Influences of pituitary-adrenal hormones on kindling. The kindling process represents a progressively augmenting electrical and behavioral response to brain stimulation, that has been proposed as a model for the development of epileptogenesis. The first experiment examined the effects of hypophysectomy on the kindling process. The effects of hypophysectomy were found to be dependent on the number of days between hypophysectomy and the beginning of kindling. The kindling rate was slowed, compared to intact controls, when hypophysectomy was performed less than 2 weeks prior to the first kindling stimulation. However, if more than 4 weeks and passed since hypophysectomy, the kindling rate was faster than that of intact controls. The second experiment tested the influence of systemic administration of cortisone (10 mg/animal), upon kindling of control and hypophysectomized animals. Cortisone was found to reverse the kindling deficit of hypophysectomized animals at less than 2 weeks and to slow kindling of intact controls, but to have no effect on hypophysectomized animals at more than 4 weeks (at this dose). These results are interpreted as indicating that pituitary-adrenal hormones have profound influences on the kindling process, but it is unclear whether the influence is upon brain excitability or more directly upon modification of synaptic function.


Aging and unusual catecholamine-containing structures in the mouse brain. Brains of C57BL/6J mice, aged 4, 8 and 20--29 months, were examined by the Falck-Hillarp histochemical fluorescence technique. Numerous large, intensely fluorescent green to yellow-green spots (LIFS) were observed in the brains of senescent mice. LIFS were generally round to ovoid in shape and ranged in size from about 10 micrometer to about 30 micrometer. Histochemical and pharmacological procedures and spectral analysis indicated that the formaldehyde-induced fluorescence of the LIFS was due to the presence of catecholamines (CA) rather than aging pigment. Their distribution in the brain suggests an association with nerve axons or terminals rather than cell bodies. The number of LIFS in the hypothalamus increased progressively during aging. It is proposed that LIFS may represent age-related, unusual CA accumulation in enlargements proximal to axonal or terminal portions undergoing spontaneous degeneration.


Effects of transecting lateral neural connections of the medial preoptic area on maternal behavior in the rat: nest building, pup retrieval and prolactin secretion. In lactating female rats bilateral parasagittal cuts transecting the dorsolateral neural connections of the medial preoptic area (MPOA) abolished nest building and retrieving components of maternal behavior, while crouching and nursing were unaffected. While few animals with these cuts were suckled when presented with pups the prolactin secretion response was undiminished when suckling did occur. Whereas previous studies have demonstrated that extensive surgical separation of the medial preoptic area-anterior hypothalamic continuum from the lateral preoptic area-lateral hypothalamus disrupts all aspects of maternal behavior, the present study has determined more specifically the zone of fibers essential for the active components of maternal behavior, i.e., nest building and retrieving. These fibers appear to enter/leave MPO dorsolaterally beneath the crossing of the anterior commissure in the region of the bed nucleus of the stria terminalis. These neural connections are not the same as those that regulate prolactin secretion in the lactating rat.


Operant conditioning of vertical eye movements without visual feedback in the midpontine pretrigeminal cat. An operant conditioning of vertical eye movements was achieved in the midpontine pretrigeminal cat in total darkness by contingent reinforcement of spontaneous eye movements with lateral hypothalamic (LHT) reward stimulation, when each movement (upward direction was chosen in this experiment) exceeded a preset amplitude. However, the response rates in the dark were lower than those in the light and the time to reach the peak response rate was much longer. Recording of evoked potentials to optic chiasma (OC) stimulation revealed enhancement of late components of the visual cortex (VC) and superior colliculus (SC) responses in relation to eye movements. Sequential records of the averaged evoked responses associated with eye movements indicated that the amplitudes of the late components of the VC and SC waves gradually increased in the course of establishment of the operant conditioning, and decreased gradually during extinction. In a yoked control test, increase in amplitudes of the late components was much less significant during non-contingent reinforcement given independently of the eye movements. These results suggest that 'corollary discharge' may play a critical role as a cue in acquisition of the operant conditioning of vertical eye movements when visual feedback is absent in total darkness.


The relationship of Schwann cell migration in vitro to injury, using normal, Wobbler, and dystrophic mice. A quantitative in vitro study of the cellular outgrowth from mouse sciatic nerve explants has been carried out using both normal untreated nerves and nerves taken at various times after the in vivo application of trauma. The results obtained have been compared with the results for outgrowth from sciatic nerve of two neurological mutants: 'the Wobbler mouse' and the 'ReJ 129 Dystrophic mouse'. It has been shown that the in vitro response to peripheral injury does reflect the activity known to occur in vivo. Outgrowth from explants of mutant mouse nerves, although differing from normal has been found to be less profuse than that occurring after mechanical nerve injury.


Computer separation of unitary spikes from whole-nerve recordings. A practical and efficient off-line computer technique is described for automatically separating unitary waveforms from multiunit whole-nerve spike train data with no a priori knowledge about the number of units or their waveforms. The procedure requires two recording eletrodes which provide 3 measures on each putative unit: (1) peak-to-peak amplitude on the proximal channel, (2) amplitude on the distal channel, and (3) temporal offset (depends on conduction velocity) between proximal and distal spikes. On the basis of these 3 measurements, individual unitary spikes are automatically separated into clusters according to empirically-determined limits of variability. The results of the program are displayed in 3-D plots of the 3 measures on each unitary spike and in plots of superimposed waveforms from each cluster. These plots can be used to interactively correct clustering errors. The procedure is illustrated with a 1-min segment of spike train data recorded in vivo from the siphon nerve of a freely-behaving Aplysia. We routinely obtain about 10 relatively well-isolated units in such segments. By utilizing the average waveforms and conduction velocities for individual clusters, it may eventually be possible to separate unitary spikes from compound waveforms resulting from simultaneous of two or more units.


Participation of brain catecholaminergic neurons in a self-sustained circadian oscillation of plasma corticosterone in the rat. Circadian rhythms of locomotor activity and plasma corticosterone were determined simultaneously in individual rats which were injected intraventricularly with 6-hydroxydopamine (6-OHDA), a specific depletor of catecholamines. In light-dark cycles (LD), 6-OHDA-treated rats showed essentially normal circadian rhythms of both functions. In 200 lux continuous light (LL) the locomotor activity in the drug-treated rats ran freely with a period slightly longer than 24 h: free-running parameters (mesor, amplitude and period) of the locomotor activity were the same as those control rats. The circadian rhythm of plasma corticosterone in control rats also ran freely in LL, resulting in a reversal of their phase after 12 days exposure to LL. However, the rhythm disappeared in 6-OHDA-treated rats under LL: instead in these rats 3--4 episodes of secretion were obsered over a 24 h period. These results suggest a difference in the biochemical background between the regulatory mechanism of circadian rhythm of locomotor actitivity and that of plasma corticosterone. It is also apparent that brain catecholaminergic components are indispensable for the circadian rhythm of plasma corticosterone to freerun normally in LL, but are dispensable in LD. A plausible model consisting of two oscillators is proposed to explain these findings.


Conformation of exocyclic amino groups in purines and pyrimidines: crystal structure and conformation of 1-methyl-N4-hydroxycytosine hydrochloride. The hydrochloride salt of 1-methyl-N4-hydroxycytosine crystallizes in the triclinic space group P1 with cell dimensions: a = 8.232(1), b = 9.293(1), c = 5.416(1) A (1 A = 0.1 nm); alpha = 91.95(1), beta = 91.72(2), gamma = 71.56(1) degrees (SE in parentheses). The structure was solved by direct methods and refined to R = 3.7% for 1514 reflections. Despite the absence of an intramolecular hydrogen bond in the solid state, the N4-hydroxy substituent is syn to the ring N(3). This conformation, which probably prevails also in the neutral form, is of relevance to the mechanism of attack of cytosine by hydroxylamine, known to involve predominantly the cytosine cation, as well as to the mechanism of hydroxylamine mutagenesis. Such conformational aspects are also relevant to other phenomena, including translation and restriction.


Products of mitochondrial protein synthesis in Tetrahymena. The products of mitochondrial protein synthesis have been investigated in Tetrahymena after labelling with [35S]methionine in the presence of cycloheximide. The labelled proteins were analyzed by sodium dodecyl sulfate slab polyacrylamide gel electrophoresis. We have identified 13 electrophoretically discrete bands as well as 4 other bands with a more variable occurrence. These proteins ranged in apparent molecular weight from 8100 to 57,500. The cycloheximide-resistant incorporation could be blocked with chloramphenicol. The mitochondrial proteins appeared to be in a disaggregated state and were stable to agents such as trichloroacetic acid (hot or cold) and chloroform-methanol. The pattern of proteins was similar following labelling times ranging from 30 min to 3 h.


Isolation and translation in vitro of poly(A)+RNA from the free-living nematode Panagrellus silusiae. Polysomal RNA was isolated from the free-living nematode Panagrellus silusiae. Passage of this RNA through a cellulose column resulted in the fractionation of the input RNA into poly(A)-RNA (ca. 97.5% of the total) and poly(A)+ RNA (ca. 2.5% of the total). RNase digestion, followed by polyacrylamide gel electrophoresis, revealed that the poly(A)+ RNA contained poly(A) tracts that ranged from 75 to 104 nucleotides in length with a mean value of about 90 residues. There was no evidence of poly(A) sequences in the poly(A)- RNA fraction. Poly(A)+ RNA gave a 25- to 50-fold stimulation (over background) of amino acid incorporation in the wheat germ cell-free protein-synthesizing system. At least 26 proteins were evident after electrophoresis in cylindrical sodium dodecyl sulfate-polyacrylamide gels. Poly(A)-RNA was capable of stimulating protein synthesis in vitro with about five discrete proteins being produced. In summary, the properties of mRNA from a simple organism such as P. silusiae are very similar to those of more complex eukaryotes.


Characteristics of glutamine metabolism by rat kidney tubules: a carbon and nitrogen balance. The metabolism of glutamine by a suspension of rat kidney tubules was studied in vitro. The influence of duration of incubation, glutamine concentration, and metabolic state of the donor animals was investigated. The relative importance of glucose synthesis, amino acid production, and oxidation to CO2 was estimated by drawing a complete balance of the nitrogens and the carbon chains of the extracted glutamine. It was found that the initial (first 15 min) rate of glutamine utilization was significantly greater than the subsequent rate due to an initial, but transient, extracellular accumulation of glutamate. This phenomenon was suppressed when a small amount of glutamate was added to the incubation medium. Glucose production constitutes the major fate for glutamine metabolism. No net oxidation of glutamine could be detected with 1 mM glutamine during the first 30 min. However, glutamine oxidation becomes significant after prolonged incubation (16% at 120 min). The metabolic fate of glutamine differs when 5 or 10 mM are presented to the tubules, glutamate production and oxidation to CO2 becoming more important. Metabolic acidosis or a 48-h fast increases glutamine extraction and enhances its utilization glucose synthesis while they depress glutamate accumulation and oxidation to CO2. Metabolic alkalosis has the opposite effect. It is concluded that the metabolism of glutamine in vitro is dependent on the conditions of the study. Furthermore, total oxidation to CO2 is not a major fate for glutamine metabolism at physiological concentration and is not enhanced by acidosis in the rat kidney in vitro.


Inhibition of carboxypeptidase A catalyzed peptide hydrolysis by 3-phenylpropanoate at activating and nonactivating substrate concentrations. The carboxypeptidase A catalyzed hydrolyses of five structurally related dipeptide substrates in the presence of the inhibitor 3-phenylpropanoate have been studied. At nonactivating substrate concentrations, 3-phenylpropanoate is a mixed inhibitor of carbobenzoxyglycyl-L-phenylalanine hydrolysis and a noncompetitive inhibitor of the hydrolyses of benzoylglycyl-L-phenylalanine, cinnamoylglycyl-L-phenylalanine, hydrocinnamoylglycyl-L-phenylalanine, and acetylglycyl-L-phenylalanine. When carbobenzoxyglycyl-L-phenylalanine and benzoylglycyl-L-phenylalanine exhibit substrate activation, inhibition by 3-phenylpropanoate is mixed but appears to be mostly competitive. Proposed here is a site for the binding of 3-phenylpropanoate along with a kinetic mechanism consistent with these data.


Organic mercurial diuresis: inhibition of glutamine utilization in the acidotic rat. Organic mercurials inhibit mitochondrial glutamine metabolism in vitro while metabolic acidosis, a condition in which the predominant renal fuel is glutamine, potentiates mercurial diuresis. The following studies were undertaken to determine whether potentiation of diuresis reflects mercurial inhibition of glutamine utilization. (1) All three mercurials employed (mersalyl, chlormerodrin, and p-chloromercuribenzoate) are diuretics in the rat and this effect was potentiated by NH4Cl. (2) Despite reabsorbing less sodium, mercurial-treated rats had lower kidney ATP content (4.35 +/- 0.26 and 3.84 +/- 0.43 mumol/g dry weight (mercurial plus NH4Cl) than did controls (4.95 +/- 0.31 and 4.87 +/- 0.39 mumol/g dry weight (NH4Cl). (3) Isolated kidneys from NH4Cl and NH4Cl plus mercurial treated rats were perfused with 1 mM L-[U-14C]glutamine to determine rates of extraction and oxidation. Mercurial-treated acidotic rat kidneys had a reduced rate of glutamine uptake (40.8 +/- 7.4 vs. 64.8 +/- 5.8 mumol/h per kidney), a diminished rate  of glutamine conversion to CO2 (14.8 +/- 3.6 vs. 26.4 +/- 5.2 mumol/h per kidney), and a reduction in glucose production (16 +/- 5 vs. 27 +/- 4 mumol/h per kidney). These results are consistent with an effect of organic mercurials upon glutamine utilization, limiting ATP availability, and thereby reducing tubular active sodium reabsorption.


Control of stiffness by the medium latency electromyographic response to limb perturbation. It is hypothesized that the medium latency electromyographic (EMG) response (ML) to limb perturbation functions to preset limb stiffness to a constant initial level. Three predictions are derived from this hypothesis: Firstly, in the presence of an instruction calling for opposition to limb perturbation, a control signal, ML, will be observed and will lead to the establishment of a constant level of limb stiffness. Secondly, in the absence of an instruction to oppose, no control signal will be observed and correspondingly a constant stiffness will not be generated. Thirdly, the latency of onset of stiffness control will covary with the latency of onset of ML. These predictions were tested in experiments involving perturbation of the human forearm about the elbow joint, with surface EMG measurements and computation of the limb stiffness function. The results are in accord with these predictions, and support the hypothesis that ML functions in the feedforward control of limb stiffness.


The effects of gonadectomy on the hepatic activities of aryl hydrocarbon hydroxylase, epoxide hydratase, and glutathione S-transferase in Wistar rats pretreated with oral methadone . HCl. Methadone . HCl given in the drinking water for 4 weeks increased microsomal epoxide hydratase activity in the liver of adult male Wistar rats, with no change in aryl hydrocarbon hydroxylase activity. In contrast, in female rats it raised aryl hydrocarbon hydroxylase with no change in epoxide hydratase activity. Gonadectomy altered the effect of methadone on epoxide hydratase, but not on aryl hydrocarbon hydroxylase activity, in both sexes. In ovariectomized rats, but not in controls, methadone nearly doubled the epoxide hydratase activity, whereas in male rats castration decreased the inductive effect of methadone. Gonadectomy had a significant effect on the results of methadone treatment with respect to glutathione S-transferase activity in female rats. A sex difference was noted in the control levels of aryl hydrocarbon hydroxylase and glutathione S-transferase, but not of epoxide hydratase activity. The glutathione S-transferase and aryl hydrocarbon hydroxylase activities were decreased in castrated male rats, whereas epoxide hydratase activity was unaltered. It is concluded that sex hormones play an important role in the induction of epoxide hydratase and glutathione S-transferase by methadone, but not of aryl hydrocarbon hydroxylase, at this particular dosage regime.


The effects of periarterial nerve activation on coronary vessel tone in an isolated and perfused slab of beef ventricle. The direct effects of extrinsic nerve stimulation on coronary artery tone are unclear because of the complications arising from alterations in myocardial dynamics which themselves alter flow. An isolated and perfused nonbeating slab of beef ventricle was utilized in the present experiments to eliminate secondary complications and the efects of periarterial nerve activation on coronary perfusion pressure were examined. It was found that stimulation induced vasoconstrictor responses which were enhanced by physostigmine, a cholinesterase inhibitor, and blocked by atropine. These responses were duplicated by exogenous acetylcholine both in the perfused preparation and in isolated strips of coronary artery. Although added noradrenaline gave vasodilatation, no response attributable to the release of noradrenaline from nerves was obtained. It is concluded that the coronary vasculature of the beef receives a cholinergic innervation and that its activation, especially under conditions of reduced transmitter degradation, may induce considerable coronary vessel constriction.


Cytochrome P-450 and hepatic drug biotransformation during progressive cardiac disease in cardiomyopathic hamsters. Reductions in cytochrome P-450 levels and aminopyrine N-demethylase activity of hepatic microsomes obtained from cardiomyopathic hamsters (BIO 14.6) occurred at all stages of the disease before the development of congestive heart failure (CHF). Cytochrome b5 levels were reduced only in animals with CHF when compared with age-matched controls (BIO.RB). Total microsomal protein and p-nitrophenol glucuronidation were not affected by the disease process. We conclude that the reduction in cytochrome P-450 levels and N-demethylase activity in cardiomyopathic hamsters is not a consequence of CHF, but is one of the manifestations of the disease process.


The ultrastructure of blebs induced in the hamster jejunum by ethanol. Previous light microscopic studies showed that perfusion of the hamster jejunum with 4.8% ethanol (ethanol period) in vivo produced fluid-filled subepithelial blisters (blebs) on the villi. These blebs had virtually disappeared within 45 min after the discontinuation of the ethanol perfusion (recovery period). The present study examined these ethanol-induced changes in the jejunum by scanning (SEM) and transmission (TEM) electron microscopy. TEM revealed that ethanol did not damage epithelial cells in areas where blebs were not present. In these areas the basal surfaces of the epithelial cells were attached to the basal lamina, and the lateral intercellular spaces (LIS) were open. In the areas where blebs formed, the stretched epithelial cells which covered the blebs lost their basal anchoring and so could not maintain their LIS. Both SEM and TEM indicate that there was a decrease in the quantity of glycocalyx at the surfaces of cells which covered blebs. Our findings indicate that ethanol does not directly damage epithelial cells but that the cellular damage is due to detachment over the blebs. It is likely that ethanol at first traverses the epithelial layer and then produces stasis in the villus core. Continued fluid transport by the epithelial layer in the presence of statis results in accumulation of the fluid and widely dilated LIS. With subsequent enlargement of the LIS the bases of the cells detach from the basal lamina and blebs are formed.


Altered effect of insulin and catecholamines in brown adipose tissue of cold-acclimated rats. Data are presented indicating that in brown adipose tissue (BAT) of cold-acclimated (CA), but not cold-exposed (CE) rats, there was an alteration in the relative response to catecholamines and insulin as evidenced by increased binding of alprenolol and decreased binding of insulin to plasma membrane enriched fractions. In addition, the stimulatory effect of insulin on glucose incorporation into glycogen and its inhibitory action on adenylate cyclase activity were both blunted in the CA tissues. It is proposed that shifts in the capacity of BAT to respond to catecholamines and insulin may be involved in the mechanism of cold acclimation.


Dopamine modulation of gill reflex behavior in Aplysia. We have studied the effects of dopamine on the gill withdrawal reflex evoked by tactile siphon stimulation in the margine mollusc Aplysia. Physiological concentrations of dopamine (diluted in seawater) were perfused through the gill during siphon stimulation series. The amplitude of the reflex was potentiated by dopamine and habituation of the reflex was prevented. This occurred with no change in the activity evoked in central motor neurons. These results lead us to conclude that the dopaminergic motor neuron L9 is modulating habituation in the periphery and that the central nervous system facilitatory control of the peripheral nervous system may act via a dopaminergic pathway.


Renal trauma in children.

Renal trauma in children. In children the kidney is the organ most frequently injured as a result of blunt abdominal trauma. Controversy exists as to the management of injuries of intermediate severity. At the Hôpital Sainte Justine in Montreal, from 1970 to 1976, 71 children aged 2 to 15 years were admitted because of renal trauma caused by blunt abdominal injury. Class I or II lesions (minor injuries) were found in 69% and class III or IV lesions (major or critical injuries) in 31%. Several severe injuries were treated conservatively. There was one death due to multiple associated injuries. Ten patients underwent surgery; nephrectomy was performed in one and heminephrectomy in two patients. One patient with an avulsion injury to the pedicle survived after "bench surgery" and reimplantation of the bruised kidney. Follow-up was obtained in 57 patients; 2 showed posttraumatic scarring. None required subsequent nephrectomy for hypertension or infection.


Computerized axial tomography and fine-needle biopsy in surgery of the pancreas. Notable advances have been made in the investigation of pancreatic disorders. However, many of the diagnostic tests required are still of an invasive nature and are attended by difficulty and risk. The authors have found that the noninvasive method of axial tomography is highly reliable for the evaluation of pancreatic lesions, especially in cases in which a pancreatic mass is present or the duct of Wirsung is dilated. This procedure can also be helpful in the follow-up of patients who have suffered from acute or chronic pancreatitis. The same diagnostic problem is present at operation. To obtain a quick and reliable diagnosis of pancreatic lesions, the authors performed fineneedle aspiration biopsies followed by immediate staining and examination of the specimen. Among 43 patients an accurate diagnosis was obtained in 41 instances and no complication was ascribed to this diagnostic procedure.


Periampullary tumours: advances in diagnosis and surgical treatment. Forty-five carcinomas of the region of the ampulla of Vater were resected at the Toronto General Hospital during a 16-year period. In 26 the presenting symptom was pain and in 32 it was jaundice. The most useful means of investigation was endoscopic retrograde cholangiopancreatography. Angiography was of value in determining resectability prior to operation, and percutaneous aspiration biopsy allowed a preoperative diagnosis in the case of large pancreatic tumours. In 39 patients who had a Whipple procedure the operative mortality was 8%. Total pancreatectomy performed in two patients and local excision of ampullary carcinoma in four patients were attended by no operative deaths. Long-term survival was best in patients with ampullary carcinomas and worst in those with pancreatic cancer.


Preinfarction diagnosis of acute mesenteric ischemia by simple measurement of inorganic phosphate in body fluids. Acute mesenteric ischemia is extremely difficult to diagnose because peritoneal signs are absent until the bowel becomes necrotic and irretrievably damaged. So far the only reliable diagnostic procedure has been mesenteric angiography. The present study verifies that significant elevations of serum inorganic phosphate concentrations occur in dogs after mesenteric occlusion; the authors' initial clinical studies in humans support these experimental findings. Detailed analysis of body fluid and soft tissue phosphate content shows that the high phosphate load originates in the sloughing intestinal mucosa; if this phosphate escapes filtration by the liver it enters the systemic circulation. Simple measurement of the inorganic phosphate concentrations of the serum and peritoneal fluid may lead to earlier diagnosis of acute intestinal ischemia and a successful revascularization procedure to prevent its progression to infarction.


Digital replantation: a functional assessment. With the advent of microvascular anastomosis it has become technically and practically feasible to replant amputated digits. In the last 5 years the achievements in this field of surgery have shown considerable improvement. Success is initially measured in terms of survival of the amputated digits but finally in terms of function. This paper presents a functional assessment of the authors' 33 digital replantations in 20 patients. In all of these patients the period of follow-up has been longer than 2 1/2 years. An 85% survival rate for the replanted digits was obtained. Of the 17 patients who have surviving digits function in 15 was judged to be significantly improved by the procedure. These results have permitted the development of guidelines for selecting patients who will benefit most from the procedure.


Multiple primary cancers involving the lung. Of 150 consecutive patients with resectable bronchogenic carcinoma, 11 were found to have multiple primary tumours of the respiratory tract. Five patients had more than one primary tumour of the lung and six had previously received treatment for carcinoma of the larynx. In the same group of 150 patients, 14 had one or more cancers involving other organs. The appearance of a new solitary lung lesion in a patient with another cancer demands special attention to determine the exact diagnosis and to decide upon the best method of treatment. Physicians should be aware that such a lung lesion may represent a new primary lung cancer rather than a metastasis. The criteria are defined for the pathological definition of two separate primary tumours in these cases.


Iatrogenic femoral nerve injuries.

Iatrogenic femoral nerve injuries. Eighteen cases of iatrogenic femoral nerve injury are described. In two patients the damage was incurred as a result of an intra-abdominal operation. In three others the nerve was injured at the level of the inguinal ligament. In the majority femoral nerve palsy followed surgery to the hip joint and was attributable to a lesion-in-continuity. Only one of the patients in the series made a full recovery, but because only severe cases were included these disappointing results by no means represent the expected outcome. To avoid this serious and distressing complication of surgery, the surgeon must be familiar with the anatomic features of the region and must take care to avoid compression of the femoral nerve by retractors and its overstretching during operations on the the hip joint.


Zollinger-Ellison syndrome associated with parathyroid adenomas and ectopic gastric tissue in the lower esophageal mucosa. A rare case of the Zollinger-Ellison syndrome associated with hyperparathyroidism and ectopic gastric tissue in the lower esophageal mucosa is reported. Preoperatively the patient, a 53-year-old woman, had hyperchlorhydria and her fasting serum gastrin concentration was mildly elevated. There was a considerable increase in the gastric acid output and concentration of serum calcium after secretin infusion. At operation the patient had a gastric ulcer 10 cm in diameter, an islet cell tumour of the pancreas 14 cm in diameter, and ectopic gastric mucosa in the distal third of the esophagus. A gastrectomy was perfomed, the pancreatic tumour excised and part of the distal esophagus removed through a left thoracotomy. Four months after the operation the gastrin concentration had returned to low normal, but the serum calcium values remained high. One month later two parathyroid adenomas were removed which effectively cured the hypercalcemia.


Pneumothorax complicating a fracture of the clavicle. Fractures of the clavicle, while common, are associated with few serious complications. The authors report the case of a 29-year-old man with a simple fracture of the middle third of the clavicle that was associated with a 30% pneumothorax. The force and mechanism of the injury, severe pleuritic pain and reduced breath sounds suggested the diagnosis which was confirmed roentgenographically. The possibility of pneumothorax must be considered in any patient with a fracture of the clavicle, especially in the unconscious patient who has sustained multiple injuries.


Restoration of gastrointestinal continuity (Pauchet's operation). Restoration of continuity of the gastrointestinal tract following resection has always presented a challenge to the general abdominal surgeon. Restoration of the left colon has been especially dangerous. In the early days the mortality approached 90% due mainly to breakdown of the anastomosis. Recently, with a better understanding of the blood supply to the colon and more careful preparation of the colon, the mortality and morbidity have been reduced. In a small group of cases, in which previous surgery has interfered with the blood supply to the colon or a secondary pathologic condition exists, continuity cannot be restored by end-to-end anastomosis. In this group the interposition of the ileum between the transverse colon proximally and the rectum distally has resulted in functional continuity of the colon with no adverse metabolic effects.


Recurrent gastrointestinal bleeding due to smooth muscle tumours of the small intestine. The cause of recurrent gastrointestinal hemorrhage can be very difficult to identify. When the source of bleeding is beyond the ligament of Treitz the bleeding is often from a smooth muscle tumour of the small intestine. A review of the records of the Royal Victoria Hospital, Montreal, for the past 25 years discovered 14 instances of such tumours, in more than half of which the presenting symptom was recurrent gastrointestinal hemorrhage of obscure origin. Barium contrast roentgenography, endoscopy and radionuclide scanning have not been found helpful in diagnosis. Selective angiography followed by laparotomy is the best mode of management with respect to both investigation and treatment. The data obtained from our series of cases are compared with those of other series reported in the literature.


Chain-saw facial injuries.

Chain-saw facial injuries. Accidents caused by kickback from chain saws produce facial injuries with consistent features. These features include oblique, destructive, ragged lacerations of the left side of the face. Although eyelid damage may be severe, damage to the globe itself is minimal. An analysis of 10 such accidents revealed this consistent pattern. Of this group, eight injuries were left-sided and six involved mainly the eyelid and adjacent structures. Only one patient was left with permanent damage to the globe and with slightly impaired (20/60) vision. The upper lid was always more severely damaged than the lower. The author discusses the merits and disadvantages of protective devices for both operator and machine.


Experience with polytetrafluoroethylene grafts in patients on long-term hemodialysis. Expanded polytetrafluoroethylene (PTFE) is a new material now being used to create subcutaneous arteriovenous anastomoses for vascular access in hemodialysis. The authors have been impressed with the versatility of grafts made from this material and, where failure occurs, the ease with which surgical revision can be carried out. Two cases are described to illustrate the adaptability of this material to reconstruction. The authors' initial impression based on 22 months' experience is that PTFE grafts have appreciably modified the management with respect to vascular access, of many patients on long-term hemodialysis.


Anterior intranasal carcinoma.

Anterior intranasal carcinoma. In a series of nine consecutive cases of anterior intranasal carcinoma seen between 1965 and 1975, a single treatment failed to control the disease in four. This failure rate is much higher than that reported for squamous cell carcinomas of the skin in general and appears to indicate that tumours at this site require aggressive therapy.


Transpleural end-to-end repair of esophageal atresia and tracheoesophageal fistula. Successful surgery for esophageal atresia and tracheoesophageal fistula is a relatively recent development, and progress has been rapid over the past 10 years. Because the surgical technique is still controversial, the authors reviewed their experience in treating 38 infants with the condition. Transpleural end-to-end repair was carried out in all cases. In 21 cases a two-layer repair was done and in 17 a one-layer repair. After 10 days, if no anastomotic leak was detected radiologically, esophagoscopy and dilatation at the anastomotic site were performed; dilatation was carried out routinely once or twice thereafter when necessary. The most common complication was stricture of the anastomosis (eight cases), which required more than the three dilatations routinely performed. Other complications were recurrent fistula (two patients) and anastomotic leak (two patients). Six of the 38 infants died; all had other serious anomalies. The results overall compared favourably with those of other published series. The authors conclude that end-to-end repair using a transpleural approach is a safe and effective method for surgical repair of esophageal atresia and tracheoesophageal fistula. The approach provides excellant exposure so that anastomotic tension can be evaluated, thus allowing improved mobilization of the esophagus. Both factors contribute to a low frequency of anastomotic complications.


Nontraumatic hemobilia: disparate episodes 7 years apart in the same patient. A case is reported of nontraumatic hemobilia, which occurred twice in the same patient. Initially it was due to carcinoma of the gallbladder and 7 years later it was due to a ruptured intrahepatic aneurysm. The management of these two conditions is reviewed. The clinical marker of nontraumatic hemobilia originating in the gallbladder is the hemocholecyst and the treatment is cholecystectomy. Ruptured intrahepatic aneurysm can be diagnosed only by angiography. Cholangiography is indicated to rule out pathologic conditions of the ducts. In the absence of hepatobiliary sepsis selective hepatic artery ligation is the preferred treatment, otherwise hepatic resection is required.


Methylmethacrylate as an adjunct in the internal fixation of pathologic fractures. The authors evaluated methylmethacrylate as an adjunct to internal fixation of 47 pathologic fractures of long bones (10 of the humerus and 37 of the femur) in 43 patients with metastatic disease. In their experience this method proved to be vastly superior to other methods of internal fixation. All patients were relieved of pain and, if able to walk, could do so almost immediately after fixation of the fracture. In the others comfort was enhanced and nursing greatly facilitated. The surgical technique of internal fixation is described in detail. Correct selection of the metal implant, meticulous attention to the biomechanical considerations and restoration of bone continuity by means of methylmethacrylate are most important if a gratifying result is to be obtained.


Opportunities for research in rural practice. The contributions of Denis Burkitt, William Budd, Sir James MacKenzie and Will Pickles, among others, are examples of the research that can be accomplished by busy doctors in a general practice or a rural setting with a minimum of equipment. It is still possible to undertake worthwhile research in rural areas of Canada. This contention is supported by many examples of published work from northern Newfoundland and Labrador. The studies have dealt with conditions that are particularly frequent in each region, including those due to nutritional deficiency, infection, extremes of climate and genetic factors. Epidemiologic studies have compared the occurrence of disease in different geographic regions and in different races. The content of general practice and methods of health care delivery have also been investigated. It is suggested that some of these observations could have been made only in the context of rural medical practice.


Community air pollution in Canada: a review and predictions for the 1980s. The main trends in Canadian air pollution since the national program of surveillance began are reviewed in this paper. In common with the United States, significant improvements in sulfur dioxide and particulate pollution have been recorded in a number of cities after the institution of control measures. However, some areas with a concentration of certain industries still have considerable particulate pollution. Since emission of nitrogen dioxide is increasing in the United States, the consequent photochemical pollution in southern Ontario will probably continue to increase. Nitrogen dioxide concentrations in the air are elevated in some western Canadian cities, presumably because of the presence of plants that burn natural gas to generate electricity and increasing pollution from automobiles. There is increasing concern about community air pollution in cities with large metal-fabricating plants, and community exposure to asbestos fibres is likely to be an important concern in the 1980s.


Planning for psychiatric emergencies.

Planning for psychiatric emergencies. Hospital emergency services have been used increasingly in recent years. This has resulted in questions as to the true nature of patients' complaints and the appropriateness of this type of care. Since the increase in the number of psychiatric emergency patients has paralleled that for patients at other types of emergency clinics a study was conducted at the Clarke Institute of Psychiatry, Toronto, to examine the situation prior to the inception in 1977 of a crisis intervention unit. It was found that most patients had both psychiatric and social difficulties, and it was considered that planning should concentrate on strategies for efficient management of the clinical problems.


Carotidynia: a cause of neck and face pain. Carotidynia is a form of vascular neck are face pain in which the vascular change occurs in the carotid artery in the neck. The disorder is not uncommon, and most patients have a prior history of migraine. They present with pain in the neck and face, and are often thought to have a disorder such as chronic sinusitis or trigeminal neuralgia. Diagnosis can be made from the type and location of the pain and the finding of a tender and swollen carotid artery on the same side. Carotidynia responds to the prophylactic medications used for migraine, often disappearing in weeks or months. In some patients the syndrome may become recurrent or chronic, with a variable response to medication.


Management of 41 persons exposed to a rabid dog: unplanned experience with human diploid vaccine. Thirty-six persons -- veterinarians, technicians and students at a veterinary clinic -- were unwittingly exposed to a rabid dog over a period of 21/2 days. One veterinarian received a penetrating bite, two other individuals were grabbed by the dog but the skin was not penetrated, and many were exposed to saliva or urine or both. In addition, the owner of the dog and his wife and three children, while not bitten, were exposed to saliva. The diagnosis was made post mortem when specimens of the dog's brain were examined by indirect fluorescent antibody testing. All but one of the students had been vaccinated against rabies with hamster kidney vaccine, but eight members of the veterinary college's staff had not been so vaccinated. Treatment started with duck embryo vaccine; if necessary, rabies (human) immune globulin was also given. When one student reacted severely to the first dose of duck embryo vaccine permission was sought to bring a human diploid vaccine into Canada. In five patients the human diploid vaccine was substituted for the duck embryo vaccine because of severe reactions to the latter. Twenty-five staff members and the family of five received both vaccines. Reactions to the human diploid vaccine were minor and transient. Recommendations include the early licensing of the human diploid vaccine in Canada.


Neonatal respiratory distress: potential for prevention. A prospective study was conducted of 100 consecutive admissions to the neonatal intensive care unit of the Hospital for Sick Children, Toronto, of infants with respiratory distress syndrome or transient tachypnea of the newborn. It was found that in 15% of cases the illness was completely preventable, being the result of unintentionally premature termination of pregnancy. Significant intrapartum asphyxia occurred in 44% of the infants in whom respiratory distress syndrome developed. Factors placing the pregnancy at high risk were present antenatally in most cases, and most of the deliveries took place in hospitals without adequate facilities or staff, or both, for the requirements of the infant at and following birth.


Noise-induced hearing loss and blood pressure. From a group of industrial workers who had a noise-induced hearing loss of at least 30 dB at 4000 Hz 62 were randomly selected after stratification. Controls matched for age and duration of employment were also selected. Resting blood pressures were measured and audiometry was repeated. The findings are presented by age group and for the two groups as a whole. No relation between systolic or diastolic blood pressure and hearing loss was found, and equal proportions of each group had blood pressures exceeding 140/90 mm Hg. Persons with greater hearing loss (more than 60 dB at 4000 Hz) did not have significantly higher blood pressures than their matched controls.


Lymphocyte transformation studies in drug hypersensitivity. In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents.Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects.For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test.It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs.


Early diagnosis of ovarian cancer.

Early diagnosis of ovarian cancer. Ovarian cancer is the most common fatal gynecologic malignant disease. Unfortunately 60% to 70% of patients present initially with advanced disease. Progress in the treatment of this condition will be made only if it can be diagnosed early. Pelvic examination is still the best screening test despite attempts to make an early diagnosis with the use of cytology, ultrasonography, and serum determinations for fibrin degradation product; haptoglobin, protein-bound fucose and tumour-associated antigens. The best prospect for a screening test for ovarian cancer probably lies in the field of tumour immunology.


5-Fluorouracil, adriamycin, and mitomycin-C (FAM) chemotherapy for adenocarcinoma of the lung. Twenty-five patients with advanced measurable adenocarcinoma of the lung were treated with combination chemotherapy consisting of 5-fluorouracil, adriamycin, and mitomycin-C (FAM). Objective response (1CR, 8PR) was obtained in 36% of patients. The median duration of response was 7.0 months and the median survival for responders is greater than 8.5 months. Five responders are alive 5.5 to 23.5 months after starting therapy. Three of four patients evidencing stabilization of disease are alive at 10-23 months. Non-responding patients had a median survival of 2.5 months and none lived beyond seven months. Tumor response and survival suggested correlation with initial performance status and limited disease. The FAM regimen was tolerated well, with moderate bone marrow suppression and gastrointestinal symptoms being the only clinically significant toxicities. These results indicate that patients with advanced pulmonary adenocarcinoma can obtain objective tumor regression with FAM chemotherapy.


Complete remission of widely metastatic endometrial stromal sarcoma following combination chemotherapy. A 21-year-old female underwent a hysterectomy with the finding of an endometrial stromal sarcoma (7-9 mitoses/10 HPF) confined to the uterus. However, within 30 months of hysterectomy, metastases occurred in the spinal cord, femur and lungs. Treatment consisted of surgery and irradiation for the spinal cord metastases and ten courses of combination chemotherapy, Adriamycin, vincristine, cyclophosphamide (6 courses) and megestrol acetate (continuous since course 7). This therapy resulted in a complete clinical remission which has been maintained for eight months since completion of chemotherapy. It is suggested that this regimen be employed in patients with this rare and lethal tumor.


Actinomycin-D, levamisole chemoimmunotherapy of refractory malignant melanoma. Sixty adult patients with disseminated melanoma refractory to DTIC or Dacarbazine were given chemoimmunotherapy with intermittent high single dose Actinomycin-D and Levamisole. Actinomycin-D was given at a dose of 1.5-2.0 mg/m2 intravenously every 3 to 4 weeks. Levamisole was given in a dose of 150 mg/day for two consecutive days each week (50 patients) and in a dose of 200 mg every other day (10 patients). Antitumor responses consisted of 2% complete remissions (CR), 2% partial remissions (PR), and 33% disease improvement less than PR or stabilization (S). Comparison of these patients who received Actinomycin-D + Levamisole with those on an immediately preceding study in a similar population where Actinomycin-D was given as a single agent revealed no difference in response rates. Patients who responded to Actinomycin-D + Levamisole (CR + PR + S) survived significantly longer (35 weeks) than nonresponders (12 weeks, p less than 0.01). Survival was not longer (p less than .05) in responding patients (CR + PR + S) receiving Actinomycin-D + Levamisole (35 weeks) compared to those responding to Actinomycin-D alone (18 weeks, p = 0.09). Hematologic toxicity was tolerable with median lowest granulocyte counts of 1.6 x 10(3)/microliter and platelet counts of 134,000/microliter. Other toxic effects were predominantly nausea, vomiting, and mucositis. In those patients who received alternate day Levamisole there was greater gastrointestinal upset as well as fever, rash and central nervous system toxicity which was unacceptable.


Solid tumor models for the assessment of different treatment modalities: VIII. The scheduling of treatment for a chemotherapeutically resistant experimental solid tumor. Single, large doses of adriamycin, cyclophosphamide and 5-fluorouracil (5-FU) have been compared to the same amount of drug given in divided doses daily over a 3 or 5 day period in a solid tumor model which metastasizes to the regional lymph nodes and lungs. No significant increase in life expectancy occurred following adriamycin or cyclophosphamide. However, a significant reduction in life expectancy occurred after 5 fractionated doses of 5-FU but not after the large single dose. The increase in mortality following fractionated doses of 5-FU is attributed to the prolongation of the onset of recovery of bone marrow. Tumor volume reduction following a single dose of each agent was equal to or greater than the fractionated doses. The results of these studies on this chemotherapeutically resistant solid tumor indicate that small daily fractionated doses of adriamycin, cyclophosphamide or 5-FU result in increased morbidity and mortality without therapeutic benefit in tumor control. The time sequence of recovery of the limiting organ of the host (i.e., bone marrow) is similar to the time sequence of recovery of the tumor. Large intermittent single doses of chemotherapeutic agents given following recovery of the host from a previous treatment would be expected to be less toxic to the host and equally effective in control of tumor growth. None of the 3 chemotherapeutic agents was successful in tumor eradication. Previous studies of this series have shown that the utilization of sequential chemotherapy combined with radiotherapy can be successfully used for eradication of another solid tumor which did not metastasize. A similar therapeutic strategy using sequential combined modality therapy should also be effective in the control of the primary H-4-II-E tumor as well as its metastatic dissemination. Information gained from these experimental studies should eventually provide information which should be helpful in the clinical management of chemotherapeutically resistant solid tumors in man.


Malignant myelosclerosis (acute myelofibrosis): report of two cases following cytotoxic chemotherapy. Malignant myelosclerosis or acute myelofibrosis is a rare acute myeloproliferative disorder characterized by pancytopenia, myeloblastosis and marrow fibrosis. We describe two patients who developed malignant myelosclerosis after receiving cytotoxic chemotherapy, one for Hodgkin's disease, and the other for membranous nephritis. In view of the known leukemogenic effect of cytotoxic drugs, we presume that chemotherapy played a role in the pathogenesis of malignant myelosclerosis in these two patients.


Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG. One hundred and five patients with metastatic breast cancer were treated with 5-fluorouracil, Adriamycin, cyclophosphamide and BCG (FAC-BCG). The results were compared to those observed in a group of 44 patients treated with FAC chemotherapy alone. Although the overall response rates were similar (76% for FAC-BCG and 73% for FAC), the duration of remission was of 9 months for FAC and 14 months for FAC-BCG (p = 0.04). Similarly, survival or responding patients treated with FAC-BCG was significantly longer (24 months) than that observed in the chemotherapy alone treated group (15 months). There was no difference in survival or duration on study for non-responders. Response rates were not influenced by dominant site of disease, menopausal status or disease-free interval. The duration of remission and survival, however, were significantly longer for patients with bone and soft tissue involvement than for patients with visceral metastasis. Similarly patients with 1 or 2 metastatic sites survived significantly longer than those with more than 3 organ sites involved (p = 0.02). This chemotherapeutic combination is highly effective in inducing remissions. In addition, nonspecific immunotherapy with BCG appears to prolong duration of remission and survival for responding patients.


Long term follow-up of combination chemotherapy-radiotherapy of stage III Hodgkin's disease: a Cancer and Acute Leukemia Group B study. The Cancer and Acute Leukemia Group B studied the effect of combination chemotherapy-radiotherapy on Stage III Hodgkin's disease. Chemotherapy consisting of 4 weekly doses of vinblastine and one dose of mechlorethamine hydrochloride was followed by no therapy (CT), radiation to involved fields (CTIF) or total nodal radiation (CTTN). Two other treatment arms included total nodal radiation alone (TN) or total nodal radiation followed by chemotherapy (TNCT). Maximum follow-up is ten years. Complete remission percentages were 36 (8/22) for CT, 71 (17/24) for CTIF, 100 (21/21) for CTTN, 86 (19/22) for TNCT and 89 (16/18) for TN. Disease-free survival in patients receiving radiation +/- chemotherapy is 23% (19/73) at 5 years, but even after 9 years relapses were observed in two patients. Forty-one percent of all patients are alive and 32% have survived for five years. Ability to administer adequate therapy was the main determined for response duration and survival. Factors influencing the outcome of the disease include histology, age, splenectomy, initial white blood cell count and performance status, whereas symptomatology, initial absolute lymphocyte count and sex played no role on survival.


Results of radiotherapy in control of stage I and II non-Hodgkin's lymphoma. We retrospectively analyzed 114 patients with non-Hodgkin's lymphoma, clinical stages I and II, classified by the criteria of Rappaport and treated by radiotherapy alone. Of 84 patients classifiable, one-third were nodular and two-thirds diffuse lymphomas. Berkson-Gage actuarial and relapse-free survivals were determined for these two groups and for subgroups stratified by histology, stage, and by presence or absence of extranodal disease. Five year relapse-free and overall survivals were 83% and 100%, respectively, for the nodular group and 37% and 59% for the diffuse group. Extranodal involvement was less frequent in the nodular (19%) than in the diffuse (52%) group, where it was associated with Stage IE disease and increased relapse-free and actuarial survival. Histopathological subtype in the diffuse group (histiocytic versus combined lymphocytic poorly differentiated and mixed lymphocytic-histiocytic) did not influence survival. Extranodal involvement and stage I disease were associated with better survival in the diffuse histiocytic group. Successful radiotherapy for all stages of disease, all histologies, was not correlated with extended versus involved fields, and 89% of the relapses in the entire series were by wide dissemination.


An evaluation of total nodal irradiation as treatment for stage III A Hodgkin's disease. Between April 1969 and December 1974, 37 patients with surgically staged III A Hodgkin's disease were treated with total nodal irradiation (TNI). Their probability of relapse-free survival at 7 years is 51% and overall survival 82% with the majority of patients remaining disease free after retreatment with MOPP (10 of 16). In contrast, 21 stage III B patients treated with TNI and MOPP chemotherapy over the same time period have a relapse-free survival of 74% and overall survival of 91%. Because of superior results in treating stage III B patients with combined modality treatment, we fell that a relapse-free survival of 51% may not justify continuation of TNI as the only modality of treatment for patients with stage III A disease, and we have initiated a trial of combined radiation therapy and MOPP chemotherapy in these patients. The most effective treatment of stage III A Hodgkin's disease, however, remains uncertain and depends both on the ultimate risk of combined modality treatment and the success of retreatment following relapse after radiation.


Radiation management of carcinoma of the cervical stump. In spite of a low incidence of carcinoma of the cervical stump at the present time, the management of this interesting disease deserves special attention because of the success which can be obtained with proper treatment. We have reviewed our cervical stump cases treated at the University of Maryland Hospital, Department of Radiation Therapy, from 1962 to 1973. Of 107 cases treated, only 100 cases were "true cases" of carcinoma of the stump and were eligible for this study. 7 cases were excluded from the study because they were probably coincidental carcinomas and were treated soon after subtotal hysterectomy. The lesions were staged according to the FIGO system. 93 cases (93%) were invasive squamous cell carcinoma, 6 cases (6%) adenocarcinoma and 1 case (1%) transitional cell carcinoma. Of 100 cases with a minimum 5 year follow-up, the absolute 5-year cure rate for various clinical stages is as follows: Stage I 83.3% (20/24); Stage IIA 75.0% (9/12); Stage IIB 62.5% (20/32); Stage IIIA 50% (1/2); Stage IIIB 48% (12/25); Stage IV 20% (1/5). The overall absolute 5-year cure rate for all stages combined is 63% (63/100) compatible with a series reported by M.D. Anderson. A better result in Stage IIIB as compared to several previous reports is thought to be due to extensive and aggressive interstitial radium therapy properly combined with external supervoltage irradiation. Techniques of treatment stage by stage including computerized dosimetry will be discussed along with complications and failures.


Therapy-related leukemia: a panmyelosis. Fifteen patients developed acute nonlymphocytic leukemia (ANLL) 31 to 182 months following chemotherapy and/or radiotherapy for various malignancies and one non-neoplastic disorder. The ANLL was commonly heralded by a brief preleukemic phase consisting of cytopenias and a variety of morphologic abnormalities. At diagnosis of ANLL, all of the patients had a panmyelosis with variation in the predominant abnormal cell line. Neutrophilic and erythroid abnormalities were most striking in 12 of the patients, megakaryocytic abnormalities predominated in 2 and monocytic abnormalities in 1. Pancytopenia, marked anisopoikilocytosis, normoblastemia, large hypogranular platelets, hypogranular neutrophils, pseudo-Pelger-Huet nuclei, low myeloblast counts and basophilia were the most common abnormalities in the blood. Bone marrows were hypercellular with increased myeloblasts and basophils, abnormal neutrophil precursors, occasional monocytoid blasts, dyserythropoiesis with PAS positive erythroblasts, ring sideroblasts and micromegakaryocytes. All of the 7 patients who had bone marrow chromosome studies exhibited major chromosomal abnormalities. Response to anti-leukemic therapy was poor. The morphologic and clinical findings of these 15 patients appear to define a clinical-pathologic entity.


Adjuvant immunotherapy of malignant melanoma. A vaccine made of irradiated Vibrio cholerae neuroaminidase (VCN) treated autochthonous tumor cells plus BCG was utilized in combination with surgery or with chemotherapy for Stage II and Stage III malignant melanoma, respectively. A few patients with Stage I melanoma were treated with surgery and BCG. Most of the studies were carried out on a prospective, randomized protocol. When the results with conventional therapy were compared with the results of conventional therapy plus immunotherapy, no beneficial effects of the immunotherapy were seen. Stratification insured comparability in both immunotherapy and nonimmunotherapy groups. We conclude that VCN treated tumor cells plus BCG, when administered according to the protocol utilized here, offer patients with malignant melanoma no substantial benefit when compared with conventional therapy.


Circulating immune complexes in colon cancer patient sera. Sera from 29 colon cancer patients and 16 elderly normal controls were compared using the Raji radioimmunoassay and the Clq binding assay. By the Raji assay 11 of 29 cancer patients had evidence of circulating complexes, while by the Clq assay only 4 of the 29 patients had complexes. There was no significant difference between the levels of circulating complexes in the patient or control groups. With respect to individual patients the results obtained by the Raji assay did not correlate with those obtained by the Clq binding assay.


Metabolic changes following the intravenous infusion of Corynebacterium parvum in man. The acute changes in concentrations of key blood metabolites and liver function tests were measured following intravenous infusion of Corynebacterium parvum in 9 healthy patients who had recently undergone resection of a colorectal cancer. The following results were obtained: 1) Blood glucose, lactate and ketone body concentrations significantly increased over a 5 hour study period; 2) blood alanine fell during the same period; 3) plasma bilirubin, GOT and urea were significantly elevated 24 hours after C. parvum 4) plasma albumin and cholesterol concentrations were significantly lower 24 hours after C. parvum. These changes are similar to the alterations in hepatic metabolism previously described in clinical bacterial infections, and indicate parenchymal cell damage and reduced synthetic activity. They are potentially important in relation to the treatment of cancer with combined modalities where drug metabolism or excretion may be affected.


Hairy cell leukemia: an autopsy study.

Hairy cell leukemia: an autopsy study. Autopsy material from 5 patients with hairy cell leukemia was examined. In addition to the expected widespread involvement of the hematopoietic system and of the liver, all of the patients had various amounts of pulmonary infiltration by leukemic cells. This infiltration was so severe in one instance that the resulting pulmonary insufficiency was the cause of death. Other areas of hairy cell infiltration included the peripancreatic connective tissue in all cases, kidneys in 3 cases, pericardium in 2 cases, and skin in 1 case. Association of plasma cells with the infiltrating neoplastic cells was prominent. In one patient, foci of large, bizarre cells were found in several lymph nodes and in the pericardium. Whether these cells represent transformation of the hairy cells into a larger, less differentiated cell type, or the emergence of a second hematopoietic neoplasm, is unknown.


Chromosomes and causation of human cancer and leukemia: XXXI. Dq- deletions and their significance in proliferative disorders. Three cases with myeloproliferative disorders associated with Dq- deletions (13q- and 15q-) in their marrow cells are described. In addition, a summary of the experience with 14 cases of Dq- at Leuven, Belgium and the cases in the literature is presented. The findings indicate frequent involvement and susceptibility to deletion of the long arms of chromosomes No. 13 and No. 15 in lympho- and myeloproliferative disorders, thus adding these chromosomes to the list of those involved nonrandomly in human neoplasia.


Nickel sub-sulphide-induced leiomyosarcoma in rabbit white skeletal muscle: a light microscopical and ultrastructural study. Nickel sub-sulphide-induced leiomyosarcomas in rabbit white skeletal muscle were studied by both light and electron microscopy. Two types of tumor cells, small spindle cells and elongated smooth muscle cells, are revealed by light microscopy. Nevertheless, their ultrastructure displays the same general feature. The most differentiated cells have abundant cytoplasmic filaments 7 nm in diameter, kept together in bundles by dense bodies. There also exist many 10 nm filaments and a large number of microtubules. The nuclei have prominent nucleoli with an extensive nucleolonema which form an irregular tridimensional network. Distinct fibrillar nuclear bodies were observed. Sometimes there exist desmosomes or gap junctions. The Golgi apparatus produces coated vesicles with secretory function. In the tumors were generally found the Ni3S2 implantations surrounded by a capsule, the major component of which were collagen fibers, degenerated nuclei and rod-like structures with a transverse periodicity of 15.5 nm. From these observations, several characteristics should be pointed out: 1) Many tumor cells contain large nucleoli and distinct intranuclear inclusions of undetermined nature. 2) The coated vesicles represent a secretory activity of the tumor cells; the coat material is probably used during the formation of cell membranes. Another possible function of coated vesicles could be the sequestering of calcium ions. 3) The rod-like structures in the Ni3S2-including capsule are not of Z-line material. 4) The tumoral stem myoblast in heart and skeletal muscle arise from mesenchymal cells.


Possible role of mumps virus in the etiology of ovarian cancer. Eighty-four ovarian cancer (OCa) patients and 84 controls with nonmalignant conditions matched by age and ethnic origin were interviewed with regard to clinical mumps history and their sera were tested for complement fixation (CF) mumps antibodies. OCa patients differed from the controls in the response to past mumps infection in two respects: 1) They appeared to be more likely to have developed subclinical mumps as evidenced by a lower rate of clinical mumps history in the presence of serological evidence of similar infection rates among those with positive and those with negative clinical mumps history. 2) They tended to present lower persistent mumps CF antibody titers. These results may be interpreted to indicate that an immunological incompetence enables the development of OCa possibly through a direct etiologic role of mumps virus.


Duodenal carcinoid (apudoma) with psammoma bodies: a light and electron microscopic study. An extremely rare case of psammomatous calcification in a nonfunctioning duodenal carcinoid tumor was studied by light and electron microscopy. The psammoma bodies were found most frequently within the lumina of the neoplastic glands. The ultrastructural features of the psammoma bodies were the marginal needle-shaped crystals and a coarse granular matrix in which a few organelles were embedded. The psammoma bodies appeared to be occasionally intracytoplasmic in position, showing no distinct limiting cytoplasmic membrane. Electron probe x-ray microanalysis revealed that the needle-shaped crystals contained calcium. The mechanism by which the psammoma bodies are formed has not been clearly explained. The above findings support the view that the psammoma bodies may occur initially in the cytoplasm of the tumor cells, followed by their release probably in a way of active excretion.


Relation of pancreatic duct hyperplasia to carcinoma. In order to find a relationship between ductal hyperplasia and carcinoma of the pancreas, histological and histochemical examinations were made on pancreatic specimens of 1,174 autopsy patients with special attention to the age incidence of the former. Ductal hyperplasia was divided into 3 types; nonpapillary, papillary, and atypical hyperplasia. All three types of hyperplasia and ductal carcinoma showed a similar tinctorial property in mucous histochemistry. In general, atypical hyperplasia was seen in the pancreas having papillary hyperplasia which was found in the pancreas associated with nonpapillary hyperplasia. All three types of hyperplasia were apparently more frequent in cancerous pancreases than in non-cancerous ones. They were also more common in the head of the pancreas than in the body and tail. Age incidence also suggests a sequential change from nonpapillary hyperplasia through papillary and atypical ones to carcinoma.


Adenoma of parotid gland with sebaceous and oncocytic features. A parotid tumor having sebaceous differentiation and a particular histologic picture previously undescribed is reported. The tumor showed features of an adenolymphoma but almost completely lacked a lymphoid component. Sebaceous differentiation was seen in the epithelium of many cysts. Additionally, groups of oxyphilic cells were scattered throughout the tumor. The literature concerning sebaceous differentiation in normal and tumor bearing parotid glands, as well as that concerning tumors with some sebaceous component, is briefly discussed.


Plasma triiodothyronine concentrations in breast cancer. Plasma triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were measured in 44 early breast cancer patients, 48 with advanced breast cancer, 20 with cancer of the colon, and 56 healthy women of similar age. The plasma T3 concentrations were reduced significantly in both early and advanced breast cancer, but only in those colonic cancer patients with metastatic disease. The mean plasma TSH levels were higher in the breast cancer patients than in the other groups, but the increase was significant statistically only in the advanced disease. There was a negative correlation between plasma TSH and T3 in early breast cancer, but not in advanced breast cancer. All cancer groups had normal plasma T4 levels. It is concluded that a proportion of breast cancer patients are mildly hypothyroid, as judged by elevated plasma TSH and reduced T3 levels. In advanced cancer, other "nonspecific" factors also act to reduce the plasma T3.


Clear cell carcinoma of the endometrium. The clinical data of 22 patients with clear cell adenocarcinoma of the endometrium treated at the University of North Carolina Memorial Hospital are reported. In addition, the data with particular reference to survival, site of recurrence, and treatment are combined with information from two previous reports of clear cell adenocarcinoma of the endometrium to better define survival. It is noted that the patients with clear cell adenocarcinoma of the endometrium were older and had an overall poorer survival than is reported for adenocarcinoma of the endometrium (nonclear cell). Patients with Stage I clear cell carcinoma of the endometrium, however, had a similar five-year survival to Stage I adenocarcinoma of the endometrium. The paper also examines treatment methods and correlates these with site of recurrence as well as survival.


Human chorionic gonadotropin and malignant mesothelioma. A 56-year-old male presented with ascites and gynecomastia. Laparoscopy demonstrated peritoneal tumors which were biopsied. Conventional histology and electron microscopy revealed the tumor to be a malignant mesothelioma. The ascitic fluid and tumor cell lysate, but not serum, contained hCG by specific assay, and the immunoreactive hCG had characteristics similar to purified hCG in filtration on Sephadex G-100. Malignant mesothelioma is a tumor which may be associated with elevated hCG concentrations. Demonstration of hCG in ascitic fluid should suggest the presence of neoplasm.


Evaluation of the office endometrial biopsy in the detection of endometrial carcinoma and atypical hyperplasia. The purpose of this study is to assess the accuracy and limitations of the outpatient endometrial biopsy in detection of endometrial carcinoma and atypical hyperplasia. This was done by reviewing all the endometrial material from the 891 women at this clinic whose first endometrial sample in 1974 was by the biopsy technique. The results of this material were correlated with subsequently available additional uterine samples obtained over a three year period by biopsy, dilatation and curettage, or hysterectomy. The detection rate by biopsy for the 21 cases of endometrial carcinoma proven by hysterectomy was 81%. There was a 5% false negative rate and no false positives. For the 25 cases of atypical hyperplasia proven by hysterectomy, the detection rate by biopsy was 68%. There was lack of hysterectomy confirmation in 33% and 24% false negatives. Insufficient material was obtained initially in 9% of the 891 women. Five percent of this group were found at hysterectomy to have either endometrial carcinoma or atypical hyperplasia. With an understanding of its limitations, the endometrial biopsy, although somewhat less accurate than the D & C, is considered to be a useful diagnostic tool for detection of these lesions.


Axillary lesions in patients with acute leukemia: evaluation of a preventive program. Axillary skin lesions can cause significant morbidity in patients with acute nonlymphocytic leukemia. The incidence in relation to the level of circulating granulocytes and the microbiology of 15 such lesions among 150 patients over a three year period were determined. Lesions occurred predominantly during periods of profound granulocytopenia (0-499 cells/microliter). Gram-negative bacilli were the most common pathogens isolated from these lesions. The initiation of a supervised preventive program for 84 patients over 19 months which includes the regular swabbing of each axilla with povidone-iodine cotton sticks in addition to measures to avoid skin trauma has virtually eliminated inflammatory axillary lesions in this high risk patient population.


Multiple myeloma masquerading as chromophobe adenoma. A 62-year-old woman presenting with intracranial lesion eroding the sella with compression of optic chiasma was found to have plasmacytoma of the pituitary area. At the time of initial surgery, the patient had no biochemical, immunologic or marrow findings of multiple myeloma. The intracranial tumor was interpreted initially as chromophobe adenoma on light microscopy, but the diagnosis of plasmacytoma was established by electron microscopic examination of the tumor. The case illustrates the usefulness of electron microscopy as a diagnostic tool.


Cancer of the nasal cavity and ethmoid/sphenoid sinuses. During the period from October 1964 to September 1975, 32 patients were treated at the University of Florida for a variety of malignant tumors of the nasal cavity and ethmoid/sphenoid sinuses. All were treated with radical irradiation, 6091 to 7972 rad, in 6 to 9 weeks, cobalt-60. Pretreatment work-up revealed evidence of orbital invasion in 7 patients and involvement of the cranial contents, base of skull, or nasopharynx in an additional 15 patients. Local control was achieved in 95% of nasal cavity cases and 71% of ethmoid/sphenoid sinus cases at 2 years or more. The 5-year actuarial survival rate was 59%, and 5-year survival without evidence of disease was 50% (13/26). Patterns of extension in advanced lesions are clues to potential undetected extension in early cases which must be included in the treatment volume. Eye complications were minimal when it was possible to avoid treatment of the entire eye, but developed in all cases requiring treatment of the entire orbit. Acute and chronic complications involving the eye, ear, central nervous system, sinuses, and nose were reviewed and correlated with initial tumor extent, dose, and radiation treatment technique.


Laryngeal mycosis fungoides.

Laryngeal mycosis fungoides. Mycosis fungoides presented as a tumor of the arytenoid cartilage and epiglottis of the larynx of an 80-year-old female. The tumor was initially interpreted as an undifferentiated small cell malignant neoplasm and treated with radiation. Two years later the patient developed widespread cutaneous involvement with mycosis fungoides, including mycosis fungoides bullosum. The mycosis fungoides progressed to death over the next two years. At autopsy widespread visceral involvement was present. The larynx was extensively infiltrated with mycosis fungoides, and the histology was similar to the original laryngeal biopsy. Although mycosis fungoides is generally thought of as a cutaneous disease, it may rarely present in a squamous epithelium-lined organ other than the skin.


Pulmonary neoplasms diagnosed with transthoracic needle biopsy. Results of transthoracic needle biopsy have been evaluated on the basis of fourteen years experience comprising 5300 procedures on 2726 patients. In 90.7% of the cases a diagnosis was established. Of these, 46.4% showed cytological evidence of primary or secondary malignancy. In 2.4% false positives and in 3% false negatives were noted. The most important complication was found to be pneumothorax, which was noted in 27.2%, but these cases did not as a rule call for treatment. Hemoptysis was observed in 2-5%. There was minor local bleeding around the lesion in 11% of the patients but this only required observation. In one case out of 1264 malignancies an implantation metastasis was found. There was a single case of air embolism with spontaneous recovery, but no mortality in this series. In our experience, needle biopsy represents a minor, inexpensive and safe procedure, which--with a simple technique--permits a direct approach to all kinds of localized lung lesion with a high degree of accuracy.


Thin-needle aspiration biopsy: the diagnosis of head and neck tumors revisited. Results of 567 thin-needle aspiration biopsies of head and neck lesions are reviewed. Cases included lymph nodes, salivary glands, thyroid, soft tissue and bone lesions. For the entire series, 17 patients had unsatisfactory aspirations. There were 12 false negative reports and 4 false positive reports, rates of 2.1% and 0.7%, respectively. No radical treatment resulted from false positive diagnoses and no patient delay in treatment occurred because of false negative reports. In the case of benign and malignant tumors, reports were histologically specific in more than 98% of the cases. This technique is simple to perform and saves time and hospital costs. Thin-needle aspiration biopsy can be effectively used in the management and diagnosis of head and neck tumor patients where close cooperation of the clinician and cytopathologist exists.


Adenocarcinoma of the esophagus.

Adenocarcinoma of the esophagus. The relevant literature is reviewed in an attempt to clarify the true frequency of intraesophageal adenocarcinoma and to evaluate the different treatment modalities and survival of this uncommon type of tumor. The incidence of intraesophageal adenocarcinoma in reported clinical series is about 1%, and data from cancer registries show the incidence to be about 2% for upper and the middle thirds, a more reliable figure than that for the lower third in which lesions of cardia, or stomach infiltrating the lower esophagus have been included. The benefits of any particular treatment modality are difficult to evaluate in view of the rarity of this type of tumor, and the treatment results are as poor as those obtained in the treatment of squamous cell carcinoma.


Endometriosis of the urinary bladder in a man with prostatic carcinoma. A case of endometriosis of the urinary bladder in a man is described. The patient had been treated with estrogen for several years following radical prostatectomy and orchiectomy for prostatic carcinoma. The only other reported case of endometriosis in a male presented in a strikingly similar manner. Pathogenic speculations are briefly presented.


Written informed consent in patients with breast cancer. One hundred breast cancer patients, 35 adjuvant and 65 advanced, were interviewed 0-24 months after the start of chemotherapy to assess their knowledge and perceptions of the purposes, risks and benefits of treatment. Prior to therapy, all had been given verbal explanations and had signed informed consent forms explicitly detailing drugs, objectives and possible adverse effects of therapy. Seventeen percent of adjuvant and 29% of advanced patients were unable to name any of their drugs. While most patients recognized distressing side effects such as nausea and hair loss, less than 50% were aware of the potentially lethal complications of infection and bleeding. While the purpose of adjuvant therapy was cure, only 29% of the adjuvant patients were aware of this. In contrast, 35% of the advanced patients incorrectly stated that they were told their therapy was potentially curative. Explanations given by a nurse in addition to a physician were better understood than those given by a physician alone. We conclude that, in spite of intensive efforts at improving informed consent procedures, current results are unsatisfactory.


Extrapyramidal tract syndrome following intensive MOPP therapy for stage IV-B Hodgkin's disease in childhood. An extrapyramidal tract syndrome is reported in an 11-year-old boy following treatment of Hodgkin's disease. Results of investigations and the possible pathophysiology of this disorder are discussed.


Pulmonary toxicity of bischloronitrosourea: report of a case with transient response to corticosteroid therapy. A case of interstitial pulmonary fibrosis secondary to bischloronitrosourea (BCNU) in a 49-year-old man with carcinoma of the pancreas is reported. The diagnosis was suggested by deteriorating oxygenation, restrictive changes on pulmonary function studies, and increased interstitial markings radiographically in the lower lung fields. Transbronchial biopsy excluded infectious etiologies and confirmed a bland nonspecific interstitial pulmonary fibrosis of recent origin. The patient responded dramatically to high dose corticosteroids, but relapsed when the corticosteroids were decreased. We believe there is now convincing evidence that prolonged use of BCNU can cause potentially fatal interstitial pulmonary fibrosis. Patients should be followed with serial chest radiographs and pulmonary function studies. If diagnosed early, this process may respond to high dose corticosteroid therapy.


Nodular non-Hodgkin's lymphoma (NHL): factors influencing prognosis and indications for aggressive treatment. In this study we have analyzed a group of 86 consecutive previously untreated patients with nodular lymphoma in order to determine those factors which adversely effect survival. Sixty-two percent of these patients are still living; 23 patients for greater than 36 months. In contrast, 38% have died; 28% of them within 24 months of diagnosis. Striking correlations with short survival were seen with histiocytic cell type, Ann Arbor B symptoms and advanced age. Survival also declined with advanced stage but was A or B symptom dependent. The group was further subdivided into those with exclusively nodular and those with mixed nodular and diffuse histology in order to determine whether the presence of a diffuse component had a negative influence. No significant differences were found in survival patterns between these 2 groups. Our results clearly define a subgroup of nodular lymphoma patients with a poor prognosis which is likely to benefit most from aggressive treatment. The remaining patients are surviving for longer periods of time (albeit many not disease free) and the appropriate treatment for this group remains controversial.


Malignant fibrosarcomatous mesothelioma and benign pleural fibroma (localized fibrous mesothelioma) in tissue culture: a comparison of the in vitro pattern of growth in relation to the cell of origin. Two cases of fibrous mesothelioma are presented. The first is a malignant tumor containing bundles of spindle-shaped cells with a dense reticulin network and nests of epithelial-like cells. The second is a benign tumor made up of spindle-shaped cells arranged in bundles with abundant reticulin and collagen fibers. Tissue culture in the first case revealed plagues similar to those formed by epithelial tumors. The second case had a fibroblastic pattern with single isolated spindle-shaped cells. These findings confirmed the mesothelial nature of fibrosarcomatous mesothelioma and supported the view that the so-called localized fibrous mesotheliomas could be fibroblastic neoplasms derived from the submesothelial connective tissue.


Alveolar soft part sarcoma: a report of two cases with some histochemical and ultrastructural observations. In a survey of all malignant soft tissue tumors in the extremities and limb girdles in Finland between 1960 and 1969, only one alveolar soft part sarcoma was found among 246 tumors (0.4%). Another alveolar soft part sarcoma, diagnosed in 1976, was more thoroughly studied. There was evidence that the characteristic crystals of alveolar soft part sarcoma are formed from the dense granules. Both were PASM-positive at ultrastructural level. No monoamines were detected in the cells by formaldehyde-induced fluorescence. This is a further fact to nullify the theory of the paraganglionic origin of alveolar soft part sarcoma, but the question of the histogenesis of the tumor still remains open.


A nonfunctioning paraganglioma of vagus nerve: an ultrastructural study. The clinical, histological, and ultrastructural aspects of a cervical paraganglioma of the vagus nerve, in a 66-year-old white man, have been discussed in detail. Ultrastructurally, the tumor chief cells contained characteristic membrane-bound and dense-cored neurosecretory granules which ranged in size from 85 millimicron to 190 millimicron. Unlike earlier ultrastructural reports, the present study showed the presence of sustentacular or supporting cells. These cells were smaller, darker, polymorphic, and were commonly located at the periphery of a single or group of chief cells. Furthermore, unlike earlier reports on vagal paragangliomas, nonmyelinated nerve fibers and an occasional axon were identified in the present fine structure study.


Latent thyroid carcinoma at autopsy: a study from Oporto, Portugal. Thirty-nine (6.5%) latent thyroid carcinomas were found in 600 thyroid glands removed at autopsy in Oporto Medical School Laboratory of Pathology. The prevalence of latent thyroid carcinomas was significantly higher in women (sex ratio 4.3:1) and in elderly people (p less than 0.005) and appeared to be independent from the existence of another malignant neoplasm. The mean thyroid weight and the concurrent thyroid pathology of patients with thyroid carcinomas were not significantly different from those of patients without them. The study of cervical lymph nodes in the first 400 autopsies did not show any significant difference concerning histologic pattern, number of germinal centers and sinus histiocytosis between patients with thyroid carcinomas and those without them. Further investigation is required to evaluate the role of host factors on the peculiar characteristics of latent thyroid carcinomas.


The cell kinetics of human mammary cancers. The cellular kinetics of human mammary tumors were studied by in vitro methods. These techniques include single 3HTdR labeling to measure the 3HTdR LI, double labeling with 3HTdR and 14CTdR to measure DNA synthesis time, and an estimation of the growth fraction by the PDP index. Calculations of the potential doubling time and cell cycle time were made from these measurements. The 3HTdR LI of primary malignant tumors was greater than that of benign tumors, but only half that of metastatic lesions. There was considerable heterogeneity in the 3HTdR LI of primary tumors, but the DNA synthesis times were relatively invariant. Estimation of the growth fraction by the PDP index also revealed extensive heterogeneity, but the primary tumors were not different from metastases. There appear to be subsets of tumors with high and low proliferative values that correlate with some clinical parameters, such as age and nodal positivity. This material provides a data base for stratification of patients for future protocols and the use of cell kinetics in treatment programs.


Mucoepidermoid carcinoma of the bronchus: an electron microscopic study of the low grade and the high grade variants. Two cases of mucoepidermoid carcinoma of the bronchus--one a low grade tumor and the other a high grade tumor--are presented with findings by light and electron microscopy. This represents the first report of the ultrastructure of mucoepidermoid carcinoma of the bronchus and demonstrates the ultrastructural similarities between the low grade exophytic tumor confined to the bronchus and the high grade infiltrating tumor with lymph node and pulmonary metastases. The ultrastructural features are similar to those described for mucoepidermoid carcinoma of the salivary gland and are consistent with the proposed origin of the tumor from the submucosal bronchial gland duct. These two cases and a review of previously reported cases indicate that, analogous to mucoepidermoid carcinoma of the salivary glands, mucoepidermoid carcinoma of the bronchus may occur as either a low grade or high grade variant which can be identified on the basis of growth characteristics and histologic features.


Ploidy and proliferation in human bladder tumors as measured by flow-cytofluorometric DNA-analysis and its relations to histopathology and cytology. Biopsies from bladder tumors of 41 patients were investigated by flow-cytofluorometric DNA analysis and compared with exfoliated cells. The degrees of ploidy and proliferation were determined. Good agreement was found between the degrees of ploidy and proliferation in the biopsies and the exfoliated cell material. Tumors Grade I-II were either euploid or aneuploid. All Grade III tumors were aneuploid. The S-phase fractions were about 6% in the diploid tumors and 17% with large variations in the aneuploid tumors. The histological grading was well correlated to the number of S-phase cells and the occurrence of aneuploidy. When the Grade II tumors were divided into two groups having lesser and more pronounced atypia, the two groups differed significantly with regard to their degrees of proliferation. In addition to aneuploidy as an important criterium for malignancy, the degree of proliferation appears to be of major biological significance.


Idiopathic myelofibrosis without splenomegaly. The patient described has had idiopathic myelofibrosis for 8 years. At the time of presentation, 12% of the circulating white cells were myeloblasts. In the past two years, the white blood count has been as high as 18,000/mm3 with 50% myeloblasts. Of significance is the absence of splenomegaly over the eight year period of observation. The rarity of the absence of significant splenomegaly and the presence of large numbers of circulating myeloblasts in idiopathic myelofibrosis are reviewed.


Glycoproteins and human cancer. 1. Circulating levels in cancer serum. Total protein and sialic acid levels were determined in the supernatant of serum treated with perchloric acid. Patients with either localized or advanced metastatic malignancy have significantly elevated mean serum values. The highest levels occur in patients with lung, GI, GYN cancer, lymphoma and malignant melanoma. Patients with leukemia and multiple myeloma have slightly elevated values, but they were not significantly different from normal. Patients following curative surgery have normal values while patients in clinical remission following chemotherapy have elevated mean serum protein and NANA levels. Elevated values also occur in patients with benign tumors and 12% of patients with nonmalignant disease. Tumor cells appear to shed macromolecules which contribute to the observed elevation of serum protein and sialic acid levels.


Hairy cell leukemia and sarcoid.

Hairy cell leukemia and sarcoid. A 45-year-old female simultaneously developed both hairy cell leukemia and acute sarcoid. A defect in suppressor T lymphocytes which allowed an unrestrained B-cell proliferation manifested as both hairy cell leukemia and sarcoid is proposed.


Screening for breast atypias using exfoliative cytology. A sample of 1744 self-selected, mostly asymptomatic women was used to evaluate exfoliative cytology of nipple secretions as a screening technique for breast atypias. Results indicated: 1) overall frequency of breast fluid recovery was 49%, and related to age, phase of reproductive life, parity, history of lactation and birth control pill use at the time of sampling. 2) Frequency of satisfactory smears was 36% of breast fluid specimens, and related to subject's phase of reproductive life. 3) 2.8% of all satisfactory smears exhibited atypical cells. Biopsy of 4 subjects with atypical smears indicated 3 with nonmalignant epithelial atypias and 1 with early ductal carcinoma. Follow-up of women who did not have atypical smears indicated 12/1092 (1.1%) with nonmalignant epithelial atypias and none with carcinoma. 4) The number of cases of malignant (1) and nonmalignant (7) breast disease detected was close to the expected number in the population sampled (1.98 and 7.25, respectively).


Pure and mixed Brenner tumors of the ovary: clinicopathologic and histogenetic observations. Fifty-six Brenner tumors of 51 patients were analyzed. The incidence of bilaterality was 9.8%. Most tumors were smaller than 2 cm, and constituted incidental finding. Most of the patients were 30-49 years old (mean 49.7, main 44). A high incidence of associated malignant neoplasms was noticed among the patients with Brenner tumor but was considered coincidental. No evidence of hormone secretion by the tumor was found. Out of 31 tumors, 27 occupied the cortex. Urothelial metaplasia of the ovarian surface epithelium was demonstrated in one case, and continuation of the Brenner column with the surface of ovary in another. There were 12 cases of mixed Brenner tumor in this series (21.1%). The most frequent associated constituents of the mixed Brenner tumors are mucinous cystadenomas. These tumors represent a single mixed neoplasm originating in a multipotential celomic cell which proliferates and differentiates into several mullerian forms. The histogenesis of medullary and hilar Brenner tumors can be explained on the basis of celomic metaplasia. Uncertainty persists in explaining the histogenesis of Brenner tumors mixed with mature cystic teratoma.


Adenomatous lesions of the large bowel: an autopsy survey. A comprehensive autopsy survey of the large bowel showed that adenomas were very common lesions occurring in about one-half of the 518 cases studied. The great majority were small adenomatous polyps (tubular adenomas), 86.7% measuring less than 10 mm in diameter. Adenomas with a more complex tubulovillous pattern were larger with a mean diameter of 19.0 mm. There was no apparent incresae in mean size of adenomas with age. Nineteen clinically unsuspected cancers were discovered. Fourteen (8 in situ and 6 invasive) cancers had areas of residual benign adenoma. Five invasive cancers had no residual benign component. No in situ carcinomas or small (less than 10 mm) invasive cancers not containing residual adenoma were found. The results suggest that, although adenomas of the large bowel are very common, the vast majority are simple adenomatous polyps which do not undergo progressive growth and malignant change. Conversely, it appears that cancers may arise from benign adenomas which have the characteristics of large size and a more complex villous architecture.


Spinal cord involvement in chronic lymphocytic leukemia. A patient with typical chronic lymphocytic leukemia (CLL) who developed central nervous system involvement is presented. The CLL was of B-cell origin and the neurological involvement consisted of perivascular infiltration in the spinal cord.


Hodgkin's disease, stages I and II occurring below the diaphragm. Between February 12, 1968 and August 17, 1977, 473 consecutive patients with Hodgkin's disease were entered into protocol studies at Stanford University Medical Center (SUMC). 242 of these 473 patients were pathological Stage I or II; 223 patients had disease above the diaphragm and 19 patients had disease confined below the diaphragm. When compared to patients with disease above the diaphragm, patients with Hodgkin's disease below the diaphragm were more frequently male (74% vs. 53%, p = 0.14), were on the average older (40 vs. 27, p less than .005) and more frequently had the histologic subtype of mixed cellularity (32% vs. 12%, p = .04). There was no difference in either survival or relapse-free survival between patients with Hodgkin's disease above the diaphragm and patients with disease below the diaphragm receiving similar treatment plans.


Carcinoma arising in eccrine spiradenoma. Two patients had carcinoma arising in eccrine spiradenoma. In both patients, recent changes in a long-standing cutaneous nodule prompted excision, and microscopic examination disclosed carcinoma intimately associated with and apparently arising from typical benign eccrine spiradenoma. One patient had lymph node metastasis.