectomy.


Rapid glucose absorption in Arabs in Saudi Arbia compared with that in Africans in Zambia. Glucose absorption rates in 14 Arabs in Saudi Arabia were determined by a jejunal perfusion technique and compared with those in 18 Africans in Zambia. None of the subjects had clinical evidence of systemic infection, gastrointestinal disease, malnutrition, or diabetes mellitus. The mean absorption rate was significantly higher in the Arabs. This was associated with a higher incidence of subclinical chronic systemic infection in the Africans. Other factors possibly responsible for the difference, including genetic difference, have, however, not been excluded.


Lumbar spondylosis and neuropathic bladder: investigation of 73 patients with chronic urinary symptoms. Seventy-three patients presented with either chronic urinary symptoms such as incontinence, retention, and recurrent urinary infection or chronic low back pain and neurogenic claudication. Lumbar spondylosis was considered to be the major cause of the urological and skeletal symptoms; the diagnosis of a neuropathic bladder depended as much on features in the history as on the results of urological and neurological investigations. The preoperative demonstration of significant lumbar spondylosis was often difficult, but decompressive laminectomy in 34 patients produced relief of urinary symptoms and improvement in bladder function in 75%.


Mortality of bereavement.

Mortality of bereavement. The death rate of a group of 87 widowers and 279 widows was followed for two years from the death of their spouses. The life tables for England and Wales 1970-2 indicated that the expected number of deaths would be 6 men and 11 women. The actual numbers (9 men and 11 women, 5.5%) were not significantly different, though there were more widowers' deaths during the first six months of bereavement. There was no significantly greater mortality among those whose spouses had died in hospital; but when this had occurred the health of the second spouse was likely to have been poorer than that of those whose spouses had died at home.


Hippocampal theta rhythm. I. Depth profiles in the curarized rat. Systemic injection of curare changes the depth profile of theta rhythm seen in the hippocampus of the freely moving rat. Under curare, dorsoventral microelectrode advancement reveals the presence of a sudden phase reversal and null occurring at the level of the stratum radiatum of CA1. Further advancement reveals the presence of an amplitude peak in the vicinity of the hippocampal fissure. In addition to the change in depth profile, curare alters the relationship between the amplitudes of the two phasereversed components of the theta rhythm. The change in theta rhythm brought about by curare outlasts the paralytic effect of the drug.


Further studies on the cortical connections of the Tegu lizard. The efferent fiber connections of the caudal half of the cerebral cortex, the lateral cortex and the pallial thickening were studied using the Nauta-Gygax and Fink-Heimer techniques. The following observations were made, (1) In the caudal half of the hemisphere corticoseptal and corticohypothalamic fibers originate from the small-celled part of the mediodorsal cortex and the thickened caudal part of the dorsal cortex in its whole mediolateral extent. (2) The dorsal cortex in the middle of the hemisphere projects by way of both the pre- and postcommissural fornices. Its rostral pole distributes its fibers solely to the postcommissural fornix, whereas its caudal part projects via the precommissural fornix. (3) The posterior pallial commissure carries fibers that arise caudally in the small-celled part of the mediodorsal cortex and terminate in the contralateral ventral cortex. (4) Projections to the dorsal striatum originate from the lateral cortex, the dorsal cortex and the superficial portion of the pallial thickening. In addition, the latter two zones project to the nucleus accumbens. (5) The deep portion of the pallial thickening projects to the ventral striatum.


Brain stem neurons that fire selectively to a conditioned stimulus for shock. In the brain stem reticular formation of rats, 10 neurons (1 in each of 10 animals) were found that responded by an increase in activity to a CS paired with foot shock but not to a neutral CS nor to a CS signalling the delivery of water to a thirsty rat. Nine of these neurons showing a conditioned response to shock (CR-S cells) were clustered in the region of nucleus pontis caudalis; the other CR-S cell was localized to nucleus gigantocellularis. The possibility that the increase in firing to the CS for shock was an unconditioned response to the specific stimulus used as this CS was controlled for. No correlation was observed between the activity of CR-S cells and gross movements of the rat. The data suggest that neurons in the pontine reticular region of the brain stem may participate in the reaction of a rat to an aversive situation such as fear.


Stimulation of rat medial or sulcal prefrontal cortex during passive avoidance learning selectively influences retention performance. Low-level unilateral electrical stimulation was delivered during passive avoidance learning through a bipolar electrode to the prefrontal cortex of the adult albino rat. No brain stimulation was applied during a retention test measured 24 h later. Ventromedial prefrontal cortex stimulation produced retention impairment over and above that observed with chronic electrode implantation. Sulcal cortex stimulation, in contrast, actually attenuated the retention deficit produced by chronic implantation in the sulcal cortex. Stimulation of an afferent common to both prefrontal regions, the dorsomedial thalamus, resulted in retention disruption, but stimulation of another common afferent, the locus coeruleus, did not. Acquisition of the inhibitory response was not affected by stimulation of any of the above brain regions. The present results demonstrate, again, that the functional role in memory of particular brain regions can be dissected by low-level electrical stimulation. The functional separation of rat sulcal and medial cortices revealed by the effects of stimulation suggests that these prefrontal subfields subserve different functions in the information storage process.


Effects of glutamic acid relatives on the electrical activity of an identified molluscan giant neurone (Achatina fulica Férussac). Effects of glutamic acid and its relatives were examined on the electrical activity of two kinds of neurones (the PON, periodically oscillating neurone, and the TAN, tonically autoactive neurone) identified in the suboesophageal ganglia of an African giant snail, Achatina fulica Férussac. L- and D-Glu, L-Asp, Gly and beta-Ala did not show any effect on the two neurones. However, beta-hydroxyglutamic acid (BHGA) showed a remarkable inhibitory effect on the PON. Erythro-L-BHGA had the strongest effect of these stereoisomers, and the critical concentration of this substance to produce the effect was 10(-6)-3 X 10(-5) g/ml (6-18 muM) when administered in the bath application. We confirmed by the microdrop application that erythro-L-BHGA directly hyperpolarized the PON neuromembrane. When the curve of current-voltage relationships (I-V curve) of the PON neuromembrane measured under erythro-L-BHGA at 10(-5) g/ml (61 muM) was superimposed on the curve of the normal state using the firing level as the common standard, these two curves showed concordance in a wide range of membrane polarization level. This concordance implies that the membrane resistance was maintained normally under erythro-L-BHGA at this concentration. A higher concentration of 10(-4) g/ml (0.61 mM) of this substance caused a decrease of PON membrane resistance and a remarkable elevation of its firing level. The TAN was not sensitive to BHGA, but sensitive to GABA and its derivatives.


Anatomical, physiological and biochemical studies on the cerebellum from mutant mice. III. Protein differences associated with the weaver, staggerer and nervous mutations. The protein composition of subcellular fractions of the cerebella of normal and weaver, staggerer and nervous mutant mice and of X-irradiated rats are studied by polyacrylamide gel electrophoresis in sodium dodecyl sulphate. The patterns observed are compared with those of granular and Purkinje cells purified from rat cerebella. In particulate fractions from weaver and X-irradiated rat cerebella, several protein bands are missing. These bands are present in purified rat granular cells. The most obvious deficit concerns a nuclear protein of apparent molecular weight 30,000, presumably the F1 histone. In these agranular cerebella the total DNA content is approximately 7 times lower than in the control animals and the DNA to protein ratio decreases approximately by a factor of two. In the cerebella from homozygous staggerer and nervous mutant mice, where the Purkinje cells are either abnormal or absent, a protein of apparent molecular weight 400,000 is markedly reduced. This membrane-bound protein is present in preparations of purified Purkinje cells.


Single unit study of binaural interaction in the auditory cortex of the chinchilla. The primary aim of this investigation was to systematically compare for various stimulus conditions the relative influences of contralateral and ipsilateral acoustic stimulation on cortical single units in an unanesthetized preparation and to study the effects upon single unit responses of the dominant stimulus cues for sound localization--interaural intensity difference (deltaI) and interaural time difference (deltat). Recordings were obtained from 133 units in chinchillas immobilized by gallamine triethiodide. All units were found to be influenced by input from both ears. Unit thresholds for contralateral stimulation were lower and more discharges were elicited than for ipsilateral stimulation over a range of intensities from unit threshold intensity to 80 dB sound-pressure level. A predominance of contralateral influence was also observed when the number of stimulus-evoked discharges was plotted as a function of the deltaI or deltat. For 62% of the deltaI functions maximal responsiveness occurred for binaural stimuli that were more intense at the contralateral ear. Similarly, of the 36 units that showed sensitivity to deltat parameters for tone stimuli, 22 (61%) were maximally responsive at the contralateral-leading deltat intervals. For click stimuli, maximal responsiveness for all 21 deltat-sensitive units also occured for contralateral-leading stimuli. Certain observations in the study question the generality of the hypothesis that a particular cell invariantly encodes a specific deltat, i.e., that cells have 'characteristic delays'. First, most units tested at more than two frequencies showed maximal responsiveness at different deltat intervals depending upon stimulus frequency. Second, the deltat intervals for maximal responsiveness for half of the units tested were greater than the maximal interaural delays the animal could encounter naturally. Third, deltat functions from the same unit for click and tone stimuli showed poor correspondence. These findings suggest that the encoding of interaural time and intensity might depend on an inter-hemispheric comparison of the activity of neural populations as originally proposed by von Bekesy.


Thalamic mechanisms that process a temporal pulse code for pain. The sequential ordering of spikes emitted by single thalamic neurons which respond to noxious stimulation was studied using rats anesthetized with a mixture of alpha-chloralose and urethane. An electrical stimulus applied to the sciatic nerve contralateral to the thalamic recording site fired single thalamic SII neurons with a short latency spike burst and with long latency spikes which occurred at relatively fixed intervals. On repetition of stimulation, the short latency spike burst formed a high amplitude peak on sequential spike density histograms (I of Fig. 2B); the long latency spikes formed peaks of relatively low amplitude (M1, M2, M3 of Fig. 2B). Histograms of touch and light pressure relay neurons found within the thalamic SII differed conspicuously from that of Fig. 2B. Further experiments revealed that the I peak contained frequency coded information about the stimulus intensity, whereas the M peaks with their temporal relationship to the I peak coded information pertaining to a particular sensory modality. The M peaks are formed by timed firing in a positive feedback loop found between the thalamic SII and the nucleus centrum medianum-nucleus parafascicularis (CM-Pf) neurons. Consequently, the M peaks can be abolished without losing the I peak by a lesion placed in a portion of the CM-Pf complex or by the administration or morphine which is able to disorganize the timing mechanism of the feedback loop. Therefore, it is reasonably certain that the modality coded by the M peaks is pain.


Electrophysiological identification of pontomedullary reticular neurons directly projecting into dorsal column nuclei. In cats 'encephale isole', cerebellectomized and curarized, neurons projecting from the bulbopontine reticular formation to the cuneate nucleus were identified by stimulating their axons in this nucleus by means of Eide micropipettes and by recording both field potential and antidromic responses from single somata in the nucleus gigantocellularis. Of 130 neurons responsive to cuneate stimulation, 17 (12%) were found that were antidromically activated. The small proportion of antidromic responses might reflect the small size of the projection pathway. However, there are reasons to believe that a certain number of neurons might have been missed because of biasing factors introduced by the microstimulation technique. Neurons that were activated orthodromically were also observed, responding after latencies spread over rather wide ranges. The possible pathways for this activation are discussed.


Localization of function in corpus callosum: tactual information transmission in Macaca mulatta. Different portions of the corpus callosum were transected in 28 juvenile rhesus monkeys. These animals were then taught a tactual roughness discrimination task while using their right hands and tested for transfer of training while using their left. Animals with some part of the posterior body region of the corpus callosum preserved exhibited intermediate or high levels of transfer of training. Animals with other portions of the commissures preserved, including the splenium, the anterior body, the genu, and/or the anterior commissure but with the posterior body region transected generally failed to show such transfer. It is concluded that tactual information is transmitted between the hemispheres through the posterior body region of the corpus callosum.


Electrophysiological and behavioral effects of transcortical polarizing current: comparison with the behaviorally determined characteristics of learning. Passage of polarizing current through the cerebral cortex, with the anode at the surface (Anp), produces neurophysiological changes which may be related to those which occur during learning. This relationship was evaluated at the visual cortex of unanesthetized, Sprague-Dawley rats, under a number of experimental conditions, with chronic light flash (LF)-evoked electrocortical response recording and LF-shock avoidance. During experimental treatments electrophysiologically studied animals received either 30 paired presentations of Anp and LF or parametrically equal, unpaired presentations; behaviorally studied animals received either these treatments or 30 presentations of LF alone. Each LF presentation contained 15 LF at the rate of one/sec. Anp presentations consisted of a 15-sec rise of current from 0 to 9 muA/sq.mm, 15 sec of steady 9 muA/sq.mm, and a 15-sec period of current decrease from 9 back to 0 muA/sq.mm. Each presentation was separated from the next by a randomized interval of 45-120 sec. Paired Anp and LF produced large waves (50 muV or greater) in the late negative phase of the evoked response. These waves appeared towards the end of pairings, were evident in recordings made 48 h after pairings and again diminished, but rapidly reappeared when pairings were reintroduced. Anpp and LF pairings also produced a 55% decrease in the number of trials needed to reach criterion on the LF-shock avoidance task as compared to the performance of the group treated with LF alone. Unpaired Anp and LF had no discernable electrophysiological or behavioral effects.


Anesthetic-dependent field potential interactions in the olfactory bulb. The effect of anesthetic upon olfactory bulb field potentials evoked by paired stimuli to the lateral olfactory tract (LOT) was examined in male rats. Experiments were performed on rats anesthetized with urethane or barbiturates and on unanesthetized rats with midcollicular brain stem sections. Anesthetic doses of urethane (1.5 g/kg) produced an increse in the test response for condition-test intervals of 15-60 msec or more. With barbiturate anesthesia there was a decrease in the test response for all intershock intervals up to 150 msec. In unanesthetized rats with midbrain sections there was an increase in the test response with low intensity shock pairs and a decrease in the test response with high intensity shock pairs. Simultaneous use of both anesthetics produced either an increase or a decrease in the test response, depending upon the relative doses and upon the stimulus intensity. Paired stimuli to  the olfactory nerve produced results similar to those with LOT stimulation. Augmentation of the olfactory bulb field potential produced by paired olfactory nerve shocks was not abolished by lesions which sectioned the LOT and produced extensive damage of the anterior olfactory nucleus.


The periaqueductal gray: site of morphine analgesia and tolerance as shown by 2-way cross tolerance between systemic and intracerebral injections. The periaqueductal gray was shown to be an important component of morphine analgesia and tolerance. Two-way analgesic cross tolerance was obtained between systemic and intracerebral morphine administrations when the intracerebral site was the periaqueductal gray. Rats were pretreated with intraperitoneal morphine and tested with intracerebral morphine in the periaqueductal gray. A dose-dependent reduction in analgesia as a function of morphine pretreatment level was obtained. Conversely, when rats were pretreated with intracerebral morphine in the periaqueductal gray and tested with intraperitoneal morphine, significant reductions in analgesia were obtained.


Compartments and barriers in the sciatic nerve of the rabbit. Near constant concentration of various radioactively labelled polar nonelectrolytes were maintained in the blood plasma of renal ligated rabbits. The uptake of [14C]urea, [51Cr]EDTA and [14C]inulin into sciatic nerve was interpreted in terms of a two-compartment model. There was a rapidly equilibrating space representing about 20% of the tissue weight which is almost certainly the interstitial fluid of the epineurium and outer layers of the perineurium. Urea penetrated the blood-nerve barrier at a similar rate to the entry of this compound into brain. Sucrose, chromium-EDTA and sulphate passed into the true interstitial fluid approaching a total volume of distribution of about 36% of the tissue weight at 6-8 h. Since movement of these 3 solutes is severely restricted by the blood-barrier, the blood-nerve barrier in the  rabbit must contain channels of greater than 1 nm which are not present in the developed blood-brain barrier. Uptake of [3H]3-O-methylglucose into nerve was examined but the results did not give a conclusive answer to the question of whether there is specific transport of sugars at the blood-nerve barrier. The wet nerve contained (in mmole/kg) sodium 74.3; potassium 42.6 and chloride 48.8. Water was 64.6 ml/100 g. Intracellular electrolyte concentrations were estimated. Approximately 30% of the total sodium content cannot be accounted for as being free in the interstitial fluid at a Gibbs-Donnan distribution with plasma. Analysis of metabolically poisoned nerves which have equilibrated with salt solution in vitro suggests that negatively charged polyelectrolyte molecules retain about 14 mmole of sodium/kg wet normal nerve.


Osmosensitive neurons in the rat's dorsal midbrain. In experiment 1, multiple unit recordings were taken simultaneously from lateral preoptic and dorsal midbrain areas during a series of intracarotid hypertonic and isotonic NaCl injections. Subjects were 15 hooded rats (11 males and 4 ovariectomized females) under urethane anesthesia. Results showed that the neuronal reactions to a series of hypertonic NaCl injections (0.30 M, 0.45 M, 0.60 M and 0.75 M) were at least as strong in the dorsal midbrain as in the lateral preoptic area. Strength of neuronal reaction correlated with osmolarity of the NaCl solution injected. Control isotonic NaCl injections were ineffective, and the (monitored) force of injection was found not to affect the results. In experiment 2 with 15 hooded rats (9 males and 6 ovariectomized females), and two male Wistar rats under urethane anesthesia, recording from dorsal midbrain units were made during intracarotid injections of hypertonic and isotonic NaCl solutions. In addition, other sensory stimulations, including tail pinches, were presented. Of the 52 units studied, 39 cells (75%) reacted to injections of hypertonic NaCl, but not the isotonic (control) solution (Normosol-R). Again, strength of neuronal reaction correlated with osmolarity of the NaCl solution injected, and force of injections was found not to influence results. Eleven cells reacted to hypertonic NaCl injections but not to tail pinch. This and other evidence indicated that certain dorsal midbrain cells were specifically osmosensitive, and not merely showing general 'arousal' reactions to the injections. These results indicate that, for the rat, the osmosensitive zone extends into the midbrain. The functional significance of these findings is discussed.


Relation of uptake and metabolism of (1,2,6,7-3H)testosterone to individual differences in sexual behavior in male guinea pigs. Male guinea pigs were given 3 tests for sexual behavior. Animals that never ejaculated were classified as low activity (LA), animals that ejaculated on one test were classified as medium activity (MA), and animals that ejaculated on two or more tests were classified as high activity (HA). Subsequently, animals from each group were castrated and given an s.c. injection of 43 muCi of [1,2,6,7-3H]testosterone and were killed 0.5, 1, or 4 h after injection. There were no significant differences in uptake or metabolism of radioactive testosterone among LA, MA, and HA males in homogenates of anterior and posterior hypothalamus, cerebral cortex, midbrain, or seminal vesicle. Thus, differences in sexual behavior could not be attributed to differences in testosterone uptake in tissue homogenates. At the 1 h time interval (time of peak plasma radioactivity), radioactivity in the seminal vesicles of all males was primarily in the form of steroids with the chromatographic mobility of dihydrotestosterone. In all males, anterior and posterior hypothalamus contained a higher proportion of steroids with the mobility of testosterone than did midbrain, and midbrain contained more testosterone zone radioactivity than cerebral cortex at 1 h. The highest proportion of dihydrotestosterone zone radioactivity in neural tissues was found in anterior hypothalamus. These results are discussed in terms of androgenic mediation of sex behavior by the anterior hypothalamus in guinea pigs.


An electrophysiological study of amygdalohypothalamic projections to the ventromedial nucleus of the rat. The influence of the amygdala on the activity of single neurons within the hypothalamic ventromedial nucleus (HVM) was studied in pentobarbital or urethane anesthetized rats. The results are summarized as follows: (1) Stimulation of different amygdaloid nuclei or of the stria terminalis (ST) evoked a prominent field potential within HVM and altered the spike discharge patterns of the majority of HVM neurons. (2) More than 80% of 428 HVM neurons tested with single amygdala shocks exhibited excitation or excitation-inhibition sequences; the remainder displayed inhibitory responses of 100-150 msec duration at latencies slightly longer than for most of the observed excitatory responses. ST stimulation also evoked excitation or excitation-inhibition sequences from 85% of 240 HVM neurons tested; of the remainder, those with spontaneous activity displayed inhibitory responses with durations of 100-150 msec at latencies slightly longer than for most observed excitatory responses. (3) Evoked potential interaction studies suggested that stimulation of either ST or the amygdala activated the same population of HVM neurons. Single cells tested with both amygdala and ST stimulation displayed similar patterns of response. HVM field potentials and single unit responses to amygdala stimulation were markedly diminished by lesions of ST. Thus, in the rat, only one pathway, i.e., the stria terminalis, contains amygdalofugal fibres to the ventromedial hypothalamic nucleus. (4) The orthodromic responses of HVM neurons were dependent on the frequency of amygdala stimulation. Less than 50% of HVM neurons responded to amygdala stimuli at frequencies greater than 33Hz. Many cells could not be activated at stimulation frequencies greater than 10 Hz, and the spontaneous discharges from certain HVM neurons were effectively abolished at this stimulation frequency. (5) Evidence of prominent postsynaptic inhibition was present throughout HVM. Seventeen HVM neurons displayed amygdala evoked unitary activity different from that of the majority of HVM neurons, and these cells were considered to represent possible inhibitory neurons. In contrast to most HVM neurons activated via probable monosynaptic amygdalohypothalamic pathways, these putative inhibitory neurons were apparently activated via polysynaptic pathways. (6) In summary, these results suggest that the amygdala exerts a prominent monosynaptic influence on the activity of many HVM neurons, coupled with polysynaptic activation of powerful local postsynaptic inhibitory mechanism. In the rat, these amygdala evoked events depend on the integrity of the stria terminalis.


Tuberoinfundibular neurons in the basomedial hypothalamus of the rat: electrophysiological evidence for axon collaterals to hypothalamic and extrahypothalamic areas. In pentobarbital or urethane anesthetized rats, the activity of 889 mediobasal hypothalamic neurons was studied for evidence of a response to median eminence stimulation. Evidence of antidromic invasion, which indicated a projection to the median eminence, identified 134 cells (15%) as 'tuberoinfundibular' neurons. Antidromic spike latencies ranged from 0.5 to 14.0 msec (4.3 +/- 2.9 S.D.); conduction velocities were under 1.0 m/sec and were generally slower for tuberoinfundibular neurons located closest to the ventral surface of the hypothalamus. Certain tuberoinfundibular neurons followed paired median eminence shocks at frequencies up to 500 Hz; an increase in both the threshold and the latency for the second antidromic spike was observed with interstimulus intervals under 4 msec. Only 38% of tuberoinfundibular neurons were spontaneously active; 24 of 29 spontaneously active neurons displayed evidence of recurrent inhibition with durations up to 150 msec and at latencies which approximated that of the antidromic spike but which did not depend upon antidromic invasion. Similar responses were observed from 33 spontaneously active non-tuberoinfundibular neurons. Evidence of orthodromic excitation in response to median eminence shocks was observed from 22 other medial hypothalamic neurons. Latencies for excitation ranged from 1.5 to 9.0 msec (mean 4.5 +/- 2.1 S.D.). Simultaneous antidromic invasion from other hypothalamic and extrahypothalamic sites was observed from 8 tuberoinfundibular neurons. These sites included the anterior hypothalamic area (2 cells), the preoptic area (3 cells) and the thalamic nucleus medialis dorsalis (3 cells). These results indicate the presence of axon collaterals within the tuberoinfundibular system; some appear to terminate locally within the hypothalamus, while others extend rostrally and dorsally into extrahypothalamic areas. These connections may provide pathways for extrahypothalamic distribution of peptides which regulate adenohypophyseal secretion, and suggest that these peptides may subserve alternate regulatory roles within the central nervous system.


Asymmetry of motility of the eyes and change of binocular properties of cortical cells in adult cats. Immobilization of one eye in the adult cat following section of the oculomotor cranial nerves causes a decrease of the proportion of binocularly activated cells in the striate cortex. This change in the binocular properties of cortical cells also takes place if the animal is deprived of vision from the day on which the nerves are cut to the day of the electrophysiological recording. No similar change in the proportion of binocular cortical cells is observed in cats where both eyes have been immobilized.


Prefrontal unit activity and delayed response: relation to cue location versus direction of response. Two monkeys were trained to perform 3 kinds of spatial tasks (right-left DR, up-down DR, and conditional position discrimination with delay). In the conditional position task, the animal was required to respond to the right (left) choice key when the cue had been presented on the upper (lower) position. Single unit activity was recorded from the principalis area of the dorsolateral prefrontal cortex while the animal was performing the tasks. Once a differential delay unit (i.e., unit showing specificity during the delay period for two kinds of trials) was found in right-left DR (or up-down DR), the same unit was tested in the other tasks. A total of 32 differential delay units were investigated sufficiently to allow comparison of all 3 conditions. The results indicate that there are two types of differential delay units. The first type showed a clear dependence on the cue location, while the second type was related to the direction of the impending response. Activity of the second type of differential delay unit during the delay period served to predict the occurrence of errors, whereas this relation between unit discharge and correct or incorrect responses was not seen for the first type of differential delay unit.


Frontal-striatal control of behavioral inhibition in the rat. The direct application of crystalline dopamine, D-amphetamine or scopolamine in microgram quantities to the ventral anterior region of the corpus striatum (VAS) of rats increased their responding for food on a modified DRL-30 sec schedule of reinforcement. Similar applications of norepinephrine were less effective than dopamine, while the anticholinesterase eserine depressed responding. Electrolytic lesions of the ventrolateral, but not the dorsomedial, prefrontal cortex of rats also increased their response rates. These results were interpreted as being consistent with the idea of a dopamine-acetylcholine antagonism in the VAS whose net output modulate behavioral inhibition. This striatal mechanism may be influenced by the ventrolateral prefrontal cortex.


The study of human dentine with secondary ion microscopy and electron diffraction. The highly polished surface of serial transverse ground sections of human coronal dentine were coated under vacuum with an aluminium grid and studied with a SMI 300 ion microanalyser (Cameca, Paris) based on mass spectrography. Secondary ion microscopy demonstrated a qualitative distribution of calcium, phosphorus, magnesium, sodium and potassium. A higher content in Ca, P and Mg was noted in peritubular dentine. Selective area electron diffreaction patterns of this zone, using LiF as standard, showed the presence of whitlockite in peritubular dentine where about 1% in weight of magnesium seemed to be incorporated.


The growth of calcium phosphates on natural enamel. The kinetics of growth of calcium phosphate on seed materials prepared from human tooth enamel has been studied at 25 degrees C and pH 7.40 in stable supersaturated solutions of calcium phosphate. The grown material was characterized chemically, by specific surface area (SSA) measurements and by subsequent dissolution experiments. The marked increase in SSA in the early stages of the precipitation reaction parallel the results obtained with synthetic hydroxyapatite seed crystals and the results of the dissolution experiments indicate a chemical composition close to that of octacalcium phosphate for this intermediate phase. At low supersaturation it is possible to avoid the formation of the precursor phase.


Age related Ca-Mg content and strength in turkey tendon. The age related variation in magnesium and calcium content and mechanical properties of turkey tendon from ages 9-14 weeks has been studied. The results show that magnesium content decreases with age during this period and calcium content remains essentially constant. This is in accord with a previously proposed mechanism of calcification, namely, that the local concentration of magnesium and calcium may be an important factor relating to the initiation of calcification in a given tissue. The tensile strength of the turkey tendon has been found to decrease with age during the precalcified period of 9-12 weeks, after which there is an increase in tensile strength coincident with the onset of calcification. The ultimate elongation decrease of approximately 4% between 9 and 13 weeks is attributed to the difference in extensibility of the "wavy" collagen fibers observed in uncalcified turkey tendon vis a vis the straight fiber bundles in turkey tendon specimens observed at the onset of calcification.


The effects of age on baroreceptor reflex function in man. The relationship of age to baroreceptor reflex activity was determined in 35 healthy volunteers ranging in age from 19 to 65 years. Intra-arterial catheters were placed and blood pressure and pulse rate responses of each subject were observed during a Valsalva maneuver (31 subjects) and during the Pressor Test (33 subjects). The Valsalva maneuver consisted of a forced expiration sufficient to raise a column of mercury 40 torr for 10 seconds. This resulted in a reduction in pulse pressure (Baroreceptor stimulus) during the maneuver followed by a transient overshoot in diatolic pressure (response) following its termination. In comparison to younger subjects, older subjects had a greater reduction in pulse pressure but similar overshoot in diastolic pressure. The pressor test consisted of observing the effect of increasing systolic blood pressure (stimulus) on pulse duration (response) following the intravenous administration of phynylephrine. By relating each systolic pressure to the immediately succeeding R-R interval, a linear relationship was found. Its slope expressed in milliseconds of R-R interval change per torr increase in systolic pressure is an index of baroreflex function. Older subjects have less cardiac slowing compared to younger subjects and a hyperbolic relationship exists between age and slope (r = 0.84, p less than 0.05). These tests indicate that baroreceptor reflex function decreases with aging.


Control, monitor and alarm system for clinical application of a membrane oxygenator. Membrane oxygenators, now commercially available, are undergoing clinical trials as long-term (days) respiratory support devices for patients in potentially reversible respiratory failure. However, these devices must be used in an integrated system of controls, monitors and alarms if they are to be reliable and easy to operate in the clinical environment. This paper describes such a system. The tubing circuits for blood and for oxygen are described first. Next, details of the blood pump controls are presented. The system features servo control of pump speed to match blood inflow, and deactivation of the pump in the case of excessive output pressure. Gas circuit controls are described which allow the independent adjustment of both oxygen flow through the gas phase of the membrane lung and oxygen pressure developed at the inlet gas port. Audible alarms are provided for low blood inflow to the system, excessive blood outflow pressure, changes in oxygen flow and failure of the electric power supply to the system. In addition to pressure and flow monitors in the blood and gas circuits, blood oxygen saturation is continuously monitored at both input and output of the system. The membrane oxygenator system has proved to be reliable and easy to operate in both animal and human long-term perfusions.


Carbon dioxide output in anaesthesia.

Carbon dioxide output in anaesthesia. In a Mapleson D circuit the carbon dioxide content of gases, sampled at the breathing bag or near the bellows of the ventilator, is virtually constant throughout the phases of respiration. Assuming that after induction of anaesthesia the fresh gas inflow, if kept constant, is essentially equal in volume to the gas vented at the expiratory valve, CO2 output can be calculated by multiplying the fresh gas inflow by the CO2 content of the vented gas measured with a suitable CO2 analyzer. Anaesthesia with nitrous oxide-oxygen, supplemented with low doses of alphaprodine or halothane was compared in two groups of young patients who underwent dental surgery and who were breathing spontaneously. While the CO2 output in the group supplemented with alphaprodine increased from about 100 to 130 ml/m2/min, the halothane group showed a constant CO2 output of about 90 ml/m2/min followed by a significant rise within 5 minutes after halothane was discontinued. In 42 patients on controlled ventilation, no significant difference was found in the CO2 output estimated one hour after induction of anaesthesia in nitrous oxide-oxygen anaesthesia supplemented by halothane, ethrane or alphaprodine. The values obtained were 87 +/- 11 ml/m2/min for halothane (11 patients), 98 +/- 19 ml/m2/min for ethrane (14) and 93 +/- 13 ml/m2/min for the narcotic supplemented anaesthesia (17). The mean CO2 output for all 42 patients was 93 +/- 14 ml/m2/min. Six markedly obese patients under the same anaesthetic technique had a CO2 output of 114 +/- 17 ml/m2/min; however, their CO2 output was similar to normal patients when calculated on the basis of body weight. A marked increase in CO2 output to a mean of 160 +/- 25 ml/m2/min was found in eight patients undergoing operation while on hyperalimentation. The technique described appears suitable to monitor CO2 output under anaesthesia. In order to avoid hypercarbia when using a partial rebreathing system, the fresh gas inflow must be increased above recommended values in cases with increased metabolic activity (e.g. patients receiving hyperalimentation). In obese patients the fresh gas inflow should be calculated on the basis of body weight.


Dobutamine and general anaesthesia: a study of the response of arterial pressure, heart rate and renal blood flow. The effects of dobutamine, a new catecholamine, have been studied during anaesthesia with halothane, halothane and nitrous oxide and alphaprodine. Renal blood flow is increased by dobutamine as are mean arterial pressure and heart rate. The increase in rate is less marked during alphaprodine anaesthesia than when halothane is administered. Dobutamine may prove a useful agent in the management of acute circulatory failure but it is capable of inducing dysrhythmias under the conditions of these experiments.


A disposable condenser humidifier for use during anaesthesia. A disposable heat and moisture exchanger ("Artificial Nose") which is designed for use during endotracheal anaesthesia is described together with an evaluation of its performance. It has a low dead space, minimal resistance to gas flow, and is potentially capable of conserving 50 per cent of the respiratory water loss in the intubated patient.


The results of therapeutic acupuncture in a pain clinic. Acupuncture has been used to treat various conditions of chronic pain in a pain clinic. Six hundred and six acupuncture treatments were administered within the space of 12 months to 72 patients who had not responded well to conventional treatment. At completion of the acupuncture treatments 19 patients showed marked improvement, 20 showed improvement and 21 transient improvement. Long-term results were also investigated at a mean of four months after the final treatment. The results of this follow-up study showed marked improvement in 11 patients and improvement in 20 others. In terms of conditions treated, best responses were obtained in patients with musculo-skeletal disorders, degenerative or osteoarthritis and headache.


Effect of propylthiouracil-induced hypothyroidism on phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin synthesis in chick liver microsomes. Biosynthesis of phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin was studied in liver endoplasmic reticulum obtained from newly hatched chicks which were made hypothyroid by feeding 0.2% propylthiouracil. In vitro measurements were made of the specific activities of phosphorylcholine-glyceride (cholinephosphotransferase (EC 2.7.8.2), hosphorylethanolamine-glyceride (ethanolamine-phosphotransferase (EC 2.7.8.1)), and phosphorylcholine-ceramide (ceramide cholinephosphotransferase (EC 2.7.8.3)) transferases in control and hypothyroid chick liver for a period of 40 days. The specific activity of all three transferases began to decline after the chicks were on the propylthiouracil-containing diet for 5 days and steadily declined, reaching levels 10-15% of the controls after 15 days. These low levels were maintained for as long as the chicks were on this diet. Administration of L-thyroxine (15 mug/100 g of body weight) to the hypothyroid chicks caused a marked increase in the specific activities of all three transferases, reaching levels similar to those seen in the control chicks in 36-48 h. The specific activities then declined as the chicks were maintained on the diet of propylthiouracil, reaching the former low levels after 120 h. Administration of cycloheximide alone to the hypothyroid chicks caused a rise in the specific activities of the transferases after 24 h approximately equal to that caused by thyroxine alone, while thyroxine and cycloheximide together were no different than either alone. These studies indicate that in some manner circulating thyroxine controls the activities of enzymes involved in the biosynthesis of phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin in chick liver endoplasmic reticulum. There was no evidence that induction of  hypothyroidism by propylthiouracil had any effect on the activities of these enzymes in the CNS.


Enzymes of the orotate biosynthetic pathway in Crithidia fasciculata. A study of the enzymes of the orotate biosynthetic pathway in the kinetoplasid flagellate Crithidia fasciculata has revealed a number of differences between them and those of other organisms, either prokaryotic or eukaryotic. Carbamyl phosphate synthesis could not be demonstrated in cell-free extracts. However, the incorporation of both CO2 and the ureide carbon of citrulline into pyrimidines occurs in growing cells, the latter predominating over the former. The aspartate transcarbamylase of the flagellate has properties which are similar to those of this enzyme as it occurs in mammals rather than other microorganisms. Two enzymes, dihydroorotate synthetase and dihydroorotate hydrolase, are present, the former being responsible for the conversion of carbamylasparate to dihydroorotate. Dihydroorotate hydroxylase, a soluble enzyme requiring a reduced pteridine as a cofactor, converts dihydroorotate to orotate. The hydroxylase is inhibited by orotate, but not by pyrimidine or purine ribonucleotides. Thus orotate serves to control its own biosynthesis.


Amino acid composition of sperm histones in the house cricket Acheta domesticus. Histones were isolated from late spermatids and spermatozoa of the house cricket Acheta domesticus, and the individual histone fractions were separated by electrophoresis on polyacrylamide-urea gels. The stained gels were cut so as to isolate the different histone fractions,  and the amino acid compositions were determined using the technique of Houston (Houston, L.L.: Anal. Biochem. 44, 81-88 (1971). Five of the histones had amino acid compositions resembling those for the histones of calf thymus and were thus identified as fractions F1, F3, F2a2, F2b, and F2al. Another protein (SH) located exclusively in the late spermatids and spermatozoa was found to be basic and histone-like. It is a protein containing relatively high amounts of arginine (12.6%) and low amounts of lysine (7.6%), and, as a result, it has a low ratio of lysine-arginine (0.6). Other noteworthy features are its high contents of serine, glutamic acid, and glycine. It is arginine rich histone and in this regard resembles other such proteins, but it does contain unique features which distinguish it from all previously described histones.


Reagentless determination of L-asparagine and L-arginine via the combined use of immobilized enzymes and an ion-selective electrode. New methods for the determination of L-asparagine and arginine are described. Solutions containing L-asparagine were pumped through an asparaginase tube, which catalyzed the hydrolysis of L-asparagine to L-aspartis acid and ammonium ion. For L-arginine determination, solutions containing L-arginine were pumped through an arginase-urease tube. This dual enzyme tube catalyzed the conversion of L-arginine to L-ornithine, carbon dioxide, and ammonium ion. The ammonium ion concentrations in the effluent of the enzyme tubes were determined quantitatively by an ammounin-ion-selective electrode. The potentiometric response of the electrode was directly proportional to the logarithm of the concentration of L-asparagine and L-arginine in the range of 0.1-50 mM. An equation relating the electrode response and the substrate concentration is derived.


Physodes and the phenolic compounds of brown algae. Isolation and characterization of phloroglucinol polymers from Fucus vesiculosus (L.). A series of vanillin-reactive compounds has been isolated from extracts of the brown alga Fucus vesiculosus. The first three members of this series have been examined by mass spectrometry, nuclear magnetic resonance spectrometry, and chemical methods, and were shown to be phloroglucinol, its phenyl-linked dimer, and a timer also composed of phloroglucinol units. Evidence is presented for the presence of tetrameric, pentameric, and hexameric phloroglucinol derivatives. Polymeric vanillin-reactive compounds were isolated and separated into two fractions. Oxidative hydrolysis of the major one produced phloroglucinol and related oligomers in low yields. The classical vanillin reactivity of physodes may thus be attributed to phloroglucinol-containing derivatives, as originally proposed by Crato (Crato, E.: Ber. Dtsch. Bot, Ges. 10, 295-302 (1892)).


Synthesis of hemopexin with and without hormonal supplementation in rat hepatocyte suspensions: comparison with that of albumin and of fibrinogen. The rate of hemopexin synthesis in adult rat hepatocyte suspension (0.17 +/- 0.019 (6)) (mean +/- SEM (n) mg/g hepatocytes per hour) was found to be linear for 48 h. By contrast, the rate of synthesis of albumin and fibrinogen was close to linear for only 12 h after which it continued at a diminished rate. Supplementation of the incubation medium with insulin, cortisol, glucagon, triiodothyronine, and growth hormone affected no significant increase in the synthesis rate of hemopexin but by contrast did do so in that of albumin (22%) and of fibrinogen (123%) (although not to the point of causing these last to become linear). The pattern of hemopexin synthesis and its response to hormones is clearly different from that observed with other plasma proteins studied in this hepatocyte system. Hempoexin synthesis appeared to be at its maximum and to be independent of hormone supplementation, and it was continuing linearly at a time when the synthesis of other plasma proteins was falling.


Nonpolar lipids of a halotolerant species of Staphylococcus epidermidis. The nonpolar lipids of a halotolerant Staphylococcus epidermidis, isolated in pure culture from a growth medium for extreme halophiles containing 25% sodium chloride, were found to contain squalene, menaquinone-7, free fatty acids (mainly anteiso-15:0 and anteiso-17:0), undecaprenol, nonaprenol with predominately cis-isoprene residues, heptaprenol, with predominately trans-isoprene residues, and 1,2- and 1,3-diglycerides containing anteiso- 15:0 and anteiso-17:0 branched chain fatty acid residues. The above compounds were isolated in pure form by column and thin-layer chromatography and were characterized by ultraviolet, proton magnetic resonance, and mass spectra. Fatty acid moieities were characterized by gas-liquid chromatographic retention times of their methyl esters.


In vivo and in vitro phosphoarylation of nuclear proteins in rat liver. The incorporation of 32P into nuclear nonhistone proteins was compared in rat liver in vivo, in liver slices incubated in vitro, and in isolated nuclei incubated with gamma-[32P]ATP. The highest specific activities of nuclear phosphorproteins were obtained by incubating isolated nuclei. However, the Radioactivity profiles of polyacrylamide gel electrophoretograms of these proteins differed from those obtained in vivo or in liver slice experiments. A group of low molecular weight nonhistone proteins exhibited a very high incporation of labelled phosphate. These proteins could be obtained from the interface when the phosphoproteins were isolated by the buffered phenol extraction procedure. Phosphorylated proteins were also obtained from three cytoplasmic fractions (mitochondria, microsomes, and cytosol). The specific activities of these proteins were much lower than of the nuclear phosphoproteins.


Characterization of tryptic peptides from porcine haptoglobin light chain and an amino acid sequence. The tryptic peptides derived from porcine haptoglobin light chains have been separated and characterized by composition, chromatography, electrophoretic mobility, and partial sequencing. Depending on homology with the corresponding human polypeptide, the amino acid sequence of the chain is proposed. Twenty differences from the human chain are indicated in the total of 84 residues.


Uptake and binding of dissaccharides in human erythrocytes. Disaccharides (sucrose, lactose, melibiose, cellobiose, trehalose, maltose, and isomaltose) are not transported across the human erythrocyte membrane. Maltose alone is bound in appreciable amounts to the intact cell as well as ghost membranes and competes mutually for uptake with D-glucose. In (NH4)2-SO4-precipitated membrane preparations, maltose binds more strongly than other disaccharides (KD = 1.3 X 10(-5) M; maximum binding capacity, 71 pmol/mg protein) and again competes mutually with D-glucose. Phloretin inhibits the binding of glucose much more than that of maltose.


Measurement of dissolved carbon dioxide. Several probes for measuring dissolved carbon dioxide (CO2) concentration were installed in a 68-litre fermentor and their effectiveness compared. Submerged silastic rubber tubing gave reproducible results over a wide range of operating conditions and was generally superior to all other probes evaluated. The silastic rubber probe was used to compare the partial pressure of CO2 in viscous fermentation media with that in the fermentor exhaust gas. No significant difference was found. Results show that determination of the CO2 partial pressure in the exhaust gas gives an excellent approximation of the partial pressure of dissolved CO2 in the liquid medium, eliminating  the need for measurement of CO2 concentration in the broth.


Electron microscopy of vesicular-arbuscular mycorrhizae of yellow poplar. IV. Host-endophyte interactions during arbuscular deterioration 1,2. Scanning electron stereoscopy and transmission electron microscopy were used to correlate morphological alterations and cytological phenomena associated with deterioration of arbuscules in yellow poplar mycorrhizae. Arbuscular degradation was initiated at the tips of the finest branches and progressed basipetally. Cytoplasm in arbuscular hyphae progressively deteriorated and was followed by collapse of the fungal walls. Degraded portions of the arbuscules aggregated into clumps comprised of host wall material and the distorted fungal walls. Host nuclei, abundant mitochondria, and proplastids were closely associated with arbuscular branches undergoing cytoplasmic deterioration and with clumped portions of the arbuscule which contained degraded hyphal branches. Most of the arbuscules observed had deteriorated to the clumped stage. Some cortical cells contained several clumped arbuscules and nearly mature, intact arbuscules which indicated that reinfection occurs even as degradative phenomena are in progress. It is suggested that substantial quantities of mineral nutrients may be made available to the host via degradation of fungal cytoplasm in the arbuscular hyphae preceding aggregation of degraded hyphae into discrete clumps.


Two-dimensional SDS-polyacrylamide gel electrophoresis of heat-modifiable outer-membrane proteins. An examination has been made of the effect which temperature of solubilization has upon the subsequent migration in SDS-polyacrylamide gel electrophoresis of proteins from the cell envelopes of Escherichia coli K12 and Neisseria sicca ATCC 9913. Conventional electrophoresis in tubes revealed substantial differences in the staining patterns of gels, depending upon whether the envelope samples were solubilized at 37 degrees C or 100 degrees C; in the case of N. sicca at least 6 of 13 discernible bands displayed heat-modifiable behavior. The relationship of the bands produced by each of the two temperatures was investigated by a two-dimensional electrophoresis procedure, in which a sample was solubilized at 37 degrees C and run in a usual cylindrical gel; the entire gel was then resolubilized at 100 degrees C, and laid along an acrylamide slab for electrophoresis in the second dimension. It was found that "free endotoxin" of both organisms examined contained the same major proteins as the total envelope fraction, and that these free endotoxin proteins showed the same heat-modifiable properties as when present in total envelopes.


Maintaining cultures of ectomycorrhizal and plant pathogenic fungi in sterile water cold storage. Mycelial cultures of 64 isolates of 14 species of ectomycorrhizal fungi and 27 isolates of 15 species of plant pathogenic fungi were grown on agar medium in Petri dishes. Mycelial discs, 8 mm in diameter, were removed from the cultures and stored in sterile distilled water in test tubes at 5 degrees C. Sixty-four, 61, and 41 isolates of the symbiotic fungi were viable after 1, 2, and 3 years storage respectively. Only 19, 10, and 8 isolates of the pathogenic fungi were viable after 1, 2, and 3 years storage, respectively. Time in pure culture before water storage did not affect viability of any fungal species following water storage. After 3 years storage, four fungi (three symbionts and one pathogen) were tested and found to have retained their original growth rates and root-infecting abilities on pine seedlings. The same four isolates, however, maintained on agar slants at 5 degrees C and subcultured every 4 to 6 months, grew slower and did not infect as many feeder roots of pine as the water-stored isolates.


Methane fermentation of rubber (Hevea brasiliensis) latex effluent. Four species of bacteria capable of CH4 fermentation of rubber latex effluent were isolated and identified as a Methanococcus, a strain of M. vannielii, a Methanobacterium and a strain of M. omelianskii. Auxanographic tests using the four strains showed growth and CH4 formation on a basal medium containing mineral salts or added H2 and Co2. Varied response was obtained when the basal medium was added to formate, acetate, butyrate, methanol, ethanol, and glucose. Previous work has established acid fermentation of Hevea latex arising from bacterial contamination and decomposition of the non-rubber constituents which consist of N-compounds, 2% quebrachitol, and smaller concentration of carbohydrates. This suggests that reduction of CO2 and fermentation of acids formed during metabolism of Hevea latex are possible pathways of CH4 production.


Phosphopantothenic acid--the major product of pantothenic acid accumulation and a significant growth stimulatn in Lactobacillus plantarum. Non-proliferating cells of Lactobacillus plantarum accumulated about 1.3 mug of pantothenic acid (PA) per milligram dry cells when placed in a phosphate-buffered solution containing glucose, NaCl, and PA for 21 h. Under the conditions applied for PA uptake, pH 7.5 and 38 degrees C, the accumulated PA existed almost exclusively in a bound form. Free PA was observed only occasionally and then at questionably significant levels. All bound PA was released quantitatively by enzyme hydrolysis with alkaline (intestinal) phosphatase. Chromatographic analysis coupled with differential microbiological analysis of cell extracts using Saccharomyces cerevisiae, Lactobacillus helveticus, and L. plantarum identified the accumulated PA as phosphopantothenic acid (P-PA). Assay of P-PA loaded cell extracts (devoid of free PA) by L. plantarum before and after alkaline phosphatase hydrolysis showed that the growth of this primary assay organism was stimulated by 8.3%.


Studies on cardiolipin biosynthesis in Mycobacterium smegmatis. Supplementation of a growth medium with 5% glucose has been found to stimulate the formation of cardiolipin and phosphatidylethanolamine five- and threefold, respectively, in Mycobacterium smegmatis. The presence of both cytidine diphosphate diglyceride and phosphatidylglycerol pathways of biosynthesis of cardiolipin in cell-free extracts has been demonstrated. The enzymes were localized in the fractions which contained membranes. Isonicotinic acid hydrazide and streptomycin sulfate inhibited the formation of cardiolipin.


Selection of synchronous bacterial cultures by density sedimentation. A procedure previously used to select synchronous cultures of Chlorella was found to produce similar results with the bacterium Lineola longa (Bacillus macroides). A midlog culture of L. longa was layered onto a 31-42% dialyzed Ficoll gradient and ceitruged at 51 000 3 g. The culture sedimented into a broad band in 30 min. Continued centrifugation failed to cause further migration. Cells taken from the top of the band and reinoculated into the broth in which they had previously grown, pH adjusted to 7.0, grew without a lag, doubled in optical density at the same rate as midlog cultures, and divided synchronously. Coulter counter sizing of these cells showed a doubling in volume just before division followed by a halving of volume after division. The major advantages of this method are the low osmolarity of Ficoll and the large volume of cells that can be separated.


Ultrastructural changes in Cladosporium cucumerinum during pathogenesis. Three ultrastructural patterns, each one associated with a different stage of pathogenesis, were observed in Cladosporium cucumerinum infecting cucumber cytoledons. (i) Fungal prepenetration structures (conidia and germ tubes) contained numberous lipid bodies. Microbodies were abundant and often associated with lipid bodies. Mitochondria were also abundant. (ii) During the invasion stage, no lipid bodies and relatively few microbodies were observed. Mitochondria were abundant, but differed markedly morphologically from those observed in the prepenetration structures. (iii) In the colonizing hyphae, microbodies were the most abundant organelle, lipid bodies were seldom found, and mitochondria were as observed during invasion. These changes in numbers of organelles may be associated with differences in the metabolic activities of the pathogen at various stages of pathogenesis.


The distribution of the isocitrate lyase serine pathway amongst one-carbon utilizing organisms. A study of several one-carbon-utilizing organisms was conducted to determine the distribution of the recently found isocitrate-lyase-positive serine pathway of C1 assimilation. The results showed that this pathway is restricted to soil-isolated, non-pigmented Pseudomonas, initially isolated in methylamine enrichments, and to certain species of Hyphomicrobium. It was not detected in any organisms possessing a pink pigment.


Sucrose-mediated giant cell formation in the genus Neisseria. Growth of Neisseria perflava, Neisseria cinerea, and Neisseria sicca strain Kirkland in media supplemented with sucrose (0.5 to 5.0% w/v) resulted in the formation of giant cells. Response to sucrose was specific in that a variety of other carbohydrates did not mediate giant cell formation. Giant cells appeared only under growth conditions and did not lyse upon transfer to medium lacking sucrose or upon resuspension in hypotonic media. Reversion of giant to normal cells occurred when giant cells were used as inocula and allowed to multiply in media lacking sucrose.


Studies on mode of action of a bacteriocin from Clostridium septicum. A bacteriocin was found in the supernatant fluid of Clostridium septicum strain Ovinus. Sensitivity to the bacteriocin was confined to other strains of C. septicum and to strains of C. chauvoei; the other Gram-positive and Gram-negative bacteria tested for sensitivity were unaffected by the bacteriocin. The bacteriocin killed sensitive cells rapidly but cell lysis did not appear to be involved. The bacteriocin inhibited protein and RNA synthesis immediately after its addition to sensitive cells; DNA synthesis was inhibited 10 min later.


Von Hippel-Lindau's disease.

Von Hippel-Lindau's disease. A patient with Von Hippel-Lindau's disease was followed from the time of diagnosis to the time of his death 13 year later. He was asymptomatic when the diagnosis was made, although a hemangioblastoma of the medulla was found on angiography. The patient's course and autopsy are described and the features of this disease are reviewed.


Cerebral blood flow in patients with intracranial pressure elevation due to traumatic brain edema. The object of this study was to determine if traumatic brain edema (BE) and increased intracranial pressure (ICP) reduce cerebral blood flow (CBF). Two groups of patients were studied, one with slight BE and ICP less than 20 mm Hg., the other with pronounced BE and ICP over 20 mm Hg. Although ICP was higher and cerebral perfusion pressure lower in pronounced edema there was only a small and non-significant reduction in CBF and no difference in cerebro-vascular resistance. Since traumatic BE does not increase resistance to blood flow through the brain, cerebral perfusion can be maintained if an adequate perfusion pressure is established. This in turn, demands the monitoring and control of ICP.


The relative significance of factors affecting postoperative survival in astrocytomas, grades one and two. The records of 107 patients with supratentorial astrocytomas, Grades 1 and 2 treated surgically between 1960 and 1970 were analyzed. Abstracted clinical data was retrospectively analyzed with respect to the relative significance of different factors affecting survival. Twenty-eight patients were alive at the time of follow-up in 1974. Age, clinical grade at surgery and radiation therapy were the most important determinants of prolonged postoperative survival. The more malignant astrocytomas occurring in the Province of Alberta had previously been reviewed. The present study was carried out to demonstrate the relative influence of histologic grade of astrocytomas and to analyze the factors affecting postoperative survival in the low grade, supratentorial astrocytomas.


Polyglycolic acid suture in peripheral nerve II: sutured sciatic nerve. This experiment investigates the holding property of polyglycolic acid suture in repair of divided dog sciatic nerves and the influence of absorption of this synthetic material on regeneration. The conclusion is that PGA maintains its tensile strength sufficently long to allow both physical union and good regeneration of the divided nerve. The suture absorption does not influence regeneration.


Transient responses of rabbit retinal ganglion cells to photic and electrical stimuli. The relationships between the center and the surround of the receptive field of the rabbit retinal ganglion cell were investigated. This was done by coupling localized light spots and electrical activation of the retina and by analyzing the time of the excitatory and inhibitory periods. The responsiveness to the electrical transretinal pulse revealed a) that ON stimulation in OFF-center cells and OFF stimulation in ON-center cells, elicited a primary period of inhibition with a short latency; b) the long latency response of surround stimulation was not preceded by an inhibitory period unless the center was simultaneously stimulated in the same direction; c) a transient response to a stationary spot of light is followed by a period of inhibition. These results are discussed in relation to the known cellular retinal networks.


Patterns of medical drug use - a community focus. The pattern and extent of medical use of drugs was examined by survey in a rural Ontario community (Smithville) and a suburban (Burlington) family practice. Changes in established patterns of drug use that occur after the introduction of a nurse practitioner were also examined in the suburban practice. In both surveys 60% of respondents were using at least one medication and 30% were taking at least one medication prescribed or suggested by a doctor. There were consistently high rates of use of nonprescribed drugs at all ages, especially among females. Vitamins and tonics were the most commonly used drugs, and were taken by 25 to 28% of the respondents, 40% of whom used them on the advice of a physician. From 8.8 to 10.5% of respondents used sedatives or tranquillizers, and reduction in the prescribed use of these drugs was found among patients managed by the nurse practitioners. Self-medication is apparently unrelated to the frequency of medical consultation.


Intussusception in the older child.

Intussusception in the older child. During its first 6 years of operation a large pediatric unit in a suburban general hospital treated 13 children over the age of 2 years for confirmed intussesception. During the same period 14 infants under the age of 2 years were treated for intussusception. It is suggested that the true age incidence of the disease is reflected more accurately by these figures than by those reported by large children's hospitals. The clinical course was often less acute in the older child and hydrostatic reduction was usually effective (in 11 of 12 attempts). Prompt operation is recommended when the condition recurs more than 1 week after reduction because of the increased risk of an underlying intestinal lesion. Practitioners are urged to keep intussusception in mind when assessing an older child with intestinal colic.


Rubella 1974 and its aftermath, congenital rubella syndrome. An epidemic of rubella reached its peak in the Atlantic provinces in 1974, subsiding in early 1975. With the exception of Quebec the remainder of Canada showed a reverse trend, with a large increase in the numbers of cases reported in the first 41/2 months of 1975. The Halifax virus laboratory reported 106 serologically proven cases of rubella in 1974, 44 of them in pregnant women. In the aftermath of the epidemic many infants were born with the congenital rubella syndrome (CRS). A study carried out from Sept. 1, 1974 through Apr. 30, 1975 showed an 80% correlation between clinical diagnosis and the presence of rubella-specific IgM antibodies in 35 of these infants. Of the 23 infants in whom the diagnosis of CRS was made by laboratory or clinical findings or both, laboratory criteria were met in 20 (87.0%), clinical criteria in 19 (82.6%) and both laboratory and clinical criteria in 16 (69.6%).


Role of nephrectomy in hypertension with renal artery occlusion. Nephrectomy was performed in 12 patients with complete renal artery occlusion and hypertension refractory to intensive medical therapy. Renal vein renin was assayed preoperatively in 10 of the 12, and in 8 the ratio was at least 1.5:1, strongly suggesting renal artery occlusion on the side with the higher concentration of renin in venous blood. In two patients peripheral plasma renin activity was very high before operation, then decreased greatly afterwards. Three patients were considered cured and eight improved (overall improvement rate, 92%). The results were predicted by the renin ratio.


Disseminated histoplasmosis and necrotizing vasculitis. A 74-year-old man with congestive heart failure was found to have Histoplasma capsulatum in a lesion of the right nasal septum. His initial treatment with amphotericin B was inadequate because of severe intolerance to the drug. Three months after initial presentation H. capsulatum was detected in his blood and bone marrow. Slightly elevated purpuric lesions on the arms, lower legs and trunk showed the typical features of necrotizing vasculitis. Cutaneous anergy was reversed after treatment with transfer factor. Skin involvement in disseminated histoplasmosis is unusual and there are no previous reports of vasculitis associated with this infection.


Cystic fibrosis in adults: the unsuspected pulmonary diagnosis. The clinical spectrum of cystic fibrosis is insufficiently appreciated. This disease may occur in adolescents or adults who had minimal or no symptoms in childhood. In three patients the diagnosis was made on the basis of respiratory disease (including bronchiectasis, pneumonia and chronic bronchitis), a family history of respiratory disease, and elevated concentrations of electrolytes in the sweat. Two of the patients had pancreatic insufficiency, but this feature was not considered necessary for the diagnosis. It is important to make the diagnosis of cystic fibrosis in affected adults in order to prescribe appropriate therapy, avoid unnecessary operations, anticipate complications that are not common to other respiratory diseases, provide genetic counselling and initiate appropriate screening procedures to detect the disease in close relatives.


Utilization of health services in Western Canada: basic Canadian data from the World Health Organization/International Collaborative Study of Medical Care Utilization. In a household health survey more than 15 000 individuals in four areas of Canada were interviewed as part of the World Health Organization/International Collaborative Study of Medical Care Utilization. Data were collected to describe the health services system in each area and to measure the population's utilization of health professionals, hospitals, medicines and selected preventive services, perceived acute and chronic morbidity, attitudes and beliefs about health and health care, and sociodemographic characteristics. The proportion of persons with perceived morbidity was twice that of persons reporting visits with a physician in the same 2-week period. Prescribed and nonprescribed medications had been used by more than 50% of respondents in each area in the 2 days before the interview, nonprescribed medicines accounting for more than half of this use. Respondents were found to be more sceptical of medical doctors than of medical science.


Preschool detection of asymptomatic bacteriuria: a public health program. A total of 95% of parents registering their children for kindergarten agreed to screening for urinary tract infection (UTI) in their children. Urine specimens from 1591 children (87%), obtained at the school or at home, were tested. Only minor problems were encountered when parents prepared the specimens at home and mailed them to the laboratory for reading; the proportion of false-positive results was higher in these samples. If screening for UTI becomes established, it appears worth while to conduct this at the time of registration for kindergarten, either in the school by lay persons or in the home by parents.


Part-time hospitalization programs: the neglected field of community psychiatry. Part-time hospitalization for persons with psychiatric disorders is underdeveloped, underutilized and often poorly understood, but should be encouraged in view of the unsatisfactory living conditions of patients discharged from hospital who still require care, the reductions in psychiatric impatient populations and numbers of beds, the increasing costs of health services and the current fiscal restraints. Day and night hospitals can provide an alternative to inpatient or outpatient treatment, rehabilitation for the long-term patient or treatment for the patient in transition from inpatient to outpatient status. The day hospital can also provide a diagnostic setting. Such programs help preserve the patient's position in the family and the community, minimize the ill effects of hospitalization, and lower capital and operating costs of the psychiatric services. Awareness by medical and paramedical services of the value of these programs would increase their utilization. Shifting the emphasis of administrative and fiscal policies from inpatient to part-time hospitalization programs is also required.


Toxic nephropathy after low-dose methoxyflurane anesthesia: drug interaction with secobarbital? Vasopressin-resistant nonoliguric renal insufficiency developed in a 57-year-old man after 2 1/2 hours of low-dose methoxyflurane anesthesia. Secobarbital, 100 mg daily, had been taken for 1 month before. Of 13 patients in whom the influence of methoxyflurane on renal function was being studied, he was the only one to have taken a drug that induces microsomal enzymes. Blood values of methoxyflurane in this patient were lower than group means on all five occasions during anesthesia. Postoperatively his serum inorganic fluoride value reached 114 mumol/l -- more than two standard deviations greater than the group mean. Peak values for serum urea nitrogen, creatinine and uric acid and postvasopressin urine osmolality, and the lowest creatinine clearance in this patient also differed by more than 2 SD from the group mean, and the peak amount of oxalate excreted in his urine was double the group mean. Pretreatment with the barbiturate appears to have altered methoxyflurane metabolism and led to toxic concentrations of metabolites in the blood.


Primary care for nontraumatic illness at the emergency department and the family physician's office. A total of 1117 visits by patients to two hospital emergency departments and 15 family physicians' offices for nontraumatic complaints over two 2-week periods were studied. Patients visiting the two settings fell into two distinct subgroups, and they appeared to select where to seek care by the acuteness and duration of the complaint. Several highly significant differences were noted between the two groups: those who visited an emergency department had complaints of shorter duration, underwent more investigations (which more often gave abnormal results), were more likely to undergo investigation for mental symptoms, had more consultations, received counselling and drug therapy less often (but intramuscular injections more often), were admitted to hospital more often, returned for further care for the same complaint less often, complied with disposal instructions less often, were more likely to receive fewer than 5 days' care and were less likely to receive more than 31 days' care; those without a family physician more often received additional care (were referred, admitted or asked to return).


Colposcopy in the follow-up of women with lower genital tract or perianal carcinoma. Colposcopy has gained acceptance in the management of patients with abnormal cytologic smears or visible lesions of the lower genital tract. The well documented potential for the development of multifocal neoplastic disease in these tissues provides the rationale for the suggested use of the colposcope in the follow-up of patients with a previously treated carcinoma of the lower genital or perianal region. The value of colposcopy in such a patient is discussed.


The droopy shoulder syndrome.

The droopy shoulder syndrome. Three patients with the droopy shoulder syndrome are described. This condition occurs most often in young women who are mildly or moderately depressed. Their shoulders are painful and the only clinical sign is drooping of the shoulders. There are no signs of neurologic abnormality. A lateral radiograph of the cervical spine shows all seven cervical vertebrae, the first thoracic vertebra and part or all of the second thoracic vertebra.


Serum ferritin and the iron status of Canadians. Serum ferritin concentration was determined in 1105 Canadians aged 1 to 90 years. Geometric mean values (ng/ml) were as follows: children 1 to 4 years old, 12; children 5 to 9 years old, 15; adolescent girls, 17; adolescent boys, 18; women 20 to 39 years, 23; women 65 years and older, 52; men 20 to 39 years, 93; and men 40 and older, 92. Ranges were side in all age groups, reflecting variations in size of body iron stores. From analysis of the ferritin values it is highly probably that iron stores were greatly reduced in approximately 25% of children, 30% of adolescents, 30% of menstruating women, 60% of pregnant women and 3% of men. Iron-deficiency anemia was noted in only 2% of subjects. If "normality" requires more than small amounts of storage iron to meet physiologic demands, the study results suggest a high probability of iron deficiency in 60% of the pregnant women and in 19% of the other subjects; but if normality is defined as maintenance of adequate iron stores for erythropoiesis, the prevalence of iron deficiency was zero in the pregnant women and 2% in the other subjects.


Long-term survival after isolated replacement of mitral valve with ball-valve prosthesis. In 111 patients whose diseases mitral valve was replaced with a ball-valve prosthesis the actuarial survival rate, including the hospital mortality of 10.8%, was 66% after 5 years and 59% after 8 years of follow-up. This suggests that in patients with moderate or severe symptoms due to mitral valve disease, replacing the valve can prolong life. However, in patients with no cardiac symptoms or with sinus rhythm and mild symptoms, it is doubtful that mitral valve replacement can prolong life, for the prognosis in these patients is favourable without operation.