Serum requirements for in vivo modulation of thymus-leukemia antigens on mouse leukemia cells and thymocytes. Mouse leukemia cells and normal thymocytes bearing thymus-leukemia (TL) cell surface antigens were previously shown to acquire resistance to lysis by guinea pig complement (C) during incubation with TL alloantiserum in vitro at 37 degrees C due to heat-labile serum activity resulting in deposition of mouse C3 onto the cell surface. The role of heat-labile serum activity and C3 in modulation of TL+ cells in vivo in mice actively or passively immunized against TL antigens was investigated. Mice of the TL-/TL+ C57BL/6J (B6) strain and the B6 congenic strain B6-Tiaa possessed poorly modulating sera, and the radiation-induced A-strain leukemia RADA1 transplanted into B6 mice passively immunized with heated (56 degrees C) TL antiserum failed to modulate; thymocytes of B6-Tiaa mice immunized similarly also did not modulate. A specific requirement for mouse C3 deposition onto RADA1 cells to achieve a modulated state was demonstrated in actively immunized TL- (B6 X A-Tiab)F1 mice in which circulating C3 and modulating activity were depleted by administration of cobra venom factor. In immunized (B6 X A-Tiab)F1 mice bearing RADA1 transplants and repeatedly given injections of B6 serum, tumor cells escaped immune destruction despite a lack of modulation. Thus modulation of TL antigenicity on tumor cells in vivo, but not tumor escape, required cell-bound C3.


Nonspecific T-cell reactivity in mice bearing autochthonous tumors or early-generation transplanted spontaneous mammary tumors. The mitogenic response to phytohemagglutinin (PHA) by spleen cells from C3H/HeJ mice bearing either autochthonous tumors or early-generation transplanted spontaneous mammary tumors was depressed in some, but not all, tumor-bearing animals. T-cell hyporesponsiveness in both groups was associated with the larger (more rapidly growing) tumor burdens. The growth patterns of the transplanted tumors and the associated PHA-induced responses were not affected by the initial tumor cell dose or by the number of in vivo passages of the tumor cell lines. Suppressor cell activity was detected in the hyporesponsive spleens of mice bearing transplanted tumors. Depletion of phagocytic macrophages, rayon wool-adherent cells, or theta-positive lymphocytes did not remove the suppressor cell activity. The mitogenic response of some but not all hyporesponsive spleens from autochthonous tumor bearers was restored after removal of phagocytic macrophages. The results demonstrated the heterogeneity of the factor(s) influencing non-specific T-cell reactivity in animals bearing spontaneous mammary tumors. Furthermore, our data suggest that nonspecific immunosuppression does not precede spontaneous tumor appearance but is probably a late result of rapid, extensive tumor growth.


[Differential use of glucagon in acute period of myocardial infarct]. The work demonstrates the efficacy of glucagon in acute myocardial infarction and its complications, particularly in bradycardia, hypotension, disorders of cardiac rhythm and conduction, cardiogenic shock, cardiac insufficiency in complete atrioventricular heart block and recurrent forms of ventricular fibrillation. A differential approach and dynamic control over the effect of the drug on the values of hemodynamics, respiration, and metabolism are necessary under the conditions of units of intensive therapy and cardioresuscitation.


[Possibilities of emergency coronary surgery in acute myocardial ischemia (clinico-experimental study)]. The work is based on the analysis of data on 20 patients with acute myocardial infarction who underwent emergency operations for aorticocoronary shunting and on the findings of 50 dog experiments. Comparison of experimental and clinical data showed that the extrapolation of experimental parameters to a sick person should be undertaken with caution and with a greater probability for groups of patients suffering from myocarial infarction for the first time and with no chronic ischemic heart disease. A time period of six hours from the moment symptoms of myocardial infarction develop is the optimum term for emergency aorticocoronary shunting. A successful operation, however, is also possible at later periods, 15 to 18 hours form the time myocardial infarction develops.


[Indications for a multiple aortocoronary bypass]. Coronarograms recorded from 101 patients with ischemic heart disease are appraised. Four hundred coronary arteries were examined, a marked stenosing process was found in 259, i. e. 2.5 affected arteries on the average per each heart. In diffuse coronary sclerosis, the most complete myocardial revascularization is only possible when the blood flow is restored in several coronary arteries. A shunt should be created on no more than 4 arteries. The anterior interventricular and right coronary arteries and the diagonal and lateral branches of the left coronary artery are used most frequently for establishing aorticocoronary shunts. The volume of the operation in multiple shunting is determined by the number of affected arteries and their anatomical distribution and physiological importance in the myocardial blood supply. It is necessary to create 2.3 shunts on the average.


[Characteristics of the hemodynamics after an aortocoronary bypass and resection of a heart aneurysm]. Autovenous aortocoronary shunt was performed in 136 patients and resection of aneurysm of the heart in 38 patients. The immediate postoperative period was studied scrupulously in 48 patients. A significant reduction of cardiac output is observed in the first 24 hours after operation for aortocoronary shunt, which is linked with the patients' severe condition before operation, the operative trauma, completeness of revascularization, and the size of the blood flow in the shunt. Study of correlations between the most important indices of hemodynamics showed that the mean pressure in the left atrium and the diastolic pressure in the pulmonary artery may reflect the functional condition of the left ventricle in the immediate postoperative period with high significance.


[Primary hereditary cristalline corneal dystrophy of Schnyder. Histopathology and ultrastructure (author's transl)]. The present study consists of light- and electron-microscopic examination of excised cornea in a case of lipid keratopathy (Schnyder) in which a perforating keratoplasty was performed. It demonstrates the deposition of cristalline and non-cristalline substances in the corneal epithelium as well as the anterior half of the corneal stroma. Histiocytic elements infiltrate the subepithelial connective tissue. Bowman's membrane is conspicuously almost totally missing. The paper concludes with a discussion of the above findings.


Increased prevalence of mature females bearing pigmented oocytes from populations of Minnesota Rana pipiens. Mature female leopard frogs, Rana pipiens, collected from several sites in Minnesota from 1967 through 1977, were examined for the presence of pigmented oocytes. An increase in the percent of mature females with pigmented oocytes was observed in the frogs captured in 1977 compared to those captured earlier. Coincident with the increase in prevalence of females with pigmented oocytes, there was a decline in abundance of the frogs.


Angina following myocardial revascularization. Does time of recurrence predict etiology and influence results of operation? To assess the operative mortality and long-term results in patients undergoing repeat revascularization for recurrent angina, we analyzed 48 consecutive patients operated upon at New York University Medical Center between 1970 and 1978. Between January, 1970, and July, 1973, 15 patients underwent repeat revascularization with five operative deaths (33 percent). Thirty-three patients underwent similar operations from July, 1973, to July, 1978, with only one operative death (3 percent). Technical factors and improved methods of myocardial protection during the operation directly influence this decrease in operative mortality rate. The indication for reoperation was incapacitating angina developing within 2 months of the inital operation in 18 patients (early failures) and after more than 2 months in 30 patients (late failures). The early failures were most commonly attributed to technical factors (33 percent) and graft occlusion by exuberant pericardial scarring (33 percent). The late failures were commonly related to the development of new native coronary lesions (47 percent) and selection of an incorrect site for distal anastomoses (23 percent). The prognostic and therapeutic implications of these findings will be discussed in detail. Angina was abolished or significantly decreased in 90 percent of the survivors, and there were only two late deaths occuring 18 and 20 months postoperatively. These data indicate that patients undergoing repeat myocardial revascularization can be operated upon with low operative mortality rates and symptomatic improvement comparable to that of patients undergoing coronary artery bypass for the first time.


Effects of methylprednisolone in cardioplegic solution during coronary bypass grafting. The effects of adding 500 mg. of methylprednisolone to each liter of cardioplegic solution were studied in patients undergoing coronary artery bypass grafts. Patients were randomly assigned to control (12 patients) or steroid-treated groups (10 patients). The cardioplegic solution was identical in the two groups except for the added methylprednisolone. Contractile element velocity (VCE and left ventricular end-diastolic pressure (LVEDP) were recorded immediately before and after perfusion in the operating room. There were no differences between the two groups with respect to these two variables or the postoperative courses. Thus this study fails to demonstrate a beneficial effect of methylprednisolone when added to cardioplegic solutions.


Diagnosis and management of fibrositis syndrome and psychogenic rheumatism. Diffuse aching and stiffness may be caused by a fibrositis syndrome or by psychogenic rheumatism. If fibrositis is present, a careful search for underlying disease is made, and appropriate therapy started depending upon the results of all diagnostic studies.


[Neurootological findings in multiple sclerosis (author's transl)]. After clinical examination of 104 patients with multiple sclerosis sensory-motor dysfunctions of the extremities turned out to be the predominant symptoms. Hypacusis, tinnitus and dizziness were mentioned by less than 15% of the patients. The investigation of the vestibular system showed often an enhanced caloric reaction and dysfunctions of the optokinetic mystagmus as well as the eye tracking test. Moreover the threshold for temperature and gustatory sensations was often enhanced. Hypacusis was found only in a few patients, in less than 30% the SISI and the tone decay test indicated neuronal dysfunctions.


[How useful is the intersaccadic interval analysis of vestibular nystagmus for clinical diagnostic (author's transl)]. The intersaccadic interval analysis of vestibular nystagmus was proposed by Cheng et al. in 1974. This method gives a statistical and sequential description of intersaccadic intervals. Until now there were no reports concerning the clinical diagnostic relevance of this method in vestibular disturbancies. Therefore, we checked 8 normal probands and 7 patients (3 peripheral, 3 central vestibular lesions, one congenital nystagmus). Compared to common nystagmus parameters like maximum speed of slow phase or minimum frequency normal probands showed a relatively high variability, as well as the patients - excluding congenital nystagmus. The maximum of intersaccadic intervals of the latter was very marked between 0,9 and 1,0 seconds. In the other cases the normally monomodal distributed maxima were between 0,2 and 0,6 sec. A multimodal distribution, as described by Cheng et al. in 1974, were to be found very seldomly. The comparison of intersaccadic interval analysis with the common nystagmus parameters showed, that in clinical diagnostic this method should not be too necessary. However, regarding scientific research - including mathematical models of vestibular nystagmus - the intersaccadic interval analysis could be useful.


[Adverse reactions in metrizamide-meatocisternography (author's transl)]. To avoid disantvantages and possible late reactions of oily contrast medium we performed 18 Meatocisternographies using the watersoluble contrast medium Metrizamide (Amipaque). Anti-convulsive premedication and clinical observance over a period of 24 h are necessary due to adverse reactions.


The visible vessel as an indicator of uncontrolled or recurrent gastrointestinal hemorrhage. Although endoscopic examination in patients with bleeding of the upper gastrointestinal tract has improved diagnostic accuracy, it has not been useful in predicting clinical outcome and has not been shown to improve the patients' prognoses. This article describes a subgroup of patients with acute upper gastrointestinal bleeding whose clinical outcome can be predicted at the time of endoscopy. In 28 of 317 patients who underwent endoscopy, a "visible vessel" was seen in an ulcer presumed to be the bleeding site. All 28 were later recommended for operation because of recurrent (86 per cent) or uncontrolled (14 per cent) hemorrhage. In contrast, 75 per cent of the remaining 289 patients in whom vessels were not seen, whether or not bleeding from ulcers, had single bleeding episodes managed medically. Since patients with a "visible vessel" can be expected to have uncontrolled or recurrent hemorrhage, surgical treatment should be considered at the time of endoscopy if such a vessel is seen.


[Laminar analysis of the synaptic organization of the frog optic tectum]. Distribution of axo-axonic and axo-dendritic synapses, nervous terminals and neuron somata in the depth of the optic tectum was studied in frog Rana temporaria L. in norm and 6-9, 60 and 134 days after contralateral eye enucleation. In outer plexiform layer 9 density of synapses was found to be maximal near the surface of the tectum; it decreased in deeper levels. In the outer zone of layer 9 (about 0.30 micrometer from the surface) many axo-axonic synapses were found. Terminals of myelinated optic fibres of large diameter ("dark" terminal degeneration) were widely distributed in layer 9. Density of axo-dendritic synapses in deep plexiform layer 5 was similar to that in layer 9. Numerous nervous terminals containing not only light synaptic vesicles, but also granular vesicles were seen in layer 5 and in adjacent zones.


[Hypothalamic hyperosmolarity in childhood (author's transl)]. Hypothalamic lesions occasionally lead to excessive hypernatraemia and hyperosmolarity which cannot be explained by defective ADH secretion alone. As osmoregulation is a complex system the clinical features differ widely from one patient to another. In general central dysregulation of osmolarity is due to diffuse hypothalamic lesions, e.g. inflammatory inflammatory infiltration by histiocytosis X or by large suprasellar tumours. We report on a ten-year-old girl suffering from a suprasellar spongioblastoma and a twelve-year-old-girl, who had been operated for a large craniopharyngioma. Polyuria and polydipsia were not present. Whereas one patient presented hypernatraemic crises and showed normal osmolarity at the intervals, the other patient suffered from sustained hypernatraemia and hyperosmolarity. In the first patient water loading led promptly to clinical and laboratory normalisation. In the other case water loading failed to decrease hyperosmolarity but led to oedema. In the first patient hypernatraemic crises were combined with decreased serum potassium levels and elevated urinary aldosterone excretion. Therefore acute and long-term trials of spironolactone treatment were successful. Exogenous ADH-derivatives failed to normalize hyperosmolarity. In the other patient, however, DDAVP decreased the serum sodium level seen with small doses.


Synaptosomal uptake of hypothalamic monoamines and recovery of pituitary-adrenal activity following medial forebrain bundle lesions in rats. The normal diurnal variation in plasma corticosterone (COR) was abolished and the response to ether stress was enhanced at 3 days following the production of medial forebrain bundle (MFB) lesions in male rats. However, by 7 days following surgery, basal plasma COR levels and the response to ether stress appeared normal. These alterations and subsequent recovery of pituitary-adrenal activity were accompanied by decreasing hypothalamic synaptosomal uptake of serotonin (5HT) and increasing synaptosomal uptake of dopamine (DA), evident at 3 and continuing at 7 days following the lesion. Uptake of norepinephrine (NE) was not affected at 3 days but showed a reduction at 7 days following surgery. The results suggest that disruption of ascending 5HT and NE fibers to the hypothalamus can alter pituitary-adrenal activity but that normal activity recovers by 7 days following the lesion. The correlation between recovery of pituitary-adrenal activity and increases in the normal uptake of hypothalamic DA suggest that DA may interact with 5HT and NE systems in the normal control of adrenocorticotrophin (ACTH) release.


L-5HTP treatment and serum 5-HT level after L-5-HTP loading on depressed patients. Based on 5-HT hypothesis, L-5-HTP (150 or 300 mg/day) was given orally to 18 depressed patients. The global estimates were 2 very much improved; 8 much improved; 3 minimally improved, and 5 unchanged. The action of L-5-HTP was usually rapid. The elevation of the serum 5-HT level 1 week after L-5-HTP administration was relatively lower in the 5-HTP nonresponder group, compared with the responders. The chronological change of the serum 5-HT level in depressed patients after an oral loading dose of 3 mg/kg of L-5-HTP showed a gradual and slight elevation, compared with manic and normal groups. It seemed that the therapeutic effect of L-5-HTP on responders was related to lower 5-HT level in the brain for their pathogenesis, and that there was a metabolic disturbance of L-5-HTP into 5-HT in some depressed patients.


Humoral immunity before and after thymectomy in myasthenia gravis. Humoral immunity was studied in 10 patients with myasthenia gravis before thymectomy, in 15 different patients over 10 years after thymectomy, and in normal controls. Antibody titers to acetylcholine receptor were significantly (p less than 0.01) lower in the post-thymectomy group. However, other antibody titers to common viruses, and to Escherichia coli, and isohemagglutinins showed no significant change. Levels of IgM and IgE (with atopic subjects excluded) decreased following thymectomy (p less than 0.05). Autoantibodies persisted, apart from those directed against the acetylcholine receptor. The absence of any significant changes in humoral immunity after thymectomy for myasthenia gravis suggests that there is no generalized loss of helper T-cell function.


Optic neuropathy and ophthalmoplegia in herpes zoster oticus. A 55-year-old man with herpes zoster oticus and minimal cutaneous involvement developed reversible optic neuropathy, and ocular motor and cerebellar abnormalities. Serologic changes confirmed infection with herpes zoster. A demyelinating process seems likely to have been responsible for these lesions. It is suggested that herpes zoster antibody titers should be measured whenever the syndrome of polyneuritis cranialis of acute onset is being investigated.


Lanthony's new color test. II. Clinical evaluation. The desaturated 15 Hue test is estimated to give about 7% false-positive single protanopic confusions. Confusions between tetartanopic and protanopic directions are not infrequent. The New Color Test findings, in general, reflect the AOH-R-R pathology but, among other things, because of the difference in their size, the classifications of both tests should not be compared. The New Color Test proves to be valuable, and can be easily employed in a routine clinical procedure. An examination scheme is proposed.


Dihydropteridine reductase deficiency associated with severe neurologic disease and mild hyperphenylalaninemia. A deficiency of hepatic dihydropteridine reductase (DHPR) activity was found in a neurologically impaired infant with mild hyperphenylalaninemia and normal levels of hepatic phenylalanine hydroxylase. DHPR is required for the regeneration of tetrahydrobiopterin, an essential cofactor in aromatic amino acid hydroxylation, a necessary step in the biosynthesis of the neurotransmitters, dopamine and serotonin. Evidence for decreased synthesis of these transmitters in this patient was provided by the finding of reduced levels of homovanillic acid and 5-hydroxyindole acetic acid, metabolites of dopamine and serotonin, respectively, in the cerebrospinal fluid and urine. Treatment with dopamine and serotonin precursors, L-3,4 dihydroxyphenylalanine and 5-hydroxytryptophan, respectively, was associated with improvement in temperament and motor tone and less frequent seizures. However, there was no improvement in gross motor function or language development.


Treatment of Haemophilus influenzae type B epiglottitis. During 1969-1977, 48 children with blood cultures proved positive for Haemophilus influenzae type B epiglottitis were evaluated and treated. The fatality rate was 2%; one child died and another developed irreversible hypoxic brain damage. Ninety-five percent of the children were intubated and none required tracheostomy. The endotracheal tubes remained in place for 3.3 +/- 1.5 days. Short-term parenteral antimicrobial therapy, 4.0 +/- 1.4 days, was sufficient to eradicate bacteremia and prevent metastatic infectious foci. This report demonstrates the excellent results achieved in the treatment of epiglottitis with brief intubation and parenteral antimicrobial therapy.


Upper gastrointestinal bleeding in children and adolescents. This is a retrospective study of upper gastrointestinal hemorrhage in 68 children and adolescents who were less than 19 years old. In descending order of frequency, the five most common causes were duodenal ulcers, gastric ulcers, esophagitis, gastritis, and esophageal varices. There was male predominance in all diagnoses except gastric ulcers and gastritis. Signs and symptoms correlated poorly with the source of bleeding. Endoscopy was the most reliable method of identifying the bleeding site. Mortality correlated with the following: (1) initial hematocrit or hemoglobin level of less than 20% or less than 7 gm/100 ml, respectively, (2) transfusion requirements of greater than 85 ml/kg of blood without surgical intervention, (3) failure to identify the source of bleeding, (4) presence of a coagulation disorder, and (5) coexistence of another life-threatening disease.


Ototoxicity in neonates treated with gentamicin and kanamycin: results of a four-year controlled follow-up study. This article reports the results of a four-year follow-up study initiated in 1970 on the long-term effects of gentamicin and kanamycin use in newborn infants. Audiometric, vestibular, and psychometric evaluations were performed on gentamicin-treated, kanamycin-treated, and untreated, matched control infants and children. No substantial sensorineural hearing loss or vestibular dysfunction was identified in these patients that could be attributed to aminoglycoside therapy. Performances on the Illinois Test of Psycholinguistic Abilities, Beery Test of Visual Motor Integration, the Peabody Picture Vocabulary Test, and on fine and gross motor examinations were comparable for the three study groups.


Physical growth in phenylketonuria: I. A retrospective study. A retrospective cross-sectional survey of phenylketonuria (PKU) was conducted in 1967. Questionnaires on 693 patients, clinically thought to have PKU, were reanalyzed to obtain information on growth in height and head circumference in patients with untreated and previously treated PKU. To provide a comparison to the growth findings of the Collaborative PKU Study, a definition of PKU was adopted to correspond to the one used in that study. Stature in 232 outpatients with untreated PKU was normal but, in 31 institutionalized individuals, the mean height was -1.4 standard deviations below the mean of a normal population. Head circumference in patients with untreated PKU was normal at birth, but showed an increasingly negative deviance with age and was -1.4 SD in untreated adults. Height measurements of 135 children with PKU in whom treatment was started before 121 days of age (age chosen to coincide with criteria for the Collaborative Study) had a significant reduction in height growth, -.8 SD. Head circumference measurements of 115 children treated for PKU were -.7 SD of normal. The depression in head circumference was less in treated subjects with PKU than in untreated ones of the same age. These findings are corroborated by a review of the literature, which contains no convincing report of normal growth during treatment of PKU.


Physical growth in phenylketonuria: II. Growth of treated children in the PKU collaborative study from birth to 4 years of age. Height, weight, and head circumference data up to age 4 years are reported for 124 children with phenylketonuria (PKU) who had been started on diet management before 4 months (121 days) of age and who were participating in the Collaborative Study of Children Treated for Phenylketonuria. Growth measurements of both the children and their parents corresponded with national and international standards. The growth of children with PKU was compared also with that of a group of normal children in the United States in whom corresponding longitudinal growth data had been obtained at the Fels Research Institute (FRI). Statistically significant differences betweeen the groups were not noted at any age. However, when these groups were compared on coefficients using curve fitting, a trend toward a greater increase in weight as they became older, noted in both sexes in the PKU study group, was significantly higher (P less than .005) in the PKU study girls compared with the FRI sample. Height growth was identical in both groups, and comparison with family data showed that the children with PKU grew as expected for their genetic endowment.


NBD-5-acylcholine: fluorescent analog of acetylcholine and agonist at the neuromuscular junction. We have studied the properties of N-7-(4-nitrobenzo-2-oxa-1,3-diazole)-omega-aminohexanoic acid beta-(N-trimethylammonium)ethyl ester, a fluorescent analog of acetylcholine at the cellular level by using pharmacological and electrophysiological techniques and at the molecular level by measuring the kinetics of interaction with solubilized acetylcholine receptor and with acetylcholine esterase (EC 3.1.1.7). The fluorescent drug is a powerful agonist of acetylcholine at the neuromuscular junction and also strongly desensitizes muscle fibers. Interaction with acetylcholine receptor is accompanied by large changes in the drug's fluorescence. From the kinetics of interaction studied by means of a stopped-flow fluorimeter with laser light source, we obtained a second-order forward rate constant in excess of 1 X 10(8) M-1 sec-1 and an initial dissociation rate constant (k1) of 0.5 sec-1 for receptor from Electrophorous electricus. Interaction of this analog with acetylcholine esterase from E. electricus is accompanied by a transient decrease in fluorescence followed by an increase leading to a stable plateau value at a level near the original one. The initial decrease in fluorescence followed second-order kinetics with k2 of the order of 10(9) M-1 sec-1. The slower consecutive reaction which could be blocked by phosphorylation of the esteratic site, was of first order with k1 = 0.05 sec-1.


Human platelet membrane receptor for bovine von Willebrand factor (platelet aggregating factor): an integral membrane glycoprotein. The platelet membrane receptor for bovine von Willebrand factor, platelet aggregating factor, has been reported to be a property of a soluble glycoprotein, glycocalicin, that is loosely attached to the platelet surface and represents one of the major glycoproteins of the platelet glycocalyx. The studies reported here, however, demonstrate that fractions from human platelets containing glycocalicin have no bovine von Willebrand factor receptor activity. Instead, only fractions containing platelet membranes have receptor activity. By using a nonionic detergent, Brij 99, active receptor can be solubilized from the membrane. Some quantitation of the intact or solubilized receptor activity is possible because the aggregation curves produced by mixtures of various dilutions of membranes and a constant concentration of standard normal bovine plasma are linear when plotted against the logarithm of the concentration of receptor. The dose-response curve obtained with Brij 99-solubilized membranes is not parallel to that obtained with intact membranes. Lectin-specificity studies of the bovine von Willebrand factor receptor, soluble in Brij 99, demonstrate binding to a wheat germ agglutinin-Sepharose 4B affinity gel but little or no binding to similar affinity gels of concanavalin A or Lens culinaris lectin. By using wheat germ agglutinin-Sepharose 4B as a lectin affinity column, partial purification of the receptor is possible. Stability studies of the receptor in intact membranes show essentially no loss of activity for at least 6 days when membranes are stored at 4 degrees C in buffers containing 1 mM EDTA. One freezing and thawing cycle results in minimal loss of initial activity but the receptor activity of the thawed material is less stable over time than is fresh material. Repeated freezing and thawing destroys the activity and, once lost, it can not be recovered, even with detergents.


Formation of 5-hydroxykynurenine and 5-hydroxykynurenamine from 5-hydroxytryptophan in rabbit small intestine. In order to clarify the role of indoleamine 2,3-dioxygenase [indole:oxygen 2,3-oxidoreductase (decyclizing), EC 1.13.11.17] in the metabolism of serotonin, DL-5-hydroxy[methylene-(14)C]tryptophan, a precursor of serotonin, was incubated with slices of rabbit ileum. Resulting metabolites were separated by DEAE-cellulose column and polyamide column chromatography and identified by various chromatographic techniques and enzymatic analysis. Metabolites obtained in significant amounts were serotonin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophol, 5-hydroxykynurenine, 5-hydroxykynurenamine, and 4,6-dihydroxyquinoline, representing 13.2, 15.8, 7.0, 21.9, 1.3, and 2.6% of the total metabolites, respectively. The first three compounds were previously reported to be major metabolites produced from 5-hydroxytryptophan by the action of aromatic L-amino acid decarboxylase and monoamine oxidase, whereas the last three are formed by the cleavage of the indole ring by the action of indoleamine 2,3-dioxygenase. In the presence of pargyline, a monoamine oxidase inhibitor, the major metabolites obtained were serotonin, 5-hydroxykynurenine, and 5-hydroxykynurenamine, representing 29.6, 26.6, and 5.4% of the total metabolites, respectively. In the presence of RO4-4602, an aromatic amino acid decarboxylase inhibitor, 5-hydroxykynurenine was the sole major product. These results strongly suggest that the newly discovered metabolic pathway involving the cleavage of the indole ring of 5-hydroxytryptophan operates in vivo to a significant extent and that indoleamine 2,3-dioxygenase plays an important role in the regulation of serotonin levels in the small intestine of the rabbit.


Dual control of cell growth by somatomedins and platelet-derived growth factor. Quiescent BALB/c 3T3 cells exposed briefly to a platelet-derived growth factor (PDGF) become "competent" to replicate their DNA but do not "progress" into S phase unless incubated with growth factors contained in platelet-poor plasma. Plasma from hypophysectomized rats is deficient in progression activity; it does not stimulate PDGF-treated competent cells to synthesize DNA, demonstrating that somatomedin C is required for progression. Various growth factors were tested for progression activity and competence activity by using BALB/c 3T3 tissue culture assays. Multiplication stimulating activity and other members of the somatomedin family of growth factors are (like somatomedin C) potent mediators of progression. Other mitogenic agents, such as fibroblast growth factor, are (like PDGF) potent inducers of competence. Growth factors with potent progression activity have little or no competence activity and vice versa. In contrast, simian virus 40 provides both competence and progression activity. Coordinate control of BALB/c 3T3 cell growth in vitro by competence factors and somatomedins may be a specific example of a common pattern of growth regulation in animal tissues.


Vasopressin stimulation of mouse 3T3 cell growth. Vasopressin is shown to be a potent mitogen for Swiss 3T3 cells. The hormone (1--10 ng/ml) causes a striking shift of the dose--response curve for the effect of serum on thymidine incorporation by cultures of 3T3 cells arrested in the G1/G0 phase of the cell cycle. In the absence of added serum, the effect of vasopressin on DNA synthesis is greatly potentiated by insulin, epidermal growth factor, and a factor isolated from medium conditioned by simian virus 40-infected baby hamster kidney cells. The mitogenic effect of vasopressin is dependent on time and hormone concentration. In the presence of insulin, the half-maximal effect elicited by the peptide is obtained at 0.6 ng/ml. [Arg]Vasopressin and [Lys]vasopressin are equally potent. The vasopressins are 10(3)-fold more potent than oxytocin. In the presence of a low (2.5%) concentration of serum, vasopressins stimulate cell proliferation.


Stereocilia mediate transduction in vertebrate hair cells (auditory system/cilium/vestibular system). The vertebrate hair cell is a sensory receptor that responds to mechanical stimulation of its hair bundle, which usually consists of numerous large microvilli (stereocilia) and a single true cilium (the kinocilium). We have examined the roles of these two components of the hair bundle by recording intracellularly from bullfrog saccular hair cells. Detachment of the kinocilium from the hair bundle and deflection of this cilium produces no receptor potentials. Mechanical stimulation of stereocilia, however, elicits responses of normal amplitude and sensitivity. Scanning electron microscopy confirms the assessments of ciliary position made during physiological recording. Stereocilia mediate the transduction process of the vertebrate hair cell, while the kinocilium may serve primarily as a linkage conveying mechanical displacements to the stereocilia.


Serotonin-norepinephrine interactions in the tremorolytic actions of phenoxybenzamine and trazodone. Phenoxybenzamine (5 mg/kg IP) and trazodone (5 mg/kg IP) reduced tremors produced in mice by administration of oxotremorine (10 mg/kg), harmaline (80 mg/kg), catechol (60 mg/kg), kepone (200 mg/kg) and clonidine (100 mg/kg). Azapetine (10 mg/kg IP) in combination with L-5-hydroxytryptophan (50 mg/kg IP) reduced the tremor induced by oxotremorine, catechol, kepone and clonidine. In mice with lower thoracic spinal cord transection, phenoxybenzamine and trazodone reduced catechol-induced tremor above and below the site of transection. These findings suggest that an alpha noradrenergic-serotonergic neuronal balance in the spinal cord may modulate tremors of different etiologies.


Evaluation of the non-specific effects of catecholamine and serotonin neurotoxins by injection into the medial forebrain bundle of the rat. Low doses of 6-hydroxydopamine (6-OHDA), 5,6-dihydroxytryptamine (5,6-DHT) and 5,7-dihydroxytryptamine (5,7-DHT) that have previously been shown to produce behavioral change following intracerebral infusion were injected into the medial forebrain bundle of the rat. This site contains serotonin (5-HT), norepinephrine (NE), and dopamine (DA) fibers whose anatomical locations have been described. Damage to these fiber systems was quantified by measuring depletion of telencephalic 5-HT, NE and DA. The effects of infusions of 6-OHDA, 5,6-DHT and 5,7-DHT were compared to the effects of unequivocally non-specific electrolytic lesions and copper sulfate infusions. Survival time was varied to evaluate the amount of regeneration that could be expected over periods from 8 to 60 days. Amine levels were found to be stable over the time period examined. With the doses used, evidence was found to support the position that non-specific damage caused by general cytotoxic effects of 6-OHDA and 5,7-DHT is minimized sufficiently to permit the acquisition of useful data on the function of central catecholamine and indoleamine systems.


"Tennis elbow"; evaluation, treatment, and prevention. This paper will assist the physical therapist in selecting and applying proper treatment for the disorder commonly referred to as "tennis elbow." The information 1) offers guidelines for determining the cause of pain; 2) assists in choosing a differential treatment plan; 3) outlines a complete, effective, and detailed rehabilitation program; and 4) includes an informative preventive program for the therapist and for the patient. The purpose of this paper is to present the information that the physical therapist needs to know in order to help the patient with "tennis elbow" return to the level of fitness necessary for participating in the athletic activity of his choice.


Detection of dilated cerebral ventricles in infants: a correlative study between ultrasound and computed tomography. Cross-sectional ultrasonic (US) and computed tomographic (CT) scans were obtained to compare their relative accuracies in determining cerebral ventricular size in 20 infants less than one year of age. The goal was to determine whether ultrasound imaging techniques could replace CT in the serial evaluation of the lateral ventricles, particularly in patients with ventricular shunts. The US images were obtained with a servo-controlled real-time sector and trapezoid scanner of the authors' own design. In 85% of the infants, biventricular width by US and CT differed by less than 0.5 cm, and in 95% by less than 1 cm.


[Contribution of EMG to the diagnosis of facial nerve and muscle involvement in neurinoma of the VIIIth nerve]. An examination of 5 cases of acoustic nerve neurinoma, and 3 cases where the diagnosis was suspected, showed that EMG signs of a possible facial nerve compression in the ponto-cerebellar angle were represented by abnormal activity at rest, sub-clinical signs of progressive neurogenic atrophy in the hemi-facial muscles, and a significant increase in the latency of the oligosynaptic R1 reflex response.


[Pulmonary function and clinical pattern in homozygous (PiZ) alpha1-antitrypsin deficiency (author's transl)]. A group of 6 males with severe alpha1-antitrypsin deficiency, underwent clinical and pulmonary function evaluation. Findings were compared to those in a group of males with different degrees of airflow obstruction, comparable ages and tobacco consumption, but with normal serum levels of alpha1-antitrypsin. The deficient group was characterized by: (1) a relatively early appearance of symptoms; (2) disturbed lung scans, mostly in the basal zones; (3) radiological evidence, in most cases, of pulmonary emphysema with, in particular, bullae in the lower lung zones; (4) hypoxemia without hypercapnia and a decreased TCO/VA, and (5) a more or less severe reduction of maximal expiratory flows largely, but not exclusively due to a decrease in lung elastic recoil. Clinical and functional parameters did not permit a clear distinction between the deficient and non-deficient groups.


Respiratory gas transport by the incompletely separated double circulation in the bullfrog, Rana catesbeiana. To investigate respiratory gas transport in the bullfrog, Rana catesbeiana (mean body weight 249 g. ambient temperature 25 degrees C), O2 uptake and CO2 output were determined, and blood gas parameters (PO2, PCO2, pH, O2 content, O2 capacity and hematocrit) were measured in blood samples taken from various heart cavities and blood vessels. Analysis of the data on the basis of a simplified circulatory gas transport model allowed to estimate the cardiac output and its distribution, and to describe the O2 and CO2 exchange in lungs, skin and tissues. The total cardiac output (average 20.5 ml/min) was estimated to be distributed about equally to the pulmocutaneous (56%) and systemic arterial vessels (44%), whereas the systemic venous return (62%) was larger than the pulmonary venous return (38%). The marked difference in oxygenation between aortic and pulmocutaneous arterial blood (average O2 saturation 85% and 47%, respectively) showed a highly effective separation of systemic venous and pulmonary venous blood in the ventricle and conus arteriosus. After enlargement of the ventricle produced by incision of the pericardium, the separation of arterialized and venous blood was markedly reduced, but not abolished.


Regulatory influences on the response of rabbit T cells to concanavalin A and phytohaemagglutinin. The proliferative response, induced in rabbit spleen cells by concanavalin A (Con A) and phytohaemagglutinin (PHA), is abolished when T cells are killed with antibody against rabbit thymus lymphocyte antigen (RTLA) in the presence of complement. The response was examined with purified spleen T cells, to which various helper cell fractions were added; it could be shown that B cells help the responding T cells. The helper effect in the response to PHA is abolished and the response to Con A is reduced by any manoeuvre which destroys or removes B cells. Help by B cells is given when helper cells have lost proliferative capacity as a consequence of mitomycin-C treatment. Spleen cells adhering to the walls of culture tubes help suspended T spleen cells in their response to Con A. This help could be abolished by complement mediated cell kill with antibody to rabbit bursal equivalent lymphocyte antigen (RABELA). On the other hand, the helper effect in Con A response was increased when T cells were removed. Thus the response of T cells to Con A is regulated by helper B cells and suppressor T cells.


Macrophage requirements of PPD-induced blastogenic factor production by T and B lymphocytes in the guinea-pig. An attempt has been made to characterize the cell type which releases blastogenic factor(s) (BF) on purified protein derivative (PPD) stimulation in complete Freund's adjuvant (CFA)-sensitized guinea-pig system and, further, to examine whether macrophages (Mphi) are required for antigen activation of T or B lymphocytes to produce this lymphokine. Both T and B lymphocyte populations from guinea-pigs 2-3 weeks after CFA sensitization (early-stage T and B cells) failed to produce significant amounts of BF in response to PPD, whereas both the populations from 10 to 14 weeks after sensitization (late-stage T and B cells) acquired the ability to produce BF by themselves. It is noteworthy that readded autologous Mphi not only functioned well to augment BF production by the late-stage T and B cells but also completely made up for the inability of the early-stage T and B cells to produce BF. From these data it is reasonable to conclude that in the guinea-pig sensitized T and B cells can both release BF on exposure to PPD and that Mphi either reconstitute or augment the BF synthetic response of T and B cells.


[Principal symptoms in hemostasis disorders]. In a retrospective study the results of laboratory investigations were correlated with actual or previous bleeding symptoms of 40 patients. In 22 patients, a defect of hemostasis was documented in the laboratory, whereas the bleeding disorder, suggested by severe hemorrhage, could not be classified in 3 additional patients. In the remaining 15 individuals, no abnormality could be detected by the available laboratory methods. In the group with a documented bleeding disorder, 13 of 22 patients had prolonged bleeding following dental extraction or other surgery of the oral cavity. Other bleeding symptoms were equally distributed among patients with and without a documented defect. 3 patients had a positive family history, i.e. relatives with a hemorrhagic tendency. In 6 patients, a correlation between bleeding and the ingestion of acetylsalicylic acid could be established, while in 4 it was probable. Hemorrhagic complications following oral surgery, particularly in combination with drugs known to interfere with platelet function and a positive family history, strongly suggest an abnormality of hemostasis. Among the 22 patients with a documented defect of hemostasis, only 6 were found who did not present at least one of these leading symptoms.


The role of central 5-hydroxytryptamine in acupuncture analgesia. The role played by central 5-hydroxytryptamine (5-HT) in acupuncture analgesia (AA) has been studied in rats with the tail-flick response as the antinociceptive test. The analgesic effect of acupuncture can be enhanced or lowered by the increment or the decrement of the 5-HT level in the CNS. Furthermore, the turnover rate of 5-HT in the CNS has been found to be greatly facilitated during the period of acupuncture. The results imply that 5-HT in the CNS may be one of the most important neurochemical agents mediating AA.


Voltage dependence of junctional conductance in early amphibian embryos. Isolated pairs of blastomeres from early amphibian embryos (Ambystoma, Rana, Xenopus) are electrontonically coupled. Junctional conductance and permeability to the dye Lucifer Yellow are markeldy and reversibly decreased by moderate transjunctional polarization in either direction. The relationship between junctional conductance and transjunctional voltage is sufficiently steep that a physiological role in regulation of intercellular communication is plausible.


Left main coronary artery disease.

Left main coronary artery disease. Eighteen patients with significant stenosis of the left main coronary artery are reported and compared with 1,040 patients described in the ten largest published series. In comparison to previous reports, our patients have a higher incidence of congestive heart failure, previous myocardial infarction (especially inferior wall), poorer left ventricular function, and more advanced coronary artery disease. Despite this, there was no increased risk during catheterization and bypass surgery. This small group of patients reflects the modern experience that, with increasing awareness of this lesion, there need not necessarily be a higher risk during diagnostic studies and therapeutic intervention.


Reflux oesophagitis resembling varices.

Reflux oesophagitis resembling varices. Three cases of established reflux oesophagitis resembling varices are presented. Although the condition is rare, the importance of distinguishing oesophagitis from varices is pointed out in order to avoid unnecessary arteriography and surgery.


Determinants of restricted aorta-coronary bypass graft flow. Several causes of restricted graft flow in a series of 99 patients could be identified by intraoperative measurements of aorta-coronary graft flow and poststenotic pressure. Mechanical stenosis as well as functional restriction of graft flow caused by competition between vein and native artery flow were noted in cases with a mildly stenotic artery or in cases with multiple coronary stenoses grafted to the same vessel. Also, analysis of regional wall motion showed that graft flow may be restricted when supplying areas with reduced wall motion. Knowledge of preoperative coronary anatomy and left ventricular function and careful intraoperative measurement of graft haemodynamics may aid in distinguishing between technical, functional, and myocardial factors of low graft flow.


Thermocardiography--a method for continuous assessment of myocardial perfusion dynamics in the exposed animal and human heart. In the exposed animal and human heart, coronary flow reduction results in a significant decrease of regional myocardial temperature. Epicardial temperature can be recorded instantaneously by the use of thermography. In contrast to other techniques, this method allows continuous assessment of rapid coronary flow changes and shows exactly the extent of myocardium involved. Value and limits of thermocardiography in animal experiments and during coronary bypass surgery are discussed and typical examples of myocardial thermograms obtained at various interventions are shown.


Clinical and pathologic studies of gastrointestinal hemorrhage in acute leukemia. One hundred and sixty cases of acute leukemia observed at our Department between 1953 and 1977 were reviewed as to the presence and nature of the accompanying gastrointestinal hemorrhage. A massive gastrointestinal hemorrhage requiring blood transfusions occurred in 29 cases (18%). The most common lesion was hemorrhagic necrosis of the small intestines. There were three forms of hemorrhage: Type I: thrombocytopenia, hemorrhagic diathesis, diffuse hemorrhage of mucosa and submucosa, but no erosion nor ulceration. Type II: no specific pathologic findings. Diffuse hemorrhage, superficial erosions, bacterial and fungal invasions were observed. Type III: single and/or multiple ulcerations, necrosis and perforation of the small intestines and colon. Thrombocytosis was almost always present at the prebleeding phase in these cases. Intravascular microthrombi at the basis of ulceration were seen. Usually, more than one process were seen in each case. An appropriate approach to the severe gastrointestinal hemorrhage with a combination of anti-leukemic chemotherapy, anti-coagulant therapy, platelet transfusion, etc. would further add to the number of long-term survivors in acute leukemia.


[Examinations carried out in order to determine the effects of a radiotherapy on the immunity situation of tumor patients (author's transl)]. In order to evaluate the immunity situation, the percentage of B- and T-lymphocytes in the peripheral blood of tumor patients was determined before, during, and after radiotherapy. Corresponding to the tumor types, the patients were submitted to adequate irradiations with different localizations, field sizes, and doses. Most of the patients had a reduced percentage of T-cells which partly was accompanied by a so-called reverse effect, i.e. a relative increase of the percentage of B-cells. It was not possible to demonstrate any connexion between the decrease of the number of B- or T-cells and the field size, localization, and dose height.


Vein allografts for arterial replacement in rats: an immunological and histological study. Vein allografts were studied in the rat using the major histocompatibility complex-incompatible DA and Lewis inbred strains. Allografts were performed in the Lewis to DA and DA to Lewis combinations, with Lewis to Lewis isografts serving as controls. Vein grafts were performed by interposing a 1 cm length of fresh iliolumbar vein into a defect of the iliac artery, using microsurgical techniques. The grafts were under observation for 18 weeks for (1) patency, (2) gross structural changes, (3) histological changes, and (4) antibody responses. No immunosuppression was used. All grafts remained patient throughout the period of observation, although aneurysm formation was noted in some allografts toward the end of the observation period. Histologically, allografts and isografts were indistinguishable. In the first 2 weeks, they showed patchy areas of necrosis in the vein walls, with subsequent intimal hyperplasia and medial fibrosis. In both strain combinations a lymphocytotoxin response was induced in most animals, the response being particularly strong in the DA to Lewis combination. All cytotoxic activity could be absorbed out using red blood cells, suggesting that the specificity of the antibody was mainly or entirely directed against SD antigens.


Decreased hybrid susceptibility to murine myeloma grafts. The behavior of BALB/c myeloma transplants in (C57BL/10 X BALB/c)F1 hybrids was investigated. The F1 hybrids were less susceptible to the grafts than were the parental BALB/c hosts. Host susceptibility was X-ray and cyclophosphamide sensitive, but an immune hypothesis was not favored since no memory was demonstrable. Males were less susceptible than females, and rabbit antithymus serum had no effect on susceptibility.


Improved results of carotid endarterectomy in patients with symptomatic coronary disease: an analysis of 1,546 consecutive carotid operations. The significant risk of fatal myocardial infarction after carotid endarterectomy in patients with coronary disease long has been recognized. In 1,546 consecutive carotid endarterectomies performed in 1,238 patients over the last 10 years, angina pectoris was present in 17% (212/1,238) of patients; a further 32% (396/1,238) of patients were asymptomatic, but had a history of myocardial infarction. The perioperative mortality (30 day) in the 1,306 consecutive endarterectomies in 1,026 patients without symptomatic coronary artery disease was 1.5% (15/1,026 patients). Of the 212 patients with symptoms, 85 carotid endarterectomies were performed in 77 patients without prior coronary bypass operation with an operative mortality of 18.2% (14/77 patients). The remaining 135 patients had 155 carotid endarterectomies but were treated by either prior coronary artery bypass (84 patients) or simultaneous carotid endarterectomy and coronary artery bypass (51 patients) with an operative mortality of 3% (4/135 patients). The greatly improved survival in those patients with symptomatic coronary disease who had a coronary artery bypass prior to or at the same time as carotid endarterectomy, and the absence of permanent neurological deficit in the 51 of these 135 patients who had simultaneous carotid endarterectomy and coronary artery bypass suggests that significantly improved survival can be achieved after carotid endarterectomy in these high risk patients by the use of simultaneous coronary artery bypass surgery.


[Clinico-endoscopic classification of Mallory-Weiss syndrome]. Mallory--Weiss syndrome was diagnosed in 153 of 1373 patients subjected to endoscopy for acute gastroduodenal and esophageal bleeding. Besides, this syndrome was first diagnosed at operation in 10 cases, at roentgenoscopy in 8 cases and at autopsy--in 8 cases. A classification of Mallory--Weiss syndrome with regard to the localization of fissures of the organ mucous membrane, the depth of the injury to the organ wall, the degree of the acute blood loss, and to the forms of manifestations of the syndrome has been devised. The classification has a practical importance for it helps the surgeon to choose the method of the treatment of the patients with Mallory--Weiss syndrome.


Gastrointestinal complication of high-dose corticosteroid therapy in acute cerebrovascular patients. Corticosteroids are commonly used in the treatment of stroke, although their clinical effectiveness has not been established. Side effects, especially gastrointestinal complications, occur in patients with cerebral disease. A necroscopy study of 124 patients investigated the occurrence of gastrointestinal lesions in patients with acute stroke treated with high-dose of corticosteroids compared to untreated patients with stroke and to patients dying from non-vascular neurological diseases. A significant relationship between the use of steroids and gastrointestinal lesion in strokes is demonstrated.


The Warren shunt in treating bleeding esophageal varices. In patients who have impaired hepatic reserve, the Warren shunt has been proposed as an effective operation because it decompresses the esophageal varices without disturbing portal perfusion of the liver. However, early reports of high operative mortality and technical difficulties have impeded acceptance of the procedure. The operation was done in a series of 17 patients. All patients in whom elective variceal decompression with a patent splenic vein was required and without clinical ascites were candidates for this operation. Follow-up ranged from 2 to 48 months. Six patients had alcoholic cirrhosis, two had primary biliary cirrhosis and seven had postnecrotic cirrhosis; in two the cause of the liver disease was unknown. Five patients were categorized as Child's class A, nine as class B and three as class C. No intraoperative or early postoperative deaths owing to hemorrhage occurred. However, there was one death two weeks postoperatively from pulmonary sepsis and one death five weeks postoperatively due to antigen-positive hepatitis. Two patients died from hepatic failure six weeks and five months after operation, respectively; in the first of these, chronic active hepatitis was diagnosed at the time of operation. In one patient hemorrhage recurred and transfusion was required. Although ascites, which eventually resolved, developed in eight patients after operation, the results in 76 percent of patients have been good without new episodes of hemorrhage or encephalopathy. We conclude that the Warren shunt is a safe and effective elective operation for the treatment of patients in whom hemorrhage from esophageal varices has occurred.


[Anodically moving thermolabile antigen (ATA) of Gram-negative bacteria. Its antibody-forming capacity in rabbits and mice]. Injection of purified ATA as well as of ATA-containing crude sonic extracts of gram-negative bacteria into rabbits or mice causes rapid occurrence of anti-ATA antibodies. Thus, the retarded occurrence of anti-ATA antibodies after immunization with living bacteria can be explained by the rather deep localization of ATA in the cell wall.


Value of apexcardiography for the timing of left ventricular events in man. The time relationship between left apexcardiogram and left ventricular pressure was studied in 56 patients with heart disease. The apexcardiogram was recorded by means of a pressure transducer in 20 patients (group I). In 36 patients a displacement transducer was used (group II). The beginnings of the systolic upstroke of left ventricular pressure and left apexcardiogram were nearly simultaneous in both groups. The protodiastolic nadir of the apex tracing, however, preceeded the corresponding point on the pressure tracings by 23.8 msec in group I and 7.8 msec in group II (mean values). The peak of the first derivative of the apexcardiogram in group II preceeded the peak of the first derivative of the intraventricular pressure by a mean of 13.4 msec. In group I the time difference was small and statistically insignificant. It is concluded that apexcardiography allows an accurate determination of the onset and time course of ventricular contraction but is less precise for the determination of the protodiastolic nadir.


In vitro studies on lymphocytotoxicity to synovial cells and Chang cells in rheumatoid arthritis patients and healthy controls. Lymphocytotoxicity to autologous or allogeneic synovial cells and Chang cells was studied in 27 patients with rheumatoid arthritis (RA), in 5 patients with osteoarthrosis of the hip or knee and in 17 healthy controls. Ficoll gradient-separated lymphocytes from the peripheral blood, T cells and non-T cells were used as effector cells. T lymphocytes were isolated as E-rosette forming cells 10 percent of which carried Fc- receptors. The differential counts for T and B cells in the peripheral blood of the RA and osteoarthrosis patients were approximately the same as in the blood of the healthy controls. The counts of Fc-receptor-bearing cells in the RA patients were, however, significantly higher. Cytotoxic reactivity of lymphocytes from RA patients, osteoarthrosis patients or healthy controls to synovial cells of autologous or allogeneic origin could not be demonstrated in our study, in which 125I-iododeoxyuridine labelled target cells were used in the microcytotoxicity test of Cohen et al. However, lymphocytes of the peripheral blood showed an increased cytotoxicity to Chang cells, an effect for which Fc-receptor bearing cells were responsible. Serum did not affect the cytotoxicity of lymphocytes. The results are interpreted as demonstrating an enhanced natural killer (NK) cell activity in RA patients; they do not indicate a specific cell mediated immune reaction to synovial cells.


Influence of resting ECG abnormalities on the ECG response to maximal exercise in women suspected of coronary heart disease. Coronary arteriographic data have been compared with the ECG response to a maximal exercise test in 53 women with typical or atypical complaints of angina pectoris (AP). All patients with factors known as influencing the repolarization at rest were eliminated and the cases were subdivided according to the presence of a normal (n=26) or abnormal (n=27) resting ECG. The sensitivity (88%) and specificity (81%) of the exertional ECG was not affected by the clinical history nor by the resting ECG data. False positive responses were frequent (32%), particularly among women with atypical AP (50%), but their prevalence was not influenced by the resting ECG data. We conclude that, even in the absence of drug therapy, non-specific resting ECG abnormalities do not influence the ECG response to exercise in women and that they cannot be considered as a factor contributing to the false positive responses: the latter appear to be related to the low prevalence of coronary artery disease in women.


[Scintigraphy in the diagnosis of tumors of the 8th cranial nerve]. The indications for and the diagnostic value and the method of radioisotope gammaencephalography (GEG) in tumors of the 8th nerve and similar diseases (47 cases) were studied. The optimum time for conducting scintigraphy for the detection of tumors of the 8th nerve is 2 1/2-3 hours after injection of the isotope. Small tumors up to 2 cm in size are not revealed by GEG, stage II and stage III tumors are clearly demonstrated. GEG makes it possible to differentiate tumors of the 8th nerve from arachnoiditis of the cerebellopontine angle and stem encephalitis.


[Reversible sinus dysfunction during treatment with lithium carbonate]. The case reported concerns a symptomatic transitory sinus node abnormality in a 75 years old woman treated with Lithium Carbonate (750 mg/d) for a manic-depressive psychosis. This patient, admitted to the hospital for bradycardia and repeated episodes of syncope was shown to present sinus pauses greater than 3 seconds. Lithium therapy was discontinued. 72 hours later electrophysiologic studies, performed to evaluate sinus node function, were normal. It is therefore the author's opinion that in patients receiving Lithium therapy who present syncope, dizziness, or bradycardia a sinus node abnormality of iatrogenic origin must be considered. The importance of this diagnosis is in the rapid reversibility of the sinus node dysfunction with discontinuation of therapy.


[Conduction abnormalities in Kearns-Sayre syndrome. Observation of 2 clinical cases]. The authors describe 2 cases of Kearns-Sayre Syndrome associated with conduction defects. In one case permanent pacing was performed. The progressive development of severe conduction defects warrants close follow-up.


Transient abnormal Q waves during acute myocardial infarction. A 65 years old woman with an acute myocardial infarction, as it was judged by serial enzyme changes, developed transitory Q waves in V2-V4 and II, III and AVF during the attack of chest pain. These Q waves were not present 12 hours later. It is suggested that these changes represent a focal block in the septal fibers of the left bundle system. This defect could explain the transient right precordial Q waves seen in myocardial infarction or ischemia, as well as the fixed Q waves of many patients without septal infarction at autopsy.


The contribution of nuclear medicine and ultrasounds in cardiac surgery. The constant progress in surgical techniques during the last few years have prepared the way for important developments in the field of noninvasive cardiac exploration. Their non-traumatic character, appreciable in diagnostic and preoperative examinations, become indipensable whenever there is a need to repeat the examination in order to evaluate the effects of a treatment or to monitor progress both in the short and long term. In order that such methods be adopted in cardiac surgery it is important that not only must they be without risk but also that the results obtained be clearly presented, if possible in the form of images, and allow a quantitative interpretation. It is necessary also that the results can be justified both by clinical experience and also by comparison with other examinations. No procedure, not even radiologic, can at the same time explore the myocardium and its perfusion, the central circulation and the cardiac haemodynamics. By reason of their respective principles, radioisotopic methods and ultrasounds tackle cardiac problems in different ways and facilitate, by appropriate choice of methods, the selection of one diagnostic response from among several. This paper contains first of all, a resume of the principal nuclear and ultrasonic techniques used together with their basic principles. Next we try to show how these non-invasive techniques, most with dynamic imaging, can assist cardiac surgery. For this, we successively look at the different pathologies, working from the exterior (pericardium) towards the interior (intracardiac structures and central circulation) and covering the different aspects of the myocardial pathology. In each case the mutual contributions of physical techniques is specified as well as the preference for either isotopic or ultrasonic methods.


[Left ventricular ejection time in aortic valve diseases. 1. Multidimensional relationship with biometric and physiologic findings]. The purpose of this work is to settle biometrical and physiological factors linked to changes in ejection time in aortic valvular disease. The relationship between the various considered variables is submitted to multivariate statistical analysis, and expressed by a prediction formula. Data are provided by a series of 160 aortic patients whose examination notably includes measurement of cardiac output and of pressures in left ventricle and aorta, a cineangiography in the ascending aorta, and a search for aortic valvular calcifications with an image intensifier. Moreover, the already published results of a reference series of 200 subjects without aortic disease, are also used. Multivariate relationship of ejection time appears to be, on the whole, similar in the reference series and in the aortic series, with besides, in the latter, a significant effect of aortic "gradient" and incompetence. Consequently these two marks of aortic disease may be indirectly predicted from the residuals of the reference formula applied to aortic patients.


Left ventricular ejection time in aortic stenosis and insufficiency: 2. Indirect assessment of the severity of the lesion. The purpose of this work is to reconsider practical value of three prediction formulae of left ventricular ejection time (LVET): the Wood's coefficient, the Weissler's residual and the multivariate residual. Two series of patients are presented: (1) an aortic series of 160 patients, with pure or nearly pure stenosis in 46 cases, pure insufficiency in 57 cases, and stenosis plus insufficiency in 57 cases, and (2) a reference series of 200 patients without aortic disease. All the patients were catheterized, with measurement of cardiac output by Fick's method. In all the aortic patients, the aortic "gradient" was measured, the amount of aortic regurgitation assessed by cineangiography, and the presence of absence of aortic valve calcification checked with an image intensifier. LVET tends to increase according to the importance of the "gradient" and of the insufficiency. However, the isolated use of this increase as a predictor of severity of aortic lesions is not more rewarding than just looking for aortic valve calcification except in pure aortic insufficiency. Sensitivity or specificity of the prediction can be increased by various combinations of both observations--LVET and calcification--; their respective interest will depend upon the target. Probability of false positive or negative predictions can be estimated in both series of patients and in various subgroups of aortic lesions. False negative predictions have been analysed in patients with pure or nearly pure stenosis and a "gradient" of 50 mm Hg or higher . Based on any of the three LVET predictions formulae, they are chiefly observed in the absence of calcification--i.e. in younger patients--probably because stenosis here is less severe. Based on the Wood's or Weissler's coefficient, false negative predictions are also relatively frequent in patients with a decreased stroke volume; this doesn't occur if the LVET prediction formula takes stroke volume into account, as in the multivariate residual. Three types of patients with pure or nearly pure stenosis and a "gradient" of 50 mm Hg or higher can be described: (a) without calcification and with a normal stroke volume: the patient is young, his stenosis is moderately severe, and LVET tends to increase but most often remains within normal limits; (b) with calcification and a normal stroke volume: the patient is notably older, his stenosis is severe, and LVET is most often increased; (c) with calcification and a decreased stroke volume at rest, which suggests a decreased myocardial performance; here, age and stenosis are similar to the preceding subgroup observations, but LVET is often normal if stroke volume is not taken into account.


Rheumatic tricuspid stenosis. A clinical overview. The clinical, hemodynamic findings and surgical results of forty patients with rheumatic tricuspid stenosis are presented. It is concluded that tricuspid stenosis is a frequent lesion. Its signs should be sought carefully and documented by simultaneous measurements of the right ventricular diastolic and right atrial pressures. Tricuspid stenosis is usually associated with other valvular lesions, whose clinical and hemodynamic findings might be altered. Surgical procedures on these patients involved tricuspid valve repair, commissurotomy or prosthetic valve replacement, in addition to the procedures necessary to correct other associated valvular lesions. Results of surgery were gratifying with significant improvement in 87 percent of patients and a mortality of 3 per cent.


[Quantitative evaluation of the efficacy of anti-arrhythmia agents in chronic ventricular arrhythmia]. The authors describe a computer system for the analysis of ventricular arrhythmias and its use in the evaluation of anti-arrhythmic drugs. Provided the arrhythmia is stable, this method allows an estimation of the onset and duration of action of the drug and gives guidelines for the choice of an appropriate drug regimen. Using this system, a comparison can be made between different drugs based on quantification of their efficacy.


Aortic root motion for the assessment of left ventricular function in acute myocardial infarction. In a group of patients with various cardiac disorders positive correlation between aortic root motion amplitude and stroke volume was observed: (y=3.41 + 0.061 chi, r=0.719n=27), where y is the aortic wall motion amplitude in mm and chi is the stroke volume in ml. During the serial investigation of 40 patients with acute myocardial infarction aortic root systolic motion amplitude was significantly different between patients groups, selected by the categories of Killip (1967). Biggest amplitudes were found in patients with complicated course, smallest amplitudes in cardiogenic shock. Aortic root systolic motion increased in a parallel direction with the clinical improvement of the patients. Aortic root echos are easily detectable, independent from segmental dysfunction, therefore useful in monitoring of left ventricular function of patients with acute myocardial infarction.


Temporary tinnitus suppression in man through electrical stimulation of the cochlea. While investigating the possibilities of electrically induced hearing in cases of profound deafness, we observed that very often an appropriate stimulation of the cochlea could result in tinnitus cancellation. We present here a progress report on that phenomenon, including 15 subjects. Such a cancellation was restricted to tinnitus subjectively localized in the ear under test, we observed no effect on noises localized in the other ear, or centrally. This suppression occurred so long as the cochlea was stimulated and stopped when the stimulation ceased. This phenomenon was very reproducible and did not seem to affect simultaneous normal acoustic hearing. It is hypothesized that this phenomenon acts through an inhibition of abnormal activity of sensorineural elements of the electrically stimulated cochlea.


Conflicting electrophysiological and anatomical data from drug-impaired guinea pig cochleas. In guinea pigs that had been treated with very large doses of the aminoglycoside amikacin (14 x 450 mg/kg/day, i.m.) clear, short-latency responses to various click stimuli could be recorded at the round window. When the same cochleas were examined histologically, no outer or inner hair cells could be found along the entire length of the basilar membrane, save for a very few outer hair cells remaining at the apex. The response patterns resembled that of the compound action potential, and various characteristics suggest that they were of neural origin. Vestibular function, investigated by electronystagmography during rotation, appeared normal, as did most of the saccular and utricular hair cells. Transmission electron microscopy revealed a significant number of cochlear nerve fibres still innervating the remnants of Corti's organ. In other cochleas with similarly extensive destruction induced by another aminoglycoside (sisomycin, 14 x 125 mg/kg/day, 15 days as well as 3 months post-Rx), no responses could be recorded from the round window. Cochleas that were less affected, with the upper turns preserved, gave only small, long-latency responses. These preliminary observations are confirmed by further experiments now in progress. They suggest that unless a considerable number of inner hair cells remained undetected in the lower basal turn, a possibility that appears highly unlikely, there was either a direct mechanical excitation of cochlear nerve fibres, or an acoustical stimulation of vestibular sense organs.


Prospects and limitations of systematic monitoring in patients with laryngeal cancer. The authors report the first results concerning the systematic use of "immunological monitoring" in patients suffering from well-developed laryngeal cancer. The authors have also studied, in 50 cases in different stages of development, the activity of T-cells using the cutaneous tests (BCG, PPD, PHA and SK-SD), the E-rosette test and the PHA-induced lymphocytic blastization test (it is well known that the T-cells are responsible for a cytotoxic effect against neoplastic cells). The authors have also studied the activity of B-lymphocytes by means of the EA and EAC rosette test and of IgG, IgA, IgM and complement serum titles. They have observed a progressive depression of the T-cell activity after surgical intervention, whereas the B-cell activity in several cases tends to increase. The authors discuss these immunological results and the possibility that these findings may represent the basis for a complementary immunotherapy following the surgical treatment and/or radiotherapy or chemotherapy. Finally, the authors discuss the possibilities and the limitations of these immunological methods from the point of view of clinical application.


New concepts in otitis media.

New concepts in otitis media. Pneumatic otoscopy increases the physician's diagnostic acumen. Movement of the tympanic membrane is observed and measured more precisely by tympanometry and acoustic impedance. Ampicillin-resistant strains of Hemophilus influenzae are appearing. It is possible to detect these with deep nasopharyngeal cultures. New reports show the value of antimicrobial prophylaxis in recurrent otitis media. High-risk populations that deserve special attention are children with cleft palate and Down's syndrome.


Occlusive disease confined to the right coronary artery: clinical features, surgical treatment and long-term follow-up in 124 patients. The clinical presentation and surgical results in 124 consecutive patients who underwent aorta to right coronary arterial bypass surgery from January 1970 through June 1977 were reviewed. Preoperatively, 75 percent of the patients were in New York Heart Association functional class III or IV, 9 percent presented with unstable angina and 5 percent had life-threatening ventricular arrhythmias. All patients had high grade occlusive disease confined to the right coronary artery; 34 percent of the patients had associated nonsignificant disease (less than 50 percent intraluminal narrowing) of the left anterior descending or circumflex artery. Left ventricular function was normal in 63 percent and minimally impaired in 37 percent. The operative mortality rate was 1.6 percent. The course of the 122 survivors was followed up for 3.7 years. There were four late deaths, and the 5 year mortality rate was 4.0 percent. Eight patients were reoperated on because of recurrence of symptoms and occlusion of the graft or progression of occlusive disease of the other major coronary arteries, or both. Of the remaining 110 patients, 98 are either in functional class I or II, 60 are taking no cardiovascular medications, 52 are working full time without angina nad 73 are asymptomatic. In summary, bypass surgery for isolated right coronary artery disease has a low mortality rate and results in excellent long-term symptomatic improvement.


Revascularization of the right coronary artery. This study was undertaken to evaluate revascularization of the right coronary artery with regard to factors that enter into the decision to graft less significant lesions, such as graft flow, graft patency and progression of proximal disease. The results of grafting the right coronary artery were studied in 23 patients with lesions reducing luminal diameter by less than 50 percent (Group 1), 35 patients with luminal narrowing of 50 to 70 percent (Group 2) and 112 patients with greater than 70 percent luminal narrowing (Group 3). At operation there was no significant difference in saphenous vein graft flows among the three groups. Postoperatively the mean follow-up period was 20, 27 and 26 months, respectively. Graft patency was not significantly different among the three groups. Progression of the proximal lesion was studied and compared with that in 71 ungrafted right coronary arteries, 60 with less than 50 percent stenosis and 11 with more than 50 percent stenosis. Among vessels with less than 50 percent narrowing, the proximal lesion showed progression in 26 percent of the ungrafted vessels and in 83 percent of the grafted vessels (P less than 0.005); progression to total occlusion occurred in 3 percent of the former and in 28 percent of the latter (P less than 0.005). Progression to total occlusion was more frequently associated with a patent than with an occluded graft (P less than 0.05). The occurrence of significant progression in ungrafted vessels and the lack of effect on graft patency of the severity of the proximal disease suggest that revascularization of less significant lesions may be of value. However, the resultant increase in progression of proximal disease makes the patient dependent on the long-term patency of the vein graft.


Reduction of intimal thickening in canine coronary bypass vein grafts with dipyridamole and aspirin. The potential benefit of platelet inhibitor drugs on coronary arterial bypass vein grafts was assessed in dogs with magnification-corrected angiographic luminal measurements and quantitative histologic evaluation of the vein grafts. There were 11 control animals and 11 animals treated with dipyridamole, 55 mg/day, plus aspirin, 325 mg/day. Eighteen animals with patent grafts were studied when electively killed 2, 4 or 6 months after grafting. At 14 days, there was greater angiographic narrowing in the most distal 1 cm of vein grafts in control than in treated dogs (P less than 0.01). This same angiographic narrowing persisted in control dogs until they were killed (P less than 0.03). Computer-assisted measurements of the entire area of intimal thickening were done on vein graft cross sections taken 1 cm from the distal anastomosis. The circumference of the vein grafts at the intimal-media junction was measured from the same section and the potential maximal luminal area calculated. The calculated luminal narrowing due to intimal thickening was greater in control than in treated dogs (P less than 0.03). These data correlate well with the demonstrated angiographic narrowing. The findings indicate that the degree of early intimal thickening that persists 2 to 6 months postoperatively in canine coronary bypass vein grafts may be reduced by the platelet inhibitor combination of dipyridamole plus aspirin.


Relationships among crude fiber, neutral detergent fiber, in vitro dietary fiber, and in vivo (rats) dietary fiber in wheat foods. The in vivo dietary fiber contents of wheat milling fractions and wheat foods, determined in rat feeding experiments, were compared with dietary fiber values determined in vitro with pronase alpha-amylase digestion. Both types of dietary fiber values were compared with crude fiber and neutral detergent fiber values in the same materials. Regression analyses indicated close correlation amongst all values determined. It appears that laboratory analysis for crude fiber, neutral detergent fiber, or in vitro dietary fiber accurately predicts in vivo dietary fiber (rats) for wheat milling fractions when the laboratory result is adjusted by means of an appropriate regression equation.


Effect of postnatal malnutrition on pancreatic zymogen enzymes in the rat. In order to characterize the response of the pancreas to undernutrition during the critical neonatal growth phase, acquired postnatal malnutrition was induced in the rat, using the expanded litter. An experimental nursing litter of 16 rats and control litters of 7 to 8 rats were formed. At 19 days of age, the pups were killed. Mean pancreatic wet weight was decreased in the malnourished rat to a greater extent than the decrease in total body weight (49 versus 60%). Decreased organ weight was predominantly the result of a decrease in DNA content and cell number. Enzyme activities expressed per total organ were all diminished; lipase to the greatest extent; trypsin and amylase to an intermediate extent; followed by chymotrypsin and the carboxypeptidases. The specific activities of lipase and trypsin were decreased with lipase, the most severely effected. The low trypsin levels can be attributed to trypsin inhibitor. It is possible therefore, that only the specific activity of lipase is significantly decreased. The decrease in enzyme activities, expressed both as specific activities and as total organ activities were decreased in a nonparallel fashion.


I. Depressed immunological function in zinc-deprived rats as measured by mitogen response of spleen, thymus, and peripheral blood. The in vitro responses of splenic, thymic, and peripheral blood lymphocytes to two T-cell mitogens (phytohemagglutinin and concanavalin A) and one B-cell mitogen (pokeweed mitogen) were investigated in zinc-deprived and pair-fed control rats. The responses to phytohemagglutinin of splenic, thymic, and peripheral blood lymphocytes from zinc-deprived animals were depressed by at least 50% in comparison with those of controls, and the difference between the two groups was significant for each tissue (P = 0.05). The responses to concanavalin A of splenic and peripheral blood lymphocytes were suppressed in zinc-deprived animals, and splenic and thymic responses to pokeweed mitogen were depressed by about 50% in comparison with those of controls; these results were significant at the P = 0.05 level. This study is the first to evaluate the effects of diet-induced zinc deprivation on lymphocyte transformation and immune function in rats.


Endophthalmitis associated with Haemophilus influenzae type b bacteremia and meningitis. The unusual occurrence of endophthalmitis associated with Haemophilus influenzae type b bacteremia and meningitis was confirmed in three young children during a five-year period. In contrast to bacterial endophthalmitis attributed to other microorganisms, these three infections resolved completely within a few days with conventional antimicrobial therapy. Endophthalmitis is but one of the apparently increasing number of unsuual complications that may be observed as a result of H influenzae type b bacteremia.


Vitreous wick syndrome.

Vitreous wick syndrome. A 67-year-old man had vitreous wick syndrome after an uncomplicated intracapsular cataract extraction with a sector iridectomy in the left eye. The intraocular infection cleared with antibiotic therapy including intravitreal antibiotic injection, but a residual anterior cyclitic membrane and shallow anterior chamber persisted. An anterior vitrectomy was performed later in the course of treatment after the intraocular infection subsided, to relieve the shallow anterior chamber, prolonged hypotony, and ciliary body detachment. Final visual acuity was 6/15+(20/50+) in the left eye.


Mechanism of insulin action on resting membrane potential of frog skeletal muscle. At a concentration that stimulates the Na pump, insulin hyperpolarizes the plasma membrane of frog sartorius in the presence of substrate-free Ringer. The hyperpolarization ranged from 3.5 to 7.3 mV and averaged 4.7 mV. Ouabain, 10(-4) M, completely blocked the effect of insulin on the membrane potential. Moreover, ouabain completely reversed the insulin-induced hyperpolarization within 20 min. The hyperpolarization produced by insulin was not associated with a detectable increase in the ratio of K+ permeability to Na+ permeability nor with a detectable increase in the concentration of intracellular K+, although a depletion of K+ near the external surface of the membrane cannot be excluded. The results clearly indicate that the hyperpolarization is secondary to stimulation of the Na pump by insulin.


Metabolic requirements for anaerobic active Cl and Na transport in the bullfrog cornea. In the bullfrog cornea, the relationships between the rates of aerobic and anaerobic glycolysis and active Cl and Na transport were studied. In NaCl Ringer (glucose-free), the short-circuit current (SCC) declined much more slowly under aerobic than under anaerobic conditions. The aerobic lactate effluxes in glucose-free and glucose-rich NaCl Ringer were 0.08 and 0.23 micromol/h.cm2, respectively. The transition to anoxia caused these values to increase significantly and was accompanied by depletion of endogenous glycogen in glucose-free Ringer. In Na2SO4 Ringer, amphotericin B (10(-5) M) stimulation of the aerobic SCC was not dependent on the presence of glucose but under anoxia, SCC stimulation required glucose. In Na2SO4 (glucose-rich) Ringer, amphotericin B stimulated the aerobic lactate efflux from 0.26 to 0.36 mumol/h.cm2 and anoxia increased it to 0.55 micromol/h.cm2. In NaCl Ringer, the addition of either 0.5 mM adenosine or 1 mM ATP with 26 mM glucose restored the anaerobic-inhibited SCC and lactate efflux of glucose-depleted corneas. The results show that the reactions of glycolysis are a sufficient energy source for supporting active Na and Cl transport.


Effects of colchicine and vinblastine on in vitro gastric secretion. The effects of colchicine and vinblastine on in vitro bullfrog gastric mucosal preparations were studied with respect to H+ and pepsinogen secretion. In the concentration range of 1--50 mM, an initial but transient colchicine-mediated stimulation of H+ secretion is followed by a dose-dependent inhibition. The transient stimulation of H+ secretion can be confirmed in resting preparations in the absence of added secretagogues. In the same concentration range, colchicine inhibits pepsinogen secretion to a greater degree than H+ secretion. Vinblastine (10(-5)--5 X 10(-4) M) was more effective than colchicine in inhibiting both H+ and pepsinogen secretion. The kinetics of inhibition of secretion by both colchicine and vinblastine were slow. Cytochalasin B had no effect on either secretion.


Suppressor cell function in sarcoidosis. We investigated the role of suppressor cells in the depressed cellular immunity of patients with sarcoidosis. The mean response in 16 patients with active sarcoidosis to three concentrations of phytohemagglutinin was significantly (P less than 0.01) less than control values. Passage of the cells over glass wool resulted in a 116% increase in response to phytohemagglutinin in patients and a 39% decrease in control subjects. Addition of indomethacin to phytohemagglutinin cultures increased the response of cells in patients with sarcoidosis by 192% +/- 32% versus a 112% +/- 18%-increase for control subjects (mean +/- SEM, P less than 0.05). Patients had an increased percentage of monocytes in peripheral blood mononuclear cell preparations, and the percent monocytes correlated with the percent increase in phytohemagglutinin response after glass wool passage (r = 0.62, P less than 0.05). Thus, several factors contribute to the depressed phytohemagglutinin response in sarcoidosis patients: an increased suppression by the prostaglandin-producing suppressor cell, an increased percentage of monocytes, and an as yet undefined factor.


Hairy cell leukemia-associated familial lymphoproliferative disorder: immunologic abnormalities in unaffected family members. Three generations of a family were affected by hematologic malignancies: the proband had hairy cell leukemia, his brother chronic lymphocytic leukemia, his nephew cutaneous and central nervous system lymphoma, and his father chronic granulocytic leukemia. There was no clinical evidence for immune deficiency in 17 unaffected family members. Most family members had normal serum immunoglobulins and peripheral B-cells, but some had decreased T cells. Lymphocyte responses to phytohemagglutinin and concanavalin A were markedly reduced, while pokeweed mitogen responses were essentially normal. Delayed hypersensitivity responses determined by response to a 23-antigen skin test panel were markedly diminished, as were viral antibody titers. The decreased immune function in these family members suggests a role for the immune system in the emergence of hairy cell leukemia and other lymphoid malignancies, though further follow-up will be needed to see if other family members develop malignancies.


Chronic Lyme arthritis. Clinical and immunogenetic differentiation from rheumatoid arthritis. Ten patients with Lyme arthritis have developed chronic involvement of one or both knees. Lyme arthritis was diagnosed by onset with erythema chronicum migrans (six patients); residence in Lyme, Connecticut (eight); seasonal onset in summer and early fall (nine); early periods of short recurrent attacks (nine); absence of rheumatoid factor (nine); and absence of symmetrical polyarthritis, morning stiffness, subcutaneous nodules, or antinuclear antibodies (in all). Five patients had synovectomies; pannus formation and underlying cartilage erosion were present in all. Seven of the 10 patients had the same B-cell alloantigen, DRw2 (frequency in normal control subjects, 22% [P less than 0.005]), but did not have an increased frequency of the alloantigens associated with rheumatoid arthritis. Chronic Lyme arthritis, the result of an apparent tick-transmitted infection, resembles rheumatoid arthritis pathologically but generally differs from it in both prearticular and immunogenetic characteristics.


Cerebral color blindness: an acquired defect in hue discrimination. In contrast to the traditional view that striate visual cortex (area 17) is surrounded by two homogeneous cortical areas (areas 18 and 19), recent studies have shown that mammalian extrastriate visual cortex contains several anatomically and functionally distinct subregions. One such region, the V-4 complex of the rhesus monkey, is highly specialized for the analysis of color information, suggesting that a lesion in a homologous region might produce a defect in color vision while sparing other visual functions. We have studied a patient whose clinical syndrome supports this suggestion: a 44-year-old man with normal color vision suffered two cerebral infarctions that produced first a right and then a left superior homonymous quadrantanopia and also caused prosopagnosia, topographical disorientation, and severely impaired color vision. Computed tomography demonstrated extensive lesions in both inferior occipital lobes in the territories of the lateral branches of the posterior cerebral arteries, involving the lingual and medial occipitotemporal gyri bilaterally; these gyri contain the inferior portion of striate cortex and segments of extrastriate visual cortex. The patient had no difficulty in giving the correct color names associated with common objects presented either verbally or in outline drawings. Standardized testing with the Farnsworth-Munsell 100-hue test, the Nagel anomaloscope, and a method that tests for just-noticeable differences between monochromatic stimuli all showed that the patient's ability to distinguish one color from another was markedly imparied but not totally absent. In contrast, visual acuity, reading, visually guided eye movements, and stereopsis were normal. Cells in the V-4 complex of monkey extrastriate cortex are highly specialized for distinguishing one color from another; the hue discrimination deficit that was demonstrated in this patient with cerebral color blindness indicates that a region or regions with similar function has been damaged.


Suppressor cell function in multiple sclerosis: correlation with clinical disease activity. Concanavalin A (Con A)-activated suppressor cell activity was determined in multiple sclerosis (MS) patients who had been assigned to one of three subgroups, those with active disease, those recovering from a flare-up, and those with stable disease. The level of suppression induced by the Con A-activated suppressor cells on the mitogenic response of autologous peripheral blood lymphocytes was reduced in patients with active disease (3 +/- 8%) compared with stable patients (30 +/- 8%), patients recovering from a flare-up (62 +/- 5%), and controls (40 +/- 5%). As a measure of the actual amounts of suppressor factors released, the effect of supernatants from the Con A-activated cells on the proliferative activity of a dividing cell line (L cells) was determined concurrently. The inhibitory effect of supernatants from activated cells was reduced in active and stable MS patients (7 +/- 3%) compared to controls (21 +/- 4%). Three of 4 with active MS showed mildly elevated immune complex levels as measured by the Raji cell technique; each of these patients had low suppressor activity. Levamisole (1 microgram per milliliter) failed to alter suppressor cell activity in our in vitro system.


Colour vision deficiency among two populations of Chamars, a scheduled caste population of Uttar Pradesh (India). On n = 320 nonrelated Kureel Chamars (160 males, 160 females) from Lucknow and neighbouring villages and n = 314 nonrelated Jaiswar Chamars (160 males, 154 females) from Jaunpur the frequency of colourvision deficiency was examined. In the Kureel Chamars the frequency of deuteranopia comes to a total of 1.25% (males: 25%, females: 0.0%), in the Jaiswar Chamars to a total of 1.91% (males: 3.13%, females: 0.65%). Protanopes were only found in the Kureel Chamars (0.63%; males: 1.25%, females: 0.0%). These observations are discussed and compared with those obtained on other Indian populations.


Adenoids and otitis media with effusion. At adenoidectomy specimens for bacteriological, virological, and histological investigation were obtained from the adenoids of 144 children, 53 of whom suffered from otitis media with effusion, or frequently recurring otitis media. Comparison of findings in children with ear diseases with those obtained in the rest of the material showed that Hemophilus influenza was cultured from 50% of the specimens from the children with ear diseases, while only 14% of the cultures from the other children yielded H. influenza. Virus isolates were made from 17 adenoids. In children with ear diseases a virus was isolated from 28% of the specimens, whereas positive isolates were obtained in only 3% of the rest of the speciemens. Both findings are statistically significant and support the view that the adenoid tissue may play an important role in the etiology of otitis media with effusion. The infected adenoid may be the direct source of the primary infections, or continuous microbial irritation in the nasopharynx may indirectly be the cause of otitis media with effusion, as persistent infection and edema maintain chronic dysfunction of the eustachian tube. Thus adenoidectomy may be beneficial in the treatment of frequently recurring otitis media, preventing otitis media with effusion from developing.


An immunosuppressive serum factor in widespread cutaneous dermatophytosis. A patient had a widespread dermatophytosis and a serum factor that specifically suppressed his T-cell rosette formation and the phytohemagglutinin responsiveness of his lymphocytes. The patient was also unable to mount a delayed hypersensitivity reaction to a standard anergy panel, although he did exhibit an immediate type hypersensitivity reaction to the trichophytin skin test antigen. Although many immunosuppressed patients succumb to severe bacterial and fungal infections, it is our contention that in certain cases the infectious process itself may generate a serum factor that is capable of inducing immunosuppression, thereby rendering the patient susceptible to further spread of the infection.


Influences on the coiling of the cochlea. The growth and shape of the cochlea appears to be controlled by the formation of the cartilaginous capsule. Coiling of the cochlear duct is apparently the result of the physical barrier and support provided by the cartilage cells differentiating from mesenchyme surrounding the ventral portion of the otocyst. In addition, tissue interactions between this mesenchyme and the developing cochlear duct will influence the formation of the cartilaginous capsule and they may also be the origin of one of the controlling agents for the coiling mechanism.