Epiglottitis: incidence of extraepiglottic infection: report of 72 cases and review of the literature. A review of 72 cases of epiglottitis seen at the Children's Hospital of Denver was undertaken to determine the incidence of extraepiglottic and septic foci in this disease. A parallel review of the literature was also undertaken. The clinical, bacteriologic, laboratory, and radiologic findings of this patient population are described. A 25% incidence of both pneumonia and cervical lymphadenitis was found to be associated with this illness. Exudative tonsillitis and otitis media were the only other complications, although they were infrequently noted. No cases of septic arthritis or meningitis were encountered, although 50% of these patients were recognized as bacteremic. A low incidence of septic complications (eight cases of meningitis and one case of periarticular abscess) is noted in a review of the literature. Recommendations for antibiotic management and definition of the population at risk for septic complications are given.


Cleavage map of bacteriophage phiX174 RF DNA by restriction enzymes. phiX RF DNA was cleaved by restriction enzymes from Haemophilus influenzae Rf (Hinf I) and Haemophilus haemolyticus (Hha. I). Twenty one fragments of approximately 25 to 730 base pairs were produced by Hinf I and seventeen fragments of approximately 40 to 1560 base pairs by Hha I. The order of these fragments has been established by digestion on Haemophilus awgyptius (Hae III) and Arthrobacter luteus (Alu I) endonuclease fragments of phiX RF with Hinf I and Hha1. By this method of reciprocal digestion a detailed cleavage map of phiX RF DNA was constructed, which includes also the previously determined Hind II, Hae III and Alu I cleavage maps of phiX 174 RF DNA (1, 2). Moreover, 28 conditional lethal mutants of bacteriophage phiX174 were placed in this map using the genetic fragment assay (3).


[Risks attendant on the use of electrical equipment in anaesthesia and intensive care units]. The physical principles of electricity and types of electrical injuries are reviewed. The extent of such injuries depends on the strength of the current: ventricular fibrillations can be induced by a current of 10mA, and even of 10 muA if the current passes directly through the heart. The extent of electrothermal injuries depends on the duration of the current flow and the contact area. Indirect electrical injuries may arise from interferance with cardiac pacemakers or monitoring equipment. Risks attendant on the use of even the "safest" electrical apparatus are discussed, with special reference to the risks arising from interaction between, e.g., high frequency diathermy and monitoring equipment or domestic appliances (beside lamp, razor) and monitoring or electrical therapeutic equipment. A number of safety measures to minimize the risk of electrical injuries are discussed.


Induction of splenic granulopoiesis in vitro. Murine spleen cells were cultured in vitro to study the induction of committed granulopoietic stem cell (CFU-C) proliferation and maturation. Marbrook-type diffusion cultures were established with and without the addition of colony-stimulating activity (CSA) and harvested at intervals up to 14 days for viable and differential cell counts, [3H]TdR autoradiography, and quantitation of CFU-C by the agar plate method. Without CSA there was poor cell viability and little proliferative capacity. In CSA-stimulated cultures there was a prominent rise in viable cell counts and [3H]TdR labeling indices rose from a mean of 2% at 0 time to 47% after 5 days in vitro. CFU-C increased by 70-fold in these cultures. Peak numbers of CFU-C, immature cells, and [3H]TdR-labeled cells occurred at about 7 days. Thereafter, mature granulocytes and macrophages predominated in culture. Because the liquid spleen cell culture system begins in a resting state and undergoes a wave of proliferative activity in response to CSA, it can provide a useful model system for studying phenomena associated with stem cell activation and differentiation in vitro.


Human lymphocyte subpopulations: the effect of pregnancy. Peripheral blood lymphocytes from pregnant and nonpregnant females were studied for the presence of the following surface receptors: (i) Receptor for heat-aggregated human IgG (AggIgG); (ii) Receptor(s) for complement components; (iii) Receptor for sheep red blood cells (SRBC). Absolute numbers of lymphocytes with receptors for complement and those with receptors for SRBC were present in equal numbers in both groups. However, in the pregnant females there was a significantly lower number of lymphocytes with receptors for AggIgG. It is hypothesized that some of the immunological changes which occur during pregnancy may be mediated partly through changes in the total numbers of certain lymphocyte subpopulations.


Corticotropin releasing factor (CRF) activity in rat plasma. The ACTH-releasing activity of hypothalamic extract and rat plasma was examined with the dispersed rat pituitary cell technique of Swallow and Sayer (8). Although both plasma and serum caused ACTH release which was dose-related, stress did not enhance the ACTH releasing activity. Furthermore, separation studies of plasma using ultrafiltration and gel separation suggest that the CRF activity in plasma is associated with molecules of a molecular weight greater than 15,000.


Central monoamine deficiency in depressions: causative of secondary phenomenon? There are indications for a functional deficiency of 5-HT and DA in certain kinds of depression. The question arises if these biochemical disturbances are primary or secondary, whether they contribute to the pathogenesis of the depression or whether they result from it. From research with MA precursors we drew the tentative conclusion that they are presumabely primary and interrelated with the depression in a causal and/or predisposing way.


The effects of intramyometrial injection of prostaglandin F2alpha on severe post-partum hemorrhage. Effectiveness of prostaglandin F2alpha (PGF2alpha) in controlling postpartum uterine hemorrhage was evaluated with the following results. (1) Systemic administration, whether by continuous i.v. infusion or by gluteal i.m. injection, was not a completely adequate method for hemostasis. (2) Local administration by directly injecting into the uterine musculature, whether transabdominally or transvaginally, resulted in a dramatic reduction of the rate of bleeding. Routine clinical application of the direct intramyometrial injection of PGF2alpha for severe post-partum hemorrhage is recommended in view of its easy performance, excellent hemostatic effect, minimal side effects and good prognosis.


[Electrical stimulation therapy and its effects on the general activity of motor impaired cerebral palsied children; a comparative study of the Bobath physiotherapy and its combination with the Hufschmidt electrical stimulation therapy (author's transl)]. The purpose of this study was to answer the following questions: (1) Is it more effective to treat spastic cerebral palsy with the Hufschmidt electrical stimulation therapy combined with the Bobath neuro-development treatment or only with the Bobath therapy? (2) Can a general increase in activity be obtained by the electrotherapeutic muscle stimulation? A test group (combined Hufschmidt/Bobath therapy) and a control group (Bobath), both consisting of 10 subjects, were observed for four months. The duration of observation was divided into two four months treatment periods with a rest interval of two months in between. At the start of therapeutic measures, motor activity and psychic condition were tested with corresponding motormetric and psychodiagnostic techniques; three check-up examinations were carried out at the end of the first, and at the beginning and end of the second period of treatment. The motor-metric control examination showed that at the end of the first period the test group had achieved by far the better results, but at the end of the second therapeutic period, both groups were equally successful. The combined electrophysiotherapy hence reached in a relatively shorter time - as it were by leaps and bounds - the optimal obtainable state of functional improvements which, with the Bobath therapy alone, can be effected more slowly but with more continuity. The psychodiagnostic controls clearly indicate that the electrical stimulation produced an unspecified increase in activity, especially after the first phase of treatment, whereas in the second phase this could only be proven in a graded form. The report closes with an examination of the results and their consequences for the implementation of the treatment for cerebral palsied children.


[Pharmacokinetics of benziodarone labelled with I-131]. Regarding the importance of benziodarone (Retrangor) -- 2-ethyl-3-(3',5'-diiodo-4'-hidrovibenzoyl)benzofuran -- in medical practic, in respect of its vasodilator and uricosuric action, a working plan was developed intending to study the biological distribution of the drug in rats Wistar and, using the plasmatic curve, to find out the existence of other compartements besides the intravascular one. With these data, the rhytms of benziodarone exchange were established, simulating its distribution in the organism. It was possible to develop this working project because the benziodarone structure could be labelled with iodine-131, using an isotopic exchange reaction, having chloramine T as an oxidant agent. The labelled compound was employed as radioactive tracer, and its specific activities varied from 18 uCi/mg to 20 uCi/mg.


Hearing loss as a sequel to chloramphenicol and ampicillin treatment of Haemophilus influenzae meningitis. 20 patients with Haemophilus influenzae meningitis who had been treated with chloramphenicol over the period 1959-1970 and 23 patients who had been treated with ampicillin over the period 1968-1974 were re-examined by hearing tests in 1975. In all the cases the two agents had been given initially by the parenteral route, chloramphenicol in doses varying between 50 and 150 (averaging 101) mg/kg/day and ampicillin in doses varying between 125 and 350 (averaging 229) mg/kg/day. Five of the 20 patients in the chloramphenicol group were found to be deaf on one ear, whereas 1 of the 23 patients in the ampicillin group was completely deaf. A further 3 in the chloramphenicol group and 1 in the ampicillin group had slight sensorineural hearing loss on one ear. Only in 2 of the 6 deaf patients was the loss discovered during the time of hospital care. The present study has not provided any evidence supporting the recently reported observation (Gamstorp and Klockhoff, 1974) that the frequency of hearing loss might be higher after ampicillin than after chloramphenicol treatment for H. influenzae meningitis.


Potassium accumulation in muscle: a test of the binding hypothesis. Living frog skeletal muscle can accumulate potassium in vitro to concentrations up to 580 millimolar. Both the amount of potassium accumulated and the relationship between intracellular and extracellular potassium concentrations indicate that potassium is "free" under all conditions, rather than bound to cellular macromolecules. The data also indicate that at most 20 percent of the cell water is "bound" in the sense that it excludes electrolytes.


CSF enhancement for computerized tomography. Metrizamide cisternography, combined with hypocycloidal tomography, has been performed in 12 patients with possible posterior fossa or parasellar mass lesions with finely detailed images of the basal cisterns resulting. Computed tomography was performed in nine of these patients and produced exceptional images of the cisternal anatomy. The technique of cerebrospinal fluid enhancement may be efficacious in identifying small basal masses not shown with conventional computed tomography, and thus may form an important complement to enhancement by intravenous injection of contrast medium.


Total excision of the sternum and thoracic pedicle transposition of the greater omentum; useful strategems in managing severe mediastinal infection following open heart surgery. Mediastinal sepsis following open heart surgery is a significant cause of death. Open drainage of the mediastinumalone was employed originally in management of this problem. More recently, debridement, drainage, and reclosure have been used. Various irrigation solutions, such as antibiotics and Betadine, have been advocated to control severe mediastinal sepsis. Three principles of management in patients unresponsiveness to the above techniques have proved successful in two patients with life-threatening mediastinal sepsis: (1) radical, complete excision of the sternum and adjacent costal cartilages; (2) transposition of the greater omentum on a vascular pedicle to the mediastinum; and (3) primary closure with full-thickness rotational skin flaps. The radical excision of the sternum removes residual foci of sepsis in cartilage and sternal bone marrow. The transposition of the omentum provides a highly vascular, rapidly granulating covering for the contaminated great vessels and hase been successfully to prevent recurrence of suture line bleeding of an exposed ascending aortic anastomosis site. Primary closure of the wound with full-thickness skin flaps provides a suprisingly satisfactory covering for the heart. Preoperative and postoperative measurements of ventilatory mechanics have shown relatively small ventilatory impairment after the alteration of the thoracic cage imposed by excision of the sternum. Two patients have returned to active lives. A treatment failure probably due to incomplete adherence to these guidelines also is presented.


Surgical management of complicated acute coronary insufficiency. Acute coronary insufficiency (ACI) has a one year mortality rate approximating 40 percent with medical treatment alone. This report reviews our experience over 24 months with preoperative intra-aortic balloon pump assist (IABPA) in 42 patients with ACI. Abnormal left ventricular (LV) hemodynamics were present in the majority of patients; the ejection fraction was less than 40 percent in 14 patients. The endocardial viability ratio (EVR) was less than 0.7 in eight patients. The mean coronary artery score was 13, compared to 9 in an otherwise comparable group of patients with stable angina. Left main coronary stenosis greater than 75 percent was present in seven patients and combined with significant stenosis (less than 72 percent) in the dominant right system in four patients. Four patients had proximal stenoses greater than 90 percent in all three major coronary arteries. IABPA was initiated in 11 patients prior to angiography because of refractory rest pain. One of these six patients died. Twenty-five other patients were supported before and six after induction of general anesthesia. Thirty-three of 36 revascularized patients survived. Of four patients with perioperative myocardial infarctions (12 percent), three had IABPA after induction of general anesthesia. Inotropic support and duration of stay both in intensive care and in the hospital were less than in similar patients treated before the use of IABPA.


[Observation in 10 calves with a survival time of more than 100 hours after total heart replacement (author's transl)]. It is reported on 10 calves surviving total artificial heart replacement more than 100 hours. Pneumatically driven double-chambered blood pumps made of silastic were implanted. During the experiments an increase of the right atrial pressure as well as a rise of the perfusion volumes (CO) and of the blood volumes could be found regularly. At autopsy congestion of the organs especially of the liver was a regular finding. The changed hemodynamic is first seen as possible reason for this developments. The influence of anemia and the possible disturbances in the neurohumoral autoregulation of the animals by unphysiologic pressure curves are discussed.


[Silicone embolism, fat embolism, and fibrin thrombosis in dogs after extracorporeal circulation using a bubble-oxygenator (author's transl)]. Following extracorporeal circulation with a bubble oxygenator (Rygg-Kyvsgaard) silicone emboli were found in the brain-and-kidney-capillaries of all dogs evaluated. There was no obvious correlation between intensity of silicone embolism and pump time. No cellular reaction was seen around the anti-foam agent. Occasionally single small areas of embolic brain damage were found. During extracorporeal circulation and within a recovery period up to one hour no silicone excretion through the kidneys could be demonstrated. Systemic fat embolism occurred less frequent than previously reported. Use of a filter in the cardiotomy suction line reduced its intensity further. In neither of the various organs examined, disseminated intravascular thrombosis could be found.


[Double mitral valve combined with an intermediate type of persistent atrioventricular canal. A contribution to surgical correction (author's transl)]. A case of double mitral valve combined with an intermediate type of atrioventricular canal is reported. After repairing the cleft in the aortic cusp of the mitral valve there resulted a mitral stenosis, which could be corrected by cutting the bridge between the two mitral orifices. In regarding the genesis of double mitral valve it seems possible, that there are two different types of this congenital malformation.


[Anatomy and pathology of the tricuspid valve (author's transl)]. Anatomy and pathology of the tricuspid valve are presented in a short survey. Annulus fibrosus and leaflets are less firm than those of the mitral valve, whereas the tricuspid orifice is larger than the mitral orifice. Isolated tricuspid disease - congenital or acquired - occurs only rarely. Functional non organic tricuspid regurgitation is clinically of primary importance.


[Incidence and relevance of tricuspid-valve insufficiency in acquired mitral-valve defect. Analysis based on right ventricular angiograms]. To detect tricuspid incompetence (TI) right ventricular angiography was performed in 167 patients suffering from moderate to severe mitral valve disease. Holosystolic reflux of contrast medium to the right atrium through the central part of the tricuspid valve was thought to represent true TI, whereas a jet of contrast medium following the injection catheter and originating from the region of its valve passage was assumed to reflect arteficial regurgitation. True TI was found in 35% of the total group (30% mild to moderate, 5% severe TI). TI was often accompanied by atrial fibrillation (91%), pulmonary hypertension (74%) and reduced contraction of the tricuspid annulus (55%). Since tricuspid regurgitation in mitral valve disease commonly represents "functional" incompetence surgical intervention may be recommandable only in case of severe TI or concomitant valvular stenosis.


[Surgical management of acquired tricuspid insufficiency--valvular replacement or annuloplasty? (author's transl)]. 61 patient underwent operative repair of acquired tricuspid insufficiency (T.I.) during correction of multiple valvular disease. 45% presented a relative T.I. through annular dilatation, while organic lesions of the tricuspid valve were found in 56% of the patients. A tricuspid valvular replacement was carried out in 17, and a tricuspid annuloplasty in 44 patients. We believe that during surgical management of multiple valvular lesions, all tricuspid insufficiencies of even when only of a slight to moderate degree - should be corrected aggressively. Tricuspid valvular replacement should be avoided if possible and a tricuspid annuloplasty should be performed.


[Measurement of cardiac output by impedance cardiography. Experimental studies (author's transl)]. The correlation of impedance cardiography against electromagnetic flow measurement was studied in the pig. The conditions tested were normal circulation, hypo- und hypervolemia and acute pulmonary hypertension as well as the influence of respiration and electrodes location. Correct quantification of cardiac output was obtained only in normovolemic circulation during exspiration (r = 0,96, m = 1,15, b = 0,04).


[Cineradiographical studies of local ventricular motility before and after aorto-coronary bypass (author's transl)]. The purpose of this study was to observe the effect of surgical revascularization on the motility of the left ventricular segment distal to a high grade coronary stenosis. In 17 patients with LAD bypass local relative segment shortening lambda (lambda = diastolic length - systolic length/diastolic length X 100) was determined measuring the distances of coronary bifurcations and surgically implanted myocardial metal markers frame by frame in high speed cineradiography. A group of 14 patients whose angina pectoris was abolished after operation and where bypass proved to be patent showed significant increase of lambda within the first postoperative days (lambda preop. = 3,4 +/- 18,3 SD, lambda postop. = 18,9 +/- 8,0 SD, p less than 0.05). Paradoxical movement had disappeared in 4 cases. In the following two-monthly controls up to one year no significant further alterations of local motility were seen. Three patients with persisting angina did not show any increase of segment shortening. It is concluded that aorto-coronary bypass surgery can restore impaired local motility in the majority of patients. The method described is useful for repeated non-invasive controls of the success of operation.


[Direct measurement of papillary muscle dynamics in the intact canine left ventricle during acute coronary occlusion (author's transl)]. The functions of the normal and ischemic papillary muscle in the intact canine heart were studied using an ultrasonic transit time method. Miniaturized piezoelectric crystals (1.5-2 mm 0) were implanted during extracorporeal circulation into the root and tip of the anterior and posterior papillary muscle of the left ventricle. 1. Phasic changes of left ventricular geometry during the heart cycle determine the dynamic pattern of papillary muscle movements. 2. The amplitude and velocity of papillary muscle length is directly related to those of myocardial wall segments. 3. Experimental ischemia induces total dysfunction of the papillary muscle within seconds. 4. Despite total muscle dysfunction no mitral insufficiency occured.


[Effects of short time extreme hemodilution with and without hypothermia on hemodynamic and biochemical parameters in the pig (author's transl)]. Extreme hemodilution as "Total Body Washout" (TBW) is a feasible method for the clinical therapy of endo- or exogenous intoxication. This method was modified for a simple and quick setup. Landrace pigs were hemodiluted with a special heart-lung-machine. Within 4 minutes the hematocrit was lowered to less than 1%. The rectal temperature fell hereby in a normothermic group (n = 15) to 35, 1 +/- 1, 1 degrees C and in a hypothermic one (n = 13) to 31,1 +/- 1,3 degrees C. The TBW was followed by a total exchange transfusion. Most of the parameters that were studied did not show significant differences between cold and warm perfusion. The proceeding was well tolerated by the animals, they were observed up to 6 weeks. Disadvantages of initial surface cooling may be avoided by extreme hemodilution with exclusive extracorporal cooling, when cardiac arrest in hypothermia is intended.


[Modern trends in the arteriography of the lower leg arteries (author's transl)]. The anatomical situation in arteries of the lower leg and foot can be demonstrated in an optimal manner with orthograde catheter-technique, biplane seriography, magnification and the use of the Medichrome-film. Angiography would be carried out in local anaesthesia after injection from Priscolin and an oral trunk of alcohol. This technique in 580 legs had no complications. All arteries behind arterial occlusions can be demonstrated before and after vascular surgery and other therapeutic procedures.


[Results of reconstructive procedures concerning occlusive arterial disease of the full length of the trifurcation of the lower limb (author's transl)]. 42 vascular reconstructive procedures, concerning occlusions in full length of the trifurcation of the lower limb, were carried out in 40 patients. The success-rate was unsatisfactory. It was as low as 55% after 30 days and 25% after 28 months. This is thought to be due to wrong indication and unfavorable operative proceedings. The high hospital letality of 12%, observed in aged persons only, may be reduced by improving post-operative care. It is stressed that any bad result of this kind of vascular surgery is connected with a high vital danger to the patient in question. Avoiding pre- and intraoperative unfavorable factors is rewarded by better early result; thus it is not the method itself but its wrong application which is bad.


[Complications of arterial reconstructions below the knee for chronic vascular occlusion (author's transl)]. From 1967 to 1976 49 reconstructions were undertaken in the area distal of the art. poplitea: 30 femoral-crural bypasses, 12 TEA und 7 orthogradic desobliterations. Complications until clinical demission were reviewed. There were in 8 cases postop. thrombosis which led to 4 amputations. 6 patients suffered from wound infection with one consecutive amputation. 4 hemmorages had to be stopped surgically. THE OVER ALL RATE OF COMPLICATIONS WAS 36,7% WITH A PRIMARY MORTALity of 4%.


[Objective results of lumbar sympathectomy in peripheral arterial occlusive diseases (author's transl)]. A lumbar sympathectomy was performed on 36 patients with angiographical verified arterial occlusion on the upper and lower leg. Pre- and postoperative partly the lower leg flow was registered by air plethysmography and the lower leg and bridge of foot flow simultaneously registered by the Straine gauge plethysmography. Independent of the method an increase of the arterial blood flow was noticed with 40% of the patients. In spite of this improvement the registered values after the reactive hyperemia in lower leg and bridge of foot are still clearly restricted. The remaining 60% of the patients however showed a clear worthening of the blood flow conditions.


[The prognosis in, and the limitations set to concervative treatment of occlusion of crural arteries (author's transl)]. Arterial occlusions limited to the lower leg generally respond well to therapeutic measures. Claudicatio intermittens can, in most instances, be adequately improved by exercise. Major amputations at stages III/IV can be avoided in practically all cases by conservative measures, provided the poplitea pulse is distinctly palpable. Patients with crural occlusion and necrosis tend to develop trophic lesions also at later times. Sympathectomy will be unable to prevent such recurrences where nicotine inhalation, the most important factor determining the prognosis, is continued.


Protection against murine ascites tumours by lymphoid cell populations with T memory or cytotoxicity. It was possible to protect irradiated C3H mice against lethal doses of allogeneic ascitic tumor cells (RBL-3 or P-815 Y) by systemic administration of low doses of syngeneic sensitized lymphoid cells. Two types of cell populations were active at similar doses: (1) spleen cells harvested 2 months after a nonlethal inoculation of tumour cells, at which time no cytotoxic lymphocytes wer in vivo sensitization or in vitro sensitized spleen cells; sucll and dose dependent and target cell specific. The findings imply that T memory cells as well as cytotoxic cells are able to protect, although it was not possible to exclude the presence of memory lymphocytes in the cytotoxic cell population. Antiserum to cytotoxic T cells (CTL) was prepared in an attempt to distinguish memory and cytotoxic effector cells. The antiserum did not react with the majority of T cells in a normal spleen or thymus, but showed specificity for the CTL cell lineage. Antiserum treatment and complement abolished protection in all types of sensitized cell populations. Since memory and cytotoxic cells appeared to share differentiation antigens, we could not establish whether memory cells are precursors or products of cytotoxic cells.


[Perforation of gastric cancer].

[Perforation of gastric cancer]. An analysis of treatment of 85 patients with perforating cancerous tumor of the stomach is presented. Males--63, females--22. The patients' age ranged from 32 to 85 years. Sixty seven patients were operatd upon, 35 of them died. Eighteen patients were not subjected to surgery, all of them died. The following variants of complications associated with gastric cancer are noted: cancer perforation--in 32, hemorrhage and the perforation--in 35, perforation and hemorrhage occurred simultaneously--in 15, perforation followed by hemorrhage--in 3. High mortality rate was due to grave patients' condition, difficulties and errors of diagnosis, inadequacy of therapeutic measures, late operative interventions. The results obtained are described.


[Complications of benign nonepithelial tumors of the gastrointestinal tract]. The results of observations over 8 patients with complicated forms of benign nonepithelial tumors of abdominal organs are reported, including leiomyoma--in 7 cases and neurinoma--in 1. Isocomplications of this group of tumors in 5 patients were as follows: invagination of the small intestin--in 1, perforation and malignant transformation of the tumor--in 1. The patients were treated surgically. Resection of the organ involved seems to be preferable.


[Quantitative determination of Willebrand factor activity in Willebrand's disease]. Certain new data about the nature of Willebrand factors are discussed, its activity being considered as part of the activity of the antihemolytic factor VIII. An one-stage method for its determination is described based on the absence of thrombocytic aggregation in the presence of ristocetin in the patients with Willebrand disease as well as the illustration of one case.


Outpatient heroin detoxification with acupuncture and staplepuncture. Eighteen heroin addicts were treated as outpatients with acupuncture, electrical stimulation and staplepuncture. Results of treatment were compared with results in two similar groups of 18 persons in whom detoxification was carried out using methadone and propoxyphene napsylate. Withdrawal symptoms were relieved for about two hours in most of the patients after a treatment episode of acupuncture and electrical stimulation. Staplepuncture, which is the manipulation by hand of a surgical staple implanted in the concha of the ear, was reported to relieve withdrawal symptoms at least partially in approximately 40 percent of subjects. In only one person of the group treated with acupuncture or staplepuncture was complete detoxification achieved, compared with 13 and 10 persons, respectively, in the methadone and propoxyphene napsylate groups (p<.001). Use of acupuncture and staplepuncture in outpatient clinics may be limited unless techniques can be found that will relieve withdrawal symptoms for a longer period than that observed in this study.


[Diagnosis, therapy and sequelae of upper gastrointestinal haemorrhage in acute pancreatis]. Gastrointestinal bleeding complicating pancreatitis is a grave development which carries a high mortality rate. Ten out of 450 patients treated by us for pancreatitis developed gastrointestinal haemorrhage; 7 of these patients died, 6 of whom had a haemorrhagic necrotic, and one a so-called oedematous form of pancreatitis as diagnosed at autopsy. Nine operations were performed, most of them being only drainage procedures. Persistent shock or recurrence of severe symptoms with constant chemical pathological changes in the course of acute pancreatitis call for the rapid initiation of an aggressive approach towards diagnosis (endoscopy, angiography) and therapy, with radical surgical procedures, as indicated, aimed at rectifying the extensive pathology. We believe that these are the only possible means of achieving a reduction in the extremely high mortality rate in these cases and of avoiding late complications such as pseudocysts with the inherent danger of bleeding, abscesses and portal hypertension.


[Chronic lymphadenosis--short review].

[Chronic lymphadenosis--short review]. It was tried to show in form of a survey some molecular-biological, immunopathological and kinetic aspects of the CL (chronic lymphadenosis)-lymphocytes, which seem to be significant for the pathogenesis of chronic lymphadenosis. Apart from this, the modern therapeutic possibilities concerning the inhibition of proliferation as well as the depletion which seem to be suitable for influencing the still fatal course of chronic lymphadenosis are discussed.


[Effect of phenylalanine-vasopressin on the lower esophageal sphincter. Possible implications in the treatment of bleeding esophageal varices]. Vasopressin and its analogs are used inthe treatment of bleeding esophageal varices. Since gastrointestinal reflux may have a deleterious effect on variceal hemorrhage, the effect of 2,3-phenylalanine-8-lysine-vasopressin upon the lower esophageal sphincter (LES) was studies by rapid pull-through manometry in 24 persons. PLV infusion up to a dosis of 2.7 mU/kg/h raised LES pressure from 15.1 +/- 1.3 (SEM) to 17.9 +/- 2.0 mm Hg. Higher doses lowered LES pressure progressively to 12.1 +/- 0.7 mmHg at 54 mU/kg/h. The serum gastrin level did neither correlate with basal LES pressure not with LES pressure changes during PLV infusion. Therefore, PLV does not appear to act indirectly through serum gastrin. Because of the danger of systemic side effects and of the undesirable in LES pressure with the usual high doses of vasoactive substances, a continuous infusion of lower doses of vasopressin analogs appears to be advantageous.


[Endoscopic diagnosis of carcinoma in the operated stomach]. In 24 000 gastroscopies at 4 medical departments 705 subjects with gastric operations done more than 5 years before had been studied. 39 of 608 patients with Billroth II, 5 of 81 with Billroth I and 4 out of 15 with gastroenterostomy were found to be suffering from carcinoma of the gastric stump. The primary gastric operations were performed at a medium age of 40 years. The interval between surgery and development of carcinoma averaged 24 years and was shorter in patients operated at a higher age. Besides age and interval since operation risk factors were apparently former gastric ulcers or polyps. Indications for endoscopic follow-up studies of gastrectomized patients to improve surgical results with carcinoma of the gastric stump have been suggested.


[Autoimmune hemolytic anemia with Donath-Landsteiner antibodies and antinuclear factors during the course of chronic-aggressive hepatitis]. With the onset of a remission phase of chronic aggressive hepatitis in a young female patient, two different auto-antibodies were found which had not previously been in evidence. These antibodies were identified as Donath-Landsteiner antibodies, the cause of a secondary auto-immune hemolytic anemia observed during this period, and anti-nuclear antibodies. Both antibodies were of the IgG class, both could be adsorbed onto the patient's own erythrocytes as well as P1-positive test erythrocytes, and both antibodies were present in the subsequent erythrocyte eluate. Separation of the two antibodies present in the serum as well as in the antibody-containing erythrocyte eluate was possible by absorption of the antinuclear factors using preparations of liver and thymus cell nuclei, but the anti-erythrocyte activity was not diminished by this procedure. Rapid remission of the auto-immune hemolytic anemia was achieved by a therapeutic application of corticosteroids. Long-term therapy has resulted in no recurrence of the auto-immune hemolytic anemia until now.


T lymphocytes in chronic lymphocytic leukemia. In cultures of lymphocytes from the peripheral blood of patients with chronic lymphocytic leukemia, the approximate magnitude of the population of lymphocytes characterized by delayed PHA reactivity was estimated. To this end, cells from cultures in an early stage of development were pulse-labeled with 3H-TdR, and their multiplication was expressed by an index of proliferation. On the basis of these data, the proportion of unlabeled blasts in the late stage of cultures was calculated in relation to the late-reacting raction to the mitogen. This fraction comprised 50-100% of blasts in late cultures (6 days). The subpopulation was not detected in only 2 of 17 cases. Its magnitude in the peripheral blood amounted to about 3% of the lymphocytes and nearly one half of the total number of lymphocytes reacting to PHA in patients with CLL. It was concluded that the number of peripheral blood lymphocytes reacting to PHA is not diminished at all in patients with leukocytosis between 11,000 and 17,000/mul. The late-reactive population was relatively resistant to X radiation, dependent on L-asparagine, and insensitive to doses of colchicine which are toxic for leukemic cells. The ability of these lymphocytes to form rosettes spontaneously with sheep red blood cells is preserved in a large measure. Only a small proportion lacked this surface marker. It seems that the population of late-reacting lymphocytes to PHA in the blood of patients with CLL is of thymic origin.


[Absecence of the antidepressant action of lithium under clinical and experimental conditions]. During a long-term treatment by lihtium carbonate of 200 patients with manic-depressive psychosis the authors did not find any antidepressive effect. In some cases administration of lithium during the depressive phases aggravated the depressive symptomatology, prolonged the duration of the phase, increased the therapeutical resistance. In experiments with lithium on animals there were no typical traits for an antidepressive effect: adrenopositive and serotoninopositive action.


Effects of lymphocytotoxins of systemic lupus erythematosus (SLE) sera on T and B lymphocytes. SLE lymphocytotoxins can be demonstrated on the lymphocytes by immunofluorescence. Complement addition lyses the cells covered with LCT. The proportion of B and T cells as determined by surface immunoglobulins and spontaneous rosette formation of lymphocytes from healthy donors remains unchanged after LCT and complement treatment. The proportion of B and T cells of SLE lymphocytes was altered after cell lysis. The B cells seemed to be relatively resistant, and the T cells more susceptible, to autologous LCT. Thus the relative decrease in the number of T cells in active SLE may be the consequence of surface bound LCT with its effect on the circulating T cells.


Assay of factors of the kinin system in plasma from patients with specific exogenous allergies. Factors of significance for the release of kinin were estimated in plasma from patients with specific, exogenous allergies and in that from healthy individuals. There was no evidence that the rapid initial kinin release in plasma from allergic patients caused by submaximum concentrations of hog pancreas kalikrein or by acetone-activated human plasma (2) was due to an increased level of prekallikrein activator (activated factor XII), to prekallikrein itself or to a factor possibly positioned between active factor XII and prekallikrein. In addition, the rapid halt in kinin release observed for the patient plasma could not be ascribed to an increased level of alpha2-macroglobulin, CI-inactivator or alpha1-antitrypsin. It is suggested that the differences in kinin release registered between the patient plasma and the normal plasma might reflect differences in the relative amounts of kininogen fractions present.


The dependence of tension relaxation in skeletal muscle on the number of sarcomeres in series. Mulieri (1972) has reported that the depth of the latency relaxation, tension relaxation, changes only insignificantly when about half of a fibre bundle is wound tightly around a small glass rod. From this observation he concludes that the tension relaxation is not correlated with the number of sarcomeres in series in a frog muscle fibre. The dependency of the tension relaxation on the number of sarcomeres in series has been reinvestigated using both Mulieri's method and other independent methods. When Mulieri's experimental procedure was repeated, his result was reproduced. In the other methods used the tension relaxation was found to be proportional to the number of sarcomeres in series which were activated initially. This result was also obtained by introducing a slight modification to the procedure used by Mulieri. The results could equally well be understood if the latency relaxation was caused by a definite elongation rather than an increase in compliance of the fibre.


An immunological approach to dementia in the elderly. A study into the relationship of immune change in the serum and the presence of senile dementia is reported. Three groups were studied, senile dementia, cerebrovascular disease and subjects without evidence of brain disease. All were aged 65 years and over. The immunofluorescent studies showed an excess of antineuronal reactivity and a fall in antinuclear antibody in females with senile dementia. There was no significant difference between the groups in respect of immunoglobulins, slide latex and a complement fixation test, against a variety of tissues. The significance of the findings in relation to other published results is discussed.


Presumptive relationships between ventricular proliferaion and development of the lateral motor columns in the spinal cord of Rana pipiens larvae. The extent of mitotic activity in the proliferative ventricular zone of the developing frog (Rana pipiens) spinal cord is a function of both the longitudinal cord level and the developmental stage. Counts of mitotic cells in the ventricular zone demonstrated higher levels of proliferation in the dorsal than ventral halves of the spinal cord with decreasing total proliferative activity from the early to late larval (tadpole) stages. Mitoses were virtually absent from the ventricular zone by the conclusion of metamorphosis. Changes in mitotic counts at different levels of the spinal cord can be correlated with the presence or absence of the brachial or lumbosacral pairs of lateral motor columns. A parallel also exists between the caudo-cephalic direction of motor column development and a similar progression of mitotic activity in the ventricular zone, a portion of which gives rise to the spinal motor neurons. It is suggested that proliferation in the ventricular zone during the larval frog stages contributes to the presumptive motor neuron population and migrates into the lateral motor columns during their later maturation.


Intraperitoneal and intragastric norepinephrine instillation in massive gastrointestinal bleeding--clinical study. Preliminary report. Intraperitoneal and intragastric instillation of norepinephrine in high concentration can arrest bleeding of various origins in the gastrointestinal tract. Of the 21 cases studied, the hemorrhage was controlled in 80% of cases. This form of therapy is simple, prompt, safe and can be performed as a bed-side therapeutic procedure to stop life-threatening gastrointestinal tract bleeding. Intraperitoneal instillation of norepinephrine should not be used more than once, if the bleeding is not controlled. Intragastric norepinephrine instillations may be repeated any number of times if required.


Idiopathic portal hypertension.

Idiopathic portal hypertension. Idiopathic portal hypertension is reported in five cases including one case of chronic arsenical intake and one case of chronic industrial vinyl chloride exposure. In all five cases the patients presented with gastrointestinal bleeding as the chief complaint. Physical examination was within normal limits except for splenomegaly in all. Results of liver function tests were normal, except for the relative clearance of sulfobromophtalein. A surgical liver biopsy specimen was obtained in all cases and showed moderate degrees of portal fibrosis, but no cirrhosis. Combined umbilicoportal, hepatic vein and superior mesenteric artery catheterization was performed in all cases. Hepatoportographies showed distortion of the intrahepatic portal venous system and cut-off of small portal venules. Porto-hepatic gradients ranged from 14.0 to 20.5 mm Hg. The portal hypertension was both sinusoidal and presinusoidal in nature but mainly presinusoidal. Hepatic extraction of indocyanine green and of albumin microaggregates was normal, thereby suggesting normal functional portal blood supply to the liver. The patients with arsenical or vinyl chloride exposure could not be differentiated from the other three patients with idiopathic portal hypertension. These results suggest that idiopathic portal hypertension may be related to domestic or industrial exposure to other hepatotoxins.


Nephrotic syndrome in Hodgkin's disease. Evidence for pathogenesis alternative to immune complex deposition. The nephrotic syndrome has been reported to occur in patients with Hodgkin's disease even in the absence of amyloidosis, tumor infiltration of renal vein thrombosis. Three patients are presented with Hodgkin's disease and the nephrotic syndrome whose renal biopsy specimens studied with light, immunofluorescence and electron microscopy were compatible with "lipoid nephrosis" (minimal change disease). A review of the literature reveals 35 patients with Hodgkin's disease and the nephrotic syndrome. Renal tissue was available for examination in only 27 patients. The majority of patients apparently had glomerular alterations consistent with lipoid nephrosis. The nephrotic syndrome in most of these patients remitted with a variety of methods of therapy (including excision, irradiation, prednisone and cyclophosphamide) and tended to relapse with a recurrence of Hodgkin's disease. In three-fourths of the patients with Hodgkin's disease and the nephrotic syndrome, the Hodgkin's disease was of a mixed cellularity type. The etiology of lipoid nephrosis, although unclear, may be a consequence of altered lymphocyte function. Hodgkin's disease is a malignancy involving T lymphocytes, and the nephrotic syndrome occurring in the course of Hodgkin's disease may be a  result of an adverse effect of glomeruli by products of tumor lymphocytes rather than of glomerular deposition of immune complexes.


Fundus flavimaculatus and Stargardt's disease. Of 42 patients studied who had fundus flavimaculatus and Stargardt's disease, most had reduced visual acuity due to an atrophic macular lesion. Family histories were consistent with autosomal-recessive inheritance. In some young patients, the yellow-white flecks developed with time, while in some older patients the flecks faded, pari passau with increasing retinal pigment epithelial atrophy. Fluorescein angiography showed that most white flecks were largely or totally nonfluorescent. Even after the flecks had faded from view, the sites where they had been usually remained nonfluorescent. In patients with lesions confined to the posterior pole, the electroretinogram and electro-oculogram were usually normal; in patients with widespread lesions, one or both tests were usually abnormal. Affected members of any one family had a similar distribution of fundus lesions.


Fluorescein angiography and vitamin A and oxalate levels in fundus albipunctatus. Two patients had fundus albipunctatus, one of the variants of congenital stationary night blindness. Neither the white dots in the retinas of these patients nor the retarded course of dark adaptation characteristically associated with the disease could be attributed to vitamin A deficiency or raised oxalate levels since both substances were present in normal amounts. Fluorescin angiography showed multiple discrete lesions in the pigment epithelium not coincident with the ophthalmoscopically visible changes. Since the pigment epithelium is the storage site for bleached visual pigment, these findings suggest abnormalities that underlie the major functional deficit in this disease, that is, the slow recovery of retinal sensitivity.


Temporal artery biopsy in herpes zoster ophthalmicus with delayed arteritis. A 58-year-old man developed herpes zoster ophthalmicus with delayed hemiparesis. Temporal artery biopsy confirmed the presence of a vasculitis. Electron microscopy of the temporal artery failed to reveal viral particles. Herpes zoster ophthalmicus with delayed arteritis appeared to be a contiguous spread of vasculitis to the carotid system and not a direct viral invasion.


Differentiation of a methylcholanthrene-induced sarcoma to a benign plexiform fibroneural tumor in an adult frog (Rana pipiens). Possible influence of host regenerative capacity. A spindle cell sarcoma appeared 20 months after implantation of a pellet of 3-methylcholanthrene in the denervated foreleg of an adult frog, Rana pipiens. Its growth rate and cellular structure were observed over the subsequent 19 months, the former remaining constant for the first 14 months, then slackening markedly during the final 4 months. Serial biopsies disclosed maturation to a well-differentiated fibroneural tumor of benign appearance, the change taking place notably during the period of decelerated growth rate. An autotransplant of the tumor to the hind leg adopted the same growth pattern and maturation. Possible causes for this behavior are discussed.


Ultrastructural study of Reed-Sternberg cells. Comparison with transformed lymphocytes and histiocytes. The ultrastructural features of Reed-Sternberg cells from 17 patients with Hodgkin's disease were compared with those of histiocytes and transformed lymphocytes in both benign and malignant conditions. Transformed lymphocytes and Reed-Sternberg cells appeared to have similar features, including large nuclei with dispersed chromatin, large nucleoli, and great numbers of cytoplasmic polyribosomes. Histiocytes contained abundant cytoplasmic lysosomal granules and microfilaments. These results are indicative of the origin of Reed-Sternberg cells from lymphocytes.


Vasopressin control of massive hemorrhage in chronic ulcerative colitis. A case of a massive colonic hemorrhage in nontoxic, quiescent ulcerative colitis is described. The source of active colonic bleeding was primarily defined with selective superior mesenteric arteriography and was completely controlled with transcatheter vasopressin infusion. A suubsequent elective segmental distal transverse and descending colectomy revealed chronic ulcerative colitis; localized marked inflammatory giant pseudopolyp formation near the splenic flexure was responsible for the bleeding.


Abnormal lymphocyte function is secondary to drug-induced autoimmunity. Abnormal lymphocyte function has been frequently reported in patients with connective tissue diseases but its significance has been uncertain. Sequential studies of lymphocyte function were carried out in patients receiving the beta-adrenergic blocking drug practolol (Eraldin) both before and during the development of autoimmune complications. No evidence was obtained that abnormal lymphocyte function presaged the onset of autoimmunity, and when these tests did show deficient responses these could be correlated with disease activity in general.


Circumflex coronary artery bypass grafting via transverse sinus. Grafting the circumflex coronary artery has been more difficult technically than the right or anterior descending because of its posterior location and the angles of its marginal branches. However, grafting this artery has been substantially simplified by a method wherein the graft is passed directly through the transverse sinus and anastomosed to the back of the ascending aorta. This follows the most direct course to the ascending aorta and the graft is much shorter than one brought anterior to the heart. There is little chance of kinking the graft, since its angle of attachment is ideal, and due to the anatomical configuration of the transverse sinus, there is more room for the graft and compression is unlikely. This allows more room on the anterior surface of the aorta for grafts to other coronary arteries. This method has been used in 50 cases and blood flows have been excellent. Twelve of these cases have been restudied postoperatively and the grafts are patent.


The problem-oriented medical record: evaluation and management of anemia before and during use. The problem-oriented medical record (POMR) is designed to rationalize and improve the structure of the medical record. This change might be expected to enhance the outcome of patient care. Therefore, I assessed the effect of the POMR on the care of the problem--anemia--in a Veterans Administration teaching hospital. The POMR concept was introduced by lectures and supported by chart audit. Four months later, the care described in 29 sequential records containing the discharge diagnosis--anemia--was compared with 31 records produced at the same period in the previous year by house officers not using the POMR. Records were graded for maintenance of the POMR format. Completeness of the "data base," as well as time to problem identification, therapy, and diagnostic description were compared. Introduction of the POMR had no observable beneficial effect on the thoroughness of data base accumulation or the process of patient care for the problem (anemia) or, in another study, on the ease or accuracy of chart audit.


Histiocytosis X and compulsive water drinking: report of a case. We describe a patient with histiocytosis X and compulsive water drinking. The association of diabetes insipidus with histiocytosis X is well recognized, and this patient was initially considered to have diabetes insipidus. It was only after further testing that the proper diagnosis was made.


Dynamics of nucleic acids and total proteins in thymus of Walker carcinosarcoma bearing rats. Thymus responses in tumoral-bearing hosts can illustrate two moments of immunological crisis corresponding to the tumour intake and its metastazic spread. These data are in accord with Burnet's (3) hypothesis that cancer is due to the inability of immunological surveillance mechanisms to reject somatic cells bearing neoplastic mutation.


A morphological study of human vestibular sensory epithelia. Surface preparations were made of the vestibular sense organs of humans from membranous labyrinths removed within ten hours of death. Total sensory cell counts and surface area measurements were made from composite photographic reconstructions. The general topographical and cytoarchitectural arrangements were found to be similar to those previously described for the guinea pig and squirrel monkey. The surface areas and sensory cell populations of the human cristae were only slightly greater than those recorded for these animals; however, the figures for the human maculae were twofold to fourfold greater. It seems possible that this exceptional enlargement of the sensory epithelia of the static labyrinth is in response to a physiological need generated by the evolutionary transition of primates from the quadruped to the biped stance.


A clinical study on the ototoxic effects of tobramycin. In a clinical, prospective, non-randomized study, tobramycin has shown its high antibacterial activity in Gram-negative bacillary infections. The incidence of ototoxic side effects was very low: none of 18 patients studied before, at the end and 9 months after completion of tobramycin therapy showed any change in pure tone audiograms. Five of these 18 patients had renal impairment: 3 of them developed subjective and objective evidence of vestibular dysfunction, as demonstrated by caloric vestibulometry. However, these bilateral vestibular lesions all proved to be reversible a few weeks after cessation of therapy. Despite the low incidence and the reversibility of the ototoxic side effects, it seems advisable to monitor patients on long-duration tobramycin therapy for signs of vestibular dysfunction, particularly in cases of renal insufficiency.


Linear densities in mitochondria of human myocardial cells. Ultrastructural study of myocardial biopsies from 5 patients who underwent myocardial revascularization procedures because of impending infarction showed mitochondria with linear densities. These densities, which occupied the intracristal space, appeared to have a high protein but low mineral content. It is suggested that linear densities may be an expression of severe, acute myocardial cell injury.


The inheritance of affective disorders: a review of data and of hypotheses. A genetic factor in affective disorders is suggested by twin and family history studies. The form of disorder (BP or UP) is transmitted within families. Early onset of affective disorder is associated with increased morbid risk of the disorder in relatives, but age at onset is not itself a transmitted factor. Female relatives have higher prevalence of illness, but sex of the ill person does not appear to be a factor in transmission. Genetic models of multifactorial or single-gene autosomal inheritance are compatible with some but not all of the family history studies reported. The hypothesis of sex-linked transmission of BP illness has been proposed, and some pedigrees compatible with X-linkage have been reported, but family studies do not suggest that this is generally present. Other possible modes of inheritance remain to be tested. Investigative strategies for identification of the "affective genotype" are discussed on the basis of biochemical, pharmacological, or other characteristics of persons with the disorders and their relatives, and on the basis of studies of known linkage markers.


Significance of angina pectoris in aortic valve stenosis. Of 60 patients aged 45 to 66 years with aortic valve stenosis, 28 (47 per cent) had angina pectoris. Significant coronary arterial obstruction was shown by selective coronary cineangiography in 14 of them. Systolic pressure gradients across the aortic valve were lower in patients with angina than in those without. In those with angina, systolic gradients were higher in those with normal coronary arteriograms than in those with demonstrable coronary arterial disease. Aortic valve replacement relieved the angina in all patients who had normal coronary arteriograms. When valve replacement was combined with coronary bypass grafting in those with coronary arterial disease, surgical mortality was higher and symptomatic relief less predictable. Incapacitating angina in patients with aortic stenosis was nearly always associated with significant coronary disease. In those with less severe angina it was impossible to predict the state of the coronary arteries. Two patients, who did not have angina and who did not undergo coronary arteriography, died after aortic valve replacement and were found at necropsy to have unsuspected severe coronary disease. We, therefore, suggest that coronary arteriography should be carried out in all patients over the age of 40 years in whom surgery is being considered for aortic stenosis.


Pathology of hearts after aortocoronary saphenous vein bypass grafting for coronary artery disease, studied by post-mortem coronary angiography. A detailed pathological study was made in 10 patients dying up to 13 months after aortocoronary saphenous vein bypass grafting for coronary atherosclerosis. The coronary arteries and vein grafts were investigated by injection with a radio-opaque mass, radiography, dissection, and histology. The report is to some extent historical since the patients died during a period when the operation was first being introduced into two cardiothoracic hospitals. About 80 operations were performed during the time the 10 deaths occurred, a mortality of 12-5 per cent (including cases followed up to 13 months after operation). Seven of the patients were operated on for intractable angina and 3 with a view to aneurysmectomy. All the patients selected for operation were severely disabled despite medical treatment. The main cause of death was extremely severe coronary artery disease and its effects on the left ventricle; in one case, over two-thirds of the left ventricle had been destroyed by infarction before operation. Other causes or contributing causes of death were pulmonary embolism, myocardial infarction complicating angiography (ostial stenosis), and cerebral damage. Ten of the 14 vein grafts (71%) were patent at necropsy. A free flow of injection medium usually occurred between patent grafts and coronary arteries. Thrombosis of a graft was thought to have contributed to death in 3 patients, but not in a fourth who died of pulmonary embolism. Since thrombosis of grafts was usually secondary to poor run-off blood into severely atheromatous coronary arteries, this was also an indirect effect of the advanced coronary arterial disease. In one case, thrombosis followed severe chronic intimal thickening of a graft in place for 13 months. The study of these deaths emphasizes that in some patients the pathological changes in the coronary arteries and left ventricle are too severe for them to benefit from surgery. Vein grafts cannot be expected to distribute blood effectively through grossly narrowed coronary arteries. In addition, when a large part of the left ventricle is infarcted or scarred, it is almost certain that improving the blood supply by grafting will not result in significant regeneration of cardiac muscle. Since the time when this study was made, there have been few deaths among the many vein graft operations subsequently carried out in the hospitals involved. The two most important factors thought responsible for the improvement are the selection of cases more suitable for surgery by continued improvement of diagnostic techniques, and also the employment of more radical surgical procedures in the form of coronary endarterectomy and the insertion of more grafts per patient.


Immunological aspects of psoriasis. II. Dissociated impairment of thymus-dependent lymphocytes. We have investigated lymphocyte subpopulations (six different markers) and T cell functions (mitogen responses and serum thymic factor determination) in twenty patients with psoriasis compared with thirty-five healthy subjects. Normal results were found for B cell markers, but significantly lower numbers of T cells were assessed by E-rosettes and anti HTLA serum. Mitogen responses were significantly higher in psoriasis than in normal subjects of the same age. These findings could be in favour of a T cell subpopulation defect involved in an auto-immune pathogenesis of psoriasis.


Radioimmunoassay of human plasma trypsin. A radioimmunoassay has been developed for the determination of human trypsin (3.4.21.4) in plasma. It allows the measurement of trypsin concentration in spite of the presence of plasma or pancreatic inhibitors. The human trypsin used as a standard and for labelling was isolated from pancreatic tissue and purified by affinity chromatography. The antiserum was obtained from guinea-pigs immunized with partially purified human trypsin. In the radioimmunoassay, the values of trypsin in serial dilutions of plasma were parallel to those of the standard curves. The assay was shown to be reproducible, sensitive and specific. However, the two antisera used did not distinguish between the enzyme and its proenzyme. In normal subjects, plasma values were found to be around 400 ng/ml. They were 10-40 times higher in patients with acute pancreatitis. The method appears to be much more specific for the diagnosis of acute pancreatitis than the current determinations of amylase and lipase activity.


Aromatic Tris-amidines. A new class of highly active inhibitors of trypsin-like proteases. A number of novel aromatic Tris-amidines have been synthesized and investigated for their antiproteolytic property. The basic structure of the compounds is that of mesitylene where each of the methyl groups has been substituted with a 3- or 4-amidinophenoxy moiety. The compounds displayed considerable activity against trypsin (EC 3.4.21.4) and thrombin (EC 3.4.21.5), but proved most effective against porcine pancreatic kallikrein (EC 3.4.21.8). With this enzyme a Ki value of 2.43-10(-8) M was recorded for alpha,alpha',alpha''-tris(4-amidino-2-bromophenoxy)mesitylene at pH 8.1 and 37 degrees C. The most potent thrombin inhibitor, alpha,alpha',alpha''-tris(3-amidinophenoxy)mesitylene, had a Ki value of 6.51-10(-7) M and was also a strong overall anticoagulant. The inhibitors were able to interfere with the kinin release by human plasma kallikrein at concentrations as low as 1-10(-10) M. However, despite this remarkable antikallikrein effect and the known importance of plasma kallikrein in the activation of Hageman factor (factor XII), the compounds had only little influence on the early stages of blood coagulation.


Affinity chromatography of the uterine estradiol receptor on estradiol-PAB-cellulose: an artefact. Estradiol-PAB-cellulose, an easily prepared adsorbent, has been proposed to purify the uterine estradiol receptor according to the principle of biospecific affinity chromatography. It apparently removes all hormone binding sites when cytosol preparations are incubated with it. A systematic study of this adsorbent was undertaken, including the synthesis and testing of the radioactive material. Two main results were obtained: 1) Estradiol-PAB-cellulose is heavily contaminated with free ligand and releases it during the normal chromatographic conditions. 2) Estradiol spacer derivatives (hydroxyethylphenyl-diazo (2 or 4)-estradiol) have a very low affinity for the receptor (Ki = 10 muM). The conclusion is that estradiol-PAB-cellulose is unsuitable for affinity chromatography of estradiol receptor.


The structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitor III. Structure of the anhydro-trypsin-inhibitor complex. The structure of the complex between anhydro-trypsin and pancreatic trypsin inhibitor has been determined by difference Fourier techniques using phases obtained from the native complex (Huber et al., 1974). It was refined independently by constrained crystallographic refinement at 1.9 A resolution. The anhydro-complex has Ser 195 converted to dehydro-alanine. There were no other significant structural changes. In particular, the high degree of pyramidalization of the C atom of Lys 15 (I) of the inhibitor component observed in the native complex in maintained in the anhydro-species.


Human lymphocyte motility: normal characteristics and anomalous behavior of chronic lymphocytic leukemia cells. The characteristics of human lymphocyte motility and its relationship to the redistribution of surface membrane antigens (capping) are poorly defined. Since chronic lymphocytic leukemia (CLL) cells cap poorly when compared with normal human lymphocytes, this study was undertaken to compare the motility of these two cell types. A modification of the Boyden chamber system was employed to quantify lymphocyte motility by placing lymphocyte suspensions on 8-mum convoluted-pore nitrocellulose filters and measuring the depth of migration of the cells into the filter at 37 degrees C. After 3 hr of incubation, CLL cells migrated significantly less into the filter than normal cells. Incubation in the presence of sodium azide or at 4 degrees C abolished all motility, indicating the active nature of the process. The relative motility of individual CLL patients' cells correlated best with the proportion of abnormal cells present as determined by surface receptor assays. The possibility that decreased cell motility in CLL was a reflection of enrichment by a "bone marrow-derived" (B cell) population was eliminated by the finding that normal B cells purified by gradient separation of rosetted cells migrated faster than normal T cells and considerably faster than CLL cells. Motility of normal and CLL lymphocytes was decreased by cytochalasin B and increased by colchicine, vincristine, and vinblastine. Thus, human lymphocyte motility appears to be dependent on microfilament integrity but not to require the colchicine-sensitive cytoskeleton. The decreased motility of CLL cells is the result of an intrinsic cell abnormality, but this finding cannot fully explain the decreased capping, since in human lymphocytes the latter is not prevented by an inhibitor of motility.


Colony growth of mouse bone marrow cells in agar contained in glass capillaries. Mouse bone marrow cells were grown in semi-solid agar contained in glass capillary tubes. Several parameters affecting colony formation in the capillaries were studied. 10(4) cells in 100 mul incubation medium within one capillary produced 22 to 30 colonies of granulocytes and macrophages. Compared with the common petri dishes glass capillaries offer several advantages under the conditions used: 1. A twofold higher plating efficiency. 2. Applicability to optical scanning by light scattering and electronic counting, allowing automation and greatly improving sensitivity, statistical accuracy and reproducibility. Kinetics of colony growth can also be monitored. 3. Diminished risk of bacterial and fungal contamination. 4. A more than tenfold lower need for materials on similar statistical errors. Substituting methylcellulose for agar resulted in colonies of fibroblast-like cells adherent to glass surface. Glass non-adherent cells showed a threefold higher plating efficiency in agar.


[Von Willebrand-Jürgens syndrome with a variant of factor VIII-associated antigen]. A family is described in which 5 out of 8 children had a marked bleeding disorder. The children showed prolonged bleeding times, abnormal platelet retention upon passage of blood through a glass bead column, the Willebrand factor activity as measured by ristocetin in a washed platelet system was low. Factor VIII/von Willebrand factor protein levels were normal even so the factor VIII-procoagulant activity. Even the parents and one child without any bleeding tendency and normal bleeding times had a reduced Willebrand factor activity. In all these patients evidence of an abnormal protein was observed on crossed antigen-antibody electrophoresis indicating a qualitative defect of the factor VIII/von Willebrand factor protein.


A comparative study of the action of gamma-aminobutyric acid and piperazine on the lobster muscle fibre and the frog spinal cord. 1 The effects of gamma-aminobutyric acid (GABA) and piperazine were compared on two in vitro preparations, the lobster muscle fibre and the frog spinal cord. 2 Both GABA and piperazine increased the membrane conductance of single lobster muscle fibres without changing the membrane potential; sigmoidal log dose-conductance curves for these agents were obtained and a similar model expressed the receptor interaction of both substances. 3 The actions of GABA and piperazine on lobster muscle were antagonized by picrotoxin and were Cl-dependent. 4 In the frog spinal cord GABA depolarized the dorsal roots presumably by mimicking the activity of the transmitter depolarizing the primary afferents; sigmoidal log dose-response curves for GABA were obtained. 5 On the dorsal roots piperazine produced either depolarizations or biphasic responses; these were mainly indirect effects as was shown by experiments in the presence of tetrodotoxin (TTX). 6 The effects of GABA on the dorsal root (in TTX-treated cords) were antagonized by picrotoxin whereas those of piperazine were more resistant to this alkaloid. The GABA-induced responses appeared to be largely Na+-dependent while both Na+ and Cl- seemed to mediate the effects of piperazine. 7 It is proposed that piperazine has GABA-agonist activity on lobster muscle but little GABA-like activity on the frog spinal cord.


A comparative study of the effects of glutamate and kainate on the lobster muscle fibre and the frog spinal cord. 1 The depolarizing actions of glutamate and its conformationally restricted analogue kainate were investigated on the lobster muscle fibre and the frog spinal cord using intracellular and extracellular recordings, respectively. 2 Bath-applied kainate was less potent than glutamate on the lobster fibre but more potent on the frog cord. From the log-log transformation of dose-response curves it was proposed that more than one glutamate molecule was necessary to activate both the lobster and the frog receptor sites. In the frog, at least three kainate molecules were thought to be required for receptor activation. 3 The ionic dependence of glutamate and kainate responses appeared different for the two tissues. 4 Some possible explanations of the differential tissue sensitivity to kainate are discussed.


Hypotension in rabbits infected with Trypanosoma brucei. 1 Blood pressures and heart rates of 12 anaesthetized rabbits chronically infected with T.brucei were measured (average infection time 39 days (range 25-67). The systolic BP was 31.4 +/- 5.7 mmHg, the diastolic BP 25.0 +/- 7.2 mmHg, and the heart rate 120.5 +/- 24.2 beats/minute. Two rabbits were already hypotensive 10 days after infection. In 12 anaesthetized control rabbits, the systolic BP was 66.2 +/- 7.3 mmHg (mean +/- s.e.), the diastolic BP 60.2 +/- 7.3 mmHg, and the heart rate 116.3 +/- 15.9 beats/minute. 2 The intravenous injection of 3 X 10(8) disintegrated trypanosomes into infected rabbits lowered the blood pressure by 41.4 +/- 22.0%. Pretreatment of two rabbits with aprotinin prior to administration of parasites prevented the fall in blood pressure. 3 Injection of 3 X 10(8) live trypanosomes complexed with hyperimmune sera produced a fall of 68.3 +/- 38.4% in the systolic BP of normal rabbits. Disintegrated or live trypanosomes, or hyperimmune sera alone had no effect. Pretreatment of animals with aprotinin prior to administration of the immune complex abolished the fall in BP. 4 The results suggest that the profound hypotension in chronic trypanosomiasis is caused by complex formation of trypanosomes with antibody. Since it can be prevented by pretreatment with aprotinin, it is likely that activation of plasma kallikrein with a subsequent release of plasma kinins contributes to this effect.


Possible influence of intrarenal generation of kinins on prostaglandin release from the rabbit perfused kidney. The effects of bradykinin and kininogen on renal prostaglandin release were studied in rabbit isolated kidneys perfused with oxygenated Krebs solution. The concentration of prostaglandin-like material in kidney effluent was determined by bioassay after extraction of the samples with organic solvents. In 7 experiments the samples were assayed after separation of prostaglandins E and F by thin layer chromatography. Addition of bradykinin to the perfusing fluid increased the venous and urinary effluxes of prostaglandin E-like substance by sixfold and fivefold, respectively, but efflux of prostaglandin F-like material was unaffected. Addition of kininogen to the perfusing fluid augmented the venous and urinary release of prostaglandin E-like substances by fifteenfold and ninefold respectively and caused a twofold increase in the efflux of prostaglandin F-like material into the venous effluent. Aprotinin, a kallikrein inhibitor, reduced the prostaglandin releasing action of kininogen but not of bradykinin. In contrast, inhibition of prostaglandin synthesis by indomethacin suppressed the release of prostaglandin evoked by either bradykinin or kininogen. This study suggests that augmented release of prostaglandins in response to kininogen is a consequence of renal generation of kinins. Thus, changes in the intrarenal activity of the kallikreinkinin system may modulate renal prostaglandin release.


Control of duodenal haemorrhage with cyanoacrylate. Three cases of massive duodenal haemorrhage refractory to conventional therapy have been successfully treated by percutaneous selective intra-arterial injection of Isobutyl 2 cyanoacrylate. Case histories, injection technique and review of the literature are presented.


Prospective comparison of double-contrast barium meal examination and fibreoptic endoscopy in acute upper gastrointestinal haemorrhage. Fibre-optic endoscopy was compared prospectively with double-contrast radiology in 53 consecutive patients admitted with acute gastrointestinal haemorrhage. The bleeding site was correctly identified by endoscopy in 94% of patients and the final diagnosis was correctly given in 89%. The corresponding figures with radiology were 83% and 74%. Among the 50 patients with a final diagnosis of a bleeding site in the upper gastrointestinal tract endoscopy indicated the site of bleeding in all and radiology indicated it in 88%. Both investigations were well tolerated by patients. Endoscopy is the investigation of choice, but when it is not available double-contrast radiology will show the site of bleeding in 80-90% of patients.


Histocompatibility antigens, autoantibodies, and immunoglobulins in alcoholic liver disease. Determination of histocompatibility antigens in 63 patients with alcoholic liver disease showed that HLA-B8 was more prevalent in patients with cirrhosis than in controls, but among those with fatty liver and minimal fibrosis the prevalence of this antigen was normal. Another noticeable difference was the absence of HLAA28 in the cirrhotic group. In the total series of 219 patients the prevalence of antinuclear and smooth muscle antibodies was raised; they were especially prevalent in patients with cirrhosis. Raised serum IgA and IgG concentrations were also common (found in 50% and 37% respectively) and were again significantly associated with cirrhosis. In contrast, serum IgM levels, which were raised in 46% of cases, were not significantly related to the presence of cirrhosis but correlated significantly with the degree of portacaval shunting. These results support recent evidence suggesting that immune responses may be implicated in alcohol-induced liver damage, particularly in its progression to cirrhosis.


Serotonin involvement in the blockade of bulbospinal inhibition of the spinal monosynaptic reflex. Bulbospinal inhibition of the extensor quadriceps monosynaptic reflex (MSR) was antagonized by the serotonin precursor, 5-hydroxytryptophan (5-HTP, 75 mg/kg), in unanesthetized, mid-collicular, decerebrate cats. Fluoxetine HCl (Lilly 110140, 0.25 - 6 mg/kg), a specific serotonin neuronal uptake blocker, also blocked this inhibition as well as bulbospinal inhibition of the flexor posterior biceps-semi-tendinosus MSR. The serotonin antagonist, cyproheptadine HCl (5 mg/kg), partially reversed the above blocking actions of 5-HTP and fluoxetine and enhanced bulbospinal inhibition when administered alone in doses of 2.5-5 mg/kg. Imipramine HCl (0.125 - 4 mg/kg) was more potent in antagonizing bulbospinal inhibition of the dorsal root-ventral root MSR when administered intra-arterially to the spinal cord than when injected intra-arterially to the brain stem or intravenously, indicating that the spinal cord is the site of imipramine's action. These results support our earlier proposal that a 5-HT system antagonizes bulbospinal inhibition of the MSR. They also indicate that the 5-HT system is tonically active and exerts its blocking action in the spinal cord.


Aortocoronary bypass made possible by coronary endarterectomy. Thirty bypass grafts to coronary arteries were made possible by manual core endarterectomy. The overall patency rate of the grafts was 57%, which is less than the patency rate of bypass grafts to nonendarterectomized vessels (75 to 80%). In the perioperative period and during follow-up to 29 months there was no increase in mortality or morbidity even when the endarterectomized vessel subsequently became occluded. These results represent early technical experience. Routine anticoagulant therapy in the postoperative period, to prevent early occlusion, was not used. The results of this and other studies suggest that coronary endarterectomy with bypass grafting is a useful procedure in situations where the coronary artery is so severely obstructed that standard saphenous vein bypass grafting cannot be performed; the procedure is superior to coronary endarterectomy alone.


Tumor-caused changes in host protein synthesis under different dietary situations. The effect of the AC33 tumor on protein synthesis in Lewis-Wistar rats was investigated under four different dietary regimens. The four diets used were: (a) 1.25 g amino acids plus 12.5 g glucose per day, (b) 1.25 g amino acids, (c) 1.25 g glucose per day, and (d) 12.5 g glucose per day. The rats were maintained on these four diets for 4 days. On the 5th day, 65 to 75 mg 99.2% [15N] glycine were added to the infusate and infused at a constant rate for the next 18 hr. The rats were then sacrificed and the liver, lung, heart, kidney, anterior tibialis muscle, and tumor were rapidly removed and frozen in liquid nitrogen. The rate of protein synthesis for these tissues was calculated from the ratio of 15N in the tissue protein to that in the tissue intracellular fluid. The protein synthesis rates were compared with the values found for a series of nontumor control rats fed the same diets. Relative to the control rats, muscle protein synthesis decreased on Diet 1, and liver protein synthesis increased with the three deficient diets.


Active T-rosette-forming cells in the peripheral blood of cancer patients. We  studied a subpopulation of the thymus-dependent rosette-forming lymphocytes from the peripheral blood of normal individuals and of untreated patients with solid tumors or hematological cancers. This subpopulation of the thymus-dependent rosette-forming cells (T-RFC), termed the "active T-RFC," may be relatively more immunocompetent than the total thymus-dependent population. The mean percentages and absolute numbers of active T-RFC of 40 healthy adult controls were 25.8 +/- 4.3 and 626 +/- 213, respectively. There was no difference in the percentage of active T-RFC between the controls (smokers and nonsmokers) and the 102 untreated patients with solid (localized or metastasized) tumors, 4 patients with Hodgkin's disease, or the 10 patients with non-Hodgkin's lymphomas. However, the absolute number of active T-RFC was significantly less in the cancer patients than in the controls. Eight patients with chronic lymphocytic leukemia had lower percentages but higher absolute numbers of active T-RFC, whereas 6 patients with multiple myeloma had higher percentage and lower absolute numbers than the controls. Following radiation therapy, 61 patients with solid tumors showed no difference in the percentage of active T-RFC, but the corresponding absolute numbers declined significantly. A good correlation was seen with patients having positive microbial skin test responses and normal percentage of active T-RFC. The significance of both the percentages and absolute numbers of active T-RFC and their relationship to patient status are discussed.


A radioimmunoassay for methotrexate and its comparison with spectrofluorimetric procedures. A radioimmunoassay procedure has been developed for the direct measurement of methotrexate (MTX) in plasma, serum, cerebrospinal fluid, or urine samples. The assay is sensitive to levels of at least 100 pg of MTX and is highly specific for MTX in the presence of folinic acid (citrovorum factor), folic acid, tetrahydrogolic acid, and other folate analogs and known metabolites. Results from this procedure have been compared with those obtained with a spectrofluorimetric method, utilizing the plasma of cancer patients undergoing high-dose MTX treatment with citrovorum factor rescue. Results indicate that the method should be usful in the future in assisting individualization of dosage regimens and in the study of the pharmacokinetics and metabolism of MTX in cancer patients.


Fetal antigens in nonneoplastic conditions. During studies that showed the presence of fetal antigens on the surface of human malignant melanoma tumor cells, polyvalent antisera specific for human fetal tissues of varying ages were developed. These reagents demonstrated varying patterns of expression of fetal antigens at different ages in various tissues of the human fetus. The possibility that nonneoplastic adult cells showing either maturation arrest or excessive proliferation also might express fetal antigens led to studies of human bone marrow. Although normal bone marrow cells expressed low levels of fetal antigens, large amounts were seen on bone marrow cells of patients with anemias due to iron, B12, or folic acid deficiencies, as well as on those with leukemia. Moreover, normal adult tissues adapted to long-term culture also expressed fetal antigens. After 3 weeks in organ culture adult human skin showed morphological changes similar to those seen in fetal periderm and strongly expressed fetal antigens. In addition, lymphoblasts in long-term cultured human lymphoid cell lines established from normal donors also carried surface fetal antigens. These latter antigens were shared with neoplastic B-cells (chronic lymphocytic leukemia) but not with T-cells. Their expression varied with the cell cycle. The reexpression of fetal antigens on malignant cells is thought to signal a basic derangement in the control of differentiation which is considered to be peculiar to neoplasia. However, these studies indicate that normal adult cells also may reexpress fetal antigens under circumstances unrelated to neoplasia but associated with either maturation arrest or rapid and excessive proliferation.


Olfactory receptor response characteristics: a factor analysis. The responses to odor stimulation of 22 single olfactory units in the frog olfactory mucosa were recorded with metal filled micropipettes. Seven purified odorants matched in concentration and a pure air stimulus were administered. The change in firing frequency for each unit to each chemical was evaluated to determine: (1) whether the response patterns developed across all units are different from chemical to chemical and, (2) whether individual units can be grouped in terms of their similarity of their responses to all odorants. The results of a Bartlett Sphericity test suggest that each odorant produces an independent pattern of responses across units. To answer the second question, a factor analysis was employed. It examined the responses of each unit to all chemicals and yielded 7 out of a possible 22 independent factors, suggesting that there are 7 ways by which the units studied look at the odorant stimuli and an air control employed in this study. These analyses were evaluated and discussed in terms of previously published data suggesting receptor site specificity.


Detection of T-cell lymphoma-associated antigens on cord blood lymphocytes and phytohemagglutinin-stimulated blasts. Absorption studies demonstrate that T-cell lymphoma-associated antigens detected by rabbit antisera to human T-lymphoblast cell lines are present in suspensions of cord blood lymphocytes and phytohemagglutinin-stimulated adult blood lymphocytes in amounts similar to those found in T-cell lymphoma tumor cell suspensions. Smaller amounts of antigen activity are found in suspensions of tonsil cells, thymocytes, and unstimulated adult blood lymphocytes. Little or no antigen activity is found in suspensions of lymphoblasts from patients with other types of leukemia or from B-cell lines. T-cell depletion removes antigen activity from suspensions of normal lymphocytes. These findings suggest that T-cell lymphoma-associated antigens may be fetal antigens expressed by activated T-cells.


Effect of midbrain raphé lesions or intracisternal 6-hydroxydopamine administration on D, L-5-hydroxytryptophan-14C metabolism after peripheral decarboxylase inhibition. Brain and blood 14C-5-hydroxyindole metabolism was studied in normal, raphé-lesioned and 6-hydroxydopamine (60HDA)-treated rats given L-(-)-alpha-hydrazino-3, 4-dihydroxy-alpha-methylhydrocinnamic acid (MK-486) (50 mg/kg) intraperitoneally and 5-hydroxytryptophan (5-HTP)-14C (5 muCi, 0.51 mCi/mmol) intravenously. Raphé lesioning and 60HDA treatment caused significant decrements in brain 5-hydroxytryptamine (5-HT)-14C and 5-hydroxyindoleacetic acid (5-HIAA)-14C levels and 5-HT concentrations compared to those in normal controls. In normal and 60HDA-treated rats there were decreased brain dopamine levels, possibly a consequence of non-specific metabolism of 5-HTP in brain. Blood 5-HIAA-14C levels were significantly decreased in 60HDA-treated but not raphé-lesioned rats. As increased brain 5-HT turnover was observed in raphé-lesioned rats, this may have prevented a decrease in blood 5-HIAA-14C levels. The results suggest that changes in blood 5-HIAA-14C following MK-486 and 5-HTP-14C may be related to changes in brain 5-HT-14C metabolism.


The ontogenesis of monoaminergic nerve fibres in the hypophysis of Rana temporaria with special reference to the pars distalis. In Rana temporaria tadpoles, fluorescent fibres appear in the prospective eminentia mediana, the pars intermedia and the pars distalis at Gosner's stage 25. During prometamorphosis the amount of fluorescent material increases around the developing primary capillary plexus in the eminentia mediana. In the pars intermedia the fibres form a dense fluorescent network but in the pars distalis the fibres are few and delicate. At stages 42-43, the onset of climax, the pars distalis fibres disappear. The possible functional significance of the pars distalis fibres is discussed. The background adaptation ability appears at stages 28-29, while the fluorescent pars intermedia innervation is observable at stage 25.


Tumours of the upper alimentary tract.

Tumours of the upper alimentary tract. Tumours of the oropharynx of domestic animals are common in most parts of the world, but squamous cell carcinoma of the upper alimentary tract shows differences in prevalence in different geographical areas and occurs at different sites in the various species. Oral tumours of the melanogenic system are more common in dogs than in man. The following main histological categories, which broadly correspond to those used in the classification of tumours of man, are described: papilloma; squamous cell carcinoma; salivary gland tumours; malignant melanoma; tumours of soft (mesenchymal) tissues; tumours of the facial bones; tumours of haematopoietic and related tissues; and odontogenic tumours and jaw cysts. Papilloma, squamous cell carcinoma, malignant melanoma, fibroma, and fibrosarcoma account for about 80% of the tumours that occur in the upper alimentary tract of domestic animals.


Tumours of the lower alimentary tract.

Tumours of the lower alimentary tract. THIS CLASSIFICATION IS PRESENTED IN TWO PARTS: (a) tumours of the gastrointestinal tract; and (b) tumours of the anal canal and margin. In the gastrointestinal tract the tumours are classified as adenoma, adenocarcinoma, and undifferentiated carcinoma, with several subtypes. Most polyps prove to be non-neoplastic, hyperplastic, or regenerative rather than adenomatous. Carcinoma of the stomach occurs mainly in dogs, but is a rare tumour in all parts of the world. Moderately differentiated, tubular adenocarcinoma of the small intestine with excessive fibrosis occurs in all six species; in some geographical locations it may occur frequently in sheep and cattle. The adenoma/carcinoma sequence in the rectum of the dog is similar to that in man but is encountered less often. Carcinoid tumours are very rare in domestic animals. Among the soft tissue tumours, those of smooth muscle and adipose tissue are found fairly frequently and congenital mesothelioma in the peritoneum of calves occurs occasionally. Tumours of the haematopoietic and related tissues are the most common gastrointestinal neoplasms in all species and most belong to the lymphosarcoma group. Tumours of the anal canal and margin are common in the dog and 90% of these are tumours of the hepatoid (perianal) glands.


Tumours of the liver and biliary system. In this histological classification of liver and gall bladder tumours the tumour types largely correspond to those found in man. The most common tumours in this group are liver cell adenoma, hepatocellular carcinoma, and cholangiocarcinoma.


Tumours of the pancreas.

Tumours of the pancreas. Tumours of the pancreas occur most commonly in dogs and cats and only rarely in other domestic species. The incidence of neoplasms, both exocrine and endocrine, increases with age. Exocrine adenocarcinomas are the most common malignant tumours and have three fairly distinct morphological patterns: small tubular, large tubular, and acinar cell (rare). They readily metastasize, usually before clinical signs are apparent. A "starry sky" pattern with clear histiocytes scattered among tumour cells is a regular feature of poorly differentiated areas of small tubular adenocarcinomas and undifferentiated carcinomas. Islet cell tumours occur in a significant number only in dogs. Metastases are found in about half of the tumours, but malignancy cannot always be predicted by the morphological appearance. Slightly more than half of the islet cell tumours reported in the dog have been associated with clinical signs of hypoglycaemia. Nodular hyperplasia and exocrine adenomas are sometimes difficult to differentiate. Adenomas are considered rare while nodular hyperplasia is common in old animals.


Tumours of the ovary.

Tumours of the ovary. Ovarian tumours are common in animals, the majority occurring in bitches and cows. The two most important germ cell tumours were dysgerminoma and teratoma; these morphologically resemble their counterparts in women, with the exception that teratomas in animals tend less to malignancy. The granulosa cell tumour is the most frequent sex cord-stromal tumour in all six species and it may contain luteinized areas or show differentiation towards a Sertoli cell pattern. The canine papillary adenoma and papillary adenocarcinoma, which are as common as granulosa tumours, have several features in common with their counterparts in women: they are of similar histological appearance, are frequently bilateral, and the adenocarcinomas have a great propensity for peritoneal implantation metastasis. Ovarian cysts are frequent in the bitch, sow, and cow and may originate from five different anatomical structures in the ovary.


Tumours of the female genital tract.

Tumours of the female genital tract. Tumours of the female tubular genital tract are comparatively rare, with the exception of leiomyomas in cows and bitches, uterine carcinomas and vaginal fibropapillomas in cows, and transmissible venereal tumours in bitches. Uterine adenocarcinomas of cows are highly scirrhous, often causing minimal gross lesions that remain undetected until metastatic lesions in pelvic nodes and lungs are found. Cats and bitches also develop uterine carcinomas, but less frequently than cows; when present, they are predominantly discrete masses of well differentiated, non-sclerosing adenocarcinoma. Fibropapillomas are caused by the virus of verrucca vulgaris and can be transmitted to the penis of the bull. Adenomyosis is not uncommon in the cat, cow, and bitch. There is a marked difference in the frequency with which cervical carcinomas occur in man compared with other mammals; in the latter we could find no instance of an unequivocal primary cervical carcinoma. There are a few reports describing invasive carcinomas involving the cervix, but invasion from either a uterine or a vaginal carcinoma could not be ruled out.


Tumours of the adrenal gland and paraganglia. This classification is arranged in two parts in order to take into account the different origins, structures, and functions of the cortex and medulla. The tabular classification is a simplified version of that suggested for adrenal tumours in man, and includes cortical adenoma and carcinoma, phaeochromocytoma, chemodectoma, neurofibroma, ganglioneuroma and ganglioneuroblastoma, and neuroblastoma. A detailed functional classification is not given, since the hormonal activity of many adrenal tumours in animals is less well known than it is in man. Of the tumour-like lesions listed, cortical hyperplasia is particularly important in several species.


Tumors of the kidney.

Tumors of the kidney. The most frequent renal tumours of animals are renal cell carcinoma and nephroblastoma. Renal cell carcinomas are seen mainly in dogs and cattle and nephroblastoma is encountered in pigs, puppies, and calves. Renal cell carcinomas are usually papillary in the dog. They show a marked propensity for vascular invasion, penetration of the posterior vena cava, and subsequent pulmonary metastasis. Nephroblastoma, which is morphologically identical to Wilms' tumour of children, is almost always a benign tumour in animals. It is one of the most frequent neoplasms of pigs, possibly owing to the fact that most pigs are slaughtered (and examined) when a few months old. Lymphosarcoma involving the kidney is particularly frequent in the cat, but is also seen in other species as part of a generalized disease.


Tumours of the prostate and penis.

Tumours of the prostate and penis. Tumours of the male genital tract, excluding the testes, are relatively rare in the six major domestic animals. The most important tumours are prostate carcinoma and transmissible venereal tumour of the penis in dogs, fibropapilloma of the penis in bulls, squamous papilloma and squamous cell carcinoma in horses, and squamous papilloma in pigs. Four histological types of canine prostate carcinoma exist: alveolar papillary, acinar, organoid, and poorly differentiated. The biological behaviour of prostate carcinomas is similar to that in man, with frequent metastasis to the regional pelvic nodes, bones, and lungs. There appears to be no relationship between the common diffuse glandular hyperplasia and carcinoma in the prostate of dogs. A unique lesion of dogs is squamous metaplasia of the prostate related to estrogen-producing Sertoli cell tumours of the testis. Three different transmissible tumours of the penis occur in domestic animals. The canine venereal tumours can be transmitted only by intact tumour cells during licking and coital contact, whereas bovine fibropapillomas and porcine squamous papillomas can be transmitted by cell-free material. In cattle, the fibropapillomas are caused by the same virus that produces cutaneous papillomatosis. All three tumours are benign and usually regress spontaneously.


Tumours of the nasal cavity.

Tumours of the nasal cavity. Tumours of the nasal cavity are rare in domestic animals, most cases occurring in the dog. Epithelial tumours are the most common type in carnivores (dogs and cats). In general, the same types of tumour occur in domestic animals as occur in man. There was no significant predisposition for breed in dogs, but in both dogs and cats far more males than females were affected. Metastases occurred only rarely.