MEDLINE services to the developing countries. Supplying MEDLINE services to a widely dispersed user population in the developing countries creates numerous problems not encountered by other MEDLINE centres. The inability to interact with the user complicates system promotion and makes search formulation sometimes a gamble. Nevertheless, an evaluation survey has shown high user satisfaction. Of great concern is the still inadequate solution of document delivery. Near-term objectives are the broadening of geographic coverage and the integration of search processing with supporting hard copy supply.


Conversion of the periodical collection in a teaching hospital library to microfilm format. The Martland Hospital Library converted many of its periodical backfiles to 16 mm microfilm cartridges. Some details of program implementation, user reactions, costs, and problems are discussed. In a teaching hospital library microfilm in cartridge format has been well accepted by patrons, in part because the need to read from a projection screen has been minimized by granting liberal printing privileges.


A hospital library building program.

A hospital library building program. A building program for a 400-bed hospital library was developed by formulating a list of questions that would help to clarify an understanding of the library's needs, by visiting nearby libraries in similar institutions, and by preparing a program planning guide.


Automated cataloging: the state of the art. The art of cataloging is in a state of constant dynamic change. The capabilities of automation are causing changes in the tools we have at our disposal, the education and training we need to work with these tools, the caliber of staff we use at various stages of the cataloging process, and the physical form of the end product of the efforts of the catalog department. But perhaps of more importance is the cooperation and sharing between libraries on both the national and international level that become possible as the result of automated systems.


Jejunal mucosal abnormalities in patients with recurrent aphthous ulceration. Jejunal biopsies in 33 patients with troublesome recurrent aphthous ulceration seen over one year showed eight with flat mucosa compatible with coeliac disease. All remitted completely on a gluten-free diet, both clinically and haematologically, and the aphthous ulceration did not recur. Gluten sensitivity is aetiologically important in patients with recurrent aphthous ulceration and flat mucosa, and patients with recurrent ulceration should undergo jejunal biopsy.


Logical approach to lignocaine therapy.

Logical approach to lignocaine therapy. Plasma lignocaine concentrations were measured during and after lignocaine infusions administered for suppressing ventricular dysrhythmias. Twenty-four patients with a primary diagnosis of acute myocardial infarction without gross circulatory disturbance received, after a bolus of lignocaine, either 4 mg/min for 30 minutes, 2 mg/min for two hours, then 1 mg/min thereafter or 1 mg/min throughout. The higher dose regimen produced continous therapeutic levels of lignocaine, which were achieved only after four hours by the lower dose. On the other hand, in patients who had undergone cardiac surgery and who had circulatory and heptic dysfunction the lower dose regimen achieved therapeutic levels early. The plasma half life was longer in the surgical group (P less than 0.02). The higher initial infusion rate is recommended for patients with acute myocardial infarction without gross circulatory impairment.


Tuberculosis infection in a paediatric department. Sputum-positive tuberculosis was diagnosed in a member of the medical staff of a paediatric department. Four children were infected, all suffering from debilitating diseases. Three of them had evidence of pulmonary tuberculosis. Eighty-two infants in the baby care unit during the eight weeks before the diagnosis of the index case were given insurance isoniazid treatment. None developed tuberculosis. Whereas nearly all the non-medical adult contacts were traced and examined, fewer than half the medical contacts attended for chest radiography. All babies in the pre-allergic phase of contact, and all children whose natural immunity is likely to be depressed, should receive antituberculosis insurance chemotheraphy.


Hospital admissions for peptic ulcer during 1958-72. Unpublished data from the Hospital In-patient Enquiry in England, Wales, and Scotland between 1958 and 1972 show that the frequency of admissions to hospital for peptic ulcer, particularly gastric ulcer, has fallen. This seems more likely to have been due to a true fall in the incidence of ulcer than to changes in treatment. Some three times as many people are admitted to hospital with duodenal ulcer in the north as in the south, but the frequency of admissions for gastric ulcer seems to vary little. The reasons for these differences are not understood.


Jolly fat: relation between obesity and psychoneurosis in general population. The relation between fatness and aspects of psychological status was investigated in a representative sample (339 men and 400 women) of a middle-aged suburban population. A significant positive relation was found between substantial obesity and low levels of anxiety (in men and women) and depression (in men).


Severity of notified whooping cough.

Severity of notified whooping cough. An analysis was made of the severity of over 8000 cases of whooping cough notified from October 1974 to March 1975. Ten per cent of these patients were admitted to hospital and there were 10 deaths. Severity was directly related to age, the disease being most severe in children under 1 year, especially those under 6 months. There was some evidence that previous vaccination reduced the severity of the disease, but the vaccination programme does not cover very young children, and for them whooping cough is a dangerous disease.


Experience of coronary care in diabetes. During 1968-1973, 94 patients with diabetes were admitted to a coronary care unit (CCU) on 99 occasions with proved myocardial infarction. Altogether 24 of them (25-5%) died, giving an overall mortality at the time of discharge of 24% for the total admissions. This was just significantly higher than the 19% mortality recorded among non-diabetics treated in the same period but was much lower than that among diabetics treated for myocardial infarction before the advent of CCUs. No definite correlation was found between the type of anti-diabetic treatment and either mortality or the incidence of primary ventricular fibrillation. Patients with "poor" control of the diabetes before admission showed a significantly higher mortality than those with "good" control, but there was no significant difference in mortality between those with previous good control and non-diabetics.


Attack rates of notified whooping cough in immunised and unimmunised children. The incidence of whooping cough among immunised children under the age of six and among children of the same age who were not fully immunised was ascertained by analysing whooping-cough notifications from several health authorities. In the first three years of the study the results showed that attack rates were much higher in children who were not fully immunised than in those who were. This finding suggests that current vaccines provide young children with substantial protection against whooping cough.


Genitourinary tuberculosis: study of 20 patients. In the past year 20 new cases of genitourinary tuberculosis were referred for treatment at Wrightington Hospital. Many of these patients had waited a long time between diagnosis and referral and the start of effective treatment. We suggest that a new short course of chemotherapy should be used, and surgery undertaken during the first three months of treatment, but after the patient has had at least four weeks' drug treatment. After chemotherapy follow-up may be reduced to two years. Genitourinary tuberculosis remains a serious disease and should be managed by a urologist.


Social network diagram.

Social network diagram. A diagram that shows at a glance the social network and support of patients was found useful in a follow-up study of patients with strokes. We believe that the diagram would prove valuable in medical case records and should be an essential part of medical-social reports, particularly for patients at risk of losing their independence.


Intestinal absorption in normal Indian and English people. The absorption of glycine, glycylglycine, water, and electrolytes was studied by intestinal perfusion in normal Indian and English people. Compared with the English people the Indians showed impaired absorption of all four substances. In the Indians the absorption of glycine and glycylglycine was impaired to the same extent, so that the kinetic advantage of glycylglycine as compared with glycine was preserved. The reduced absorption in the Indians may be the functional counterpart of the minor morphological changes seen in the jejunal mucosa of people living in southern India.


Plasma prednisolone levels after administration of prednisolone-21-phosphate as a retention enema in colitis. A competitive protein-binding assay was used to measure plasma prednisolone levels after administration of prednisolone-21-phosphate retention enemas to seven patients with colitis. Prednisolone appeared in the plasma of all patients after the enema, and concentrations rose to a peak within three hours. In five of the patients plasma prednisolone levels were also measured after the same dose of prednisolone by mouth. Although in individual patients the plasma levels achieved by enema were often quite different from those achieved by mouth, overall the levels achieved by each mode of administration were of a similar order. These findings suggest that 20 mg prednisolone given by retention enema may well exert a systemic effect.


Do placebos alter sleep?

Do placebos alter sleep? Deliberate suggestion that an inert capsule was a sleeping pill was found not to influence subjective ratings of sleep quality or anxiety or the electrophysiologically recorded features of sleep in 10 volunteers aged 41-62 years.


Importance of patient selection in evaluating a cardiac ambulance service. All patients brought to hospital by a special cardiac ambulance were followed up and compared with patients carried by routine ambulances to assess the effectiveness of a cardiac ambulance service. The overall mortality of patients with heart attacks was 51% among those carried by an ordinary ambulance and 40% among those carried by the cardiac ambulance. The apparently low mortality in the latter group was balanced, however, by a high mortality (68%) among patients carried by ordinary ambulances when the cardiac ambulance was available but not used; these patients tended to have a short duration of symptoms and heart attacks away from home, and their ambulance was more often called by a member of the public than a general practitioner. It seems therefore that low-risk cases were inadvertently selected for transport by the cardiac ambulance; such unintentional selection makes it difficult to evaluate a cardiac ambulance service.


Angiographic appearance of carotid bifurcation in pateints with completed stroke, transient ischaemic attacks, and cerebral tumour. The angiographic appearance of the carotid bifurcation was compared in groups of patients aged 50-59 suffering from transient ischaemic attacks (40 cases), cerebral infarction with completed stroke (44 cases), and cerebral hemisphere tumour (66 cases). Carotid occlusion was found in 14% of those with infarcts and 5% of those with transient ischaemic attacks. Carotid stenosis was found in 40% of those with ischaemic attacks and 14% of those with infarcts. Minor irregularity of the carotid arterial wall was equally common in all three groups.


Why do people use paracetamol for suicide? A questionnaire to assess motives for choosing paracetamol as a suicidal agent was completed by 107 patients admitted after an overdose of the drug. None of the 48 patients interviewed would have chosen paracetamol had they known that there would be an interval of two to three days before the onset of serious symptoms. Only five of the patients had obtained the drug on prescription, but the remainder had obtained it easily from a retail pharmacy. There was no apparent reason for the preference for paracetamol. It would be difficult to restrict the availability of paracetamol, and educating the public about the effects of an overdose would be more appropriate.


Radiotherapy and adjuvant combination chemotherapy for childhood rhabdomyosarcoma. The treatment of children with rhabdomyosarcoma by a combination of surgery, radiotherapy, and chemotherapy has resulted in an improved disease-free survival time. Of 11 children with regional disease eight (72%) remained well, with no evidence of disease, four to 36 months after diagnosis. Chemotherapy for one year with vincristine, actinomycin D, and cyclophosphamide was well tolerated during and after radical radiotherapy and surgery. The natural history of this malignancy has been altered in these patients when compared with that in a historical group of 17 children, only two of whom remain alive. There has been no serious short-term toxicity so far.


Support for varicose veins.

Support for varicose veins. A method has been devised to allow reliable comparison of different strengths and constructions of support hosiery. Five garments were evaluated for the compression they exerted on the leg and their ability to limit the distension of a model varicose vein. Stockings and tights which provide modest compression can achieve worthwhile control of vein distension.


Late sucessful treatment of splenic rupture in a haemophilic boy. The recognition of traumatic splenic rupture in an 11-year-old severely affected haemophilic boy was delayed for over five weeks. Splenectomy was carried out successfully after the demonstration of splenic rupture by an isotope spleen scan. Splenic rupture is difficult to differentiate from more simple causes of retroperitoneal haematomata in haemophiliacs when there is no massive acute peritoneal bleeding, but it may be identified with isotopic spleen scans so long as the possibility of rupture is borne in mind.


Further decline of breast-feeding.

Further decline of breast-feeding. In a personal survey, by structured interview, we have investigated some of the factors which led 100 healthy mothers (63 primiparae) to decide to breast-feed their healthy babies, and 100 comparable mothers (43 primiparae) to decide to bottle-feed. Past experience (either personal or that of their family and friends) was of considerable but not overriding importance, and the decisions were apparently made surprisingly early in most cases. But much more effective educational approaches are needed, perhaps starting in the schools, and concentrated in the antenatal clinic, to allow mothers to reach the right decision for themselves and their babies. The reasons for early cessation of breast-feeding were also investigated, and suggested that those mothers opting for breast-feeding need better technical information and support.


Mothers' attitudes in infant feeding at Newcastle General Hospital in summer 1975. Two-hundred successively delivered mothers were asked about their attitudes towards feeding their babies, the influences on them, and their personal and social backgrounds. Initially 39% intended to breast-feed, though in the first few weeks many gave up. Choosing to breast-feed, and success in doing so, were strongly associated with higher social class. The commonest reason given by those who chose the bottle was the embarrassment of breast-feeding. Efforts to increase the numbers of mothers choosing to breast-feed should concentrate on those mothers who remain undecided on their method of feeding. If they are to breast-feed their babies successfully they will need careful advice and support both before and after delivery.


Ballbearing-bomb injuries.

Ballbearing-bomb injuries. Ballbearings from terrorist bombs produce entrance wounds remarkably similar to those caused by bullets. This may be a source of confusion to both surgeons and pathologists.


Changes in immune status in patients undergoing splenectomy for the staging of Hodgkin's disease. The immune status of 17 patients with Hodgkin's disease was studied before and after splenectomy (undertaken in staging laparotomy) and during chemotherapy or after radiotherapy. The findings were compared with those in 19 patients not selected for splenectomy. Serum IgA and IgM levels became significantly lower after treatment in the splenectomy group. Cell-mediated immunity was depressed mainly in patients receiving quadruple cytotoxic chemotherapy. Neutrophil function was normal or enhanced and was unchanged after splenectomy and treatment despite changes in neutrophil counts. Three patients who underwent splenectomy suffered fatal septicaemia. These results suggest that humoral immunity is depressed by treatment in patients who have undergon splenectomy, and the benefits of early accurate staging must be weighed against the likelihood of infective complications.


Specialist registration: a critical look at the proposals of the Merrison report. In the general euphoria over the many views in the Merrison Report that the profession welcomed too little attention has been paid to what has been said about specialist registration. The report contains several basic confusions and a serious misunderstanding of the nature of specialist medical training and practice. It makes several cardinal errors in thinking that some notorious problems related to NHS staffing are also related to a lack of an effective specialist register, and it shows how the creation of such a register would largely destroy the authority of the colleges and faculties. Nowhere in the report is there any convincing argument to show that specialist registration would confer advantages sufficient to outweigh the disadvantages. To let specialist registration in the UK slip in on the irrelevant coat tails of EEC requirements would be a grave dereliction of the long-term interests of medical practice and patient care. The General Medical Council is holding a conference in which this topic is to be discussed on 24 February 1976 and it is still not too late for the profession to think again on this topic.


Effect of intravenous infusion of salbutamol on ventilatory response to carbon dioxide and hypoxia and on heart rate and plasma potassium in normal men. Intravenous infusion of salbutamol 10 mug/min in seven healthy subjects significantly increased their ventilatory responses to inhaled CO2 in both hypoxia and hyperoxia. These changes in chemical control of breathing are unlikely to be significant when the drug is used in severe asthma but may benefit patients with acute exacerbations of chronic ventilatory failure. The infusion also increased heart rate, which was most pronounced when hypoxia was combined with hypercapnia. The infusion produced an average fall in plasma potassium from 3-99 to 3-10 mmol/l, which was associated with an increase in plasma glucose and serum insulin, suggesting that this arose from a shift of potassium from the extracellular to the intracellular space. Routine monitoring of plasma potassium and the electrocardiogram is indicated when an intravenous salbutamol infusion is used to treat severe asthma as the drug may predispose to cardiac dysrhythmias.


Deficiency of factor B of the complement system in sickle cell anaemia. Factors B and D as well as the total activity of the alternative pathway of complement activation were measured using a functional assay in sera from 29 patients with sickle cell anaemia and 18 normal controls. Total alternative pathway activity was reduced in the patients compared with controls. In patients with abnormally low total alternative pathway activity factor D levels were normal, whereas factor B levels were significantly depressed to a mean level of about half of normal. Regression analysis in patients also showed a significant relation between total alternative pathway activity and factor B levels. A deficiency of factor B is the likely cause of the defect in the complement system in patients with sickle cell anaemia. Such a defect may contribute to the excessive proneness of such patients to severe infection.


Secondary amyloidosis due to Schistosoma mansoni infection. Four children with Schistosoma mansoni infection and the nephrotic syndrome with varying degrees of renal dysfunction were found on histological examination to have amyloidosis. In one boy who had no evidence of renal failure complete clinical regression of his nephrotic syndrome and almost complete disappearance of renal amyloid deposits followed adequate treatment of his schistosomal infection. Conditions known to cause secondary amyloidosis were excluded in all four patients. Amyloidosis in association with mansoni infection is probably more common than is currently recognised. Early treatment of the infection, before renal function becomes impaired, may result in regression of the amyloidosis.


Regeneration of central cholinergic neurones in the adult rat brain. The regrowth of lesioned central acetylcholinesterase (AChE)-positive axons in the adult rat was studied in irides implanted to two different brain sites: in the caudal diencephalon and hippocampus, and in the hippocampal fimbria. At both implantation sites the cholinergic septo-hippocampal pathways were transected. At 2-4 weeks after lesion, newly formed, probably sprouting fibres could be followed in abundance from the lesioned proximal axon stumps into the iris transplant. Growth of newly formed AChE-positive fibres into the transplant was also observed from lesioned axons in the anterior thalamus, and to a minor extent also from the dorsal and ventral tegmental AChE-positive pathways and the habenulo-interpeduncular tract. The regrowth process of the sprouting AChE-positive, presumed cholinergic fibres into the iris target was studied in further detail in whole-mount preparations of the transplants. For this purpose the irides were removed from the brain, unfolded, spread out on microscope slides, and then stained for AChE. During the first 2-4 weeks after transplantation the sprouting central fibres grew out over large areas of the iris. The new fibres branched profusely into a terminal plexus that covered maximally about half of the iris surface, and in some areas the patterning of the regenerated central fibres mimicked closely that of the normal autonomic cholinergic innervation of the iris. In one series of experiments the AChE-staining was combined with fluorescence histochemical visualization of regenerated adrenergic fibres in the same specimens. In many areas there was a striking congruence in the distributional patterns of the regenerated central cholinergic and adrenergic fibres in the transplant. This indicates that - as in the normal iris - the sprouting cholinergic axons (primarily originating in the lesioned septo-hippocampal pathways) and adrenergic axons (primarily originating in the lesioned axons of the locus neurones) regenerate together along the deneravated Schwann cell sheaths. From a comparison between the central reinnervation process and the process of reinnervation of the iris by peripheral cholinergic axons after transplantation to the anterior eye chamber, it is concluded that the regenerative capacity of central cholinergic neurones (above all the septo-hippocampal system) is not much inferior to that of their peripheral counterparts when given similar growth conditions. Moreover, central cholinergic neurones seem partly able to replace the peripheral ones in the reinnervation of a denervated peripheral target.


Transport of L-proline by rat brain slices. L-Proline is taken up into slices of rat cerebral cortex by a structurally specific 'high affinity' system which is absolutely dependent on sodium ions. The system mediating L-proline uptake in homogenates of cerebral cortex is associated with osmotically sensitive particles of the same equilibrium density as synaptosomes. Based on tissue-medium ratios, the uptake of L-proline is most efficient in slices of cerebral cortex and of hypothalamus, and least efficient in slices of cerebellum. L-Proline taken up into slices of cerebral cortex can be released from these slices by an increased potassium ioort into and out of brain slices are consistent with L-proline functioning as a synaptic transmitter in that they are analogous to observations on the transport of transmitter amino acids such as GABA.


The effect of reticular stimulation on spontaneous and evoked activity in the cat visual cortex. The mesencephalic reticular formation (MRF) of cats anesthetized with N2O was stimulated electrically, and the effects of this stimulation on activity in the striate cortex were studied. The variations of intra- and extracellularly recorded unit activity and the changes in the extracellular potassium concentration were investigated. At all levels of analysis the prevailing effect of MRF stimulation was facilitation. Half of the cells reacted with brief bursts of activity to reticular stimuli. A decrease of resting activity was rare. The cells activated by MRF stimulation had in common: (1) to show a high degree of excitatory convergence from extrinsic and intrinsic afferents, (2) to possess often corticofugal axons, and (3) to have preferentially complex receptive fields. In the large majority of cortical cells MRF stimulation facilitated responses evoked by stimulation of the optic radiation or by light stimuli. This facilitation could lead to a loss of orientation and direction selectivity. Reticular activation further led to a large increase of the extracellular potassium concentration, whereas stimulation of specific afferents led to a decrease. It is concluded that these phenomena are not merely a consequence of altered thalamic transmission, but are caused by a projection system which is organized in parallel to the specific projection and exerts a direct control over cortical excitability. The mechanism for this control appears to be a slight and rather unselective depolarization of most neurons. If disinhibitory processes are involved at all, their role is much less prominent than at the thalamic level. The functional implications of such an unselective but powerful modulation of cortical excitability are discussed in respect to corollary reticular activation as it occurs with rapid eye movements.


Antagonism of cortical excitation of striatal neurons by glutamic acid diethyl ester: evidence for glutamic acid as an excitatory transmitter in the rat striatum. Rat striatal cells that were excited by cortical stimulation were found to respond to cortical stimulation with an average latency of 12 msec. Each response consisted of a variable number of spikes with, on the average, a less than 1:1 relationship between the stimulus and the number of spikes generated. Iontophoretic application of glutamic acid diethyl ester (GDEE), a substance reported to be a glutamate antagonist, at currents of +50 to +125 nA in the vicinity of neurons exicted by cortical stimulation, almost totally suppressed the excitation in 90% of the cells, and this suppression was fully reversible. All cells were excited by glutamate. GDEE also suppressed neuronal excitation produced by iontophoretic aspartate, glutamate and DL-homocysteic acid. It is concluded from this study that an excitatory amino acid, either aspartic or glutamic, may function as the transmitter in the corticostriate projection.


Specificity of dopaminergic neuronal degeneration induced by intracerebral injection of 6-hydroxydopamine in the nigrostriatal dopamine system. The neurotoxic specificity of injections of 6-hydroxydopamine (6-OHDA) into areas containing either dopamine (DA) cell bodies (substantia nigra) or DA axon terminals (striatum) was studied. This selective effect was compared to the unspecific effects of copper sulfate (CuSO4) injection and electrocoagulation. One to two days after unilateral nigral injection of 2 mug of either 6-OHDA or CuSO4 into the nigra the volume of the unspecific lesions around the tip of the cannula was very similar. Only the 6-OHDA-induced lesions were associated with elective degeneration of the nigral DA neurons. Ten days after the administration of the same compounds the gliosis in the substantia nigra was much more extensive in CuSO4-than in 6-OHDA-treated rats; however, the reduction of DA concentrations in the ipsilateral striatum was only noticeable after 6-OHDA (-62%). A somewhat similar decrease of striatal DA levels (-52%) was observed after large electrocoagulation of the substantia nigra. Ten days after 6-OHDA (8mug) or electrolytic lesion of the striatum the Km for DA, serotonin and choline uptakes were similar in the striata of both sides, suggesting that the uptake process in the non-damaged neurons of the lesioned side was functionally normal. Following electrolytic lesion of the striatum, serotonin and choline Vmax values were decreased to about the same extent as the striatal reduction in weight and DA levels. When directly administered into the striatum 6-OHDA also produced a decline in DA concentration and Vmax but in contrast did not affect serotonin and choline uptake (Vmax), suggesting that the drug specifically destroyed dopaminergic neurons. The present data confirm that selective DA denervation can be achieved when appropriate amounts of the drug are injected into brain tissue in order to limit the unspecific lesion.


The penetration of fluorescein-conjugated and electrondense tracer proteins into Xenopus tadpole optic nerves following perineural injection. The permeability of Xenopus tadpole optic nerves to macromolecules was studied in order to evaluate the usefulness of this system for studying mechanisms of serum-induced CNS demyelination in vivo. Single injections of either horseradish peroxidase (HRP), ferritin or fluorescein-conjugated human IgG were injected around the right optic nerve and tadpoles were then sacrificed between 15 min and 48 h. Each of the tracers had penetrated the nerve parenchyma by 30 min. Entry of HRP and ferritin occurred mainly via extracellular clefts between adjacent astrocytic endfeet in the glia limitans region. A similar mode of passage was suggested for IgG. Once within the nerve, the tracers became rapidly associated with myelinated axons. HRP was also seen in the periaxonal space but did not directly penetrate the myelin sheath. By 24 h, extracellular localization of tracer was virtually absent with nearly all of the tracer now being concentrated in vesicles within astrocytic processes and perikarya. The distribution of the tracers was not confined to the optic nerve on the injected side; some was seen in adjacent cranial peripheral nerves and surrounding extraocular musculature. Also, tracers eventually penetrated the pial sheath of the contralateral optic nerve. The results of this study indicate that tadpole optic nerves are permeable to a wide range of macromolecules. Furthermore, the distribution of these tracers to nearby cranial peripheral nerves may provide an important opportunity for testing the differential effect of various substances on central and peripheral myelin sheaths.


Effects of glucocorticoid treatment on catecholamine content and ultrastructure of adult rat carotid body. Carotid bodies of dexamethasone-treated (daily injections, 10 days) adult male rats were analyzed with respect to catecholamine content and ultrastructure. Gas chromatographic-mass spectrometric assays demonstrated that norepinephrine (NE) and dopamine (DA) concentrations more than doubled after dexamethasone treatment. The increase in NE was relatively greater than that of DA. No epinephrine (E) could be detected. Morphometry revealed, as for the control carotid bodies, two subclasses of type I cells on the basis of the diameters of their dense-cored vesicles. These groups of cells were termed small vesicle cells (SVC) and large vesicle cells (LVC). Dexamethasone treatment resulted in significantly increased volume densities and diameters of the dense-cored vesicles in both SVC and LVC. The greatest increase occurred in the SVC. If these morphological changes do reflect the change in amine concentrations then it is possible to speculate that the type of cells with the greatest increase of amine storage capacity may store the kind of catecholamine most increased. Thus NE may presumably be stored in the SVC and DA in the LVC. Furthermore, these effects of administered glucocorticoids may also indicate a regulatory function for endogenous glucocorticoids on the carotid body catecholamines.


Catecholaminergic axo-axonic synapses in the nucleus of the tractus solitarius (pars commissuralis) of the cat: possible relation to presynaptic regulation of baroreceptor reflexes. A study was performed on adult cats to investigate synaptic structures of nerve terminals in the commissural portion of the nucleus of the tractus solitarius (NTS); a site where the cardiovascular afferent fibers terminate and where a dense plexus of adrenergic element also resides. Synaptic contacts observed in the commissural portion were predominantly axo-dendritic but a smaller number of axo-somatic synapses were also recognized. A third type of junction, axo-axonic, appears to be unique to the commissural portion of the nucleus, since no axo-axonic contacts were encountered in the medial and ventrolateral portions of the NTS. By labeling with the 'false' neurotransmitter 5-hydroxydopamine (5-OHDA), three types of axo-axonic contacts with different presynaptic components could be identified; namely, axon varicosities with small clear spherical vesicles, axon varicosities containing flat synaptic vesicles and others with small cord vesicles labeled with 5-OHDA. Postsynaptic components were always axon varicosities with clear spherical vesicles. After surgical denervation of the IXth and Xth cranial nerves, no degenerated axon varicosities were observed in the presynaptic side in the axo-axonic contact. The present study clearly demonstrates that the commissural portion of the NTS contains axo-axonic synapses and some of the adrenergic axons in this area provide the presynaptic components for this type of synapse. Possible roles of adrenergic nerves to presynaptic regulation of baroreceptor reflexes are discussed.


Studies on the neuropharmacological activity of bicuculline and related compounds. Bicuculline and 3 chemical derivatives were assayed on a variety of biological systems. Consistent with reports of studies on other animals, some of these compounds caused convulsions in insects and blocked inhibitory postsynaptic potentials in insect muscle. They all potently inhibited mouse brain acetylcholinesterase. Bicuculline and its analogs inhibited the binding of GABA in vitro to sites in crayfish muscle membranes which have properties of receptor sites; this site of action could explain the activity of bicuculline at arthropod neuromuscular junctions. These compounds, at high concentrations (over 100 muM), also inhibited GABA uptake by mouse brain homogenates at 0 degrees C apparently non-competitively. Bicucine methyl ester inhibited GABA transport by brain at 37 degrees C, consistent with non-specific membrane effects at high concentrations of drug. These and other observations cast doubt upon the specificity of bicuculline-like compounds for action on GABA synapses, especially for in vitro studies at high drug concentrations (over 10 muM). The neuroactivity of low doses of bicuculline is apparently not explained by these in vitro effects, and could very well be due to inhibition of GABA synapses at either receptor or ionophore sites. At physiological conditions of pH and temperature, bicuculline is hydrolyzed at its lactone moiety to the less active compound bicucine; this could lead to underestimates of the biological activity of bicuculline. More stable analogs studied so far are not more potent, however.


Effects of antisera to S-100 protein and to synaptic membrane fraction on maze performance and EEG. Topical cortical injection into rats of antiserum to the synaptic membrane fraction caused recurrent spiking activity as observed in the EEG; neither antiserum to S-100 protein nor antiserum to myelin caused any such abnormality. These same rats, when observed on a maze learning task (Lashley III) responded differently to the different antisera. Rats receiving injections of antiserum to the synaptic membrane fraction or antiserum to S-100 protein were inhibited in their performance, while rats injected with antiserum to myelin behaved like uninjected animals.


Multipotentiality of Schwann cells in cross-anastomosed and grafted myelinated and unmyelinated nerves: quantitative microscopy and radioautography. Cross-anastomoses and autogenous grafts of unmyelinated and myelinated nerves were examined by electron microscopy and radioautography to determine if Schwann cells are multipotential with regard to their capacity to produce myelin or to assume the configuration seen in unmyelinated fibres. Two groups of adult white mice were studied. (A) In one group, the myelinated phrenic nerve and the unmyelinated cervical sympathetic trunk (CST) were cross-anastomosed in the neck. From 2 to 6 months after anastomosis, previously unmyelinated distal stumps contained many myelinated fibres while phrenic nerves joined to proximal CSTs became largely unmyelinated. Radioautography of distal stumps indicated that proliferation of Schwann cells occurred mainly in the first few days after anastomosis but was also present to a similar extent in isolated stumps. (B) In other mice, CSTs were grafted to the myelinated sural nerves in the leg. One month later, the unmyelinated CSTs became myelinated and there was no radioautographic indication of Schwann cell migration from the sural nerve stump to the CST grafts. Thus, Schwann cell proliferation in distal stumps is an early local response independent of axonal influence. At later stages, axons from the proximal stumps cause indigenous Schwann cells in distal stumps from the previously unmyelinated nerves to produce myelin while Schwann cells from the previously unmyelinated nerves to produce myelin while Schwann cells from the previously myelinated nerves become associated with unmyelinated fibres. Consequently, the regenerated distal nerve resembled the proximal stump. It is suggested that this change is possible because Schwann cells which divide after nerve injury reacquire the developmental multipotentiality which permits them to respond to aoxonal influences.


Effects of pretectal lesions on rats wearing light-diffusing occluders. The study provides behavioral evidence that the pretectal region of the subcortical visual system primarily mediates responses to diffuse rather than to patterned light stimuli: pretectal lesions induced greater transoperative deficits in performance of a light-dark discrimination task for rats wearing light-diffusing occluders than for non-occluded animals. Pretectal lesions also produced less transoperative disruption in animals trained to perform a pattern discrimination task (horizontal vs. vertical stripes). These results are precisely the opposite of those which follow ablation of visual cortex.


Some observations on early myelination in the human spinal cord. Light and electron microscope study. Segments of cervical spinal cord from a 23-week-old human foetus have been examined by light and electron microscopy. Myelinated fibres were found in the dorsal, ventral and peripheral lateral tracts, while the lateral corticospinal tract was completely unmyelinated. Myelin sheaths appeared to be formed by spiral wrapping of elongated mesaxons which originated from the apposition of the plasma membranes of oligodendrocytes. Preparations stained with Sudan red and Sudan black revealed the occurrence of lipid inclusions in the interfascicular glia. The topographical relation and the ultrastructural features of these inclusions are described. The possible significance of the inclusion bodies is discussed.


Effect of thyroid deficiency on postnatal cell formation in the rat brain: a biochemical investigation. In thyroid deficiency, interference with postnatal cell formation seems to be confined to those regions of the brain where postnatal neurogenesis is significant. In comparison with controls the increase in cell number in the cerebellum is retarded in the second week of life, but a normal number is reached by 35 days. In contrast the DNA content of the olfactory bulbs is apparently irreversibly depressed. Mitotic activity, in terms of incorporation of [2-14C]thymidine into DNA, is mainly affected in the cerebellum: in thyroid deficient rats, it is depressed below control levels at day 12, but it is about 4 times higher than in controls at day 21 when, under normal conditions, cell proliferation has virtually ceased. The time course (15-240 min) of [14C]thymidine metabolism at day 14 shows regional differences in control rats. The rate of conversion of [14C]thymidine to [14C]thymidine nucleotides, and of these in turn to [14C]DNA is slower in the forebrain - where cell proliferation occurs on a smaller scale - than in the cerebellum. Consequently, in the forebrain nearly linear DNA synthesis rate is maintained for a longer time than in the cerebellum (1 h vs. 0.5 h), and since less 14C is conserved in DNA a significant efflux of unconverted [14C]thymidine is evident during the experimental period. The effect of thyroid deficiency on [14C]thymidine metabolism in the brain is only slight, and is due to an abnormally large supply of [14C]thymidine consequent to depressed systemic utilization of this precursor.


Effect of thyroid deficiency on cell acquistion in the postnatal rat brain: a quantitative histological study. The mechanisms underlying transient reduction of cell number in the developing cerebellum of thyroid-deficient rats have been studied by quantitative histological methods. Thyroid deficiency has no significant effect on the generation cycle of dividing cells in either the subependymal layer of the lateral ventricular walls or the external granulay layer of the cerebellum: the length of the cell cycle and the duration of the different phases of the cycle, including the DNA synthesis time appears to be normal. However, the external granular layer of the cerebellum contains fewer cells than in control at 12 days. Pyknotic nuclei are prominent in the granule cell layer of the hypothyroid cerebellum at this age. These amount to an estimated loss of about 1% of the total cerebellar cell population in 24 h. It is suggested that death of granule cells is for the most part a consequence of reduced Purkinje cell dendritic arborization, with failure of parallel fibre/Purkinje cell synaptogenesis. In the second postnatal week, granule cell death and reduced numbers of cells in the germinal zone can account to a great extent for the observed shortfall in cerebellar DNA content. The eventual attainment of normal cell numbers in the cerebellum of hypothyroid rats is related to a persistent external granular layer in the forth and fifth postnatal weeks.


The ionic basis of the membrane potential in a rat glial cell line. Intracellular ionic concentrations, membrane potential and Na+ and K+ flux were measured in a clonal rat glial cell line, C6. Intracellular concentrations of C6 cells were: (mmole/liter cell water) K+ 145 +/- 4 S.D., Na+ 18 +/- 4 S.D., Cl- 14 +/- 1 S.D. Cells maintained a steady state level of K+ over the duration of the experiments. This was substantiated by the close agreement between absolute values for K+ influx and efflux measured with 42K. When cells were depleted of internal Na+, K+ influx was significantly reduced suggesting that a portion of inward K+ movement is linked to Na+ extrusion. Efflux of Na+, calculated from the half-time of exchange from cells preloaded with 22Na, was higher than passive Na+ influx determined  by blocking Na+ extrusion with ouabain. Since cell Na+ concentration remained relatively constant, part of the Na+ efflux may be due to exchange diffusion. The average membrane potential of C6 cells uas -36 mV. The potential showed a 31 mV slope for a 10-fold change in external K+ so that it is determined predominantly by the ratio of external/internal K+. The potential however, consistent with the relatively large passive Na+ influx, was influenced by Na+. Replacing all but 20 mM external Na+ with choline hyperpolarized the membrane by 13 mV. The ratio of PNa/PK of 0.11 suggests that Na+ is outwardly transported to maintain the steady-state concentrations observed. Since these responses are similar to those in non-tumor glia, it suggests that the C6 cell line may provide a useful model for studying ionic regulation in glial cells.


A linked active transport system for Na+ and K+ in a glial cell line. Ouabain (5 X 10(-4) M) induced a 6-fold increase in intracellular Na+ and a 65% loss of cellular K+ in C6 glial cells which was accompanied by a 12 mV decrease in the resting membrane potential. Following ouabain washout intracellular ion  concentrations and the membrane potential returned to control levels suggesting that C6 is capable of active Na+ transport which is linked to uptake of K+. A portion of K+ uptake under steady-state conditions is also active since K+ influx was reduced 32% by ouabain. Five mM cyanide significantly increased cell Na+ and significantly decreased cell K+ and the membrane potential. The similarity in the ratio of Na+ gained/K+ lost (ouabain 1.24, cyanide 1.41) suggests that the two agents inhibit the same ion transport system. Decreased temperature had the paradoxical effect of increasing intracellular K+ while significantly decreasing both membrane potential and K+ influx. Part of this effect may be due to the marked reduction in K+ efflux at low temperature. At 6 degrees C cell loss of K+ was much less than loss of K+ with ouabain at 37 degrees C. The observation of a linked Na+-K+ transport system in C6 cell confirms the hypothesis that coupled active Na+-K+ exchange occurs in glial cells and suggests that ionic transport may regulate certain aspects of glial metabolism.


Patterns of total and ionized calcium and other electrolytes in plasma during and after general surgery. Thirteen patients were studied during two hours of anaesthesia for abdmonial operations and for an hour post-operatively. Serial venous blood samples were taken for determination of plasma total and ionized calcium, acid-base variables, Na, K, Mg, PO4 total proteins and parathyroid hormone. One group of patients received 5 per cent dextrose/water and the other 5 per cent dextrose in Ringer's solution, at 250 ml per hour. Total and ionized calcium levels decreased toward the end of operation and an hour later, associated with respiratory alkalosis. Parathyroid hormone increased at the end of operation, as an effect of the decreased ionized calcium. The general effect was mild haemodilution with all the other electrolytes decreasing, as did total protein concentration.


Alphadione (Althesin): a new induction agent. The use of Althesin for induction of anaesthesia in 57 patients showed that it is a satisfactory induction agent. However, with the exception of rapid recovery with minimal after-effects, it has no major advantages over the commonly used barbiturates.


The effects of furosemide on remal blood flow and cortical perfusion during methoxyflurane and halothane anaesthesia. Nephrotoxicity due to methoxyflurane may be due in part to alterations in intra-renal perfusion. Furosemide is believed to alter the intra-renal distribution of blood flow. Studies have been carried out to observe the effects of systemic furosemide administration during methoxyflurane and halothane anaesthesia in normotensive animals and in animals made hypotensive by increasing inspired concentrations of the anaesthetics. During halothane anaesthesia normotensive dogs showed a rise in total renal blood flow during the infusion of furosemide. Hypotensive dogs showed no increase in flow. During methoxyflurane anaesthesia no change in total renal blood flow followed furosemide administration to normotensive animals. Some diminution in total blood flow followed the administration of furosemide in hypotensive dogs during methoxyflurane anaesthesia. In normotensive dogs during halothane anaesthesia there was a significant increase in deep cortical perfusion after furosemide. Furosemide, therefore, is unlikely to mitigate the potential for nephrotoxicity which methoxyflurane possesses. Furthermore, this diuretic may adversely influence renal function when administered during halothane anaesthesia.


The effects of morphine and halothane anaesthesia on urine norepinephrine during surgery for congenital heart disease. Urine excretion rates of norepinephrine were measured in 15 children with Tetralogy of Fallot and 25 with atrial septal secundum defects anaesthetized with halothane or morphine before, during and for two hours after surgical correction of their cardiac defects. All patients were paralyzed with d-tubocurarine, the tracheae were intubated and respiration was controlled. Urine was obtained for 90 minutes before induction, during induction, before, during and after bypass and postoperative. Patients with TF had significantly higher pre-operative urine norepinephrine excretion rates than patients with ASD. In TF children anaesthetized with halothane norepinephrine excretion was significantly decreased during induction and during operation but increased post-operatively. Children with ASD and anaesthetized with halothane did not have urine norepinephrine excretion rates that were significantly different from post-operative values until the postoperative period. ASD children anaesthetized with morphine had marked elevations in norepinephrine excretion during induction and all subsequent study periods. On the other hand, morphine anaesthetized TF children did not have a significant increase in urine norepinephrine excretion until bypass had been established. Increased norepinephrine excretion was maintained in these patients during all subsequent study periods. These data, when combined with our results in patients with acquired heart disease, demonstrate that disease can alter norepinephrine responses to morphine anaesthesia. In addition our results suggest that dosage of morphine and morphine blood levels might also modify norepinephrine excretion.


A comparison of the effects of halothane and other anaesthetic agents on hepato-cellular function in patients submitted to elective operations. In an attempt to gather objective evidence of possible hepato-cellular toxicity of the halogenated anaesthetics halothane and methoxyflurane pre-operative and post-operative enzyme estimations were done on patients admitted for elective operations. The series of approximately 500 cases included 160 patients submitted to cholecystectomy, an operation associated with a high percentage of detectable alteration of hepatocellular function in the post-operative period. There was no significant difference between the groups of patients receiving halothane, methoxyflurane, or nitrous oxide and oxygen with analgesic supplement. The magnitude of the increased post-operative enzyme activity and the post-operative temperature elevation were not significantly different in the three groups studied.


An evaluation of three new blood-gas analyzer systems. Three new pH-blood-gas analyzer systems have been evaluated. These are the ABL-1, the Croning 165, the Il 513. Because of automation of analysis, accuracy, and speed of analysis, this generation of instruments represents great progress over the previous one. The ABL-1 is the most automated system: all analyses are computer controlled. The pH, P02 and PCO2 values are accurate. Calibration can not be adjusted. The Corning 165 is the least automated system. Its pH determinations are the most accurate and it is the one which uses the smallest volume of blood (125 mul). However it is the least stable and takes the longest time for completion of the analysis. The IL 513 is probably the best balanced system and its calibration can be modified. Its operation is well automated and its results are accurate.


Maculopathy of sex-linked juvenile retinoschisis. Observations in 14 eyes in 7 patients with sex-linked juvenile retinoschisis over a 4 to 8 year period show that the maculopathy tends to progress through a series of stages (Figs. 14, 15, 16) which are associated with increasing impairment in visual acuity. Electrical changes confirm the pathological state of the macula but suggest a pan-retinal disease. Desite the clinical appearance, the extramacular retina seems to be significantly affected. The basic pathological condition may be in the Muller cells. We have been unable to distinguish carriers from normal individuals.


Hereditary retinoschisis linkage studies in a family and considerations in genetic counselling. We report a family with X-linked juvenile retinoschisis. In addition to the three males with severe visual impairment, six other males in this family were found to have hitherto undiagnosed disease. The findings in these mildly affected males are described in detail. The wide range of clinical manifestations found among the affected relatives initially hampered recognition of the correct diagnosis. Once the correct diagnosis was made, proper genetic counselling could be given. The data are compatible with loose linkage between the loci for juvenile retinoschisis and the red cell antigen marker Xga.


Fluorescein angiography and retinal venous sheathing in multiple sclerosis. Venous sheathing found in 11% of a series of patients with multiple sclerosis was studied with routine color fundus photography, and fluorescein angiography. In the early phases of the disease, sheathing is seldom found. Its detection is facilitated by fluorescein angiography and ophthalmoscopy with a cobalt filter. Fluorescein leakage may disappear despite persistence of the sheathing.


Binocular visual field in strabismus.

Binocular visual field in strabismus. The binocular visual field of 100 patients with a variety of manifest strabismus was analysed using a complex visual environment and polaroid dissociation. A significant area of the picture, both nasal and temporal to fixation, was suppressed by all patients. Eighty-nine per cent showed correct localisation and identification in an area which was not suppressed and was approximately 45 prism dioptres peripheral to fixation.


B-scan ultrasonography in the diagnosis of atypical retinoblastomas. Contact B- scan ultrasonography (Bronson-Turner unit) was performed on fourteen patients with retinoblastoma. In ten cases, the patient presented with leukocoria, and ultrasonography was helpful in confirming the clinical diagnosis. In four atypical cases contact B-scan ultrasonography was instrumental in making the diagnosis. The ultrasonographic pattern for retinoblastoma is characteristic but not pathognomic. There is a solid intraocular echo corresponding to the tumor and within it are numerous dense focal echoes which persist at lower sensitivities, suggesting calcification. Calcification was demonstrated ultrasonographically and confirmed histologically in all four of these atypical cases, but routine skull x-rays failed to demonstrate calcium in three of the four children. Contact B- scan ultrasonography is a safe and simple procedure which may provide valuable diagnostic information in children with suspected retinoblastoma.


Gelatin implants in retina surgery.

Gelatin implants in retina surgery. Gelatin absorbable implants are a practical and effective material for scleral buckling. They may be used in segmental scleral buckling, meridional implants, aphakic detachments, lower temporal dialyses and macular holes. We describe the technique and the results obtained in 53 patients.


A study of dark adaptation in ocular hypertensives. Previous studies of dark adaptation in glaucoma have been hampered by lack of standardization and poor definition of clinical categories. A new method of testing has been used on ocular hypertensives. A modified Goldmann/Weekers adaptometer and an 11 degree centrally fixated test patch were used to obtain two dark adaptation threshold curves for each subject -- one for blue-green and one for yellow. Results indicate that ocular hypertensives with no field loss and normal fundi have impaired normal subjects. The differences in the thresholds for blue-green were especially noticeable with the blue-green showing the greater difference. The 2.8 minute difference in mean curve cross-over time between normal and ocular hypertensive was also found to be significant. It appears that ocular hypertensives have impaired rod and cone functions, as well as deficient rod-cone interaction.


Coats' disease: A study of cholesterol transport in the eye. An attempt to establish an animal model (rabbit) to study deposition and transport of cholesterol in the eye has been described. Interesting findings include the deposition of cholesterol in the choroid, sclera, and anterior cornea of rabbits fed on a high cholesterol diet. Injected intravitreal cholesterol is seen to leave through the retina, optic nerve head, and the trabecular meshwork. This process appears to be very slow. During the 4 months of observation the yellow preretinal deposits decreased little in size. Only 1 rabbit showed a picture typical of Coats' disease with serous detachment of the retina, subretinal lipoidal deposits and preretinal neovascularization. Although these results are preliminary, they suggest that fatty materials may pass through the retina into the subretinal space from the vitreous and might explain the pathogenesis of Coats' disease in the human.


The detection of immunologically competent cells in corneas showing an immune reaction - a simplified technique -. We wished to devise a simple in vitro test for identifying the presence of antigen sensitive lymphocytes in corneal tissue having an immunological inflammatory reaction. A number of rabbits were immunized by subcutaneous injections of human serum albumin (HSA). A final injection of the same antigen was given in the centre of the cornea to produce an immunological corneal inflammation. Other rabbits were immunized by an antigen unrelated to HSA. A non-immunological corneal inflammation was produced in another group of animals by applying sodium hydroxide. Five days after the immunogenic and non-immunogenic corneal insults, when the limbus showed vascularization, the eyes of the different groups of animals were enucleated. From each eye, small corneal discs containing a portion of the limbus were cut with a trephine. The discs (explants) were then incubated for 20-24 hours at 37 degrees C in the presence or absence of HSA or in the presence of an antigen unrelated to HSA. At the end of incubation, the extent of leucocyte migration from each explant was measured. Only in the presence of the specific antigen did leucocytes from explants of the immunized animals show marked inhibition of migration.


Twin-prism stereo-separator.

Twin-prism stereo-separator. We describe a twin-prism stereoseparator for the Zeiss fundus camera which gives high-quality stereophotographs of the optic disc and simultaneously records both images on the same frame of film. The stereobase of photographs taken with this system ranges from 2.0 to 4.5 mm. It varies linearly with the entrance pupil which ranges from 4.0 to 6.5 mm. The instrument provides a reliable method for monitoring changes in optic disc topography.


Orbital involvement in Riedel's struma.

Orbital involvement in Riedel's struma. A patient with Riedel's struma had bilateral orbital involvement. The histopathological findings were the same in the thyroid and lacrimal glands.


Lid rhinosporidiosis - simulating a tumor. A case of rhinosporidiosis is described with extensive primary involvement of the lids, bulbar and palpebral conjunctiva.


Isolation of a soluble tumor-associated antigen from human melanoma. Human melanoma-associated antigen was solubilized from fresh surgical specimens by 3 M KC1 extraction. The antigenicity of this extract was demonstrated by delayed cutaneous hypersensitivity responses and inhibition of complement fixation. Twenty-one of 33 melanoma patients had delayed cutaneous hypersensitivity responses to melanoma antigen, while only four of 28 reacted to autologous muscle. Although KC1 extracts did not fix complement directly, they reacted with antibody, thus inhibiting complement fixation by the autologous melanoma antigen extracted from tissue culture supernatants. The soluble antigenic moiety was then purified by fractionation on a G-150 Sephedex column and polyacrylamide gels, and the antigenic activity was monitored by delayed cutaneous hypersensitivity responses in melanoma patients. A 20-fold purification was achieved. Solubilization of tumor antigens with 3 M KC1 provides tumor-associated antigen of high activity which is amenable to further biochemical purification.


Changing patterns of breast cancer. Lucy Wortham James lecture (clinical). At present, through public awareness and the use of improved diagnostic aids, increasing numbers of patients are being seen with localized "minimal" breast cancer. In our own experience, the average measured size of the primary tumor has diminished from 3.2 cm in 1955 to 2 cm in 1974. Although the incidence of axillary node metastases has diminished only from about 50% to 42% during this interval, the extent of involvement and the distribution of nodal disease has improved markedly with a marked decrease in apical node involvement. Mammography has been responsible for the detection of more than 50% of our "minimal" breast cancers. This improved patient material presents a great potential for improved control of this disease. In planning the choice of surgery for primary breast cancer, its multicentric origin, and regional nodal spread to axillary and internal mammary nodal areas must be considered. There is no single ideal operation for all breast cancers. The scope of surgery should be correlated with the clinical and pathologic extent of disease in the individual patient with the aim of removing all disease present while preserving appearance and function-the main goal being removal of disease. We have utilized three operative procedures: total mastectomy with axillary dissection, radical mastectomy, and extended radical mastectomy. With this approach a 10-year survival rate of 61% with a local recurrence rate of 7.7% has been attained in a group of 565 patients with 40% axillary node involvement. The best salvage obtained in patients with "minimal" breast cancers-noninfiltrating cancers and infiltrating cancers under 1 cm in diameter with clinically negative axillae-was 95% survival at 10 years following modified radical mastectomy (total mastectomy with axillary dissection). When disease has extended to the axillary nodes the more extensive procedures have proved more effective in achieving long term control-54% 10 year survival in patients with axillary node metastases treated by the extended radical mastectomy. An increasing number of patients are being seen who can be treated adequately by less than a radical mastectomy. Careful clinical judgment and close liason with a competent pathologist must be combined in selecting the proper operative procedure for each individual patient. Statistics concerning therapeutic effects based on current material, unless they are based on accurate data covering extent of disease, cannot be compared with previous data because of the improved patient material now being encountered. Adjuvant multiple chemotherapy appears promising as a supplement to surgical treatment of breast cancer. However, it should not be used to replace or minimize the role of primary surgery, but should be combined with the optimum procedure for each individual patient.


Combined therapy to prevent complete pelvic exenteration for rhabdomyosarcoma of the vagina or uterus. Three children with rhabdomyosarcoma (sarcoma botryoides) of the vagina or uterus were managed by modified radical resection combined with pre- and/or postoperative chemotherapy and high-dose irradiation. This plan of therapy contrasts sharply with the conventional approach: i.e., pelvic exenteration consisting of cystectomy, hystovaginectomy, and oophorectomy, with urinary diversion by ureteroileostomy or ureterosigmoidostomy. Two patients had complete regressions of tumor following preoperative chemotherapy and irradiation. The third patient received no preoperative therapy, but was given postoperative radium implantation, irradiation, and chemotherapy. The surgical approach consisted of hystovaginectomy and oophorectomy without urinary diversion. These patients are free of tumor for 32, 44, and 54 months, respectively.  There were no serious toxic reactions to the drugs, nor any significant postoperative urinary tract problems. The results reported here suggest that hystovaginectomy and oophorectomy coordinated with chemotherapy and irradiation is an acceptable alternative to pelvic exenteration in patients with sarcoma botryoides of the vagina or uterus.


Multi-modality therapy for epidermoid carcinoma of the anus. Three patients presenting with surgically incurable epidermoid carcinoma of the anus were treated by radiation therapy and chemotherapy consisting of 5 fluorouracil and Mitomycin C. The first patient succumbed during the course of her therapy. The second patient is alive and well without definite evidence of disease nearly 1 1/2 years after initiation of therapy. The third patient underwent abdominoperineal resection after radiation and chemotherapy; pathologic examination revealed no residual carcinoma and the patient is well nearly 1 year after surgery. A fourth patient with previously treated epidermoid carcinoma of the anus presented with biopsy-proven pulmonary metastasis and was placed on the chemotherapeutic regimen alone. Six weeks later his chest X-ray showed essentially complete disappearance of the metastatic nodules. This experience suggests that multimodality therapy may increase salvage in even locally far-advanced and metastatic epidermoid anal carcinoma.


Non-Hodgkin's lymphoma in children. A comparative study of two modalities of therapy. Eighty-six children with non-Hodgkin's lymphoma were studied from 1964 to January 31, 1975. Seventy-six percent of the 43 patients in the nonprotocol group had far advanced disease, and 76% had Rappaport's diffuse histology. Only 11% of these patients survived free of disease. The second group of 43 patients received the LSA2L2 protocol. Seventy-six percent had advanced disease and 86% diffuse histology. Of these patients 76% are surviving free of disease with a median observation time of 25+ months. Fifty-one percent of the survivors are off therapy and without evidence of disease. Prognostic factors such as primary sites, stages, histology, and others are discussed. The most important prognostic factor is early and aggressive therapy, and the achievement of a complete response status within 1-2 months from onset of therapy.


Carcinoma of the gallbladder: staging, treatment, and prognosis. Sixty-six cases of carcinoma of the gallbladder treated at The Memorial Hospital, Danville, Virginia, and the Medical College of Virginia, Richmond, were staged according to depth of invasion and spread and graded histologically; the findings were correlated with survival. Results from the two hospitals were essentially identical and the survival figures correlated well with 399 reported cases in the medical literature which could be staged according to the depth of invasion. A simple method combining staging and histologic grading of cancer of the gallbladder, which can easily be applied to all cancers of the gallbladder removed surgically and which should prove useful in the management of this disease, is described. Essentially all of the carcinomas of the gallbladder in the series were incidental findings at surgery for gall stones which may explain a relatively high proportion of superficial carcinomas which are cured by the removal of the gallbladder.


The prognostic significance of peripheral lymphocyte counts in patients with breast carcinoma. A retrospective study evaluating five-year survival rates in relation to pretreatment lymphocyte counts was undertaken in 453 patients with breast carcinoma. Patients with early tumor stages had higher pretreatment lymphocyte counts than those with advanced tumors: five-year survival in patients with pretreatment counts above 2000 per mm3 was 87% in Stage I, 67% in Stage II, and 57% in Stage III, while the comparable figures in patients with lower counts were 82%, 51%, and 29%. The differences in five-year survival rates for Stage II and III were significant: z equals 1.6955, p equals 0.046 and z equals 1.8841, p equals 0.03. Similar differences were noted in the disease-free, five-year survival rates. The corresponding figures in the three tumor stages for patients with counts above 2000/mm3 were 80%, 63%, and 53%, while those for patients with lower counts were 74%, 44%, and 18%. The differences in Stage II and III were also statistically significant: z equals 1.8430, p equals 0.33 and z equals 2.592, p equals 0.005 respectively. The possibility that the presence of suppressant factors related to the thymus may influence levels of lymphocytes was evaluated. Comparison of pre-thymectomy and postthymectomy lymphocyte counts in a control group of patients who had thymectomy for myasthenia gravis revealed a gradual increase of lymphocytes following thymectomy. The increase was significant at the second year following thymectomy. These observations indicate that lymphocyte counts may serve as prognostic indicators in patients with breast cancer. Low lymphocyte counts may be related to the presence of suppressor substances.


Adverse effect of pregnancy on melanoma: a reappraisal. The influence of pregnancy on the prognosis of cutaneous melanoma in women of childbearing age was examined in a retrospective review of 251 surgically treated cases. There was no statistical difference in survival at five years, free of disease, for Stage I melanoma between nulliparous, parous nonpregnant, and pregnant women. For Stage II melanoma, however, a significantly lower survival rate was observed for pregnant patients (29%) and parous women who had experienced activation of the lesion in a previous pregnancy (22%), as compared with that of nulliparous patients (55%) and other patients in the parous group (51%); p less than 0.05. This discrepancy in survival, together with the observed higher frequencies of Stage II cases, melanomas occurring on the trunk, and symptoms such as bleeding, ulceration, irritation, and elevation of the lesion, strongly suggest an adverse influence of pregnancy on women with Stage II melanoma.


Survival and regional disease control after isolation-perfusion for invasive stage I melanoma of the extremities. Excision of the primary and isolation-perfusion with 1-phenylalanine mustard was the treatment in 199 patients with invasive Stage I melanoma of the extremities with the goal of improving regional disease control and long-term survival. The determinant survival in patients followed 5-15 years was 83%; Berkson-Gage survivals were 98% at 2 years, 88% at 5 years, and 84% at 10 years. The site of first recurrence was determined in all 49 (25%) patients who failed treatment: three (2%) developed local recurrence, six (3%) developed intransit recurrence, 24 (13%) developed positive regional lymph nodes, 15 (8%) developed systemic metastases, and one developed local recurrence plus positive regional nodes. Of these 49 patients failing treatment, 15 (31%) are currently surviving with no evidence of disease after retreatment of the recurrence. These data are compared to historical controls in the literature. It is concluded that regional control rates are improved by perfusion and that survival has probably been improved. In 14 patients treated by perfusion without local excision, regional control and survival was poor. Single drug (L-PAM) perfusion with the techniques employed is effective in controlling regional subclinical disease, but the primary should be widely excised.


Regional lymph node metastases and the level of invasion of primary melanoma. One hundred and nineteen patients with primary malignant melanoma had their primary lesion classified according to Clark's level of invasion by Clark and the Division of Surgical Pathology at UCLA. Thirty patients had superficial melanoma (Level II) and did not undergo regional lymph node dissection (RLND). All other patients (Levels III, IV, and V) underwent regional lymph node dissection. Thirty-two percent of patients with Level III melanoma, 67% of patients with Level IV melanoma, and 66% of patients with Level V melanoma had metastases to the regional lymph nodes. These studies suggest that the level of invasion, or the thickness of the primary melanoma, is helpful for predicting regional lymph node metastases.


Malignant melanoma. Role of node dissection reappraised. Two hundred and fifty-nine patients with malignant melanoma have been reviewed. One hundred and fifty of these were determinate. A primary excision and dissection in continuity of the tumor, the intervening lymphatics, and the regional lymph nodes achieved a 5-year survival free of disease for 67.5% of the patients. When the nodes were clinically negative but microscopically positive, 45% survived. An electric discontinuous node dissection offers no better prognosis than does a therapeutic dissection and is not indicated in the primary treatment of malignant melanoma.


Radical mastectomy versus radical mastectomy plus internal mammary dissection. Five-year results of an international cooperative study. From 1963 to 1968, the international group collected 1580 cases of breast cancer, randomized into two therapeutic groups: radical mastectomy and extended mastectomy. The data were processed on the UNIVAC 1107 computer of the I.N.S.E.R.M. Computing Center. No significant difference was observed between the two groups in the overall five-year survival rate. However, a more detailed analysis, according to certain prognostic features, showed that extended mastectomy improved the results in one subgroup: cancers of inner or medial quadrants, axillary N+. Within this group the difference was highly significant for a smaller subgroup (190 patients) including only tumors T1 and T2. In conclusion, there is no indication for extended mastectomy in any cancers of the outer quadrants or in those of the inner or medial quadrants without axillary involvement. A limited indication for extended mastectomy may be provisionally retained for T1 and T2 cancers of the inner or medial quadrants with axillary involvement.


Thymoma: a clinical and pathological study of 65 cases. A clinicopathologic study of 65 patients with thymomas was performed. The most significant prognostic feature of the thymomas was the presence or absence of gross invasion of adjacent tissue. None of 37 patients with non-invasive thymomas died of tumor or had a recurrence. Invasive thymomas resulted in the death of 3 of 17 patients. Two others are alive with unresectable tumor, and one other patient died of myasthenia gravis with recurrent thymoma. The histologic type of thymoma had no value in predicting prognosis. Thirty-five patients had possibly associated syndromes. These syndromes, particularly myasthenia gravis and red cell hypoplasia, affected survival to an equal or greater extent than did the direct effects of the tumors.


Gallium-67 citrate scanning in Hodgkin's disease and non-Hodgkin's lymphoma. Gallium-67 citrate scintigraphy was performed in 33 patients with Hodgkin's disease and 25 patients with non-Hodgkin's lymphoma. Three hundred twenty-eight sites of potential involvement were investigated. Confirmation of involvement was made by physical examination, roentgenographic evaluation and histopathologic examination of tissue obtained at diagnostic laparotomy. The results of scintigraphy correlated with all other clinicopathologic data in only 35% of patients, the true-positive rate being significantly higher above the diaphragm (61%) than below (40%). The overall true-positive and true-negative rates were 53 and 90%, respectively. A significant correlation existed between tumor histology and scanning accuracy; the true-positive rate in Hodgkin's disease was 74% compared to only 13% in patients with lymphocytic lymphoma. A similar variation of 67Ga concentration with tumor histology was also noted in 70 tissue specimens obtained from 28 patients at the time of diagnostic laparotomy or biopsy. The routine use of 67Ga-citrate to detect splenic involvement with tumor appeared to be precluded by the low true-positive and high false-negative rates of 57 and 27%, respectively. Gallium-67-citrate scintigraphy may be useful as an adjunct to established clinical staging procedures in untreated patients and in the detection of recurrent disease in treated patients. Our data indicate it is not sifficiently reliable to replace established methods presently used for clinical staging.


The single palpable thyroid nodule: evaluation by 99mTc-pertechnetate imaging. The role of 99mTc-pertechnetate thyroid imaging in the preoperative assessment of patients with single palpable thyroid nodules was evaluated. The frequency of cancer in hypofunctional nodules was similar to that found in previous studies with 131I. The 99mTc-pertechnetate image allowed a reliable separation of pathologically uninodular thyroids from those that were multinodular, and demonstrated multiple thyroid lesions that had not been detected by physical examination in over one-third of the cases. The frequency of cancer in thyroids containing a solitary or dominant hypofunctional nodule was higher (17%) than that in thyroids with a multinodular scan appearance (less than 5%).


Pathological staging of 100 consecutive untreated patients with non-Hodgkin's lymphomas: extramedullary sites of disease. One hundred consecutive untreated cases of non-Hodgkin's lymphomas were reviewed according to Rappaport's classification. There were 49 males and 51 females, almost evenly distributed between nodular (49) and diffuse (51) patterns. Only diffuse lymphomas were seen in patients under age 20 and they were twice as common as nodular lymphomas in patients over 60. Nodular lymphomas were predominantly lymphocytic (61%) or mixed (35%) while diffuse lymphomas were commonly histiocytic (43%). Standardized pathological staging was based upon the serial performance of bone marrow needle biopsy, percutaneous hepatic biopsy, peritoneoscopic hepatic biopsies and exploratory laparotomy. For all patients this sequence terminated with the first positive biopsy. Hepatic involvement was documented in 40 patients by either percutaneous biopsies,18 peritoneoscopic biopsies,9 or wedge biopsy at laparotomy.13 Thirty-seven of 49 patients who underwent laparotomy had biopsy-proven abdominal involvement. Overall incidence of biopsy-proven abdominal disease was 64%. Positive spleens varied widely in weight but all negative spleens weighed less than 270 g. Constancy of histologic type in multiple sites was observed in 90% of cases.


Cytogenetic studies in sideroblastic anemia. Cytogenetic studies were performed on bone marrow aspirates from seven patients with acquired sideroblastic anemia. In one male patient a 45,X cell line was present in each of three bone marrow aspirates. The remaining six patients had a normal chromosome complement. The abnormal stem line in the bone marrow may be unrelated to the hematologic disorder or may indicate a neoplastic process still latent. The cytogenetic literature on sideroblastic anemia is reviewed.


Results of mass screening for breast cancer in 50,000 examinations. Detection of earlier breast cancer, especially in its preclinical stage, offers the only method available today for reducing mortality from this disease. The Health Insurance Plan study, conducted since 1963 under contract with the National Institutes of Health, has achieved a one-third reduction in death rate in a study group compared to a matched control which has persisted in 7 years of follow-up. The Guttman Institute, founded in 1968 to develop practical methods for large scale screening, is operating a tandem approach using interview, clinical examination, improved mammography, and thermography for greatest yield. Emphasis is placed on motivation to accept the examination, teaching and encouragement of breast self-examination, and emphasis on periodic reexaminations. At the present time, almost 300 women receive this complete examination per day at the Institute's fixed facility. Periodic examinations leads to marked increase in number of cancers detected free of axillary nodal involvement. The tandem approach emphasizes substantial percentage of cancers detected on only one modality, two-thirds of which are without nodal involvement. Breast self-examination is necessary to detect "interval" cancers in more localized stage.


Histogenesis of tumors from the nasal cavities induced by diethylnitrosamine. Chronic subcutaneous (s.c.) or single intravenous (i.v.) injections of diethylnitrosamine (DEN) to gerbils (Meriones unguiculatus) led to the induction of carcinomas of the nasal cavities in a high incidence. These neoplasms were multifocal in origin, frequently showing mixed cellular patterns of the following cell types: large cuboidal cells, nonciliated columnar cells, ciliated columnar cells, small cells, and squamous epithelial cells. No sensory cells of the olfactory mucosa or neurofibrillar differentiations were found in these neoplasms, although several showed rosette- and pseudorosette-like formations. Dose and route of administration seemed to influence the site of origin and the patterns of cellularity of these tumors. Whereas chronic s.c. injections resulted in carcinomas of the olfactory region, being mostly composed of large cuboidal cells, single i.v. injections led to the development of carcinomas mainly originating from the respiratory-olfactory mucosal junction and composed preferentially of nonciliated and ciliated columnar cells.


Nonepithelial tumors of the nasal cavity paranasal sinuses, and nasopharynx: a clinicopathologic study. V. Skeletal muscle tumors (rhabdomyoma and rhabdomyosarcoma). In a study of nonepithelial tumors involving the nasal cavity, paranasal sinuses, and nasopharynx, 19 lesions (three rhabdomyomas, 16 rhabdomyosarcomas) showed skeletal muscle differentiation. The clinical findings associated with these neoplasms are reviewed, the histologic features are illustrated, results of treatment are presented, and clinicopathologic correlations are discussed. The rhabdomyomas grew as localized masses in the nasopharynx, were excised locally, and behaved clinically like benign tumors. The rhabdomyosarcomas were found predominantly in children and were associated with a poor prognosis; most of the patients died within 2 years following diagnosis.


Plasma dopamine-beta-hydroxylase in the diagnosis of neuroblastoma. An atypical case of neuroblastoma is described, in which the diagnosis was facilitated by the application of a new biochemical procedure, the assay of plasma dopamine-beta-hydroxylase activity. This laboratory tool is proposed as a useful adjunct to established techniques in the diagnosis of neural crest tumors.


Experience with opposite breast biopsy in patients with operable breast cancer. One hundred and nine patients with unilateral breast carcinoma and no palpable abnormality of the contralateral breast were evaluated by opposite breast biopsy. Our patient population yielded four noninfiltrating carcinomas, and one infiltrating carcinoma for an incidence of 4.5%. The one infiltrating cancer was suspected on a preoperative mammogram. We have discontinued the routine use of the opposite breast biopsy as a diagnostic tool in patients with unilateral breast cancer, in patients with no palpable abnormality and a normal mammogram.


Carcinoembryonic antigen: clinical and historical aspects. To further define and determine the usefulness of CEA, 1100 CEA determinations have been made over the past two years at The Ohio State University Hospitals on patients with a variety of malignant and nonmalignant conditions. Correlation of CEA titers with history and clinical course has yielded interesting results not only in cancers of entodermally derived tissues, for which CEA has become an established adjunct in management, but also in certain other neoplasms and inflammatory states. The current total of 225 preoperative CEA determinations in colorectal carcinomas shows an 81% incidence of elevation, with postoperative titers remaining elevated in patients having only palliative surgery but falling to the negative zone after curative procedures. An excellent correlation exists between CEA levels and grade of tumor (more poorly differentiated tumors showing lower titers). Left-side colon lesions show significantly higher titers than right-side lesions. CEA values have been shown to be elevated in 90% of pancreatic carcinomas studied, in 60% of metastatic breast cancers, and in 35% of other tumors (ovary, head and neck, bladder, kidney, and prostate cancers). CEA levels in 35 ulcerative colitis patients show elevation during exacerbations (51%). During remissions titers fall toward normal, although in 31% still remaining greater than 2.5 ng/ml. In the six colectomies performed, CEA levels all fell into the negative zone postoperatively. Forty percent of adenomatous polyps showed elevated CEA titers (range 2.5-10.0) that dropped following polypectomy to the negative zone. Preoperative and postoperative CEA determinations are important in assessing the effectiveness of surgery. Serial CEA determinations are important in the follow-up period and in evaluation of the other modes of therapy (e.g., chemotherapy). These determinations of tumor antigenicity give the physician added prognostic insight into the behavior of the tumor growth. Rectal examination with guaiac determinations, sigmoidoscopy, cytology, barium enema, and a good clinical evaluation remain the primary tools for detecting colorectal disease. However, in the high-risk patient suspicious of developing cancer, CEA determinations as well as colonoscopy are now being used increasingly and provide additional highly valuable tools in the physician's armamentarium.


The role of an intensive care unit in a cancer center. An analysis of 1035 critically ill patients treated for life-threatening complications editorial. Life-threatening complications of cancer therapy often involve multiple organ systems and offer a therapeutic challenge which can be met with efficiency and success by concentrating personnel and equipment in a facility devoted to these problems. Three years ago, an Intensive Care Unit was created at Memorial Cancer Center to offer such patients the benefit of highly skilled nursing, advanced monitoring and supportive techniques, and full-time attendance by physicians and surgeons with a particular interest in Critical Care Medicine. Since then, 1035 patients have been admitted to the eight-bed unit with a mortality rate of 22.3%, which compares favorably with those reported from other institutions. Analysis of this experience has revealed that an average of 16% of those who survived their acute problems after considerable effort and expense, subsequently died of their underlying disease within 2 months. This experience has suggested the need for prognostic criteria to facilitate recognition of those patients for whom intensive supportive measures offer a reasonable chance of worthwhile palliation.


Separate primary carcinomas of the esophagus and head and neck region in the same patient. From 1949 to 1972 at Memorial Sloan-Kettering Cancer Center, 60 patients with primary cancers of both the oral cavity, pharynx, larynx (OPL) and esophagus were studied. In 15, the cancers occurred synchronously, and in 68% they occurred within 2 years of each other, the longest interval being 27 years. The tongue and extrinsic larynx were the most common sites of origin together with the middle third of the esophagus. During the same period, over 7000 patients with OPL and over 1000 patients with esophageal cancers were seen at this institution. The majority of patients had a history of excessive smoking and alcohol intake. Four out of nine who had previous radiation therapy for their OPL cancer developed esophageal cancer within the therapeutic field (three after 16, 25, and 27 years). Thirty percent (18/60) had three primary cancers; one had four, of which two were in the head and neck region. Two patients survived more than 5 years; both also had a third primary cancer of the lung. There are broader implications in this study: multiple primary cancers in general, and this group in particular, give us especially valuable clues as to the oncogenic influence of environmental factors as well as cellular, organ, and also systemic susceptibility. With one cancer, one can anticipate formation in other related organs. This provides an opportunity for early diagnosis, more effective management, and improved survival. The cause and effect relationship of tobacco and alcohol must be emphasized at every opportunity and most particularly to those who have developed one cancer in the oropharyngeal-laryngeal region.


Transfer factor therapy in patients with cancer. The objective of this study was to utilize transfer factor to stimulate cell-mediated immunity to specific tumor antigens in cancer patients. Thirty-five selected patients with advanced recurrent cancer, who were not suitable for further conventional therapy, were treated with transfer factor. Transfer factor was prepared from cohabitants of the patients and administered at 2-week intervals. This immunotherapeutic approach produced a clinical effect in 13 patients in terms of regression of tumor (1), arrest of metastatic disease (14), or pain relief (14). Conversion of dermal reactivity to specific tumor antigens was observed during periods of clinical improvement. Despite continued immunotherapy, the duration of clinical improvement was short (2 weeks to 12 months). Seven of the 11 patients not responding to therapy exhibited serum blocking of lymphocyte responsiveness. In 11 patients there is insufficient data to evaluate the clinical effectiveness of this therapy. The results suggest that transfer factor can stimulate specific cell-mediated immunity in cancer patients and produce a clinical effect on tumor under certain circumstances.


Current status of research in detection and diagnosis. Following the passage of the National Cancer Act of 1972, the National Cancer Institute created a Division of Cancer Biology and Diagnosis. This marked the renewal of a commitment of the National Cancer Institute to diagnostic research. Within the scope of diagnostic research there are three separate subheadings: screening or detection, diagnosis itself, and prognosis. Asymptomatic individuals are studied by screening procedures to determine if they might have a cancer. Those that are selected by the screen are then subject to definitive diagnostic procedures to determine whether they have a cancer. Prognosis attempts to predict the outcome from knowledge gained in the past. At the present time the only screening method that has been proven in a rigorous manner to be effective in reducing mortality is a combination of a physical examination and mammography for carcinoma of the breast. The Pap test is accepted but precisely how much it has reduced the mortality from cervical carcinoma remains to be determined. The National Cancer Institute is now engaged in research designed to test various aspects of screening to develop new screening techniques and to evaluate them. In the diagnostic field it is particularly concerned with imaging by radiologic means and ultrasound. Visualization by endoscopy is becoming important. These aspects of screening, diagnosis and prognosis will be reviewed.


Who are we missing and why?

Who are we missing and why? The concept of "missing" is defined as failure to diagnose cancer before it has spread beyond the organ of origin. Data are presented for the 11 sites at which cancer occurs most frequently in the United States. There is a clear association between the survival of patients with cancer of a particular site and the percentage of cancers of that site diagnosed in a localized stage. However, the reasons for variation in the proportion of cases discovered while localized, which varies from 79% for uterine corpus to 12% for pancreas, appear to be varied and complex. Available data suggest that the nature of the tumor-host relationship and metastatic potential of the neoplasm are probably more important than alertness on the part of the patient and the physician, and probably have a more profound influence on stage of disease at diagnosis than currently available screening techniques.


What should the physician ask?

What should the physician ask? The physician who deals with the general public rather than with high risk groups has a considerable disadvantage to overcome. This is because the effectiveness or impact of a control program is directly related to the prevalence of the condition sought in the population at hand. Thus, the physician must develop a set of "verbal screens" which will permit him to select the sub-segments of his general population which should be screened conventionally. These verbal screens may be of two types: 1) a simple inquiry as to whether a generally accepted screening test has been applied within the last year or two, and 2) an inquiry as to whether any risk factors of the more common cancers are present. For cancer of the cervix, women who have first intercourse at an early age or who are of the lower social strata should be identified for screening. For breast cancer, women who are nulliparous, have first birth at a late age, or a family history of breast cancer should be identified.


New horizons in lung cancer diagnosis.

New horizons in lung cancer diagnosis. Lung cancer is rarely diagnosed and treated while still localized. Sputum cytology allows detection of radiologically occult tumors but conventional endoscopic procedures frequently prove inadequate for localization. It is the purpose of this report to outline the endoscopic observations and methods we have developed in successfully localizing 17 consecutive, radiologically occult carcinomas discovered in the sputum of 15 patients. A detailed examination of the upper respiratory tract demonstrated occult tumors in two patients. A segment by segment fiberbronchoscopic study under anesthesia allows multiple brushings and meticulous handling of specimens. Lesion localization is provided as well as identification of synchronous second primary tumors. Biopsies at the lobar spur and carina assist in determining the proximal extent of carcinoma in situ at potential surgical margins. Newer methods should enhance our recognition of inapparent carcinoma in situ allowing more efficient and more accurate tumor localization and a better appreciation of its extent.


Operative and endoscopic pancreatography in the diagnosis of pancreatic cancer. X-rays of the pancreatic duct can now be obtained by a nonoperative endoscopic approach (endoscopic retrograde cholangiopancreatography-ERCP). After more than 2 years experience we have found that the pancreatic duct can be visualized in 85 to 90% of patients. This test is used to detect pancreatic carcinoma in the symptomatic patient and in searching for an operative pancreatic lesion in a patient with known recurrent or chronic pancreatitis. Many of these patients have pain or a transiently elevated amylase; a few have steatorrhea or abnormalities of the duodenal sweep on barium meal. Stenosis or obstruction of the main pancreatic duct with or without proximal duct dilation are the characteristic abnormalities noted in pancreatic carcinoma. A rare pancreatic tumor which is not in juxtaposition with the duct will have a normal pancreatogram although the common duct may be obstructed by cholangiography as it passes through the head of the pancreas. In patients with chronic pancreatitis it may be difficult to differentiate an inflammatory from a neoplastic stricture by either operative or endoscopic pancreatography. In the future, cytologic and biochemical examination of the pancreatic secretions obtained at ERCP may increase the accuracy of diagnosing carcinoma.


Flexible colonoscopy.

Flexible colonoscopy. Colonoscopy with fiberoptic instruments has opened new vistas in diagnosis and treatment of colonic disease. Such endoscopy requires skill, experience, and judgment to be accomplished readily and safely but permits visual examination of the entire colon and, frequently, the terminal ileum as well. Although in experienced hands colonoscopy may have greater diagnostic accuracy than the barium enema, particularly with respect to colorectal cancer and polyps, the two are complementary modalities and with their combined use an extremely high rate of detection and confirmed diagnosis can be expected. The Beth Israel group introduced the technique of snare-cautery removal of colonic polyps via the colonoscope and has now successfully resected over 2500 such polyps without a single death. This is the largest world experience. Selected polyps can be removed endoscopically as an ambulatory procedure, reducing costs and incapacitation time. Neoplastic polyps often harbor invasive cancer and their extirpation is expected to reduce the incidence of overt colorectal cancer. Colonoscopy and endoscopic polypectomy offers the opportunity to check the rising incidence, morbidity, and mortality related to colorectal cancer.