Special diets in hospitals: discrepancy between what is prescribed and what is eaten. An assessment has been made in four hospitals of the food eaten by 40 patients on special diets restricted in energy, carbohydrate, fat, protein, or sodium.  The diets eaten by most patients were significantly different from those prescribed, partly because of patients' unrestricted access to food they possessed or could buy in the ward, but mainly because of the extra or alternative foods provided by ward staff.  Not only may the patients, progress be prevented or hindered by excessive consumption but also the lack of progress may be interpreted as indicating that the dietary treatment has failed rather than that it has not been followed.


Single extra-amniotic injection of prostaglandin E2 in viscous gel to induce mid-trimester abortion. In a preliminary study a single extra-amniotic injection of 1.5 mg of prostaglandin E-2 incorporated into an aqueous viscous gel was given to 24 patients aborted within 24 hours, and the mean induction-abortion interval (plus or minus S.E. of mean) was 13.5 plus or minus 1.5 hours. Vomiting occurred in seven patients, and transient severe uterine cramps, pallor, nausea, and shivering occurred in one patient immediately after injection. Complete abortion occurred in 20patients. A delay in the time taken to abort seemed to be associated with an immediate and rapid rise in uterine tone after the injection which required prompt analgesia; this probably reflected rapid decidual absorption and dissolution of the prostaglandins away from their site of action. The degree of distention of the catheter-retaining balloon did not influence abortion times.


Electrocardiographic abnormalities associated with raised intracranial pressure. Serial electrocardiographic (E.C.G.) recordings were taken in seven patients suffering from intracranial conditions, for which their intracranial pressure was directly and continuously monitored with a Konigsberg extradural transducer. The E.C.G. changes observed in patients with raised intracranial pressure were prominent U waves, ST-T segment changes, notched T waves, and shortening and prolongation of Q-T intervals. Two patients with normal intracranial pressure showed no E.C.G. abnormalities but also establish a relationship between E.C.G. abnormalities and changing intracranial pressure.


Incidence of early post-operative iliofemoral thrombosis. The doppler ultrasound probe was used to study 138 patients after major surgery to assess the incidence of iliofemoral thrombosis in the early postoperative period. The patients were simultaneously studied with the 125-I-fibrinogen uptake test. The accuracy of the ultrasonic technique was assessed concurrently by comparing its results with those of ascending phlebography in a separate group of patients. The ultrasound probe detected thrombus proximal to the calf but was inaccurate in locating its exact site. Of the 138 patients studied postoperatively 28 developed calf vein thrombosis detected istopically, but there was no evidence of iliofemoral thrombosis in any patient. Thus, spontaneous iliofemoral thrombosis in the early postoperative period is rare.


The Summerland Disaster.

The Summerland Disaster. The reception, admission, and subsequent management of casualties from the Summerland fire are described. A senior member ofthe staff assessed priorities and direceted casualties to different prearranged teams, and a nurse was allocated to each patient to aid continuity of treatment and documentation. Though regular revision and discussion of major accident procedures with all members of the hospital staff and co-ordination with other rescue workers is helpful expensive rehearsals are of limited value in a civilian incident.


Anaemia of pregnancy: the changing postwar pattern. A popluation survey covering over a quarter of a century has shown clearly the improvement in haemoglobin levels in women attending antenatal clinics at the Glasgow Royal Maternity Hospital. Various influences have helped to bring this about, foremost among these being routine early prophylaxis with combined iron and folate supplements. Indeed, a time-space relationship between changes in prophylactic therapy, rates of improvement, and the incidence of megaloblastic anaemia can be shown. The women at risk are still essentially the same except for a new group of young, unmarried girls, who must be watched. In our view the withdrawal of routine prophylactic therapy in pregnancy would be retrograde step.


Distribution of hospital provision: policy themes and resource variations. There has been much discussion in the past about the inequitable distribution of N.H.S. resources between different regions. This paper examines the distribution of hospital resources in terms of current revenue and beds in different specialties in eight regions (49 area health authorities). Variations between A.H.A.s are far more important than those between regions,  and indeed they are so large (even in the acute specialties) that it is doubtful whether some A.H.A.s can be considered to be offering a comprehensive service. In the light of these findings the paper explores policy problems involved in trying to secure a more equitable distribution of N.H.S. resources at a time of financial stringency.


Bromocriptine treatment of acromegaly.

Bromocriptine treatment of acromegaly. The effects of oral bromocriptine in acromegaly have been studied. A dose of 5 mg six-hourly suppressed circulating growth hormone (GH) levels in nine out of 11 patients treated for seven to 11 weeks. This was associated with considerable clinical improvement in all patients, with abolition of excessive sweating, reduction in soft-tissue thichening, loosening of rings, decrease in shoe size, improvement in facial features, and loosening of dentures. Metabolic changes included improvement in glucose tolerance and reduction in hydroxyproline excretion. Unlike the actions of growth hormone release inhibiting hormone the suppression of GH was not accompanied by a reduction in insulin or glucagon secretion, though prolactin levels were suppressed. Side effects other than mild constipation were not seen when the full dose regimen was reached by slowly increasing the dose from 2-5 mg once daily. Bromocriptine holds promise as a safe and orally effective medical treatment to augment surgical or radiotherapeutic measures directed at the pituitary tumour. Its efficacy during longterm administration remains to be established.


Prolactin in hypertensive pregnancy.

Prolactin in hypertensive pregnancy. Plasma prolactin levels were measured in 68 pregnant women with hypertension at 32 weeks gestation. They were raised in pregnancies with pre-eclamptic features, most significantly in women with a rising plasma urate level. No correlation was found between the level of the untreated blood pressure and prolactin. Proteinuria did not influence prolactin levels independently of changes in the plasma urate. The differences in prolactin levels could not be ascribed to the drugs administered.


Normal haematological values: sex difference in neutrophil count. Blood counts were performed on 100 male and 100 female staff to establish normal ranges for our hospital. Neutrophil counts were found to be on average 0.66 times 10-9/1 (660/mm-3) higher in women than in men. Statistically this difference was highly significant and was not due to the fact that many of the women were taking oral contraceptives. The neutrophil counts of the men and women were also on average 0.50 times 10-9/1 (500/mm-3) greater in the afternoon than in the morning. A correlation was observed between the neutrpphil and the monocyte counts.


Postoperative management after thymectomy. This paper reports a retrospective study of the preoperative and postoperative management of 28 patients who underwent thymectomy between 1956 and 1973. Patients who received postoperative artificial ventilation were compared with the group who did not with respect to sex, age, severity of disease, preoperative vital capacity, and thymic histology. Evidence is presented that postoperative artificial ventilation is required when the preoperative vital capacity with the patient on optimum anticholinesterase treatment is less than 2 litres. Additional features associated with a probable need for artificial ventilation were the presence of a thymoma, bulbar symptoms, especially dysphagia, and age over 50 years. These should be taken into account in any patient whose vital capacity is close to the critical level of 2 litres. When postoperative ventilation was required it was usually necessary for 12 days or more, and tracheostomy should therefore be done at or before thymectomy. Most patients in this series received the same dose of anticholinesterases after operation as before it and no evidence was found of a sudden decrease in requirements for anticholinesterase therapy. Two patients did not, and in them a myasthenic crisis was precipitated. We propose that the preoperative drug regimen can be continued in the immediate postthymectomy period, allowing selection of patients for tracheostomy and artificial ventilation primarily on the basis of the preoperative vital capacity.


Non-fatal injuries sustained by back seat passengers. Of 2,275 cases of non-fatal injuries sustained by all categories of road users 185 were inflicted on back seat passengers. Twenty-six such passengers sustained severe and 66 moderately severe injuries. Only two patients (aged 18 months and 3 years) wore any form of restraint. Back seat passengers may be injured by impact with the rear of the front seat or other objects in the rear compartment; by objects in the front compartment; or by being thrown out of the car completely. An adequate restraint system, such as the lap-and-diagnoal type of seat belt, would reduce the incidence and severity of injuries.


Hospital pharmacy committees in England: Their structure, function, and development. A total of 150 chief and group chief pharmacists in England took part in a survey of the structure and role of pharmacy committees in hospitals. Just over half of the hospitals had such a committee. About two-thirds of these dealt only with pharmacy matters and one-third dealt also with other matters. The number of new committees set up increased slowly until 1967 and then showed a sharp rise. Their terms of reference, membership, and manner of appointment varied greatly. Among subjects dealt with the cost of drugs and the introduction of new prescribing sheets were prominent. Many of the respondents believed that the work of the committees, often with the help of smaller, more specialized groups, had significantly improved various aspects of the local supply and use of drugs.


Macromolecules and behavior II.  Training induced alteration in leucine transfer RNA of goldfish brain. Goldfish were trained to swim upright after a polystyrene float had been attached ventrally. The effects of training on the amino acid acceptor activity and methylated albumin-kieselguhr column chromatography profile of several brain isoaccepting tRNA species were studied. Comparison of the kinetics of aminoacylation and chromatography profile of tRNAs from trained and control fish showed no differences for Arginyl-, glutamyl-, histidyl-, lysyl-, phenylalanyl-, seryl, threonyl- or valyl-tRNA. In contrast, training induced alterations in tRNA-Leu activity and activity profile. Training had no effect on brain amino acid pools or liver tRNA-Leu activity. Together, behavioral control experiments and plasma cortisol titers indicated that the training-induced increase in tRNA-Leu activity was not caused by stress, exertion, random disoriented swimming or the minor surgical procedures required. Rather, this activity change seems to correlate with some, as yet unidentified, aspect of behavioral training. The implications of these findings with respect to learning are discussed.


Spinal and spino-bulbo-spinal reflexes in rats with experimental allergic encephalomyelitis. Experimental allergic encephalomyelitis (EAE) often produces complete hindlimb paralysis in rats. Stimulating the dorsal root at L5 was found to produce hindleg twitches in EAE rats with complete hindlimb paralysis. In addition, it was possible to record a monosynaptic response from the ventral root at L5 after stimulating the ipsilateral dorsal root (L5) in these rats. It was also possible to elicit a reflex at L5 which was shown to involve the central nervous system above the spinal cord level. These experiments demonstrated that the motoneurons and the muscles of the hindlimbs and the spinal cord segment innervating the hindlimbs remain functional in EAE paralyzed rats. This suggests that the paralysis may be caused by dysfunction of descending pathways of supraspinal origin.


The synaptic structure of catecholaminergic axon varicosities in the dorso-medial portion of the nucleus tractus solitarius of the cat: possible roles in the regulation of cardiovascular reflexes. The study was performed on adult mongrel cats to investigate synaptic structures of nerve terminals in the dorso-medial portion of the nucleus tractus solitarius (NTS), where majorities of the cardiovascular afferent fibers terminate and a dense plexus of the catecholaminergic nerves exists. In normal control groups, axo-dendritic and axo-somatic contacts were commonly observed but no axo-axonic contacts were seen. Synaptic vesicles were almost exclusively spherical (97%) and less frequently flat (3%). Small cored vesicles were not observed in animals with formalin-glutaraldehyde and osmium tetroxide fixation. Two or three days after denervation of IXth and Xth cranial nerves, degenerated axon varicosities occupied about 15-20% of total population. Quantitative analysis after intracisternal injection of 5-hydroxydopamine revealed 3 different types of the varicosity: varicosities with spherical clear vesicles (85%), flat clear vesicles (3%) and small cored vesicles (12%). Axon varicosities with small cored vesicles predominantly exhibited axo-dendritic synapses and occasionally showed the closed apposition with those containing spherical clear vesicles. 6-Hydroxydopamine produced a minimal degree of degenerative changes in some axon varicosities (less than 5%). Treatment with 5-hydroxydopamine after IXth and Xth cranial nerve section gave intact axon varicosities with small cored vesicles. In conclusion, there is a relatively dense innervation of catecholaminergic nerves in the dorso-medial portion of the NTS, which apparently does not stem from the IXth and Xth cranial nerves. Possible roles of catecholaminergic nerves are discussed.


5-HT-and norepinephrine-induced release of ACh from the thalamus and mesencephalon of the monkey during thermoregulation. In the unanesthetized pigtailed monkey (Macaca nemestrina), trained to sit in a primate chair, the body temperature was monitored from the brain and colon. After an array of guide tubes had been implanted stereotaxically, isolated sits within the thalamus and mesencephalon were perfused by means of a push-pull cannula system. The perfusate was an artificial CSF containing 1.0 mug/ml of the anticholinesterase, neostigmine; each sample of effluent was assayed for the content of acetylcholine (ACh) on the eserinized guinea pig ileum. The micro-injection of 5-HT and norepinephrine into the monkey's hypothalamus in doses of 2.5-10.0 mug evoked a rise or fall in body temperature, respectively. In addition, these amines caused a concurrent change in the release of ACh at perfusion loci in both thalamus and mesencephalon. A composite anatomical mapping of the active releasing sites revealed that the output of ACh was elevated at 19 of 36 sites during the 5-HT-induced hyperthermia. The region of maximum sensitivity to 5-HT in terms of the percent change in ACh output at thalamic and mesencephalic sites was the rostral hypothalamus. These results provide further support for a neurochemical model of thermoregulation which postulates that 5-HT activates a cholinergic pathway originating in the hypothalamus which transmits the efferent signals for heat production.


Free and membrane-bound ribosomes and polysomes in hippocampal neurons during a learning experiment. The ribosomes of the CA1 and CA3 pyramidal cells of hipocampus were investigated by morphometric methods after the acquisition of a shock-motivated brightness discrimination in rats. A significant increase in the total number of ribosomes was observed in CA1 cells of trained animals and in CA3 cells of both active controls and trained rats. A significant increase in membrane-bound ribosomes was obtained in CA1 and CA3 cells after training only. The results confirm the suggestion of an increased protein synthesis in hippocampal neurons during and after the acquisition of a brightness discrimination, as we have concluded from out previous investigations on the incorporation of labeled amino acids under identical experimental conditions. The results lead to the assumption that the protein synthesis in some neuronal cells may probably differ not only quantitatively, but also qualitatively in trained and untrained animals.


Activity of interneurons mediating reciprocal 1a inhibition during locomotion. The activity of interneurons monosynaptically excited by 1a afferents and mediating the reciprocal inhibition of motoneurons of the antagonistic muscles was recorded in mesecephalic cats. The activity was resulted during locomotion evoked by stimulation of the "locomotor region" of the mesencephalon. The neurons turned out to be active in a definite phase of the step simultaneously with that muscle which supplied them by 1a afferent input. In preparations with de-efferent hindlimbs, stimulation of the "locomotor region" evoked a periodic process in the spinal cord ("fictive" locomotion); in this case bursts of activity in the interneurons also coincided with the activity of motoneurons of corresponding muscles. Under such conditions excitation of 1a afferents by the passive stretch of the muscle or by electric stimulation of the muscle nerve studied in an increase of the activity of interneurons, which depended on the phase of the cycle. The data obtained show that during locomotion there are at least two sources of inhibition of motoneurons of antagonistic muscles; (i) the activity of 1a afferents of the active muscle, mediating by corresponding interneurons; and (ii) signals coming through the same interneurons from the central mechanisms of generating stepping movements.


Imprinting: correlations between behaviour and incorporation of (14-C) uracil into chick brain. On the first day after hatching 106 domestic chicks were injected with (14-C)uracil and exposed to a yellow or a red rotating flashing light for 72 min. Shortly before they were killed and 115 min after injection they were given a choice between the two lights. Incorporation of the (14-C)uracil into 4 regions of the brain was measured. Differences between batches and between training conditions were eliminated as sources of variation by standardising the behavioural and biochemical measures. Correlations between the measures were obtained. Chicks that were active from the early stages of training showed lower rates of incorporation in the midbrain, forebrain base and anterior of roof of the forebrain, than less responsive chicks. When the general lowering effect of behavioural activity on incorporation was eliminated as a source of variations, a striking positive correlation emerged between the preference for the familiar object and incorporation in the anterior of forebrain roof. Since preference for the familiar is a direct measure of imprinting and since no other behavioural measure is positively correlated with biochemical changes in anterior roof, it is concluded that these biochemical changes were closely linked with the learning process.


Cholinergic-dopaminergic interaction in the striatum: the effect of 6-hydroxydopamine or pimozide treatment on the increased striatal acetylcholine levels induced by apomorphine, piribedil and d-amphetamine. Apomorphine (1 and 2 mg/kg), piribedil (15 and 60 mg/kg) and d-amphetamine (5 and 10 mg/kg) increased rat striatal acetylcholine levels without affecting choline. Pretreatment with pimozide (0.5 mg/kg) completely antagonized the effect of apomorphine and piribedil and by itself markedly decreased striatal acetylcholine levels. d-Amphetamine signigicantly antagonized the effect of pimozide. Nine days after pretreatment with 6-hydroxydopamine plus pargyline, striatal dopamine was decreased by 78% while acetylcholine and choline levels remained unaltered. Under these conditions, the effect of d-amphetamine was completely abolished while apomorphine and piribedil were just as active as in the vehicle-treated group. The results suggest that d-amphetamine acted indirectly to increase striatal acetylcholine levels probably through the release of dopamine and/or noradrenaline, while apomorphine and piribedil acted directly at dopamine receptor sites.


Transport of choline from plasma to cerebrospinal fluid in the rabbit with reference to the origin of choline and to acetylcholine metabolism in brain. The supply of choline to the brain and the interrelationship between acetylcholine metabolism in the brain, choline in cerebrospinal fluid (CSF) and choline in plasma has been investigated by studying the transport of deuterium labelled choline from plasma toCSF in rabbits. The experiments were performed either by i.v. infusion of labelled choline or by administering deuterium choline in the diet until steady state levels were reached. All assays of labelled as well as unlabelled choline and acetylcholine were carried out by gas chromatographic-mass spectrometric technique. From these experiments it was found that the half-lives of the disappearance of labelled choline in plasma and CSF were similar (15 min) and the mole fraction of labelled choline in plasma was approximately 2.4 times that in CSF. The half-life of labelled acetylcholine in brain was about 25 min. In the time interval 10-20 min, the mole fraction of brain acetylcholine was the same as that of CSF choline. When infusion was carried out during pentobarbital anaesthesia the mole fraction of labelled brain acetylcholine decreased and that of labelled CSF choline increased compared to those of conscious animals. At steady state the mole fraction of labelled choline in plasma was nearly twice as high as that in CSF which in turn was significantly higher than that of acetylcholine in the brain. From these results it is suggested that in rabbit, free and derived choline in plasma are supplied to the brain in equal amounts. Furthermore it is suggested that choline is transported from plasma, via the extracellular space of the brain to CSF. In the extracellular space a part of choline is diverted and exchanged with choline in the acetycholine metabolic pathway.


Characteristics of CA1 neurons recorded intracellularly in the hippocampal in vitro slice preparation. Intracellular recordings were made from CA1 pyramidal cells in the hippocampal in vitro slice preparation. Neurons displayed characteristics previously described for the intact preparation including: EPSPs, IPSPs, depolarizing after-potentials, bursting, frequency potentiation, double pulse facilitation, and probably dendritis spiking. Cells could be discharged when orthodromic or antidromic pathways were stimulated, with injection of a depolarizing current pulse, and from iontophoresis of glutamic acid. The apparently normal behavior of the neurons makes the isolated hippocampal slice a promising cortical preparation.


Influence of centrifugal sinus nerve activity on carotid body catecholamines: microphotometric analysis of formaldehyde-induced fluorescence. The effects of centrifugal activity in the carotid sinus nerve (CSN) on the intensity of formaldehyde-induced fluorescence of carotid body were examined in cat. Measurements of intensity were obtained from 21 to 56 sections of each carotid body with a microscope photometer attached to a fluorescence microscope. Comparisons were made between the two carotid bodies removed from each cat. In one series of experiments, one carotid body (CSN intact) served as control, while the experimental carotid body was on the side on which centrifugal activity was increased by electrical stimulation of the peripheral end of the cut CSN. In a second series, centrifugal CSN activity was increased by hypoxemia; one CSN was transected (control) and the other was left intact (experimental). In untreated cats, fluorescence intensity was significantly higher on the side with increased centrifugal CSN activity. In cats treated with either MK486, which inhibits conversion of L-DOPA to dopamine, or reserpine, increased centrifugal CSN activity caused a significant decrease in intensity of type I cells. These findings indicate that centrifugal discharges regulate, in part, the synthesis and release of catecholamines by type I cells of the carotid body.


Exteroceptive suppression and motor control of the masseter and temporalis muscles in normal man. Single electrical stimuli to the gums and mucosa inside the mouth elicit two successive exteroceptive suppressions (ES1 and ES2) in the voluntary electromyogram of the masseter and temporalis muscles in normal man. The same afferent axons appear to be involved in the two effects, as indicated by the intensity function, the electrical excitability, the afferent conduction velocity and the lack of differential effect of Xylocaine infiltration of the inferior alveolar nerve. Two similar phases of inhibition involve the monosynaptic masseter reflex and the synchronized electromyographical spikes induced by jaw vibration. Exteroceptive suppression is thought to be mediated, in the brain stem, by both an oligosynaptic (ES1) and a multisynaptic (ES2) mechanism.


Behavioral deficits in cats following early selected visual exposure to contours of a single orientation. The ability of adult cats, whose early visual experience was confined to contours of a single orientation (either vertical or horizontal), to resolve gratings of different orientations was studied by operant methods. Following selective visual exposure during part or all of the first 4 months of life, the cats were trained on a simultaneous discrimination between gratings of various orientations and blank fields of the same mean luminance. The spatial frequency of the gratings was systematically altered in order to obtain an estimate of acuity based upon extrapolation to chance levels of performance. Selectively deprived cats performed as well as normally reared cats on gratings having the same orientation as that of the stripes they saw as kittens, but their performance on gratings orthogonal to these was poorer. The deficits in acuity for gratings perpendicular to the experienced orientation varied between 0.26 and 0.87 of an octave. On the other hand, control cats whose early visual experience alternated between vertical and horizontal stripes, or who were reared in an environment containing randomly oriented contours, failed to show any difference in their acuity for vertical and horizontal gratings. The acuity deficits shown by the selectively deprived animals are long-standing since they remain unchanged even after 30 months of normal visual exposure. It is argued that these perceptual deficits are a consequence of the changes in cortical physiology that other investigators have described in cats who had undergone similar early visual deprivation. Taken together, these findings provide a basis for explaining a number of human perceptual disorders.


Directional selection for growth at two ambient temperatures in Coturnix coturnix japonica. Four lines of quail; random-selected, male-selected, female-selected and male- and female-selected lines, were subjected to 37 plus or minus 1-6 degrees C from 3 to 5 weeks of age while another four lines, similarly selected, were reared at room temperature (15 to 27 degrees C). Selection for increased growth was practised for two generations using ten females and five males as parents in each line. A significant interaction between time and temperature was observed in the third generation progeny; when exposed to heat stress, the stress-adapted lines showing a superior growth rate. A sex X temperature interaction was also observed and was due largely to the control females being more sensitive to stress than the males. A cumulative realised heritability estimate of 0-47 plus or minus 0-15 for 5-week body weight was obtained.


The role of histamine and fish meal in the incidence of gizzard erosion and pro-ventricular abnormalities in the fowl. The role of certain fish meals in the production of localised gizzard erosion is confirmed. Lesions typical of gizzard erosion could be produced by the addition of histamine to the diet. The amount of histamine occurring naturally in fish meal depends on the species of fish and the extent and nature of bacterial spoilage. These variables may explain why histamine has not been implicated previously and also why there have not been consistent associations between the condition and geographical source or common factors in bulk consignments of the meal.


The effect of reserpine on plasma LH concentrations in intact and gonadectomised domestic fowl. Reserpine was found to inhibit the secretion of luteinising hormone when injected into intact and gonadectomised fowl at a dose rate which caused heavy sedation. This could indicate that reserpine or its derivatives should not be used for breeding poultry.


The microstructure of the cuticle-less shell of the eggs of the domestic hen. Open pores were a notable feature of the shell of hens' eggs which were naturally devoid of cuticle. In contrast with normal eggs, the surface of the cuticle-less shell was irregularly contoured and, in many instances, deeply fissured.


The fine structure of the pores in the shell of the hen's egg. No fibrous or crystalline material was present in the lumen of pore canals which were exposed by radial fracture and examined with a scanning electron microscope. The walls of the canals were rough, but they did not have a characteristic ultrastructure. The campanulate outer orifice of the pores was plugged with cuticle in which radial cracks formed channels through which the respiratory gases presumably diffuse.


Protective effect of immunoglobulins in serum and milk of sows exposed to transmissible gastroenteritis virus. Experimental exposure of susceptible pregnant sows by various routes to the gut-origin transmissible gastroenteritis virus stimulated production of milk and serum antibodies. These antibodies neutralized the cytopathic effect of transmissible gastroenteritis virus propagated in cell culture. This in vitro neutralizing antibody resided in the IgG and IgA immunoglobulin classes. On the other hand, protection for baby pigs resided in the IgA class of milk immunoglobulin of sows exposed orally or intramammarily but not of sows exposed intramuscularly to the virus.


Systolic time intervals in domestic ponies: alterations in a case of coarctation of the aorta. This report describes the measurement of systolic time intervals in a nine year old female domestic pony which was found at necropsy to show coarctation of the aorta and bilateral ventricular hypertrophy. Electrocardiogram, phonocardiogram and direct arterial blood pressure were recorded from the pony in a standing unmedicated state and systolic time intervals were measured from the resulting tracings. A prolongation of left ventricular ejection time and shortening of the pre-ejection period were observed in comparison to a group of normal ponies similarly examined. Such changes are consistent with outflow tract obstruction. The pony was also hypotensive and this condition was interpreted as a long-term compensation for the obstructive lesion. It is likely that the changes in systolic time intervals were at this stage predominantly affected by the hypotension. The report notes that the existence of such a case of spontaneous cardiovascular disease in the pony population might suggest the utility of the animal as a resource in comparative cardiovascular physiology and medicine.


A study of articular surfaces and synovial fossae of the pectoral limb of swine. Articular surfaces of the pectoral limb were studied in 50 swine and are described in detail. Synovial fossae were not present at birth but were found commonly on the articular surface of the scapula, distal humerus, proximal radius, distal radius and distal surfaces of the intermediate carpal bone after four to five months of age. When present, they were bilaterally symmetrical and were located at the depth of a concavity of the articular surface. Microscopically, synovial fossae appeared as an invagination of articular cartilage extending into subchondral bone. Evidence of endochondral bone formation was less apparent at the depth of synovial fossae than in areas of weight bearing cartilage.


New evidence for an intermediate polymer of glucose in cellulose biosynthesis by Acetobacter xylinum. The results of sucrose-density-gradient centrifugation of a cell-free particulate enzyme system from Acetobacter xylinum which was incubated with uridine diphosphoglucose indicate that there is a polymeric intermediate in the biosynthesis of cellulose. This intermediate has the properties of an oligomer of glucose, is normally attached to the heaviest particle of the suspension, but, when released by hydrolysis, is preferentially adsorbed to fragments of preformed cellulose. It may form short segments of microfibrils when precipitated from alkaline solution by ethanol. The presence of this intermediate raises again the question of a primer in cellulose biosynthesis.


Endosymbiosis in a leafhopper, Helochara communis Fitch (Cicadellidae: Homoptera): symbiote translocation and auxiliary cells in the mycetome. At times, symbiote populations in mycetomes of Helochara communis are apparently increased by translocation of symbiotes from adjacent mycetocytes. These symbiotes appear to reproduce in mycetomes and become phagocytosed by 'auxiliary' cells (probably hemocytes) that invade mycetomes at zones of disruption supposedly resulting from reproduction of the translocated symbiotes. Some phagocytosed symbiotes degenerate in large vacuoles; others become lodged in smaller vacuoles that supply a third membrane. The hemocytes fuse and form additional mycetomal syncytia.


Osteomyelitis in children: comparison of hematogenous and secondary osteomyelitis. A review of osteomyelitis in 54 patients treated at the Dr. Charles A. Janeway Child Health Centre over a 4-year period revealed equal frequencies of secondary and hematogenous osteomyelitis. Although the clinical picture in patients with hematogenous osteomyelitis was classic, patients with secondary osteomyelitis presented with an altered clinical response. Patients with secondary osteomyelitis have a history of an antecedent puncture wound or an inadequately treated contiguous focus of infection; antistaphylococcal antimicrobial therapy was ineffective for most because gram-negative bacilli were isolated in this group of patients. In contrast to patients with hematogenous osteomyelitis, who frequently respond to intensive antimicrobial therapy, those with secondary osteomyelitis will frequently require surgical intervention to eradicate the infection.


Self-care program for inpatients in a mental hospital. A self-care program for selected inpatients in a mental hospital has been developed and has been in operation for more than a year. The 12-bed unit operates without any nursing or other professional staff during the night and weekend. Certain factors, including the mental hospital as an organization, tend to hamper the development of this type of program as well as the progress and growth of other programs in psychiatric hospitals. It is suggested that the much needed progress in the mental hospital would be facilitated by an open-systems approach to its organization. Mental hospitals should consider the introduction of self-care programs for selected patients, mainly in view of their therapeutic potential, but also because of the financial savings such programs offer.


Neonatal pneumopericardium.

Neonatal pneumopericardium. Pneumopericardium developed in three newborn infants, including a set of twins, with respiratory distress syndrome. The rarity of this condition and its occurrence in two newborns suggest an anatomic predisposition, especially in premature infants requiring assisted ventilation. Two of the infants died; one had undergone pericardiocentesis. From a review of the literature and from our cases we conclude that conservative therapy appears warranted in cases of isolated pneumopericardium although the number of cases reported is too small to provide a definite answer.


Effect of I,25-dihydroxycholecalciferol in renal osteodystrophy. A 23-year-old man with medullary cystic disease had been undergoing hemodialysis for 5 years and had become confined to a wheelchair because of renal osteodystrophy. He was treated with 125-dihydroxycholecalciferol, 2.0 mug (later 1.0 mug) three times a week, administered by way of the venous end of the dialysis machine. Within 1 month bone pain lessened and his ability to stand and walk improved. By 3 months he was walking short distances and by 5 months, long distances. Calcium balance was near zero before treatment and was strongly positive during treatment. Bone mineral content in the lower femur, measured by photon absorptiometry, increased at a rate of 32.2% per year. In contrast, 26 other patients on long-term hemodialysis had a mean loss of bone mineral content of 14.0% per year. Radiographs taken during treatment showed a decrease in subperiosteal bone resorption and healing of a pseudofracture. A significant decrease in the mean serum alkaline phosphatase value was noted during treatment, but no significant changes in mean serum calcium or phosphorus values were seen.


Urinary homovanillic acid, dopamine and norepinephrine excretion in patients with essential hypertension. Urinary excretion of dopamine, norepinephrine and homovanillic acid was measured in normotensive subjects and in patients with either labile of stable hypertension under conditions controlled for posture, sodium and potassium intake and time of day. Mean homovanillic acid excretion was 313.5 plus or minus 77.7 (SE) mug/4h in the normotensive patients. Mean values for the patients with labile or stable hypertension were significantly greater, at 2506 plus or minus 476 mug/4 h (P smaller than 0.001) and 795 plus or minus 170 mug/4 h (P smaller than 0.01), respectively. Urinary excretion of dopamine and norepinephrine tended to be elevated in patients with labile hypertension when compared with values in the control subjects and the patients with stable hypertension. The data are compatible with the hypothesis of adrenergic hyperactivity in labile hypertension and underline the biochemical heterogeneity of essential hypertension. Because the overlapping of values between control subjects and patients with labile hypertension was minimal, it is proposed that an elevated valve for urinary homovanillic acid could be used as a biochemical marker to identify the patients with labile hypertension.


Serum cholesterol and triglyceride measurements in Canadian physicians. In a study of serum cholesterol and triglyceride concentrations in male physicians, blood was drawn after fasting from 2071 registrants at 17 Canadian medical meetings from 1968 to 1973. Eight regional medical laboratories participated in the study. About two thirds of the samples were analysed in one of two laboratories to diminish method variations. When chylomicronemia, hyperglycemia or extremely high triglyceride values were detected, suggesting nonfasting, the data were discarded. The mean serum cholesterol value for the total study population was 233.9 plus or minus 1.22 mg/dl and the mean serum triglyceride value, 150.5 plus or minus 2.48 mg/dl. The mean values and the prevalence of elevated values (cholesterol larger than or equal to 250 mg/dl; triglyceride larger than or equal to 150 mg/dl) were related to age. Of the total study population 34.7% had elevated cholesterol values and 36.2% had elevated triglyceride values; only the cholesterol value was elevated in 17.5%, only the triglyceride value in 19.6% and both values were elevated in 16.8%. Although this was not a random sampling of Canadian physicians or of Canadian men, our findings of elevated serum lipid values were similar to those in French Canadian civic workers, American executives and Scandinavians, and somewhat higher than those in the Albany, New York and Framingham populations, but distinctly higher than those reported by a recent Nutrition Canada survey.


Hyperglycemia-induced hyponatremia: metabolic considerations in calculation of serum sodium depression. Hyperglycemia is associated with a decrease in serum sodium concentration. Previous methods of estimating the degree of decrease have not considered the fact that glucose will enter certain cells despite relative insulin deficiency; thus, glucose will not contribute directly to the osmotic gradient responsible for water shifts into or out of these tissues. The expected decrease in serum sodium concentration is 1.35 meg/l for every 100mg/dl increase in blood glucose concentration - the metabolic correction factor. Although the numerical difference between this factor and that calculated by others is small, the metabolic implications could be critical. In the hyperglycemic state the water content of tissues not requiring insulin for glucose transport could increase, and where tissue swelling is physically restricted (for example, in the brain) this expansion could seriously affect organ function.


Experience with fetal monitoring in a university teaching hospital. Fetal monitoring during labour may be expected to decrease perinatal losses and the number of infants born with brain damage. In a prospective study of intrapartum fetal monitoring in selected high-risk pregnancies in a Winnipeg hospital the monitoring rate was 26.5% and the cesarean section rate in the monitored group was 22.0%. The fetal outcome in the monitored group was better than in the unmonitored group. The establishment of a fetal intensive care unit is believed to be strongly desirable in improving fetal surveillance during labour. Fetal monitors should be stationed in the delivery room as well as in the first-stage room.


Intrarenal arterial collateral circulation. In three cases of intrarenal arterial collateral circulation the collateral channels developed between interlobar arteries in diseased kidneys. Probably these originated in hypertrophied spiral vessels that had arisen from the interlobar arteries in the area of the minor calyces. This form of collateral circulation will undoubtedly be recognized more frequently with the increased use of magnification radiography.


Career choices of physicians 15 years after entering medical school. The career status of 149 graduates of the University of Toronto faculty of medicine who entered in 1958 and graduated in 1962 was determined in 1973. The response rate to the mailed questionnaire was 96.6%. Of the graduates 4.7% were not practising medicine, 2.0% stated that medicine was not their primary gainful activity and 4.1% were untraceable or unknown. Of the 24 women in the class 17 (70.8%) were practising at least 76% of their time and 4 (16.7%) were practising 26 to 75% of their time. General practice or family medicine had been chosen by 39.0% of the class and a specialty by 55.7%; 5.4% were unknown or untraceable. The place of longest residence before entrance to university was a good predictor of ultimate location of practice but not of type of practice.


Pediatric resident staff follow-up, 1958 to 1972: their present place of practice and activities. Of 174 medical graduates who had undertaken residency training in pediatrics at the Health Centre for Children, Vancouver between 1958 and 1972, 156 replied to a questionnaire designed to determine their present activity. Excluding those still in training 58.4% are currently practising pediatrics, 28% are in family practice and 12.8% are in other areas of professional activity; 49% obtained a specialty degree in pediatrics and 5.4% obtained  certification of the Royal College of Physicians and Surgeons of Canada in another specialty. Of the total, 69% have remaind in Canada; of the Canadian graduates 83% have remained in this country, compared with 63.8% of graduates from other countries. Estimation of pediatric manpower requirements should take into account the anticipated increase in population, the pediatrician attrition rate, the contribution one province may provide for the rest of the country, and the fact that only approximately 60% of pediatric trainees will ultimately practise this specialty.


Combination chemotherapy for disseminated malignant melanoma. BCNU, hydroxyurea, and imidazole carboxamide (DTIC) were administered to 89 patients with disseminated malignant melanoma. A response rate of 27% was observed. The addition of vincristine in another 89 patients did not significantly improve the response rate (30%). This includes patients who died during or after one course of therapy (less than 28 days). If the early deaths are not considered, the over-all response rate was 38%. (he best responses occurred in patients with skin, lung, and/or lymph node involvement. Liver and brain involvement heralded poor responses. This response rate appeared to be independent of age, sex or previous therapy. Moderate and severe toxicity, predominantly nausea and vomiting, was noted in most patients. The median survival for all evaluable patients was 17 months, and was independent of the regimen used.


Comparison of the combination of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and vincristine with two dose schedules of 5-(3,3-dimethyl-1-triazino) imidazole 4-carboxamide (DTIC) in the treatment of disseminated malignant melanoma. One hundred twenty patients with inoperable metastatic malignant melanoma were randomly allocated to treatment with either a combination of BCNU 150 mg/m2 and vincristine 2 mg/m2 given every 30 days, or one of two regimens of DTIC: 300 mg/m2/day x 6 or 100 mg/m2/8 hours x 18 given every 30 days. Eight of the 51 (16%) patients who were originally treated with the BCNU and vincristine combination had 50% or more objective tumor regression, compared to 6 out of 25 (24%) patients treated with daily injections of DTIC, and 6 out of 21 (29%) patients treated with DTIC injections every 8 hours. The median duration of response to the BCNU and vincristine combination was 60 days, and the median duration of survival from initiation of treatment was 6.5 months in the responders and 3.3 months in the nonresponders. The median duration of response was 90 and 100 days for the daily and 8-hour regimens of DTIC respectively, andthe median duration of survival from commencement of treatment was 8.5 months for the responders and 3.5 months for the nonresponders. None of the 43 patients who failed to respond to the initial treatment program or whose disease progressed after initial improvement responded to the alternate treatment regimen.


BCG-induced protection against malignant melanoma: possible immunospecific effect in a murine system. This report documents for the first time BCG-induced protection against a murine malignant melanoma. Adult Balb/C mice recieved 0.1-cm3 doses of BCG prior to intramuscular challenge with 1 x 10-6 S-91 melanoma cells. A 65% reduction in melanoma incidence was noted in BCG-pretreated mice. The possibility of specific protection induced by the BCG against the melanoma exists, since the BCG pretreatment did not protect against challenge with 1 x 10-5 mammary carcinoma cells or 1 x 10-4 MCA fibrosarcoma cells in the same strain of mice. Lack of immunogenicity was not a factor in the inability of the carcinoma and sarcoma to be inhibited by BCG. The strenght of the BCG-induced protection against the S-91 melanoma was demonstrated by significantly decreased tumor incidence following three different log challenge doses of the melanoma. However, reduction of the sarcoma challenge dose to as few as 10-2 cells administered to BCG pretreated mice did not result in decreased tumor incidence. It was further discovered that as few as two doses of 0.1 cm3 of BCG were sufficient to produce a 70% reduction in melanoma incidence compared with the incidence in control animals (P less than .001). Lymphocyte-mediated cytotoxicity studies paralleled the results of the in vivo experiments. Lymphocytes immune to each of the three tumors showed significant cytotoxicity against their respective tumor target cells (p less than .001), while the only tumor cells that lymphocytes from BCG-pretreated mice showed significant cytotoxicity against were S-91 target cells (p less than .01). Nonspecific cytotoxicity was not a factor in the effect of BCG-immune lymphocytes against S-91 target cells, since BCG-immune lymphocytes were not cytotoxic to Balb/C fibroblasts.


A morphological and quantitative study of tumor blood flow. I. During growth and immune rejection. We have used serial microangiography and radioactive 133 Xe to study microvascular morphology and quantify blood flow in Walker 256 carcinomas implanted in rat tails during growth and immune rejection. No previous angiographic/quantitative studies during immune rejection are reported. Two tumor groups were identified. Group A grew rapidly, with a two- to six-fold increase in blood flow, and caused death in 10 days. Group B grew more slowly, and increased blood flow two to four times. At 6 to 8 days postimplant the B tumors diminished in size; blood flow decreased and extensive lymphocytic infiltration developed. By 21 days all evidence of the tumor had disappeared. The rejection appears to be cell-mediated, and the high incidence (65-70%) to be related to the number of tumor cells and/or presence of accumulated antigen in the innoculum. Microangiographic changes during immune rejection were specific, and included marked tortuosity of feeding vessels and a "ghostlike" fading out of tumor vessels, quite unlike the appearance of necrosis.


Ultrastructure of endometrial stromal sarcoma. An endometrial stromal sarcoma from a 48-year-old woman was studied by light and electron microscopy. Ultrastructurally most of the tumor cells resembled the stromal cells of midproliferative endometrium. There was no evidence of a pericytic differentiation of the tumor cells. These findings lend further support to the concept of an endometrial histogenesis of stromal sarcoma.


Proliferative patterns in colonic mucosa in familial polyposis. Microautoradiographic measurements of TdR3H incorporation into epithelial cells of colonic biopsies were compared in normal and eight index cases with familial polyposis, an inherited trait characterized by the development of colonic polyps and carcinomas. Colonic epithelial cells normally synthesized DNA synthesis was proliferated in the deeper two-thirds of the crypts, while DNA synthesis was repressed in the upper one-third. Patients with familial polyposis and patients with isolated single polyps incorporated TdR into epithelial cells lining the surfaces of polyps and occasionally into surface cells of intervening flat mucosa. Symptom-free members of polyposis families also demonstrated TdR3H incorporation into surface epithelial cells in biopsies of morphologically flat mucosa. The findings indicate similar proliferative behavior of epithelial cells in the formation of all adenomas, be they single isolated polyps or multiple familial adenomatous polyps. A sequence of changes occurs involving a loss of the cells' ability to repress DNA synthesis and the appearance of cells with persistent DNA synthesis at the surface and along the upper portion of colonic crypts. These defects are focal and widespread in the colonic mucosa of those with familial polyposis and are expressed at early age.


Immunologic evaluation of human bladder cancer: in vitro studies. Human bladder cancer tissue were obtained from 31 patients with the histologic diagnosis of transitional cell cancer. Attempts to grow these tumors in tissue culture resulted in 18 primary cultures but only 2 long-term cell lines. Cell-mediated and serum cytotoxicity was demonstrated in both autochthonous and allogeneic experiments. This would suggest a cross-reacting common antigen. In the patients showing positive cytotoxicity, no recurrence of tumor could be demonstrated with up to 3 years' followup after therapy.


Metastatic carcinomatosis of the liver mimicking cirrhosis: case report and review of the literature. Carcinomatous involvement of the liver mimicking cirrhosis is a rare complication of metastatic carcinoma, most frequently seen with scirrhous carcinoma of the breast. The case of a 46-year-old woman with breast carcinoma presenting with ascites, jaundice, spider angiomata, and portal hypertension is reported. On hepatic scan the liver appeared to be almost the same size as the spleen, a finding frequently seen in cirrhosis. A chemotherapeutic program was introduced, but was of no benefit, and the patient died with uncontrolled esophageal bleeding. The prominent histologic feature on autopsy was intense stromal fibrosis and intravascular tumor infiltration with compression of vessels of the portal system.


Lobular carcinoma arising in fibroadenoma of the breast. Lobular carcinoma may arise within the epithelial component of fibroadenoma of the breast, as evidenced by 5 cases reported from the files of the Mayo Clinic and 21 cases cited in the literature. The 5 cases reported here occurred in a series of 4000 cases of fibroadenoma during a 43-year period. Lobular carcinoma is the more frequent type to be seen in fibroadenoma (in 22 of 26 cases); it usually develops in situ. Extra-adenomatous carcinoma of the ipsilateral breast was identified in 11 of 26 cases, and 3 cases of contralateral carcinoma were noted in the entire series. Thus, lobular carcinoma arising within the epithelial component of a fibroadenoma has biological features similar to the behavior of lobular carcinoma of the breast in general. The prognosis has been favorable; lesions are usually encountered early; in only 2 of 26 cases were there axillary metastases.


Multicentric breast cancer. The incidence of new cancers in the homolateral breast after partial mastectomy. Multicentric microfoci of cancer are often present in patients with cancer of the breast and affect the contralateral breast as well as the originally affected one. despite the high incidence of these microfoci of cancer, the appearance of new clinical cancers is rare. In a period of 610 patient-years of exposure after partial mastectomy for cancer, six new cancers appeared in the contralateral breast and four in the affected one. These findings suggest that after partial mastectomy the danger of the appearance of a new cancer in the affected breast is less than might have been anticipated.


Adrenalectomy with radical mastectomy in the treatment of high-risk breast cancer. Bilateral adrenalectomy with radical mastectomy has been performed in a series of 17 postmenopausal women with breast cancer having metastasis in four or more axillary lymph nodes. Results to date show that both the recurrence and mortality rates are significantly lowered in this group of "high-risk" breast cancer patients by the combined treatment. Of these 17 patients, 14 are living and well with no evidence of disease. Six are surviving without recurrence 5 or more years since their primary treatment. The study also demonstrated that adrenalectomy patients on hormone replacement therapy are able to lead full and active lives for a long time without complications. This pilot study should be considered as a guide to future clinical trials rather than as an immediate recommendation for general therapy.


Lymphangiomyomatosis: report of a case with ureteral involvement and chyluria. A 54-year-old woman, presenting with chyluria and progressive dyspnea, is reported. Necropsy revealed co-existent lymphangiomyomatosis and pneumoconiosis in the lungs. Retroperitoneal lymphangiomyomas surrounded the distal ureters, and cystoscopy revealed pyelolymphatic backflow into renal lymphatic sinuses. The finding of chyluria with atypical smooth muscle hyperplasia within the ureters is extremely rare. Previously reported cases of lymphangiomyomatosis are discussed and compared with our own. Electron micrographs of involved lymph nodes are presented and the findings briefly evaluated.


The value of aspiration cytology in the diagnosis of breast cancer: experience at the Fondation Curie. Aspiration cytology was performed on 2772 breast masses, all of which subsequently had open biopsies. Of the 1745 histologically malignant tumors, 1539 (88%) had a concordant cytologic diagnosis: 54 (0.3%) were diagnosed as probably malignant; 63 (3.6%) were false negatives; and 80 (0.5%) had inadequate smears for diagnosis. Of the histologically benign lesions, 916 (89%) had a concordant cytology: only 3 (0.3%) were false positives; cancer was suggested in 42 (0.4%); and the smears were inadequate in 66 cases (6.4%). Very small or very large sized cancer and a high degree of differentation were major causes of false negative aspirates. Recurrent tumors in those breasts exclusively treated by radiotherapy were documented by cytology in 56 of 69 cases (78%). Aspiration cytology is highly reliable when the diagnosis of cancer is made, but should be ignored if no malignant cells are observed.


Prediction of the response to chemotherapy in acute leukemia. The prognostic value of the in vitro incorporation of labeled thymidine was evaluated in 53 cases of acute leukemia, by means of autoradiography and liquid scintillation (LS) count. A higher rate of incorporation before therapy with higher labeling index and LS- specific activity was observed in patients who later responded to chemotherapy with a complete remission. The in vitro depression of labeled thymidine incorporation after incubation with the two drugs selected for the induction therapy was more marked in those who responded to therapy than in the nonresponders. The in vitro incorporation of 3H-thymidine was also evaluated after 48 hours of chemotherapy ("vivo-vitro" test). A decrease of the incorporation was observed frequently in the responders. On the other hand, in the group of nonresponders, there was generally an increase of the incorporation measured by the liquid scintillation count, often contrasting with a decrease of the labeling index, and corresponding to a higher rate of intracellular incorporation. The prognostic value of these findings appears to be significant, as it allows the response to chemotherapy to be predicted, as well as allowing the selection of the various cytotoxic drugs.


Xeroradiographic detection of occult breast cancer. Seventy-five occult cancers of the breast were found in a group of 7010 patients examined by xeroradiography, an incidence of 1% of all patients referred in a group practice setting. Nonpalpable cancers can be shown as a mass with or without calcifications, or as clustered calcifications only. A technique for preoperative localization of occult cancer is discussed. This, plus accurate marking of the surgical specimen, is important in the management of these cases.


Full thickness chest wall resection for recurrent breast carcinoma involving the bony chest wall. Solitary recurrent breast cancer involving the bony chest wall (parasternal recurrence) is curable when no evidence of systemic spread is found. Radical full thickness chest wall resection is an effective mode of treatment; it remains the only available treatment for patients whose chest wall recurrence fails to respond to radiation therapy, and in those who develop complications due to heavy irradiation. This report covers a review of the records of 52 patients treated at Memorial Hospital by chest wall resection for recurrent breast cancer between 1950 and 1972. The technique of chest wall resection and immediate plastic reconstruction is described. The gross and determinate 5-year survival rates for patients who underwent chest wall resection as the initial mode of therapy for chest wall recurrence were 43% and 57%, respectively. On the other hand, when chest wall resection was performed on those patients whose chest wall recurrences failed to respond to radiation therapy, the gross and determinate 5-year survival rates dropped to 16% and 19%. Full thickness chest wall resection with immediate plastic reconstruction when employed as the first mode of therapy for chest wall recurrences provides a significant 5-year survival rate, and has a definite place in the management of recurrent breast cancer.


Carcinoid tumors of the gastrointestinal tract. This study is based on a review of the records of 107 patients with primary carcinoids of the gastrointestinal tract diagnosed at the Memorial Hospital for Cancer and Allied Diseases during the 20 years from 1948 to 1968. The tumors were classified into two major groups according to their gross and pathologic presentation, and were correlated with clinical behavior and treatment. Carcinoids which were still intramural in location were usually asymptomatic, and yielded successfully to local excision (85% 5-year overall survival); carcinoids which had invaded into the serosa and/or beyond were usually symptomatic, and hd much poorer results (5% overall 5-year result), despite radical surgery with or without palliative radiotherapy and/or chemotherapy.


Prognosis of the second breast cancer. The role of previous exposure to the first primary. With increasing evidence that cancer patients respond immunologically to their cancers, it seemed interesting to investigate whether or not the course of the second cancer differed from that of the first. If we assume that, in analogy to mammary cancer in the mouse, the cells of human breast cancers carry shared antigens (although this is by no means certain), we could expect that sensitization of the patient induced by the first cancer would enhance his immune response to the second and that this might be reflected in an altered clinical course. We evaluated 82 patients with a second breast cancer and found no difference in the course of the second cancer as compared with the first.


Skin cancer in black patients.

Skin cancer in black patients. Skin cancer is rare in black patients. The clinical course and pathology of 58 cases are presented and reviewed. These include 38 squamous cell carcinomas, 13 malignant melanomas, and 7 basal cell carcinomas. Sixty-one percent of the squamous cell carcinomas developed in unexposed areas, with sunlight exposure apparently not being an important etiologic factor. Forty-one percent of the squamous cell carcinomas had predisposing factors such as burn scars or chronic infection. Squamous cell carcinoma in black patients is an aggressive disease, with 29% developing regional lymph node metastasis, and a mortality of 29%. Malignant melanomas occurred most frequently on the plantar surface of the foot (76%). Melanoma is also a virulent tumor in black patients, with 11 of 13 patients developing lymph node metastasis and only 2 patients surviving. Skin cancer in black patients presents a very different clinical picture than that seen in white patients. It is important that these factors be considered when planning therapy.


Breast biopsy priority: cancer versus benign preoperative masses. From 1963 to 1973 at Emory Clinic 17,288 breast examinations, including history, physical examination, and mammography, were performed on 6342 patients. The resulting 2793 breast biopsies included 2056 benign and 737 malignant lesions. High-risk and low-risk groups of breast cancer patients were observed for presence or absence of a mass or masses clinically and by roentgenograph, age, and breast pathology. The breast biopsy rate was the same for all age groups studied. The percentage of cancer per biopsy varied from 0 to 100 when the various combinations of mass (masses), no mass, and age were considered. Low priority (less than 5% cancer) groups were: in all age groups no mass by roentgenograph or clinically and no mass by roentgenograph and clinical multiple masses: for the 0-32 age group, all categories except single mass by roentgenograph and clinically; and for the 0-38 age group all categories except mass or masses both by roentgenograph and clinically. Using this wide range in the ratios of cancer, priority for biopsy can be established for each group. The surgeon can use additional clinical assessment of relative risk to contribute to an increased priority scheme.


Immunologic competence of regional lymph nodes in patients with breast cancer. In 24 patients undergoing radical mastectomy, the degree of sensitization to breast cancer was compared between lymphocytes obtained from regional lymph nodes and circulating lymphocytes. Using the direct lymphocyte migration inhibition assay a greater immunologic response was observed in regional lymph node lymphocytes as compared to circulating lymphocytes when challenged with breast cancer antigen in vitro. In the breast cancer group, migration inhibition (M.I.) was 21% plus or minus 3% in the regional lymph node (R.L.N.) lymphocytes, as compared to 7% plus or minus 3% in the peripheral blood (P.B.) lymphocytes (p smaller than .01). In the control group M.I. was - 10% plus or minus 2% in the R.L.N. lymphocytes, as compared to - 2% plus or minus 3% in the P.B. lymphocytes (p equal to n.s.) indicating no immunologic response to the breast cancer antigen. A significant delayed hypersensitivity response (M.I.greater 20%) was found in 17/24 regional lymph nodes of the radical mastectomy graoup, as compared to 7/24 in the peripheral blood samples tested in the same group, indicating a superior immune response in the regional lymph node lymphocyte population. These data support the concept that regional lymph nodes in breast cancer patients are immunologically competent, and that the lymphocytes in these nodes are more reactive with a tumor antigen than are the circulating lymphocytes.


Malignant melanoma of the extremities: a clinicopathologic study using levels of invasion (microstage). A clinicopathologic study was done in 151 patients with malignant melanoma of the extremities who were surgically treated in Memorial Hospital and had 5-to 9-year followup. Microstaging was done according to the depth of invasion, as determined by Clark's levels as well as by direct measurement. This was related to treatment and to clinical course. There was a correlation between the depth of invasion by Clark's levels and the incidence of lymph node metastases in patients with Stage I melanoma who had elective node dissection. The incidence of nodal metastases was 4% for Level II, 7% FOR Level III, 25% for Level IV, and 70% for Level V. There was a correlation between Clark's level of invasion and survival aftter surgery. The 5-year cure rate was 100% for Level II, 88% for Level III, 60% for Level IV, and 15% for Level V melanoma. The presence of nodal metastases augured a much worse prognosis than Clark's level per se. In patients with Level IV melanoma, the 5-year cure rate was 82% in patients with negative nodes and 27% in those with nodal metastases after elective node dissection. Microstaging primary melanoma according to Clark's levels serves as a useful standard with which to compare surgical results. In this series of extremity melanomas there was no difference between local recurrence and lymphadenectomy for Level II melanoma. For Level III and Level IV melanoma, wide excision and lymphadenectomy gave higher cure rates than wide excision only, both at 5 and 9 years after surgery. The results were significant only for patients with Level III, however. Use of the measured depth of invasion added significant clinicopathologic information. The incidence of nodal metastases at elective node dissection was 5 to 9% for melanoma showing 0.6 to 2.0 mm of invasion, 22% for melanoma measuring 2.1 to 3.0 mm, and 39% for melanoma invading beyond 3.0 mm. The 5-year cure rate was 100% for melanoma measuring less than 1.0 mm, 83% for melanoma invading 1.1 to 2.0 mm, 58% for lesions measuring 2.1 to 3.0 mm, and 55% for melanoma invading over 3.0 mm. The microstage technique combining Clark's levels and the measured depth of invasion has an important use as a prognostic index and as a standard upon which to select treatment for primary melanoma of the extremities.


Multidisciplinary treatment of embryonal rhabdomyosarcoma in children. Twenty-nine children under 15 years of age with embryonal rhabdomyosarcoma were treated according to a multidisciplinary protocol (T-2). The protocol consisted of surgical removal of the tumor if possible, followed by chemotherapy, and also with radiation therapy in patients with gross or microscopic residual disease. Radiation therapy was given in the 4500-7000 rads range. The chemotherapy consisted of cycles of sequential administration of dactinomycin, Adriamycin, vincristine, and cyclophosphamide, with obligatory periods of rest. The drug therapy was continued for 2 years. Following surgery, clinicopathologic staging of the disease revealed 10 patients with no residual disease (I-A), 5 with microscopic residual disease (I-B), 5 with unresectable tumors (II), 6 with unresectable tumors plus regional lymph node involvement (III), and 3 with disseminated tumors (IV). Twenty-four (82%) of the patients (20 Stages I-II, 4 Stage III) are alive with no evidence of disease for 4 plus to 42 plus months. These results are superior to those achieved between 1960-1970 among 108 children treated at Memorial Sloan-Kettering Cancer Center.


Medullary carcinoma of the thyroid gland. One hundred thirty-nine surgically treated patients with medullary carcinoma of the thyroid gland (MTC) were seen in our institution between January, 1926 and December, 1973. The incidence of this tumor among all thyroid cancers was 8%. Twenty-nine patients had the familial form of MTC; they were subclassified, on the basis of the phenotype, into a group of 15 patients with Sipple syndrome (or multiple endocrine neoplasia (MEN) Type 2A) and a group of 14 patients with mucosal-neuroma phenotype (or MEN type 2B). Better survivorship was seen in the younger patients, in those with bilateral tumors, in familial MTC, and in patients whose tumor was confined to the thyroid gland at the initial surgery. The incidence of tumor recurrence was 34%. However, in those with adequate surgical treatment, the recurrence was only 23%. The 5- and 10-year survivorships were 80% and 67%, respectively. The best chance of cure lies in early diagnosis through the use of immunoreactive calcitonin measurement in family members at risk, and an aggressive surgical attack on the primary tumor and any cervical metastases.


Modified radical mastectomy.

Modified radical mastectomy. This report describes our experience with a technique of modified radical mastectomy involving incision of the lower lateral fibers of the pectoralis major muscle and detachment of the origins of the pectoralis minor muscle. These maneuvers enable sufficient retraction of these muscles to provide excellent axillary exposure while minimizing the danger of traction injury to the neurovascular structures supplying these muscles. The operation has been performed in 20 patients; statistical analysis demonstrates at least as many nodes in these specimens compared to retrospective analysis of nodes recovered from 223 radical mastectomy specimens done during the previous 5 years. The final cosmetic results are superior to those obtained with standard radical mastectomy. These results suggest that this method of modified radical mastectomy should be considered, unless the proximity of the disease to the pectoralis muscles endangers the adequacy of the surgical margins.


Analysis of survival and recurrence vs. patient and doctor delay in treatment of breast cancer. Two hundred thirty-seven patients with cancer of the breast treated with radical mastectomy were reviewed. Coefficients of correlation between patient's and doctor's delay vs. survival were not significant at p smaller than 0.05. No significant relationship between delay and time of recurrence was found.


Topical chemotherapy of lentigo maligna with 5-fluorouracil. Three patients with biopsy-proven lentigo maligna were treated with topical 5-fluorouracil. Treatment consisted of twice daily application of 5% 5-fluorouracil cream for 13, 6, and 9 weeks, respectively. Two patients demonstrated presence of invasive melanoma; in one the melanoma was evident before chemotherapy, and in the other the lesion became evident after chemotherapy. In both the lentigo was treated topically and the melanoma excised locally. Posttreatment followup times through April 1, 1974 have been 42, 24, and 22 months, respectively. There has been no evidence of metastases in any patient. Topical chemotherapy with 5-fluorouracil cream appears to offer an encouraging alternative method of therapy for lentigo maligna of the face.


Indications for pleurectomy in malignant effusion. One hundred six patients with malignant pleural effusion were treated by pleurectomy; 83 of these were available for a 2-year followup. Sixteen of 83 patients were alive 2 years following the pleurectomy, with a survival range of 2-6 years. The most common neoplasms associated with the development of effusion were carcinoma of the lung in 41 cases, carcinoma of the breast in 33 cases, and mesothelioma in 14. Indications for pleurectomy were: A) failure to control the effusion by tube drainage and instillation of chemical or radioactive agents; B) presence of a trapped lung; and C) presence of malignant effusion at the time of thoracotomy for resection of an intrathoracic tumor.


Delayed cutaneous hypersensitivity and peripheral lymphocyte counts in patients with advanced cancer. One hundred eighty-three patients with advanced solid neoplasms were tested for their ability to react to four common skin test antigens (tuberculin PPD, streptokinase-streptodornase, mumps, and Monilia) and their ability to develop delayed cutaneous hypersensitivity (DCH) to 2, 4 dinitrochlorobenzene (DNCB). All patients were followed for at least 6 months or until death. Histologic tumor types studied were: melanoma (65), sarcoma (28), squamous cell carcinoma (23), and adenocarcinoma (67). The rate of progression of disease within 6 months of testing was lower in patients who had a positive response to a challenging dose of 50 mug of DNCB. Reactivity to recall antigens had no prognostic value except in patients with adenocarcinomas. Among patients with adenocarcinoma, those who reacted strongly to DNCB and one or more skin test antigens had the best prognosis, while those who were nonreactive to all had the worst prognosis (progression rate: 18% vs. 78%). Peripheral lymphocyte counts were related to the results of DCH to DNCB and skin tests. The preseence or absence of lymphocytopenia (count less than 1000/mm3) had prognostic value in patients who had positive skin test(s). In such patients, the disease progression rate was much higher in patients who were anergic to DNCB and who were lymphocytopenic (90% vs. 40%). These data suggest that DCH to DNCB, recall antigens, and peripheral lymphocyte counts are useful immunologic measurements in patients with advanced cancer. Although the prognostic value of each individual test is relatively limited, the predictive worth can be increased when multiple tests are employed. Pertinent findings reported in the literature are reviewed.


The immunologic responsiveness of regional lymphocytes in experimental cancer. This report presents data showing that regional lymph node lymphocytes differ in their immunologic activity from distant lymphocytes and splenic lymphocytes during the initiation and progression of murine mammary adenocarcinoma. Three groups of 100 C3H/He J mice received subcutaneously 10-6 viable tumor cells (I), 10-3 tumor cells (II), or Millipore chambers containing 10-6 viable tumor cells (III). Lymphocytes from different areas in Groups I, II, III, and non-tumor-bearing controls were cultured with PHA-P, autologous tumor, or normal C3H/He J breast tissue. In all groups regional lymph node lymphocytes showed the earliest peak response to PHA-P and autologous tumor, while the splenic lymphocyte and distant lymphocyte responses were delayed, especially in Group III. These studies demonstrate the role of the regional lymph node in the initial processing of tumor antigenic information. The development of central immunity appears to be the result of dissemination of immunogenic tumor products. This may be mediated initially by the regional lymph node.


Scalene node biopsy in carcinoma of the cervix. Pelvic and para-aortic lymphadenectomy. Twenty-eight patients with advanced untreated carcinoma of the cervix had selective pelvic and para-aortic lymphadenectomy and a scalene fat pad biopsy to determine the extent of their disease prior to treatment. None of these patients had palpable supraclavicular lymph nodes, but 18 had metastatic cancer in one or more pelvic lymph nodes; in the remaining 10 patients, all lymph nodes were free of metastatic cancer. Of the 18 patients with metastatic cancer in the pelvic lymph nodes, 9 also had metastatic cancer in the para-aortic lymph nodes, and 1 had metastatic cancer in a scalene lymph node. This patient had extensive cervical cancer with positive pelvic and para-aortic lymph nodes, unilateral ureteral obstruction, and cancer growing through the posterior culde-sac into the pelvic peritoneum. From this study, it appears that scalene lymph node biopsies are of limited value in evaluating patients with advanced cancer of the cervix. Unless the patient has extensive metastases, scalene lymph nodes rarely contain metastatic cancer.


The pathologic behavior of primary vaginal carcinoma and its relationship to cervical cancer. The surgical pathology files at the University of Alabama Medical Center for 1958 through 1973 contain records of 157 cases of vaginal carcinoma. Of the 141 patients on whom complete records are available, 37 had primary and 104 secondary vaginal carcinoma. Only 3 of the primary vaginal malignancies were adenocarcinoma; the rest were epidermoid. The microscopic appearance of these carcinomas was frequently lateral spreading or papillary, but in a few instances the growth pattern was submucosal. Prognosis appeared to be related to the stage of the disease. Vaginal carcinomas associated with cervical cancer clustered either within 1 year or 5 years after the therapeutic treatment. In this paper, the relationship between primary vaginal cancer and cervical cancer is discussed.


Dose and treatment factors in radiation-related pericardial effusion associated with the mantle technique for Hodgkin's disease. A retrospective study of 83 patients with Stage I-III Hodgkin's disease treated with an upper mantle field revealed a rate of radiation-related pericardial effusion (RRP) of 28.9% (24/83). Clinical presentation was asymptomatic effusion in 10/24 and symptomatic effusion in 14/24. RRP was self-limited in all but 4 patients, who progressed to chronic effusion requiring pericardiectomy (4/24). A midplane mediastinal dose of 4000 rads in 4 weeks was given with an anteriorly weighted mantle field that resulted in an average pericardial dose of 5325 rads (1823 ret) and an average midplane cardiac dose of 4625 rads (1558 ret). The rate of RRP was correlated with increasing degree of mediastinal Hodgkin's disease. Increased incidence of RRP with increasing cardiac and pericardial dose could not be proven statistically. Factors which may facilitate pericardial effusion following a basic radiation injury are discussed.


Documented hyperparathyroidism of thirty-six years' duration. The fascinating history of the first Memorial Hospital patient who was diagnosed as having hyperparathyroidism is reviewed. The illness presented as a cystic mass in a femur in 1929, which was treated with radiation. When the patient was first seen at Memorial Hospital in 1931, the diagnosis of osteitis fibrosa cystica was made; serum calcium was 14 mg/100 ml. In 1932, 6 years after Mandl performed the first parathyroidectomy ever for osteitis fibrosa cystica, this patient's neck was explored, and a right hemithyroidectomy was done, with removal of two normal parathyroid glands. The parathyroid tumor was finally located and partially removed in 1937 after a second failure at neck exploration in 1936. Correspondence between Dr. Edward D. Churchill at the Massachusetts General Hospital and Dr. Bradley Coley at Memorial Hospital indicated the concern at that time about uncontrollable tetany, which had been fatal in some contemporary cases and which had led to the practice of only partially removing the tumor. Following this, the patient was observed with documented hypercalcemia and chemical evidence of hyperparathyrodism until age 79. The physical and chemical abnormalities over the years up to and including her last exam are presented. The case is important not only from the historical viewpoint, but because it lends a perspective to long-term parathyroid disease, which is becoming less appreciated in this day of the routine serum calcium by SMA-12 screening. The question of partial parathyroidectomy for adenoma or hyperplasia is reviewed, and the question of observation of patients with mild hypercalcemia who probably have parathyroid tumors is discussed.


Influence of staging celiotomy in localized presentations of Hodgkin's disease. Staging celiotomy was performed in 139 previously untreated patients with lymphogram negative Stage I and II Hodgkin's disease. Sixteen additional patients received definitive radiotherapy for symptomatic relief of upper torso disease prior to abdominal exploration. The overall incidence of positive abdominal findings for these two groups was 34.5% and 31.2%, respectively. Further analysis of the 139 previously untreated cases revealed notable differences in incidence of positive abdominal findings for stage, presentation, and specific histology. Stage I patients with upper cervical or inguinal presentations or a lymphocytic predominance classification had negative celiotomies, as contrasted with a 43% incidence of positive abdominal findings in patients with supraclavicular presentations. In Stage II disease, the incidence of positive findings was related to the status of the mediastinum. For mediastinal presentations, the incidence was 33.3%, as compared to 48% for nonmediastinal presentations. To date, the number of relapses in celiotomy Stage I and II patients has been low regardless of whether or not prophylactic irradiation was administered to the major lymph-node-bearing regions of the upper and lower torso. Of 9 patients with progression, extranodal spread occurred as the first evidence of new disease in 4 patients. The implication of this finding is considered in a discussion on the influence of staging celiotomy in the management of Stage I and II patients with Hodgkin's disease.


CEA as a monitor of gastrointestinal malignancy. Ninety-four patients with carcinoma of the colon have been followed with serial determinations of plasma CEA (carcinoembryonic antigen) levels over a 3-year period using the Hansen assay. Nine hundred twelve CEA determinations have been made in these patients. Plasma CEA levels rose in 90% of the instances of clinical progression documented in these patients. In 30% of patients, this rise indicated progression 6 months or more before it was detected by standard clinical methods. Unfortunately, a few patients never developed elevated CEA levels even though disease clearly progressed. False positive results have also been encountered, with significant elevations occurring in patients who have since remained without evidence of disease for several months. Our data indicate that at least two sequential elevated CEA values, the second being higher, must be a minimal criterion for consideration of possible progression of disease. Even with this standard, we have encountered false positive results in 10% of our patients, indicating recurrence or progression where none has occurred clinically. CEA measurement is of limited usefulness for 30 days after curative surgery, because the elevation of CEA levels due to the original amount of tumor present as well as due to surgery per se may persist for this length of time in a significant number of patients. On the other hand, CEA levels have responded to chemotherapy in close correlation with observed clinical course in those patients with metastatic disease treated in this series. Initial pretherapy CEA values have so far proved to be good prognostic indicators of disease course following complete resection. With an initial CEA value of less than 2.5 ng/ml of plasma, recurrent has been rare (1/20). If the pretreatment CEA was greater than 7.0 ng/ml, it has been the rule (7/9).


Primary intestinal lymphoma with paraproteinemia. Five cases of primary intestinal lymphoma are described. The main clinical features included abdominal pain, diarrhea, and marked weight loss, together with radiologic and some laboratory findings suggestive of malabsorption. Laparatomy perfomed in four cases revealed dilatation of the small intestine, with mesenteric node enlargement. In these four instances there was a definite histologic evidence of malignant lymphoma, either initially or later in the course of the disease. A characteristic feature here was the diffuse infiltration of the intestinal mucosa with plasma cells, which in the deeper layers became progressively atypical and were mixed with histiocytes and giant cells. A similar infiltrate was seen in the mesenteric nodes. Immunoelectrophoresis showed the pattern of IgA heavy chain disease. It is suggested that the latter is a variant of primary intestinal lymphoma and not a separate disease entity.


The management of abdominal neuroblastoma. Although survival of children with abdominal neuroblastoma seems at this time to be unrelated to the therapeutic effort, a method of management according to the stage of disease has been developed. Seventy-three percent of patients have metastases at the time of diagnosis. Survival is best in children under 1 year of age. Survival by stage of disease drops progressively from 90% in Stage I disease to 2.4% in Stage IV disease. Irradiation therapy seems unrelated to survival in Stage I, II, and IV disease, while chemotherapy has not been shown to alter survival rates in any stage. Surgical removal of the tumor is still the primary therapy; irradiation is of significant benefit in patients with Stage III disease.


Other abdominal tumors.

Other abdominal tumors. The management of cancers of the liver, adrenal cortex, testis, and sacrococcygeal region in children is discussed. Combined treatment methods of surgery, irradiation, and chemotherapy was now used for the management of these tumors, with improved survival.


The role of the radiologist in the management of the child with a suspected bone tumor. The radiologist's most important task in evaluating lesions of the skeleton is to recognize with a great degree of certainty the post-traumatic and the self-limiting and healing tumorous conditions which require neither biopsy nor other surgical treatment. The group of lesions that will need biopsy ranges from those that cannot be absolutely classified in the above group to frankly malignant-appearing tumors. The radiologic differential diagnosis of malignant tumors is of lesser importance because this will be performed by the pathologist. Examples are illustrated and discussed. The importance of consultation among surgeon, radiologists, and pathologist is emphasized, particularly to avoid the possibility of misinterpreting immature callus formation as ostegenic sarcoma.


The role of diagnostic radiology and radiation therapy in the management of soft tissue sarcomas in children. Soft tissue sarcomas are the fourth most frequent solid tumors in children. They arise at many sites, most frequently in the orbit, head and neck, and pelvis. Diagnostic radiologic studies play an integral role in patient evaluation, allowing direct visualization of the primary lesion, its vascular supply, its direct and regional extensions; of distant metastases; and of anomalies. They aid in staging and selecting treatment, and later, in evaluating results. Radiation therapy is a vital tool in today's multidisciplinary approach. Irradiation has produced a 90% recurrence-free rate, and a 67% cure rate, for orbital rhabdomyosarcoma. A similar improvement in local tumor control rates may apply at other primary sites when an adequate dose is delivered to the affected volume. Multidrug chemotherapy programs provide hope for an increased cure rate. Sufficient time has not yet elapsed to judge fully the late anatomical and physiological costs of these more vigorous multidisciplinary treatments.


Chemotherapy of primary malignant brain tumors in children. Numerous investigators have reported on a variety of chemotherapeutic agents tested in children suffering from recurrent medulloblastoma, brain stem glioma, and ependymoma, in efforts to improve survival and reduce morbidity. Evaluation of such studies is difficult, because there were rarely more than three or four cases of each tumor type. In medulloblastoma, 5-year survival averages 32%; recurrence follows initial therapy by months to years. The recurrence may be intracranial, spinal, or metastatic, making comparison among cases very difficult. Intrathecal methotrexate (MTX) has been successfully used to treat medulloblastoma, with responses reported in about three-fourths of the cases. Intraventricular MTX is lethal when ventricular obstruction is present. MTX has been less useful in therapy of brain stem glioma and ependymoma. BCNU and CCNU have produced responses in patients with ependymoma, medulloblastoma, and brain stem glioma. Vincristine, alone or in combination, has been useful primarily in medulloblastomas. Less experience is available with several newer methods of chemotherapy, but promising results have been reported with procarbazine, 4'-demethyl-epipodophyllotoxin-beta-D-thenylidine-glucosede (PTG, VM 26), and high dose intravenous methotrexate with citrovorum rescue. It is likely that only a nationwide cooperative effort will achieve significant improvement in the chemotherapy of malignant brain tumors in children.


The staging of Hodgkin's disease in children reviewed. The accurate staging of Hodgkin's disease is of greater importance in children than in adults, because the deleterious effects of extensive radiation therapy and of prolonged multiple-agent chemotherapy are of greater significance in this age group. The physician concerned with Hodgkin's disease in children must separate those aspects of developments in this field which are applicable to the pediatric age group from the relatively large adult experience. Isotope scanning is effective in demonstrating disseminated disease in pediatric patients. Lymphangiograms are useful, but are more difficult to perform and to interpret in children. When laparotomy is performed in children with clinical Stage I, II, or III Hodgkin's disease, stage will be altered (upward or downward) in approximately 40% of children subjected to the procedure. As growth retardation, skeletal deformity, and secondary neoplasia follow radiotherapy in children, the major function of the laparotomy is to delineate the extent of the disease and thus define appropriate limitations of therapy.


Hodgkin's disease in children. A retrospective analysis: 1958-73. One hundred nine children with Hodgkin's disease consecutively treated at The Princess Margaret Hospital, Toronto, during 1958-1973 are reviewed. Crude 5-year survival rates, regardless of stage, were 1958-64--50%; 1965-68--73%; and 1969-73--95%. The corresponding 5-year relapse-free rates were 19%, 20%, and 57%. This progressive improvement in results was associated with the sequential introduction of lymphography and laparotomy with splenectomy, the change from involved field to extended field irradiation, and the introduction of multiple agent chemotherapy, at first for generalized relapse and recently as elective initial therapy, combined with extended field irradiation for children in advanced stages.


Leukemia in childhood: introduction and etiology. Striking improvement in the treatment of certain childhood cancers during the past decade has resulted from a combined multidisciplinary approach utilizing surgery, irradiation, and chemotherapy early in the disease process. Early use of long-term combination chemotherapy following deficitive clinical and hematologic staging has resulted in significant "cure" rates in several diseases. The etiology of childhood leukemia remains unknown. Implicated have been viruses, genetic abnormalities leading to increased susceptibility, exposure to various chemicals, and at times obscure hereditary or familial factors. The recurrence of leukemia in donor cells in a leukemic child following bone marrow transplantation is reported for the second time.


Biosynthesis of D- and L-glycero-L-galacto-octulose from pentoses and hexoses. D-glycero-L-galacto-Octulose and L-glycero-L-galacto-octulose accumulated when leaves of Kenland red clover (Trifolium pratense) were allowed to imbibe solution of D-gulose or D-xylose and L-mannose or L-arabinose, respectively. The octuloses were isolated and identified by paper chromatography and by oxidative degradations to the corresponding lower sugars. Assignments of the D and L configuration were made on the basis of optical rotation. It is suggested that formation of the octuloses from the hexoses and pentoses is mediated through transketolase and aldolase or transaldolase catalysis, respectively.


6-Thio and -seleno-beTa-D-glucose esters of dimethylarsinous acid. Syntheses of 2-Se-(1,2,3,4-tetra-O-acetyl-beta-D-glucopyranosyl)-3-N,N-dimethylselenopseudourea hydroiodide (3), 1,2,3,4-tetra-O-acetyl-6-S-dimethylarsino-6-thio-beta-D-glucopyranose (4), 1,2,3,4-tetra-O-acetyl-6-Se-dimethylarsino-6-seleno-beta-D-glucopyranose (7), 6-S-dimethylarsino-6-thio-beta-D-glucopyranose (5), and 6-Se-dimethylarsino-6-seleno-beta-D-glucopyranose (9) are described. Various spectral properties of the compounds are given. The relative rates of alkaline hydrolysis of 5 and 9 are compared.


Manganese amd electrogenic phenomena in canine Purkinje fibers. Studies were performed on canine cardiac Purkinje fibers to evaluate the effects of manganese on membrane electrogenesis. The results indicate that manganese has a calciumlike effect on the excitatory sodium current and inhibitory effects on potassium conductance and slow inward current. The calciumlike effect of manganese on sodium current was reflected through a leftward (toward less negative potentials) and downward shift in the curve relating maximum upstroke velocity to membrane potential. The inhibitory action of manganese on potassium conductance was suggested by the following observations. (1) Manganese caused an initial increase in action potential duration largely due to a lengthening of the plateau and decreases in the rates of phase 3 and terminal repolarization. (2) Manganese increased the rate of diastolic depolarization. (3) Manganes blocked the initial fall in maximum diastolic potential accompanying rapid stimulation. (4) Manganese in high concentrations caused generalized depolarization which was reversed by rapid stimulation and by increased extracellular potassium concentrations. The action of manganese to block slow inward current was indicated by the eventual shortening of the plateau and by the elimination of responses initiated from low levels of membrane potential (less than minus 55 mv). In addition to these effects, manganese also reduced membrane excitability, eliminated arrhythmic beats occurring during low-frequency electrical stimulation, and caused membrane hyperpolarization which was blocked by tetrodotoxin.


Static pressure-flow relation in the total systemic vascular bed of the dog and its modification by the baroreceptor reflex. To evaluate arterial baroreceptor reflex control of total systemic vascular resistance, we studied the relation between mean arterial blood pressure (P) and mean aortic flow (Q) before and after the reflex was abrogated. In 12 dogs with a perfusion pump interposed at the vena-caval-right atrial junction, Q was kept at 60, 80, 100, 120, and 140 ml/min kg-1 for up to 20 minutes. There was little time-dependent change in P at any of these flows. When the reflex was intact, the mean P-Q curve was only slightly convex to the pressure axis; its linearized slope was 0.55 mm Hg-min-kg/ml and its pressure axis intercept was 44 mm Hg. After section of the sinovagal nerves, administration of hexamethonium (30 mg/kg, iv) and norepinephrine (3-5 mug/kg min-1, iv), or both, the slope became 0.96 mm Hg-min-kg/ml and the pressure axis intercept was about 3 mm Hg. Similar findings were obtained in 3 closed-chest dogs in which P was servocontrolled and Q was measured. Therefore, we think that the conventional practice of calculating total peripheral resistance as P/Q and evaluating reflex control of it in terms of the changes in that value involves only a small error in the moderately sub -and supranormal flow range.