Correlation between plasma chlorpromazine and its metabolites and clinical ratings in patients with acute relapse of schizophrenic and paranoid psychosis. Nine patients diagnosed as having acute schizophrenic psychosis were treated with chlorpromazine. Their clinical response to drug treatment was measured by the use of a clinical rating scale developed from the Present State Examination, and a nurses rating scale. Plasma levels of chlorpromazine (CPZ), 7-hydroxychlorpromazine (7OHCPZ), monodesmethylchlorpromazine (NOR1CPZ) and chlorpromazine sulphoxide (SOCPZ), were monitored during the period of hospital treatment. Correlations were made between the increase in plasma levels of drug or metabolites and improvement in the different PSE scores. These showed that the most significant correlations occurred when symptoms with high diagnostic significance for schizophrenia (Group 1) and symptoms rating perceptual disorders (P) were correlated with plasma 7OHCPZ levels in plasma samples taken before the first morning dose of CPZ. The ration of 7OHCPZ to CPZ in these samples increased significantly as clinical ratings improved, this correlation being most highly significant against the Group 1 and P scores. The ratio of 7OHPCZ to SOCPZ increased significantly only in the case of Group 1 and P scores. This indicates a preferential shift of CPZ metabolism towards the formation of the active 7OHCPZ during the period of clinical improvement.


The social network, support and neurosis. The function of attachment in adult life. The psychological function of the social network is considered in terms of attachment theory. Social bonds are proposed as essential for obtaining a commodity commonly but unsatisfactorily referred to as support. Requirements for this complex commodity can be discerned in a wide range of contexts. Examples considered are the evolutionary origin of the social network itself, the concept of psychosocial supplies, the distribution of neurosis in Western and non-Western populations, the use of medical consultations, psychotherapy and habitual responses to adversity or disaster. In these and other contexts, it is apparent that individuals have, quite simply, a requirement for affectively positive interaction with others. Under stressful conditions this interaction is called 'support'. When support is lacking there is evidence that psychiatric and perhaps medical morbidity rates increase. For reaseach, the objective must now be to determine whether depleted primary group interaction is causally related to morbidity, or whether it is only an associated or a secondary factor in aetiology, or indeed wholly unrelated. Elucidating more precisely why people need people constitutes an important new task for social psychiatry.


Screening schoolchildren for high risk of emotional and educational disorder. Junior schoolchildren were screened for high risk of emotional and educational disorder. The information was gathered from the school, using standard and objective tests. The multiple criterion screen employed, comprised: (a) classroom behaviour scale (Rutter B Scale), rated by teachers; (b) sociometric tests; choice of companions by classmates. From these, lack of positive choices was taken as a measure of isolation and a high rate of negative choices, as a measure of rejection; (c) Reading quotient of 75 or below on the Young Reading Test; (d) Absence from school for reasons considered by teachers to be trivial. The number of cases identified by the screening was found to be 322 children per thousand. They may be seen as representing a high risk rate. Using extreme scores as indicative of high risk, approximately 17 per cent of children were identified on the basis of the behaviour test; 12 per cent by the reading test; 9 per cent by the isolation test; 8 per cent by the rejection test and 3 per cent by the absenteeism test. Seventy per cent of the identified children were rated clinically as disturbed. Absenteeism identified the smallest percentage of cases and made the smallest independent contribution of identification. Isolation was not impressively related to neurotic or antisocial behaviour. The three important criteria, therefore, were behaviour, rejection and reading. Corrected disturbance rates for our population of 7-8-year-old children, including those not identified by the screen, were 6-8 per cent markedly maladjusted and 33-7 per cent somewhat maladjusted.


Drug dependent individuals dealt with by London casualty departments. During a study of drug incidents dealt with in one month by 62 casualty departments in Greater London, 395 drug-dependent individuals were identified. The great majority of these patients were seen in hospital following an overdose, and barbiturates were the drugs used most frequently. A high incidence of multi-drug use was noted, and many individuals had obtained their drugs from an illicit source. A history of repeated overdosing was common, and one fifth of the patients behaved aggressively while they were in casualty. The implications of these findings are discussed, with particular reference to the demands that are made on casualty departments by drug-dependent individuals.


A framework for adolescent disorder: some clinical presentations. Seven frequently-occurring, more or less sterotyped, adolescent presentations are described to illustrate the relevance of a specific clinical framework for adolescent disorder. This recognizes the maturational background in adolescence, the family involvement in this process and the various factors that can affect it. Disorder is viewed in terms of inappropriate identity choice at this time, a state of maturational deadlock, and can be categorized according to the types and severity of the maladaptive responses. Treatment, capitalizing on the adolescent's state of change and flux, concentrates on more adaptive future identity formation, and can be most rewarding. Orthodox assessment procedures, as used with adult patients, stand the risk of reinforcing a dependent 'psychiatric patient' identity.


The husbands of agoraphobic women and their influence on treatment outcome. Thirty-three married women, all agoraphobic but most with additional phobias, were exposed to a standard four-day intensive behavioural treatment programme as out-patients. The effects of this on the patients and their spouses throughout a one-year follow-up are reported and discussed.


Provoked anxiety as a treatment of exhibitionism. A treatment for male genital exposure (exhibitionism) has been given successfully to 15 persons who have previously been resistant to change. The procedure involves the subject undressing before a mixed sex audience, followed by video-taping and subsequent replay to the patient. During the period of nakedness the subject describes in detail the events, his expectations and attitudes, and those attributed to his victim during exposure. The success of the treatment appears to depend on the profound anxiety induced. During the phase of greatly increased anxiety, cognitive changes previously resisted seem to be made possible.


Maternal age and incidence of schizophrenia in the Republic of Ireland. The excess incidence of schizophrenia reported from Ireland may partly be due to the unusual distribution of the irish population by maternal age at birth.


Prisoners' personality: a factor analytically derived structure. A factor analytic study of personality questionnaire data obtained from a group of 175 long-term prisoners revealed a factor structure which appears to be peculiar to prisoners. In particular, hostility and anxiety obtain prominence in the structure, while the theoretically significant dimension of extraversion is relegated in importance.


A report on the psychological test results of battering parents. The short form of the Wechsler Adult Intelligence Scale and Cattell's 16PF test have been given to patients attending the National Advisory Centre on the Battered Child (NSPCC) and in the case of the personality questionnaire the results compared to non-battering control adults' scores. The intelligence levels of battering parents conform to normal expectation although there is a non-significant trend to marginally lower than normal results especially in verbal tests. The 16PF test reveals immature impetuosity on the part of the mothers as a main finding and introversion in the fathers. The relevance of these findings to battering is discussed.


An experimental study of compliance and post-hypnotic amnesia. A procedure was devised to test the hypothesis that the traditional measure of post-hypnotic amnesia, which involves determining the number of items recalled before and after a 'release' signal, may be significantly biased by compliance. One group of subjects (group B) was given an opportunity to 'own-up' to compliant behaviour before being tested for post-hypnotic amnesia. Another group (group A) was only given the opportunity to own-up after being tested for amnesia. Results indicated a very strong compliance effect, group A showed significantly more post-hypnotic amnesia than group B.


Psychoticism and thinking.

Psychoticism and thinking. In view of evidence linking psychosis with high creative ability, an attempt was made to evaluate the relationship between thinking abilities and personality traits. Tests of divergent thinking and convergent thinking were administered, along with the Eysencks' Personality Questionnaire, to 100 university students. The hypothesis that 'psychoticism' is related to divergent thinking was strongly confirmed. The hypothesis that psychoticism would be related inversely to speed in a convergent-thinking task was rejected. No evidence was found for any relationship between extraversion--introversion or neuroticism--stability and either thinking style.


An investigation into disordered adolescents by means of the Brook Reaction Test. Three groups of psychologically disordered male adolescents were matched with controls for age and intelligence, on a one-to-one basis. Group a (n = 83) comprised delinquents, this designation being determined by a history of at least one court conviction. All of these were in borstals or approved schools. Group b (n = 65) were delinquent-and-disturbed: these too had had at least one court conviction and, in addition, they were having psychiatric treatment. Members of group b were also in institutions: these included psychiatric hospitals and prisons, as well as borstals and approved schools. Group c (n = 41) consisted of 'disturbed-only' youths: they had had no convictions but were receiving psychiatric treatment. Each group covered a very wide range of intelligence. All the subjects took the Brook Reaction Test, the aim of the inquiry being to ascertain whether this test differentiates (scored blind) between the experimental groups and their controls. Significant differentiation was found on the following Brook indices: (1) Number of points gained on questionable responses; (2) type of questionable response given; (3) sexual responses; (4) pattern of interests. In all six groups richness of interests proved to be associated with high intelligence.


Sex differences in response to a self-rating depression scale. Fifty-five male and 80 female psychiatric in-patients complaining of depression completed the Zung Self-Rating Depression Scale (SDS). Both quantitative and qualitative differences were found between male and female respondents. Females had significantly higher (more pathological) total scores than males and significantly higher scores on six individual items. Examination of factor profiles for males and females revealed further differences. These differences are consistent with the thesis that men and women subjectively perceive feelings of depression in disparate ways. The implication of this findings is that the clinical use of the SDS be modified to take such differences into account.


Renography in the assessment of patients with uretero-sigmoid diversion. A comparison was made between the excretion urogram and the radio-isotope renogram in 35 patients with uretero-sigmoid anastomosis. A good correlation was obtained between the 2 tests in the presence of radiographic evidence of (a) hydronephrosis, (b) poor renal function and (c) absent function. Renographic evidence of mild impairment of secretory function and of delayed excretion was associated with a significant number of normal excretion urograms and in a few instances there was later progression to severe renal impairment or hydronephrosis. Hydro-ureter associated with a normal renogram carried a good functional prognosis. Renography is recommended in the long-term supervision of patients with uretero-sigmoid anastomosis.


The behaviour of the ureters following radiotherapy and Wertheim hysterectomy. The pyelographic appearances following Wertheim hysterectomy have been studied in 19 cases. The dilatation of the lumbar segments with unusually rapid transmission through the pelvic segments has been found 6 weeks postoperatively although this dilatation has disappeared in most cases by 6 months. Late ureteric dilatation is of no value in itself in determining the presence or absence of recurrent growth.


A psychiatric study of women with urgency and urgency incontinence. 26 patients with frequency, urgency and urgency incontinence, without bladder or urethral abnormality, underwent psychiatric evaluation. They were divided into 2 groups according to the degree of neuroticism found. Treatment by group and individual psychotherapy showed that approximately one-third of the patients benefited considerably, one-third refused treatment or ceased prematurely and one-third improved slightly or not at all. The importance of excluding organic bladder or urethral disease prior to psychiatric assessment is stressed.


Closed catheter drainage and urinary infection--a comparison of two methods of catheter drainage. The incidence of urinary infection following urological operations is compared using 2 methods of closed catheter drainage in 214 patients. No significant difference was observed. The overall infection rates for the whole series were 32%. The most significant influence on the rate of infection appears to be the duration of catheter drainage. Failure of chemotherapy to eradicate infection while the catheter was still in situ was mostly due to the use of inappropriate antimicrobials. Only 2 of the 35 cases with infected urine had succeeded in clearing their infection at the 4-week follow-up without chemotherapy.


Adjuvant immunotherapy with B.C.G. in carcinoma of the prostate. 8 previously untreated patients with Stage III and Stage IV prostatic cancer who had had the bulk of their primary tumour removed by transurethral resection, and residual tumour suppressed by bilateral total orchidectomy, were given adjuvant immunotherapy by direct injection of B.C.G. into the prostate. The pyrexial reaction to, and the histological changes from B.C.G. have been more marked in the patients whose disease is no longer controlled by conventional therapy. Granulomas have been found in the lungs, liver, myocardium, spleen and bone marrow. Granulomas in carcinomatous areas have been associated with tumour cell degeneration.


Renal function in patients with hydronephrosis. The glomerular filtration rate and pelvic drainage function were reinvestigated after 3-5 years in 50 patients with hydronephrosis secondary to functional obstruction in the pelvic-ureteric junction. Pyeloplasty by the Anderson-Hynes' technique had been performed in 28 kidneys, while 12 patients were not operated upon and 10 had had a nephrectomy. The glomerular filtration rate was determined with the clearance technique and isotope renography. 16 out of 28 kidneys subjected to pyeloplasty and 11/12 non-operated kidneys had a normal renal parenchymal function at the first investigation in spite of severely disturbed drainage function. In the non-operated series the renal parenchymal function was unchanged in 11 patients. Deterioration was observed in 1 kidney, probably because of chronic pyelonephritis. Uncomplicated cases of pelvic-ureteric junction obstruction should not be operated upon unless necessitated by symptoms. A yearly control programme including a renal function test and plain films of the upper urinary tract is recommended for these patients.


Causes of renal deterioration in patients with meningomyelocoeles. The patient records of 122 children with meningomyelocoeles were analysed in an attempt to find a common factor causing upper tract deterioration. The results clearly show that grade III reflux followed by obstructive hydroureter are the commonest factors associated with significant renal deterioration.


Renography as a prognostic index of urinary tract problems in childhood. Many radiological methods are used in investigating urinary tract problems in children, and some are poorly tolerated. The simplest and most acceptable technique is isotope renography. Its value has been assessed in predicting the outcome of urinary tract problems in 91 children over the age of 2 years presenting consecutively over a period of 3 months. The results of initial assessment by renography and radiography have been compared with the final clinical assessment 7 years later. 35 patients were identified as being "at risk" and all of these had abnormal renograms and radiograms. Normal renographys was found unexpectedly in some patients with severe reflux but with a good final result. It is concluded that renography can be used to screen children with urinary tract infection, thereby excluding the less acceptable radiological investigations unless the renogram is abnormal.


Seasonal variations in the incidence of ureteric colic. A retrospective study of 1097 male in-patients with ureteric colic was conducted to try and define the aetiological effect of climate on the disease. The overall monthly incidence for the study period of 10 years was found, on statistical analysis to correlate with ambient temperature thus: (1) directly with the mean temperature of the preceding month, (2) directly with the difference between mean maximum and mean minimum temperatures of the same month, and (3) inversely with the mean maximum temperature of the same month. The correlation was interpreted on the basis that hot ambient temperatures promoted stone generation whereas cold ones promoted stone descent through cold-induced diuresis. This trend, among its other implications, could pinpoint the reason for the increase in nephrolithiasis with industralisation.


Seasonal variations in urinary crystals. Individual urine samples from normal subjects and stone-formers with idiopathic hypercalciuria have been examined for crystals both qualitatively and quantitatively at 37 degrees C. The group as a whole showed a rise in incidence of urinary crystals in the summer months of June to August inclusive. This rise was seen most clearly in overnight urines, collected on rising in the morning, and the patients appeared to be at risk overnight during the summer. In the untreated patients the summer rise in incidence of phosphate crystals was quite dramatic but was only small in the cellulose phosphate treated group, who showed a rather constant and raised incidence of oxalate crystals right through the year. Seasonal crystal incidence has been compared with seasonal changes in urinary composition. The rise in crystal incidence during the summer was associated with increased creatinine concentration in the same urine samples and with increased oxalate concentration in 24-hour urine collections.


Manometric and electromyographic assessment of urethral resistances in children. In an attempt to define urethral resistances in children, 84 cystometries were performed, combined with an anal EMG in 54 cases. The urethral pressure profile was measured in each patient. The following parameters were studied: bladder tone, activity and contractility; micturition EMG; maximal urethral pressure; aspects of the urine stream; and residual urine. It was found that each parameter considered alone is insufficient for assessment of bladder outlet obstruction. Only the complete investigation proved to be highly reliable as a complement to radiological findings, and allowed a dynamic assessment of bladder and sphincter functions.


Cystic duplication of ejaculatory duct: case report. A case of complex malformation of the genito-urinary tract, including cystic dilatation and partial duplication of the ejaculatory duct is reported. The lesion was visible on retrograde and anterograde vasovesiculography; its complete removal was possible using an abdominal approach.


Parameatal urethral cysts: a review of 6 cases. 6 cases of parameatal urethral cysts are reported in 3 males and 3 females. The condition is considered to be rare. The aetiology is thought to be obstruction of the para-urethral ducts possibly due to infection. The treatment of choice is complete excision.


Ultrasonic evaluation of scrotal swellings. Scrotal swellings in 18 patients were examined by ultrasound. Sonography can differentiate fluid from solid masses. All but 2 patients who had torsion of the testicle were correctly diagnosed prior to operation. Although this is only a preliminary report, it does demonstrate that useful information may be obtained by this method.


A papilloma of epididymis of Müllerian vestigial origin. A 20 mm diam. nodule attached to the lower pole of the epididymis was found in a 48-year-old man presenting with recurrent hydrocele. Histology showed a benign papillary tumour of a type apparently not previously described. It is believed to have arisen from Müllerian remnants.


The significance of retroperitoneal lymph node morphology in testicular tumours. The role of the regional lymph nodes in cancer is controversial. Non-neoplastic changes in lymph node histology can be correlated with prognosis for some tumour types and reactivity has been interpreted as evidence of an immune response to the tumour. Attempts to correlate the patterns of retroperitoneal lymph node activity with prognosis in patients with seminoma and non-seminoma germinal testicular tumours have not been successful. The implications of these findings are discussed.


1-alpha-hydroxycholecalciferol for renal osteodystrophy. Fourteen patients with renal osteodystrophy were treated for at least one year with 1-alpha-hydroxycholecalciferol (1-alpha-OHD3) in a dose varying from 1 microgram/week to 3 microgram/day. Plasma calcium and inorganic phosphorus concentrations increased significantly. The plasma alkaline phosphatase concentration fell in 11 of the 12 patients in whom it was initially raised and returned to normal in seven. Serum parathyroid hormone concentrations were initially raised in all patients, but they decreased significantly with treatment and became normal in eight patients within one year. The 10 patients with radiological abnormalities showed some improvement. Hypercalcaemia occurred in 11 patients, and necessitated a reduction in the dose of 1-alpha-OHD3 in some. 1-alpha-OHD3 was effective in reducing the biochemical and radiological abnormalities of renal osteodystrophy, but it should be used wtih care, and plasma calcium concentrations should be monitored.


Enhanced allergic tissue injury in Goodpasture's syndrome by intercurrent bacterial infection. Studies of 16 relapses in seven patients receiving treatment for Goodpasture's syndrome showed that intercurrent bacterial infection seemed to be the precipitating event in 13 cases, whereas a rising antibody titre to glomerular basement membrane was responsible in only one. This association between infection and relapse in Goodpasture's syndrome has several implications for the pathogenesis of antibody-mediated tissue damage, and, clearly, more experiments are needed. Whatever the explanation, however, prevention and early diagnosis and treatment of infection in anti-GBM disease are important.


Hepatic structure and function after modified jejunoileal bypass surgery for obesity. The most serious adverse effect of standard intestinal bypass for obesity is the high incidence of hepatic dysfunction and death from hepatic failure. We therefore examined the long-term effects of a modified form of jejunoileal bypass (in which a greater continuous length of ileum is retained), on liver function in 120 patients. Substantial weight loss (119-0+/-SD 23-3 kg to 82-3+/-18-8 kg) occurred during the first nine months after surgery, accompanied by a significant rise in serum concentrations of bilirubin, alanine transferase, and alkaline phosphatase, and a significant reduction in albumin concentrations. Biochemical changes were unrelated to weight loss or halothane anaesthesia. After weight stabilisation liver function reverted to normal, and four years after bypass sulphobromophthalein retention and hepatic histology did not differ from those in obese controls. There were two postoperative deaths. Three other patients died during the period of rapid weight loss with severe hepatic steatosis. While transient mild impairment of liver function is common after modified jejunoileal bypass, clinically significant hepatic dysfunction is a rare and unexplained early complication.


Lumbar epidural analgesia in labour in twin pregnancy. Fifty twin pregnancies in which the mother received epidural analgesia in labour were compared with 92 in which the mother received standard parenteral analgesia. The duration of the first and second stages of labour; the incidence of assisted deliveries when the head presented; the proportion of breech extractions when either the first or second twin presented by the breech; the incidence of low Apgar scores; and the perinatal mortality were not significantly different in the two groups. These findings suggest that lumbar epidural analgesia is safe for providing pain relief in labour for patients with a twin pregnancy. Moreover, an epidural block is preferable to conventional analgesia in these cases as it allows prompt intervention to effect delivery of the second twin.


Respiratory arrest in familial hemiplegic migraine: a clinical and neuropathological study. We describe a fatal case of familial hemiplegic migraine. A transient respiratory arrest in this patient led to a persistent "vegetative state," culminating in death four months later. Neuropathological findings included deep microinfarcts in the basal ganglia and a remarkable sparing of brain-stem nuclei associated with the function of respiration.


Mothers' experiences of induction.

Mothers' experiences of induction. Mothers of a random sample of 2182 legitimate live births were interviewed about their experiences of pregnancy, labour, and delivery. Of these, 24% reported that their labours were induced, and data about this from a subsample of mothers tallied with information obtained through the doctors in charge in 88% of cases. All but 3% of the mothers who were induced perceived some medical reason for the induction. The proportion of inductions in the 24 study areas ranged from 6% to 39%. A relatively small proportion of labours in "teaching" hospitals, small hospitals with less than 100 beds, and GP maternity hospitals were induced, but a comparatively high proportion of private patients had an induction. There was no clear association between induction and the mother's age or parity. Despite being given more pain relief, those who were induced reported similar intensities of pain during the first and second stages of labour to those whose labour started spontaneously; they also reported that they had "bad pains" for a similar period. The period they had contractions was shorter for the induced than for those starting spontaneously, and the intensity of pain at delivery was rated somewhat less by those who were induced.There was no difference between induced babies and others in the proportion who were held by their mothers immediately after their birth. Two-fifths of the mothers who were induced would have liked more information about induction; and a similar proportion said they had not discussed induction with a doctor, midwife, or nurse during their pregnancy. Only 17% of the mothers who had an induction said they would prefer to be induced if they had another baby. This contrasts with 63% of those who had epidural analgesia who would opt for the same procedure next time, while 83% of those who had had a baby in hospital, and 91% of those having had a home birth, would want their next baby in the same type of place.


Patients' attitudes to induction and labour. An attempt was made to ascertain patients' attitudes towards planned induction and labour. Twenty per cent of patients had not heard of induction before their pregnancy, and those who had had most probably heard about it from relations and friends rather than the media. Most patients had no firm opinions on induction of labour but were usually glad to have their pregnancy ended. Many considered that they had not been given enough information by the medical staff on their induction. The amount of pain experienced by patients at amniotomy was related to the "favourability" of the cervix. Possibly women with a low cervical score should be given more premedication or inhalation analgesia at amniotomy. Most patients found injections of narcotic agents adequate analgesia in labour. Those patients who did not receive adequate analgesia were principally those who had either very short or quite long labours. Patients with long labours may benefit from more liberal use of analgesia, but no satisfactory form of analgesia seems to be available for patients who are likely to deliver within two or three hours of induction.


Prospective trial of oestrogen and calcium in postmenopausal women. In a prospective trial in 72 postmenopausal women to compare the effects on bone loss of no treatment, treatment with oestrogen, and treatment with calcium the women were followed up for at least two years and examined densitometrically and morphometrically. Women in the untreated control group continued to lose bone during the two years, whereas the oestrogen-treated group lost none. Loss in the calcium-treated group was intermediate. Oestrogen appeared to inhibit endosteal bone resorption and may have stimulated subperiosteal bone apposition.


Kinetics of indium-III labelled lymphocytes in normal subjects and patients with Hodgkin's disease. The distribution in the body and the circulation in the blood of autologous lymphocytes labelled with indium-III were studied in two normal subjects and two patients with Hodgkin's disease. Four hours after injection radioactivity was identified in the spleen, liver, and bone marrow. Radioactivity, followed by imaging and whole body scanning, began to appear in the lymph nodes four to 18 hours after injection, and some, though not all, lymph node groups in the body could be readily visualised. There were no differences between the normal subjects and the patients with Hodgkin's disease. The pattern of clearance of radioactivity from the blood was consistent with a normal circulation between blood and lymphoid tissues of the labelled lymphocytes. Since indium-111 stays firmly attached to the cell, it seems an ideal label for studying lymphocyte kinetics, and the use of this technique may have further clinical application.


Demand for patient care.

Demand for patient care. A study was performed to determine the extent to which patients of all types were receiving inappropriate levels of care. The needs of patients in acute and supporting hospitals, people in residential homes, and patients cared for at home were assessed. A sixth of the hospital inpatients did not need hospital care, while 5% of those in residential homes and 5% of those at home did need hospital services. These findings indicate that a realistic provision of hospital beds would be 4 per 1000 population for all specialties except regional specialties, psychiatry, mental subnormality, obstetrics, and paediatrics. About a third of these beds need to be acute, while the rest may be in supporting or community hospitals. Thus the current provision of acute beds (2-0 to 2-5 per 1000 population) exceeds actual need.


The diagnostic process: a comparison of scanning techniques. In choosing between various scanning techniques the factors to be considered include availability, cost, the type of equipment, the expertise of the medical and technical staff, and the inherent capabilities of the system. Although it is difficult to state dogmatically which scanning technique is best for each patient and condition, one or other technique is clearly preferable in some areas of medicine. Ultrasound, for example, should be used in obstetrics, while computerized tomography has revolutionised neuroradiological diagnosis. Nevertheless, there is still no substitute for good history taking and a thorough physical examination. The most important factor determining the choice of technique is the system's ability to answer the specific question required for the management of the patient.


Regional co-ordinator for haemophilia in domiciliary practice. The North-east Thames Region has appointed a nursing sister to co-ordinate the organisation of care for haemophiliacs in the region. As a result of the appointment, facilities for home treatment have expanded rapidly. Several associate centres providing care to haemophiliacs have been set up around the region in addition to the four main haemophilia centres, which are all in the south-west corner of the region. As well as providing support and supervision of patients on home treatment, the co-ordinator helps to place haemophiliac children in suitable schools, maintains the regional register of haemophiliacs, and has a more general role in ensuring that services are available where they are needed throughout the region.


Plasma creatinine and urea: creatinine ratio in patients with raised plasma urea. We examined the plasma urea and creatinine concentrations and the ratio between them according to diagnosis in 100 unselected and 31 selected adult hospital patients with a plasma urea concentration greater than or equal to 10 mmol/l (60mg/100ml). We also examined plasma urea and creatinine concentrations in 350 unselected consecutive patients, but found no useful relation between the two values. Congestive heart failure was the most common identifiable cause of a raised plasma urea concentration in the 100 unselected patients (36%). Among these 100 patinets the plasma creatinine concentration was a more useful discriminant between prerenal uraemia and intrinsic renal failure than was the urea:creatinine ratio or the plasma urea concentration. A plasma creatinine concentration greater than 250 mumol/1 (2-8 mg/100ml) indicated intrinsic renal failure with a 90% probability.


Disproportion in the falling birth rate. Since 1962 there has been a disproportionately greater fall in the number of small (less than 1000 g) live births than total live births: this has applied to Sheffield and to England and Wales but more to the former. This may have affected falling neonatal mortality rates.


Post-"pill" amenorrhoea--cause or coincidence? The relationship of contraceptive history to diagnostic category of amenorrhoea was analysed in 131 consecutively investigated cases of secondary amenorrhoea. Amenorrhoea occurred in 52 patients immediately after discontinuing the oral contraceptive. Twenty-two had had amenorrhoea before oral contraceptive treatment and 23 patients before the episode of non-contraceptive-related amenorrhoea investigated here. When these cases were excluded from analysis there was no significant difference in the distribution of any of the diagnostic categories between those who had used the oral contraceptive and those who had not. The results suggest that using oral contraceptives does not cause subsequent amenorrhoea.


Applications submitted to regional research committees in 1976 and their outcome. In 1976 regional research committees in England and their equivalent in the Welsh Office judged 608 proposals for funding under the locally organised research scheme. Of these, 521 were new proposals and 87 were resubmissions. Medically and dentally qualified applicants made 451 (87%) of the new proposals; nearly two-thirds came from teaching areas and 21% from staff of academic departments. Two hundred and ninety new proposals were approved, 154 rejected, and 77 were referred back for modification. Approval was commoner for applications from teaching areas, from medical staff, and for the less expensive projects. Some regional committees did not support research into the organisation of health services. Under a quarter of the resubmitted projects were rejected. The scheme is not yet used by a wide range of health-care professions. Medical staff in teaching areas still use it most. In some regions prospective researchers, especially those without previous experience, need a comprehensive and easily identifiable counselling service, so that the fund may be exploited in the way originally intended and the number of unsuccessful proposals reduced.


Cytochemical localization of acetylcholine receptors at the neuromuscular junction by means of horseradish peroxidase-labeled alpha-bungarotoxin. The cytochemical localization of acetylcholine (ACh) receptors at the neuromuscular junction was investigated with a procedure utilizing alpha-bungarotoxin (alpha-BtX) labeled directly with horseradish peroxidase (HRP). Following incubation of tissues in the conjugate and reaction for peroxidase, activity was observed on the junctional folds of the motor endplate. A uniform layer of reaction product approximately 15 nm thick occurred over the apical portions of the junctional folds. Membranes at the bases of the synaptic cleft showed only small amounts of reaction product. Non-junctional regions of the muscle fiber were unreactive. Activity was also observed in the membrane of the axon facing the muscle surface, often including the axolemma overlying the "active zones" of the nerve terminal. Such presynaptic activity was still evident on nerve terminals disjuncted from the synapse by enzymatic treatment prior to incubation in the conjugate. This localization indicates the possible presence of presynaptic ACh receptors within the axolemma. In muscle denervated for 7-12 days, motor endplates were reactive and parajunctional sarcolemma showed slight activity, but most extrajunctional regions contained no obvious accumulations of reaction product. Activity at all sites was prevented by preincubation of tissues in native alpha-BTX prior to incubation in the conjugate and reaction for HRP. This procedure represents a simple and convenient method for the high resolution localization of ACh receptors.


Body weight and regulatory deficits following unilateral nigrostriatal lesions. Unilateral nigrostriatal lesions were performed in rats by punctate injection of 6-hydroxydopamine. Lesioned animals exhibited anorexia and weight loss for 7-11 days after surgery. These animals then displayed normal rate of weight gain. However, there was a chronic depression of body weight in the lesioned animals relative to sham controls, evident for over two months after 6-hydroxydopamine administration. Unilateral nigrostriatal damage also produced major deficits in the animals' water intake in tests of prandial drinking, response to water deprivation, and response to osmotic challenge. The relationship of nigrostriatal damage to the "lateral hypothalamic syndrome" and the role of dopaminergic neurons in regulation and ingestive behaviors are discussed.


Prolactin in human and rat serum and cerebrospinal fluid. Rats treated with haloperidol or bearing subcutaneous implants of prolactin-secreting tumors had elevated CSF prolactin levels compared to those observed in control rats. These levels were commensurate with the increased serum level of prolactin, although there appeared to be an upper limit to the CSF prolactin concentration. Patients with prolactin-secreting pituitary adenomas had elevated CSF hormone levels as compared to patients with non-endocrine neurologic disease. This obtained, regardless of whether the tumor was intra- or extrasellar in its growth. The implications for the route of entry of prolactin into CSF under both normal and abnormal conditions, and the potential role for CSF prolactin as part of a feedback regulatory system on pituitary prolactin release are discussed.


Antagonistic action of diphenylhydantoin and calcium on the level of phosphorylation of particular rat and human brain proteins. The opposing actions of diphenylhydantoin (DPH) and calcium on the level of [32P]phosphate incorporation into particular rat and human brain proteins have been demonstrated in this study by employing the techniques of acrylamide gel electrophoresis and autoradiography. In the presence of calcium several brain proteins showed a marked increase in the incorporation of [32P]phosphate from [gamma-32P]ATP. The calcium-induced increase in phosphorylation of two proteins, designated proteins DPH-L and DPH-M, was significantly inhibited by DPH. DPH inhibited both the calcium-stimulated initial rate and net level of [32P]phosphate incorporated into proteins DPH-L and DPH-M in homogenate and synaptosomal preparations. The data presented in this study are compatible with the hypothesis that the effect of DPH on protein phosphorylation may play an important role in mediating the stabilizing actions of this anticonvulsant on neuronal tissue and seizure discharge.


Cellular events induced in the molecular layer of the piriform cortex by ablation of the olfactory bulb in the mouse. Cellular events associated with degeneration of the projection of the olfactory bulb to the molecular layer of the piriform cortex of the mouse have been studied with rapid-Golgi and Fink-Heimer impregnations and with the electron microscope. Four classes of axon terminals: s-1, s-d, f-1, and f-d, are differentiated on the basis of whether the synaptic vesicles are spherical or flattened and whether the axoplasm is lightly or darkly stained. The majority of s-1 terminals, the predominant class in sublamina Ia of the molecular layer, degenerate after bulb ablation. Degeneration of axon terminals is associated with dilation and, eventually, degeneration of segments of dendrites in Ia. Both s-1 and s-d terminals contribute to a partial reconstitution of the neuropil of Ia during the weeks after bulb ablation.


Discharge patterns of the nucleus parabrachialis lateralis neurons of the cat during sleep and waking. Discharge patterns of the nucleus parabrachialis lateralis (PbL) neurons located in the dorsolateral pontine tegmentum were investigated in 7 unrestrained, freely behaving cats with a multiwire electrode bundle method. Among 84 PbL units recorded so far, 31% of the units exhibited a marked reduction or complete cessation of firing during paradoxical sleep (PS) (PS-off cells), while 55% of the units exhibited an increase of firing during PS (PS-on cells) as compared with quiet wakefulness (QW) and slow wave sleep (SWS). The remaining 14% of the PbL units exhibited no remarkable change of firing rate and pattern during the sleep-walking cycle. The PbL PS-off cells were further characterized by a slow and regular firing pattern during QW and SWS, and they were similar in several respects to the PS-off cells reported in the nucleus raphe dorsalis and locus coeruleus complex. Six of the PbL PS-on cells were tightly phase-locked with PGO waves, and the spikes preceded by 5-25 msec the onset of the PGO waves recorded in the lateral geniculate nucleus. Seven other PbL PS-on cells were related to the locomotor activity observed in active wakefulness. In light of the present results, the functional significance of the PbL units has been discussed.


Midbrain unit activity during classical conditioning. In behaving rats, unit activity recorded from the ventral tegmentum and from the reticular formation was monitored during classical conditioning. Rewarding electric stimulation of the medial forebrain bundle was used as the unconditioned stimulus (UCS). Only those cells possessing prior responses to the conditioned stimulus (CS) changed their responses as a result of conditioning. Responses recorded from cells which were driven by both the auditory CS and the brain shock UCS were significantly more often changed than those driven by the CS alohe. These data show that the auditory and brain shock fields of influence interact in at least some brain regions prior to conditioning and that pairing the two kinds of stimuli is more likely to influence auditory responses recorded from these regions than those recorded elsewhere. It is possible to imagine that the intersection of the two fields is a sine qua non of conditioning and that the two prior actions caused the change by interacting at or near the recording point.


Lack of acquisition in dopamine denervated animals tested in an underwater Y-maze. There are a number of conflicting reports in the literature on the ability of dopamine (DA) denervated animals to acquire various instrumental tasks, mostly conditioned avoidance responding. The interpretational difficulties stem partly from the difficulties to test an animal that is deficient in initiating voluntary movements and partly from the difficulties to produce complete DA denervations. We have tried to solve these problems by testing DA denervated animals in an underwater swim maze where even severely denervated animals will overcome their akinesia and swim the maze. 6-Hydroxydopamine was injected into the bundle of ascending DA axons in order to produce the best possible DA degeneration and the animals were tested as soon as the degeneration was complete (48 h) in order to avoid compensatory processes. We found that such animals were unable to acquire a brightness as well as a spatial discrimination task even when the experimental situation was such that they were able to overcome their difficulties to initiate voluntary movements. Possible explanations to the discrepancies between our studies and others are discussed.


Binding of [3H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by experimental diabetes. In streptozotocin-diabetic female rats acute (24 h) withdrawal of insulin significantly impairs both estradiol + progesterone-induced sexual receptivity and cell nuclear concentration of [3H]estradiol in hypothalamus, preoptic area, and pituitary gland. Omission of insulin treatment for the first 24 h of a 30-h or 54-h estradiol benzoate-conditioning period significantly reduced mean lordosis ratings of ovariectomized-diabetic rats. Insulin withdrawal at the time of progesterone treatment and behavioral testing did not diminish sexual receptivity. One-half or 2 h after an intravenous injection of [3H]estradiol-17beta diabetic rats without insulin exhibited reduced cell nuclear [3H]estradiol concentrations (2 h) and/or diminished cell nuclear/whole homogenate concentration ratios (0.5 and 2 h). Twenty-four hour insulin withdrawal affected neither whole tissue [3H]estradiol uptake nor hypothalamus-preoptic area cytoplasmic estrogen-receptor content. These results: (1) suggest that diminished estradiol binding by target tissue cell nuclei may contribute to the well-known reproductive failures of female diabetics, and (2) support the concept that estradiol acts at the level of brain cell nuclei to induce female sexual behavior.


Electron microscopic effects of thallium poisoning on the rat hypothalamus and hippocampus: biochemica changes in the cerebrum. Rats were given thallous acetate (5 mg elemental thallium/kg body weight) IP daily for 7 days and prepared for electron microscopy (perfusion-fixation) and for biochemical study. Increased incidence of Golgi zones and electron-dense bodies were observed in the anterior hypothalamus and hippocampus. Sequestrated axons were seen in the hypothalamus. Depletion of succinic dehydrogenase and guanine deaminase occurred in the cerebrum.


Stimulation increases incorporation of [3H]lysine into rat brain and liver proteins. Exposure of rats to electric footshocks or merely to the footshock apparatus increased the incorporation of [3H]lysine into brain and liver protein. The effect was present in both fore-and hindbrain. The footshock treatment was the more effective stimulus, producing larger and more significant changes. These results resemble those previously observed in C57Bl/6J mice, and thus suggest that altered protein or amino acid metabolism is a general response to stress in rodents.


Removal of olfactory bulbs in chickens: consequent changes in food intake and thyroid activity. Surgical removal of the olfactory bulbs (O.B) in the chicken caused a marked increase in food intake, which was not accompanied by development of obestiy. Oxygen consumption of the O.B. removed birds was significantly higher than that of the controls. Alcianophylic-thyrotropic cell population of the adenohypophysis and the percentage of active follicles in the thyroid gland were higher for the O.B. removed birds than for those of the controls. Feed supplementation of 0.1% propylthiouracil to the O.B removed birds abolished the previously exhibited hyperphagia and caused a significant decline in oxygen consumption. The possibility that the O.B removal caused a primary increase in thyrotropic axis activity follwoed by a secondary compensatory hyperphagia, is discussed.


Differential morphine effects on evoked impulse activity in the caudate and central grey. This study had two primary objectives: (1) to develop a new physiological method for investigating opiate action, based on the effect of morphine on evoked impulse activity in small neuronal populations, and (2) to test the hypothesis that morphine's effects would vary with response site (caudate and central grey), and with stimulation site (sciatic nerve, substantia nigra). Bipolar recordings were made from curarized, artificially respired rats. Morphine increased stimulus thresholds for sciatic evoked responses in both brain areas, with especially marked effects in the central grey. Sciatic stimulation produced phasic (transient) responses in both brain areas to mild stimulation and tonic (sustained) responses to more intense stimulation; the tonic responses were depressed more effectively than phasic responses. Substantia nigra stimulation produced only tonic responses in both areas, and morphine did not alter these stimulation thresholds. Morphine effects were blocked and reversed by naloxone. Thus, clear differential depressive effects of morphine were demonstrated in terms of function (phasic vs. tonic responses), in terms of stimulus site, and in terms of responding site.


Slow-wave sleep induced in cats by extremely small amounts of synthetic and pineal vasotocin injected into the third ventricle of the brain. A single injection of 10(-6) pg synthetic arginine vasotocin (AVT), corresponding to about 600 molecules AVT, into the third ventricle of unanesthetized cats, induced slow-wave sleep 5 min after the injection. An equivalent amount, of a partially purified pineal AVT injected into the third ventricle, produced the same effects. After incubation with trypsin, pineal AVT completely lost its ability to induce slow-wave sleep. The slow-wave sleep induced by 10(-6) pg synthetic AVT injected intraventricularly could be matched by 1 microgram synthetic AVT injected intraperitoneally. Neither synthetic arginine vasopressin, nor synthetic oxytocin, injected intraventricularly in the amount of 10(-6) pg, was able to induce slow-wave sleep. Whereas in the control animals injected with pineal AVT after incubation with trypsin, or in the control animals injected with vasopressin or oxytocin, the paradoxical sleep averaged 21.9--22.8% of the sleep time, during a total recording time of 5 hr, in the cats injected with synthetic or pineal AVT, the paradoxical sleep was completely suppressed.


Effects of intracerebroventricular L-DOPA on caudate unit firing. Single units were recorded bilaterally from the caudate nuclei of cats before and after 50 microliter injections of either Merlis solution or L-DOPA (200 microgram) dissolved in Merlis into the left lateral cerebral ventricle. After injection of L-DOPA, but not Merlis solution, there was a period of unit silence in both caudates with an onset of about 10 min and a duration of 30-50 min. This period of caudate silence was coincident with a significant reduction of systolic blood pressure and heart rate. Upon resumption of unit firing in caudate, it was found that the interspike intervals on the contralateral side were markedly increased from 30 min-2 hr postinjection while there was no change on the side of injection. The similarity of this response to that following lesions which interrupt the caudate to thalamus pathway unilaterally was discussed. It is suggested that L-DOPA injection may produce this lesion-like effect by altering the firing of caudate output neurons.


Unit responses in the ventrobasal thalamus (VPL) of the cat of bradykinin injected into somatic and visceral arteries. Under light to moderate sodium pentobarbital anesthesia one half of the thalamic neurons displaying place and modality specific responses to low intensity mechanical stimulation of contralateral receptive fields also responded, by excitation or by inhibition, to bradykinin injections into somatic and visceral arteries. Partial or complete somatovisceral convergence was commonly seen in neurons with otherwise typical lemniscal properties. The response intensities varied considerably for different neurons; the responses to somatic bradykinin were always stronger than to visceral injections. The time course of the response was comparable to that seen in peripheral nerves, other central sites, and the behavioral reaction to bradykinin. Control experiments indicated the independence of the bradykinin responses from variations in blood pressure or general arousal effects. It is suggested that modulation of ventrobasal thalamic activity may be an important factor in central nociceptive processing.


Characterization of two subcellular fractions isolated from myelinated axons. Myelin and a heavy membrane fraction (1.0/1.2 fraction) were isolated from rabbit white matter by a slight modification of the procedure for bovine CNS. The specific activities of acetylcholinesterase and Na+, K+-ATPase were higher in the 1.0/1.2 fraction than in myelin. In contrast, the cerebroside content and 2'3'-cyclic nucleotide 3'-phosphohydrolase activity in the 1.0/1.2 fraction were 4.5 and 3.4 times lower than in myelin. Total lipids accounted for only 30% of the 1.0/1.2 fracton's dry weight; for myelin, they represented 70%. Polacrylamide gel electrophoresis showed the presence of many high molecular weight proteins and glycoproteins in the 1.0/1.2 fraction but myelin components were practically missing. Cytochrome c oxidase and NADPH-cytochrome c reductase activities suggested about 15% contamination in the 1.0/1.2 fraction but less than 5% for myelin. In electron micrographs of the 1.0/1.2 fraction, there were many membraneous profiles that varied in size, some mitochondrial fragments, and only a few lamellar whorls of compact myelin. The results suggest that the 1.0/1.2 fraction is different from other myelin-related fractions and is probably enriched in axolemma.


Exencephaly in chicken-pheasant hybrids. 1. The incidence of exencephaly was investigated in chicken-pheasant hybrids. 2. With the pheasant as sire, fertility was 7-6%, but with the fowl it was 19-5%; hatchability of fertile eggs, however, was similar, 42% and 41% respectivley. 3. Only one exencephalic hybrid was obtained when the sire was the pheasant but 70 were noted when the fowl was sire. The incidence of this malformation in hatched chicks was 12 times more in crosses with the fowl as sire than in the reverse cross. 4. The frequency of exencephaly was greater with Rhode Island Red, Barred Leghorn or White Leghorn roosters than with Columbian Rock roosters.


Excess iodide and the accumulation of 125I by the thyroid, plasma and developing oocytes of the Japanese quail. 1. Developing oocytes of the Japanese quail accumulated 0-44 microgram of each 1 microgram of 125I-labelled iodide after intra-muscular injection of doses up to 500 microgram iodide as NaI but only 0-007 microgram after injection of more than this: the abrupt change in the rate of accumulation was attributed to saturation of the iodide transport mechanism. 2. The proportion of available iodide transferred into the oocytes appeared to be more dependent on the amount of iodide injected and the total weight of growing oocytes than on a requirement for either a store of iodide for the embryo or an iodide excretory pathway for the hen. 3. The thyroid was about four times more active in accumulating iodide than the oocyte. 4. The percentage of iodide accumulated by the plasma was the same at all dose rates.


Lithium induction of premature oviposition by the Japanese quail. 1. The intramuscular injection of LiCl into laying Japanese quail 6 or 12 h subsequent to an oviposition induced early oviposition of the next egg. 2. The shells of eggs from Li-treated birds were without speckling and weighed half or less as much as shells from Na-treated birds. Many eggs were also deficient in albumen.


The effect of tonicity of storage media for fowl semen on the occurrence of neck-bending spermatozoa, fertility and hatchability. 1. Semen of White Leghorn and Rhode Island Red males was stored for 24 h in diluents hypertonic (460 mOsm/kg H2O) and isotonic (340 mOsm/kg H2O) to cock seminal plasma. 2. Compared with the fertility results with semen that had been stored in the hypertonic diluent or was fresh, the fertility of the White Leghorns was not affected after storage in the isotonic diluent; a decrease (P less than 0-05) was observed, however, using Rhode Island Red semen and isotonic diluent. 3. Fresh RIR semen contained 2-3% "neck-bent spermatozoa" (NBS)  which was increased to 4-23% and 5-76% after dilution in hypertonic and isotonic diluents respectively and stored for 24 h. It is doubtful whether this increase (P less than 0-05) is the sole reason for the lowered fertility obtained with this breed after storage in the isotonic diluent.


Endoscopical biopsy in the differential diagnosis of lung diseases. The results of endoscopical sampling methods, as described in this study, were performed on 5276 patients with different pulmonary lesions. Illustrations were made of the diagnostic possibilities of biopsy methods and their dependence on size and localization of pulmonary lesions. Most appropriate sequence was outlined for the use of different sampling methods.


Persistent right oviduct in ring-necked pheasant. 1. A right oviduct, approximately two-thirds the length of the left oviduct, and with a separate opening into the cloaca was observed in a female Ring-necked pheasant. 2. It is suggested that interference of the synthesis of Müllerian inhibiting factor from the gonads may have allowed its development.


Divergent selection for yolk cholesterol in laying hens. 1. Lines were selected for divergence in yolk-cholesterol concentration for three and four generations in the Cornell Controll (Leghorn) and Athens-Canadian (AC) (meat-type) randombred populations respectively. Selection was based on both individual and family records. 2. Cholesterol values were obtained from two consecutively laid eggs when birds were 28 weeks of age. The yolks of eggs from individual hens were pooled and analysed for cholesterol content by the colorimetric assay of Zlatkis et al. (1953) on the "fat extract" obtained by a modification of the procedure of Folch et al. (1956). 3. The largest differences between high and low lines (1-27 and 1-38 mg cholesterol/g yolk) were observed in the last generation of selection. There was evidence of a lack of response in the low lines. Realized heritability estimates obtained by dividing the difference between high and low lines by half the cumulative selection differential ranged from 0-11 to 0-25 in the AC population and from 0-21 to 0-25 in the Leghorn population. Realised estimates on a within-line bassis suggest that selection for yolk cholesterol is effective only in the upward direction.


Uptake of certain amino acids in vitro in chickens previously subjected to three methods of dietary restriction. From 8 weeks of age cockerels and pullets were restricted for 8 or 12 weeks either by rationing, by feeding a low lysine diet or by feeding a diet low in protein but balanced in respect of all amino acids. 2. There was a significant decrease in growth rate of the birds as a result of the restrictive treatments. 3. The dietary treatments affected the rate of uptake of the four amino acids tested--arginine, lysine, histidine and glycine--although the effect was not significant in all cases, neither was it consistent throughout.


Incorporation of uridine and leucine by the germinal discs of quail eggs kept cool or warmed periodically during storage. Nucleic acid and protein biosyntheses are characteristic of the fertilised germinal disc and continue during storage at 20 degrees C though at a reduced rate. There is no comparable activity in unfertilised eggs. 2. Warming the fertilised eggs for 30 min/d during storage increased the rate of incorporation of uridine and leucine into proteins and nucleic acids by a factor of three.


Plasma growth hormone concentrations during growth in turkeys. The concentrations of circulating GH were low in 1-week-old birds (male plasma pool 30 ng/ml, female 32 ng/ml), reached a maximum at 7 weeks in male birds (142 +/- 26 SEM ng/ml) or 4 weeks in females (185 +/- 32 ng/ml) and then decreased to 17-3 +/- 2-8 ng/ml in males and 8-7 +/- 0-6 ng/ml in females at 17 weeks. 2. Significant inverse correlations between GH concentration and age or body weight were found (male, r = -0-693), female, r = -0-623). 3. In males, but not females, the weekly increase in body weight was correlated with the plasma GH concentration (r = 0-291).


Effect of dietary DL-ethionine on growth and liver metabolism. The effects of DL-ethionine, given in the diet or by injection, on growth, hepatic glycogen and lipids, and the activities of some cytoplasmic NAD-linked dehydrogenases and NADPH-producing enzymes were investigated. 2. Growth virtually ceased after feeding ethionine for 2 d. 3. Ethionine induced an accumulation of lipid, decreased the activities of malic enzyme and isocitrate dehydrogenase and increased the activity of lactate dehydrogenase. 4. The concentration of glycogen in the liver of ethionine-fed chickens increased for 3 d in spite of a decrease in food intake, but then decreased.


Reversal of ethionine intoxication in the domestic fowl with methionine and adenine sulphate. When DL-methionine was administered to young chickens fed on a diet containing DL-ethionine (2 g/kg) growth recommenced and proceeded linearly for the first 2 d; the rate was dependent on the amount of methionine administered. 2. Adenine sulphate did not stimulate growth but when given with methionine the response was enhanced.


The ultrastructure of the follicle wall of the domestic fowl during the phase of rapid growth. The development of a standard technique for fixing the developing follicle for ultrastructural studies is described. 2. The follicle wall is shown to be a multi-layered structure which exhibits a number of morphological changes concomitant with yolk protein transfer, the most significant of which are the intercellular channels which form between the granulosa cells during the fast phase of protein transfer.


Wheat embryo ribonucleates. IX. Generation of N2-dimethylguanylate when bulk wheat embryo tRNA is used as substrate for wheat embryo S-adenosylmethionine-tRNA methyltransferases, in vitro. Although the cellular ribonucleates in normally growing cells are virtually saturated with respect to their customary complement of methyl substituents, it has often been reported that 'marginal' levels of (homologous) methylation can be detected when ribonucleates and enzymes from the same source material are incubated, together with S-adenosylmethionine, in vitro. Experiments were designed to acquire new insights that might be useful for circumscribing the number of possible interpretations that could be advanced to account for the introduction of 'supernumerary' methyl groups during (homologous) methylation of wheat RNA by wheat enzymes, in vitro. For a large fraction of the supernumerary methyl groups that can be introduced into wheat RNA, in vitro, it was not possible to adduce convincing evidence in support of the view that any appreciable quantity of methyl groups is ever introduced at these same sites, in vivo. The possibility that these supernumerary methyl groups might have transient existence, in vivo, and the potential physiological significance of any such occurrence are dealt with as part of a more general discussion of the experimental findings.


Inhibition of rat liver CDPethanolamine: 1,2-diacylglycerol ethanolamine-phosphotransferase activity by ATP and pantothenic acid derivatives. The properties of rat liver microsomal CDPethanolamine: 1,2-diacylglycerol ethanolamine-phosphotransferase (ethanolaminephosphotransferase; EC 2.7.8.1) are studied with respect to metal ion and substrate concentration. The enzyme requires magnesium (20 mM) or manganese (1 mM) ions for optimum activity. Manganese ions are better activators of ethanolaminephosphotransferase activity than are magnesium ions. Calcium 1 mM) inhibits the magnesium-activated ethanolaminephosphotransferase by 86% and the manganese-activated enzyme by 57%. The Km for CDPethanolamine is 2.4 and 0.7 x 10(-4) M, in the presence of magnesium or manganese ions, respectively. ATP plus pantetheine significantly inhibit the manganese-activated ethanolaminephosphotransferase, while the magnesium-activated enzyme is inhibited by ATP plus pantetheine and slightly stimulated by ATP plus CoA. In the presence of either metal ion, ATP itself inhibits enzyme activity, while CoA or pantetheine when added alone have no effect. Evidence is presented indicating that the inhibition of ethanolaminephosphotransferase activity by ATP plus CoA or ATP plus pantetheine is not due to the formation of acyl-CoA or acyl-S-pantetheine esters. At the present time, however, the true mechanism of inhibition is unknown. The results indicate that the cellular levels of ATP, CoA, pantetheine, magnesium, manganese, and calcium ions may all play a role in the regulation of phosphatidylethanolamine biosynthesis.


Purification and properties of a soluble polymer of glucose from cultures of Acetobacter xylinum. A soluble nondialyzable polymer of glucose was isolated and purified by selective ethanol and ammonium sulfate precipitation from the supernatant of a culture of Acetobacter xylinum which was actively producing cellulose. This polymer was heterogeneous in size with an average sedimentation constant S20,w, of the most abundant fraction of 11.1. On drying from dilute solution in water, the polymer(s) showed extended linear fibrils or aggregates of such fibrils by transmission electron microscopy. The infrared spectrum resembled closely that of cellulose II. Preparations of the lyophilized polymer were amorphous by X-ray diffraction. Composition and structure of the polymer were established by enzymatic digestion, acid hydrolysis before paper chromatography, and methylation followed by gas-liquid chromatography. Glucose was the only component of the polymer. There were few, if any, alpha 1 leads to 4 linkages between glucose residues. The polymer(s) is a linear chain of glucose units linked beta 1 leads to 4 with single glucose residues as branches at position 2 of every third glucose on the average. The possibility that this branched glucose polymer is an intermediate in cellulose biosynthesis is examined.


Discrete electrophoretic products of mitochondrial protein synthesis in the Chinese hamster ovary cell line. Mitochondrial proteins labelled with [35S]methionine for 1 h in whole Chinese hamster ovary (CHO) cells in the presence of cycloheximide or emetine, known inhibitors of cytosolic protein synthesis, have been enumerated and characterized by their electrophoretic mobility in sodium dodecyl sulfate slab gel electrophoresis. Ten distinct electrophoretic bands were observed. The components were relatively stable during a 2 h postlabelling period. The same 10 bands were also seen with the CHO cell line tsH1, labelled at 40 degrees C, a temperature at which cytosolic but not mitochondrial protein synthesis is inhibited in this cell line, and with isolated mitochondria labelled in the presence of cycloheximide. An 11th band was present when [3H]leucine but not [35S]methionine was used for labelling. The width of the major band suggested that it consists of two components making a total of at least 12 proteins synthesized in mitochondria. The molecular weights of these mitochondrial proteins ranged from 5000 to 50 000 and there was a sixfold difference in the relative molar amounts synthesized in a 1-h period in the presence of [3H]leucine or [35S]methionine. No differences in number or electrophoretic mobility of the mitochondrially synthesized proteins were found among the seven CHO cell lines examined. These results suggest the stability of the mitochondrial genome in the CHO cell line.


Preferential in vivo accumulation of sn-2,3-diacylglycerols in postheparin plasma of rats. The stereochemical course of in vivo hydrolysis of triacylglycerols by lipoprotein lipase was investigated by determining the structure of diacylglycerol intermediates in postheparin plasma of rats which had been fed [3H]glycerol-labeled Intralipid 2 h before an injection of heparin or had been given an injection of a mixture of [3H]glycerol-Intralipid and heparin. During the clearance of both the natural chylomicrons and the artificial emulsion, sn-2,3-diacylglycerols (60-80%) were found to be the dominant enantiomers. Similar results were obtained when the contribution of the hepatic lipase was altered, either by tying off the mesentery artery and portal vein before injection of heparin, or by injection of heparin directly into the portal vein. These findings are consistent with a preferential release of the acyl group from the sn-1 position of the triacylglycerol molecule as demonstrated previously in vitro. A preferential orientation of the substrate in the enzyme-substrate complex or at the oil-water interface is discussed as a possible basis for these effects.


Biosynthesis of chlorophyll b.

Biosynthesis of chlorophyll b. Using [14C]chlorophyll a derived from a mutant of wheat lacking chlorophyll b, spinach thylakoids from very young leaves and cucumber thylakoids of irradiated, etiolated cotyledons convert chlorophyll a to b with apparent yields of 19% and 5%, respectively.


[Kinetics of transcutaneous penetration and fixation of 3-propoxy-17-methoxyestradiol and estradiol in various rat tissues]. The transcutaneous penetration of 3-propyl ether, 17-methyl ether oestradiol (POM) occurs by a diffusion phenomenon and does not seem to be modulated by a cutaneous receptor as it is the case for oestradiol. After transcutaneous administration of POM and oestradiol, a comparison of the kinetics of uptake on the uterus and of uterotrophic effects, as well as an analysis of radioactivity taken up by a partition method between petroleum ether and sodium hydroxide, indicates that cleavage of both ether groups of POM occurs leading to estradiol. It is likely that this de-etherification takes place in the liver after a period of quiescence. The lipophilic nature of POM allows an obvious uptake by the aorta and a very significant uptake by the adipose tissue. The etherification of the alcohol functions of oestradiol allows an adequate protection of the hormone against hepatic catabolism. This may explain, along with the release of metabolites taken up by the adipose tissue, that POM is bound to a greater extent than oestradiol by various tissues.


In vivo studies on the conversion of m-tyrosine to 3,4-dihydroxyphenylalanine in the rat. The question whether m-tyrosine can give rise to catechols in vivo has been investigated using labelled precursor. DL-[2-14C]m-tyrosine (38 muCi/mmol (1 Ci = 37 GBq)) was synthesized from [2-14C]glycine. Radioactive catechols in rat brain, liver, and kidneys were examined 15 min after intraperitoneal administration of DL-[2-14C]m-tyrosine (100 mg/kg). The kidney was the only organ which showed demonstrable amounts of radioactive catechols, and about 14% of the catechols formed was identified as 3,4-dihydroxyphenylalanine (dopa), 22% as 3,4-dihydroxyphenylacetic acid, and 56% as dopamine. However, when the animals were pretreated with dopa decarboxylase inhibitor, labelled catechols were also observed in liver and brain, and dopa accounted for over 95% of the catechols formed in all three organs examined. Thus it is clear that m-tyrosine can by hydroxylated in vivo. Results from experiments using [2-14C]m-tyrosine enantiomers and specific enzyme inhibitors suggest that phenylalanine hydroxylase could be the enzyme catalyzing this reaction.


Solubilization and partial purification of particulate catechol-O-methyltransferase from rat liver. Particulate catechol-O-methyltransferase (COMT) from rat liver has been solubilized by acetone treatment and partially purified. Results from the present study demonstrate that the solubilized, partially purified enzyme is similar to the cytosol COMT with respect to molecular weight, pH profile, sensitivity toward inhibitors, Mg2+ requirement, and substrate affinities. However, a comparison of the crude particulate COMT and the solubilized enzyme shows that there is a significant difference in their affinity for catechol substrates. This finding suggests that membrane protein and (or) lipid components may play an important role in catecholamine metabolism. The relationship of particulate COMT to [3H]norepinephrine binding was investigated. No correlation between the COMT and [3H]norepinephrine binding activities was observed in vitro.


Inhibition of nuclear DNA-dependent RNA polymerases from mouse ascites tumors and liver by glycerol. Nuclear DNA-dependent RNA polymerases were isolated from Ehrlich ascites carcinoma, TA3 ascites adenocarcinoma, and mouse liver and tested for inhibition by glycerol. The results confirm the finding of Smith and Duerksen ((1975) Biochem. Biophys. Res. Commun. 67, 916-923) that glycerol may inhibit nuclear RNA polymerase II, but because different grades of glycerol inhibited mouse liver RNA polymerase IIa to different extents, it is suggested that an inhibitory contaminant is present. RNA polymerases IIa and IIb from the two tumors and mouse liver were proportionately inhibited by A.C.S. reagent-grade glycerol at concentrations above 10%. RNA polymerase Ia from liver and the TA3 tumor was not inhibited by any concentration of glycerol tested (2-32.3%), but RNA polymerase Ia from Ehrlich carcinoma was inhibited by glycerol concentrations above 16%.


Estimation of gestational age from study of amniotic fluid and clinical assessment. Study of 108 samples of amniotic fluid obtained between 28 and 42 weeks' gestation from 101 patients revealed that in normal pregnancies the creatinine concentration, lecithin/sphingomyelin (L/S) ratio and percentage of fat cells correlated better with the gestational age of the newborn--assessed by clinical criteria--than did the bilirubin and sodium concentrations. A creatinine concentration of 1.75 mg/dL or more, an L/S ratio of 4 or more and a fat cell percentage of 10 or more correlated significantly with a gestational age of 37 weeks or more. In abnormal pregnancies (those with obstetric or medical complications, or both) the mean creatinine concentration in the amniotic fluid was significantly less than expected for gestational age in fetal dysmaturity and greater than expected when the mother had diabetes. The mean L/S ratio in the amniotic fluid was elevated when the mother had hypertension or smoked and in cases of fetal dysmaturity or long interval between rupture of the membranes and delivery, whereas it was significantly lower than normal when the mother had diabetes. The mean bilirubin concentration in the amniotic fluid was significantly lower than normal when the mother had hypertension. When the mother had diabetes, maturity of the fetal lung, liver, skin and brain appeared to be delayed, according to the values for the amniotic fluid constituents.


A survey of two cohorts of women who graduated from a Canadian medical school. The careers of 71 women who graduated in medicine from the University of Western Ontario between 1961 and 1970 are compared with those of 84 women who graduated from the same university between 1924 and 1958. In both cohorts approximately 65% were working full time. Fewer members of the 1961-70 cohort were doing no medical work and more were working part time.


Clinical significance of a high mean corpuscular volume in nonanemic patients. A prospective study of the clinical significance of macrocytosis (mean corpuscular volume 100 fL or more) was carried out for 9 months in a teaching hospital in 1975. Of the 140 patients with macrocytosis at the time of admission (0l7% of all hospital admissions) 46 (33%) had low activity of serum or erythrocyte folate, or both, and 16 (11%) had low serum vitamin B12 concentrations. Among the 78 patients with normal B12 and folate values the most commonly associated significant clinical conditions were alcoholism or hepatic disease (36 patients), malignant disease or the effects of chemotherapy (25 patients) and chronic obstructive lung disease (10 patients).


Infection of the skin by Mycobacterium marinum: report of five cases. Five patients 6 to 47 years of age had bacteriologically confirmed Mycobacterium marinum infections of the skin. In four patients the initial lesions were chancriform and were on a finger or a hand; ascending lymphadenitis followed. The other patient had nodular inflammatory lesions on one cheek. Biopsies were performed in four patients; all specimens showed a granuloma, and acid-fast bacilli were identified in one of the four. Four of the five patients were untreated; the fifth was given antituberculous drugs. In all five patients the condition was chronic, with progressive resolution of the lesions during follow-up periods of 1 to 6 years. M. marinum infections of the skin are rare in Canada. This may be due in part of lack of clinical awareness or failure to identify the organism. Biopsy specimens should be obtained under sterile conditions and nondigested material should be inoculated into the footpads of mice.


Ambulant management of patients with recent myocardial infarction. Thirty-two patients who had remained ambulant and active after suffering an acute myocardial infarction were observed for 6 months. Complications were present initially in 11 but proved transient. One patient died of a new coronary thrombosis 15 weeks after the initial episode. There were no recurrences among the 31 surviving patients. After the 6 months all but two patients were as well as before the attack; 21 were free of symptoms and there was no undue incidence of objective findings that could be attributed to failure to rest after the attack. It is therefore concluded that, for patients who suffer an acute myocardial infarction, immediate diagnosis and admission to a coronary care unit need not be equated invariably with immobilization in bed. Our experience suggests that selected patients can be allowed moderate activity without ill effects and thus avoid the undesirable consequences of enforced bed rest.


Normative standards of plasma cholesterol and triglyceride concentrations in Canadians of working age. Fasting plasma cholesterol and triglyceride concentrations were determined for 6407 working Canadian adults aged 20 to 69 years in Toronto and Hamilton. Means, medians and 5th and 95th percentiles were ascertained from the data for men, women taking oral contraceptives or estrogen preparations, and women not taking such medication. Mean plasma cholesterol values (mg/dL) ranged in men from 168.3 at ages 20 to 24 years to 211.5 at ages 45 to 49 years, and in women using hormone preparations from 180.3 at ages 20 to 24 years to 224.2 at ages 50 to 54 years; corresponding values in women not using these preparations were 164.9 and 220.6. Plasma triglyceride means (mg/dL) ranged in men from 108.7 at ages 20 to 24 years to 166.7 at ages 40 to 44 years, in women using hormone preparations from 115.4 at ages 20 to 24 years to 145.3 at ages 45 to 59 years, and in women not using these preparations from 77.5 at ages 20 to 24 years to 112.4 at ages 50 to 54 years.


Cervical cytology screening: experience of a general hospital. At Henderson General Hospital, Hamilton, a program was introduced whereby cervical smears were taken routinely for cytologic study from all women admitted aged 17 years or older. The procedure was performed by a specially trained nurse. In a 5-year period 53% of eligible patients were screened. Of these, 32% had not had a cervical smear taken before. In 7681 smears nine instances of invasive disease were discovered: three of the cervix, three of the endometrium and three metastatic. There were 20 cases of carcinoma in situ and 2 of severe dysplasia. Evidence of infection was present in a high percentage of the smears. Hospital admission affords an excellent opportunity of applying this valuable screening procedure.


Prognosis in anorexia nervosa as influenced by clinical features, treatment and self-perception. The use of behaviour modification in the treatment of anorexia nervosa has been controversial and has not undergone controlled studies. An investigation of 42 patients with anorexia nervosa treated a mean of 31.7 months earlier was conducted to determine factors related to prognosis. The three areas studied were (a) clinical features, (b) treatment (behaviour modification versus medical and psychologic therapy) and (c) self-perception (with a distorting photographic technique). Clinical outcome was assessed as "excellent" in 7, "much improved" in 14, "symptomatic" in 13 and "poor" In 8. Analysis of variance showed that vomiting (P less than 0.01), bulimia (P less than 0.01), poor educational/vocational adjustment (P less than 0.01) and higher global clinical score (P less than 0.001) were associated with a poor prognosis. There were no differences at follow-up between patients treated by behaviour modification and those treated by other methods; the data suggest that behaviour modification, while not harmful, does not provide long-term benefits. Self-estimates of body size were highly predictive of outcome (P less than 0.002); all patients with a poor outcome overestimated their size. Patients with only marginal improvement might be helped by treatment directed to self-perceptual disturbances.


Obstructive jaundice due to a chlorinated hydrocarbon in breast milk. A 6-week-old breast-fed infant had obstructive jaundice and hepatomegaly. When a dry-cleaning solvent, tetrachloroethylene, was detected in the mother's milk and blood, breast-feeding was discontinued. Rapid clinical and biochemical improvement followed. The child grew normally and had normal liver function during 2 years of follow-up.


Chemotherapy of malignant histiocytosis in adults. Malignant histiocytosis is a fulminant neoplasm resistent to single agent chemotherapy and resulting in death within 6 months. Sixteen patients have received chemotherapy for this disorder between 1965-1975 at Stanford. Nine patients responded to chemotherapy. Responders had a median survival of 23 months from onset of symptoms and a significantly longer survival than non-responders (p = 0.03). The most promising responses were in seven patients treated with a combination of cyclophosphamide, adriamycin, vincristine and prednisone. Five of the seven responded, with two of the five later relapsing and dying, two having equivocal evidence of disease while on chemotherapy for 6 and 9 months, and one free of disease for 17 months after completing 8 months of chemotherapy. Three patients had central nervous system (CNS) relapses, two during peripheral remission. One of these had control of CNS disease with brain irradiation and intrathecal methotrexate, but all three eventually died. It is hoped that with combination chemotherapy and prophylactic CNS treatment, long term disease-free survivals will be achieved.


Infections in patients with malignant lymphoma treated with combination chemotherapy. The records of 360 patients with malignant lymphoma treated with various forms of combination chemotherapy from 1966 to 1974 were reviewed. A total of 181 infections was found in 125 patients. The most frequent types of infection were pneumonia (31%), skin infections (17%), urinary tract infections (13%) and septicemia (11%). An etiologic organism was was identified in 133 infections (73%). The most common causative organisms were bacteria (77%), especially gram-negative bacilli. Viral infections accounted for 18% of the infections with 21 of the 24 being due to herpes zoster. These were more frequently found in patients with Hodgkin's disease (14/21) than in the other lymphomas. Among patients with Hodgkin's disease, 53% treated with COP developed infections compared to only 27% treated with MOPP (p = 0.039). Among patients with non-Hodgkin's lymphoma, infections were more frequent in patients treated with Adriamycin containing combinations than with COP. Neutropenia (i.e. less than 1,000 neutrophils/mm3) was associated with 35% of infections in this study and was seen more often in patients with non-Hodgkin's lymphoma (p = 0.048).


The ultrastructure of pulmonary hamartoma. Ultrastructural and histochemical examination of chondromatous pulmonary hamartomas revealed the epithelial component to be comprised elements similar to those lining the distal bronchioles and the alveoli of adult lung. The stromal cells nearest the epithelium include a population resembling mature fibroblasts and a population of glycogen-containing, primitive appearing cells. More deeply situated stromal cells showed features of chrondroid differentiation.


Tumor growth patterns in multiple myeloma. Serial changes in tumor mass were evaluated in 61 patients with multiple myeloma who had received intermittent courses of melphalan-prednisone until death. The variations in the kinetics of tumor reduction and relapse could be explained by a mathematical model based on two cell populations, one sensitive to and one resistant to chemotherapy. For all responding patients, the median tumor halving-time was 1.3 months and the median doubling time was 2.9 months. The duration of a constant tumor mass during remission was brief in most patients. A larger fraction of resistant cells prior to therapy was associated with a slower tumor doubling-time during relapse. With a constant fractional reduction of sensitive cells and a tumor halving-time of one month or less, all cells sensitive to alkylating agents would be eliminated with 3 years of uninterrupted intermittent therapy.


On the histology of human seminoma: development of the solid tumor from intratubular seminoma cells. Intratubular seminomas of the testis associated with solid tumors were studied by light and electron microscopy in order to obtain information about the earliest stage of emigration from the tubules and invasion of the interstitial space. Careful examination of numerous sections reveals that at this stage neoplastic cells protrude into evaginations of the tubule covered by basement membrance or directly invade that membrane. At the site of tumor cell emigration, the basement membrane is thickened and multilayered. Tumor cells devoid of basement membrane were found in the interstitium. Their transmigration through the basement membrane was never observed. Subsequent to the migration of seminoma cells the tubules are smaller in diameter and contain only Sertoli cells. From the observations described it is inferred that tumor cells in the interstitial tissue increase in number, form strands and lobules, and finally build up the solid tumor.


Metaplastic squamous cell carcinoma of bronchus simulating giant cell tumor of bone. A 57-year-old man underwent a right pneumonectomy for a bronchogenic carcinoma following bronchoscopy and bronchial biopsy. The tumor was a polypoid mass arising from the lower lobe bronchus. Microscopically it was characterized by mononuclear cells mixed with randomly distributed multinucleated giant cells similar to those seen in giant-cell tumor of bone. Also found were portions showing typical squamous cell and spindle cell carcinoma. Based on the light and electron microscopic findings, we suggest that the current case represents a metaplastic squamous carcinoma showing mesenchymal cell differentiation. A hypothesis on the histogenesis of pleomorphic carcinomas was presented. The problems of histological diagnosis generated by such a tumor should be emphasized.


Alterations in plasma sialyltransferase levels in patients with neoplastic disease. Levels of glycoprotein:sialyltransferase activity (EC 2.4.99.1; CMP-acetyl-neuraminate:D-galactosyl-glycoprotein N-acetylneuraminyl-transferase) were measured in plasma of patients with neoplastic disease, and were found elevated above normal control values in 85% of patients examined. There was a correlation between enzyme levels and course of disea-e in 46 of 57 patients studied serially during therapy. Plasma sialyltransferase may be a useful marker enzyme for monitoring effectiveness of therapeutic programs for disseminated neoplasms.


Malignant lymphoma obscured by concomitant extensive epithelioid granulomas: report of three cases with similar clinicopathologic features. Three similar cases are described of an unusual combination of malignant lymphoma and extensive non-necrotic granulomas. The three patients presented with prominent splenomegaly without peripheral lymphadenopathy. They had normal or moderately elevated lymphocyte counts, abnormal lymphoid cells in the peripheral blood and bone marrow, and abnormalities of serum immunoglobulins. The lymphoid tumor was difficult to recognize but it was best identified in abdominal lymph nodes, it was composed of small atypical lymphocytes proliferating in a vaguely nodular pattern. The presence of multiple epithelioid granulomas obscured the neoplastic proliferation in the spleens and misled or delayed the final interpretation of the malignant disease. Abdominal lymph nodes and liver also contained granulomas although to a lesser extent. Studies of the lymphocyte surface characteristics in one patient suggested that the neoplasm derived from a monoclonal proliferation of B cells. The relationship between the exuberant epithelioid granulomas and the underlying neoplastic lymphoid proliferation is not clear. Regardless of whether it represents a distinct clinicopathological entity, recognition of this remarkable association has important practical implications since the lesions may be erroneously interpreted by the pathologist.


The histologic spectrum, prognosis, and histogenesis of the sarcomatoid carcinoma of the pancreas. A series of 12 cases of pancreatic carcinoma with sacroma-like transformation were studied. Four distinctive histologic types were identified: spindle cell carcinoma, malignant giant cell tumor, pleomorphic giant cell carcinoma, and round cell anaplastic carcinoma. The spindle cell carcinoma had a predominance of malignant spindle and undifferentiated cells. Hemorrhage and sarcomatoid stroma with abundant osteoclast-like giant cells were the features in the malignant giant cell tumor. The pleomorphic giant cell carcinoma was characterized by abundant malignant giant cells. The round cell anaplastic type was formed by monotonous sheaths of small, round, and plump cells with rare giant cells. The first three types are considered to be ductal in origin, whereas the fourth type is believed to arise from acinar or possibly insular tissue. The differential diagnosis includes various types of true sarcoma. Although the malignant giant cell tumor of the pancreas might have a better prognosis, the prognosis in the other three types does not differ significantly from that of the ordinary type of pancreatic carcinoma.


Cell cycle parameters in human colon: comparison between primary and recurrent adenocarcinomas, benign polyps and adjacent unaffected mucosa. The duration of S phase and the labeling index were measured in adenocarcinomas, in polyps and in adjacent unaffected mucosa of a same patient. The in vitro double labeling technique was employed. The S phase duration in tumors was significantly longer than in unaffected mucosa and polyps. This agrees with previously reported data on human skin, colon and rectum and supports the suggestion that a long S phase might correlated with carcinogenesis. The labeling index in the mucosa adjacent to the tumors is higher than previously measured in normal tissue. Following colectomy however, the labeling index in unaffected mucosa and tumor was lower than prior to surgery. This suggests the disappearance of a systemic factor (in the colon?) which positively regulates the proliferative activity in the rectal and colonic musoca. The maintainance of a lengthened S phase duration in the recurrent tumor where L.I. is lowered, indicates that the proliferation rate and the S phase duration are regulated by separate control factors.


Prognostic significance of vascular invasion in colorectal cancer of Dukes' B class. To further characterize important prognostic factors in colorectal cancer of the Dukes' B class the pathologic material from 143 Dukes' B patients was reviewed for the presence of lymphatic and/or blood vessel invasion and correlated with the postoperative tumor-free interval and overall length of survival. In 27 patients with vascular invasion within the bowel wall, both the tumor-free interval and the overall survival time were not significantly different from the same parameters in 116 patients without vascular invasion (P = 0.28, P = 0.12 respectively). These data suggest that vascular invasion within the bowel wall per se is not an important prognostic factor among patients with colorectal cancer of the Dukes' B class.


The frequency and distribution of mitotic figures in dysplasia and carcinoma in situ. The frequency and topographical (i.e. vertical and lateral) distribution of mitotic figures in normal cervical epithelium as well as in various degrees of dysplasia and in carcinoma in situ, was studied in punch biopsies and in subsequent cone specimens from 40 patients. The frequency of cells in mitosis in the whole thickness of the epithelium increased step-wise from normal epithelium to slight-moderate dysplasia, severe dysplasia and carcinoma in situ. A difference in the frequency of mitotic figures between slight and moderate dysplasia was recorded in the superficial cell layers of the epithelium. These findings, together with earlier reported differences in the frequency of DNA synthetizing cells between the various epithelial alterations support the validity of the histological classification of cervical atypias. Areas with mitosis alternated with areas without mitosis, supporting even here previous autoradiographical findings. The possible co-existence of proliferative and non-proliferative epithelial compartments in dysplasia and in carcinoma in situ of the uterine cervix is suggested.


Squamous carcinoma arising in benign cystic teratoma of the ovary: a report of four cases and review of the literature. Four cases of squamous carcinoma arising in benign cystic teratoma of the ovary are presented, with a detailed correlation of clinical, operative and pathological findings with prognosis. Confinement of tumor to the ovary, with an intact ovarian capsule, is the most important prognostic factor since patients wih extracapsular extension succumb to their disease within 2 years. The literature dealing with this subject is reviewed.


High dose irradiation to biopsy confirmed aortic node metastases from carcinoma of the uterine cervix. Twenty-one women with biopsy proven aortic node metastases from previously untreated carcinoma of the uterine cervix were treated with high dose irradiation to the pelvis and para-aortic areas. The majority received 6000 rads to the pelvis and para-aortic nodes by split course therapy plus 2500 rads by intracavitary radium to point A; 57.1% sustained severe complications to the stomach, small intestine or colon. Only 14.2% are surviving over 2 years free of recurrence. Though approximately 40% of women with Stages III and IV cervical cancer will have metastases to the para-aortic nodes, to date there is no satisfactory therapy that results in a significant number of such women surviving free of recurrent cervical cancer.


A cohort analysis of pancreatic cancer, 1939--1969. Pancreatic cancer mortality in the United States was examined by cohort analysis for the period of 1939 to 1969. Birth cohorts at 5-year intervals were studied. White males and non-whites of both sexes showed a shift of the cohort mortality rate curves by age toward younger groups as birth cohorts went from 1870--1874 to 1900--1904. This shift disappeared in white males and diminished in non-whites of both sexes between the cohorts of 1890--1894 and 1900--1904. The shift in non-whites was larger than in white males so that although non-whites had lower rates than whites in earlier birth cohorts, their rates exceeded those of whites in the most recent cohort. In the search for environmental cause(s) of pancreatic cancer, exposure characteristics should be compatible with these observations.


Fibrous inflammatory polyps of the ileum and cecum: review of five cases with emphasis on differentiation from mesenchymal neoplasm. Five case histories of patients with fibrous inflammatory polyps of the ileocecum are reported. Clinical impression in all five cases was that these tumefactions represented gastrointestinal malignancies. Gross pathologic examination revealed polypoid intramural growths ranging from 2.5 to 7.0 cm in greatest dimension. Transmural desmoplasia through the bowel wall into subserosal fat was initially thought to be indicative of neoplastic invasion. Microscopic evaluation revealed a fibroblastic and vascular proliferative process. Pseudosarcomatous changes were identified in cellular fibroblastic areas with plemorphism and mitotic activity. The manner of dissection among bundles of muscularis mucosae and muscularis propria suggests an inflammatory process as opposed to the pushing aside of whole large muscle bundles as seen in mesenchymal neoplasms arising in bowel wall. All five patients experienced survival of 6 to 17 years following surgery. These lesions are thought by us to represent localized exuberant polypoid granulation tissue proliferations which simulate mesenchymal neoplasm.