Continuous monitoring and control of plasma glucose during operation for removal of insulinomas. A glucose-controlled insulin and glucose infusion system (Biostator system, Miles Laboratories Inc., Elkhart, Ind.) was used during operation for removal of four suspected insulinomas. In two patients the Biostator system continuously monitored plasma glucose levels and, through a computer-controlled feedback mechanism, automatically infused insulin or glucose as needed. In this way plasma glucose could be kept at approximately 110 mg/dl throughout the procedure. In one patient a rise in insulin infusion rate and a fall in glucose infusion rate followed removal of the tumor. In the other, absence of these findings was consistent with the clinical suspicion that the source of hypoglycemia had not been removed. In two other patients the Biostator system continuously monitored the patient's plasma glucose, without feedback-controlled administration of insulin or glucose. This demonstrated that, in these patients, tumor manipulation and removal did not lead to severe hypoglycemia, and thus eliminated any need to prophylactically infuse large amounts of glucose. Successful tumor removal was followed by a rise in blood glucose levels in both of these individuals. The glucose-controlled insulin and glucose infusion system appears to be a useful instrument for intraoperative management of patients with suspected insulinomas.


Life-threatening pharyngitis caused by herpes simplex virus, type 2. A 21-year-old man who had pharyngitis needed hospitalization for observation of airway patency and for parenteral fluid therapy. Infection with herpes simplex virus, type 2 (HSV-2), was diagnosed on the basis of the finding of significantly increased IgM indirect hemagglutination antibody titers. The pharyngitis appeared to have been contracted by heterosexual orogenital contact (cunnilingus). The results of this case study indicate that HSV-2 infection should be considered in the differential diagnosis in cases of severe pharyngitis in sexually active patients.


Caffeine, cyclic nucleotides, and breast disease. Methylxanthine consumption is associated with the development of fibrocystic disease of the breast. Methylxanthine abstention is associated with resolution of signs and symptoms of fibrocystic disease. Abstinence from methylxanthine consumption decreased breast biopsies and the need for major breast surgery because of benign disease. Methylxanthine consumption is associated with elevated cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) values in fibrocystic dsiease over those obtained in normal breast tissue.


The structure of a new sialic acid-containing decasaccharide from the urine of a patient with mucolipidosis. A new sialic acid-containing oligosaccharide has been isolated from urine of a patient with a type of mucolipidosis newly recognized by Orii et al. (1972). This compound was found to be composed of galactose (2 moles), mannose (3 moles), N-acetylglucosamine (3 moles) and sialic acid (2 moles). On the basis of the results of sequential glycosidase digestion, of methylation analysis, and of the Smith degradation, the structure of this oligosaccharide was elucidated as follows: NeuAcalpha2-6Galbeta1-4GlcNAcbeta1-2Manalpha1-3[NeuAcalpha2-6Galbeta1-4GlcNAcbeta1-2Manalpha1-6]Manbeta1-4GlcNAc. The increased excretion of this oligosaccharide may be caused by the impaired metabolism of glycoproteins having N-glycosidic linkage.


Isolation of urinary C-20 alpha- and C-20 beta-hydroxy-C21-steroid metabolites in cases of congenital adrenal hyperplasia, postpubertal virilizing syndrome and polycystic ovary syndrome. The proportion of 20 alpha/20 beta-epimers of the urinary C21-steroid metabolites was estimated in normal volunteers and in patients with congenital adrenal hyperplasia (CAH), postpubertal virilizing syndrome (PVS) and polycystic ovary syndrome (POS). In the normal individuals 20 alpha- and 20 beta-epimers of 5 beta-pregnane-3 alpha, 17 alpha, 20-triol (pregnanetriol) and 5-pregnene-3 beta, 17 alpha, 20-triol (5-pregnenetriol) were measured. In the other case 20 alpha- and 20 beta-epimers of the characteristic, representative metabolites were also investigated. In 26 of 27 normal persons and in all the patients with normotensive CAH, PVS and POS the 20 beta-epimer comprised 0-10% of the total pregnanetriol. The 20 beta-epimer of 5-pregnenetriol was found in only one normal case (6% of the total). The percentage of 20 beta-epimers of 3 alpha, 17 alpha, 20-trihydroxy-5 beta-pregnan-11-one, 5 beta-pregnane-3 alpha, 11 beta, 17 alpha, 20-tetrol (in the normotensive CAH, PVS and POS) and 5 alpha- or 5 beta-pregnane-3 alpha, 17 alpha, 20, 21-tetrol (in the hypertensive CAH) varied from nil to 76%. The effect of functional groups and the stereochemistry of the molecule on the direction of C-20-keto group reduction is discussed; the existence of additional factors determining this reduction in certain pathological conditions is suggested.


Concomitant T- and Tk-activation associated with acquired-B antigens. Three patients with acquired-B antigens are reported whose red blood cells also manifested T- and Tk-activation. The results of tests using purified Arachis hypogaea and Bandeiraea simplicifolia (BS II) lectins, and red blood cells either T, Tk or both T and Tk-activated by bacterial enzymes in vitro, suggest that the acquired-B phenomenon, T-activation and Tk-activation result from the action of different bacterial enzymes.


Treatment of life-threatening infections in renal transplant recipients with high-dose intravenous human IgG. This study demonstrates that large doses of human IgG can, if prepared by appropriate methods, be safely given intravenously. Antibody titers to CMV can be significantly elevated by administration of MIVIgG. While this is not a controlled trial, IgG therapy appears to be beneficial in renal transplant patients presenting with life-threatening infections.


[Active transport of organic acids in the proximal tubules of the surviving rat kidney normally and under various influences. II. The effect of exogenous cyclic 3',5'-AMP and of substances that alter its intracellular concentration]. Exogenous cyclic 3',5'-AMP (cAMP) and substances known to increase the intracellular concentration of this nucleotide (isoproterenol, theophylline, noradrenaline, lactate) were shown to inhibit the transport of fluorescein (a weak organic acid) into the rat renal proximal tubules at 20 degrees C. Carbacholine decreasing intracellular cAMP concentration stimulated the transport. Propranolol, a beta-adrenergic blockator, diminished significantly the inhibitory effect of noradrenaline on the transport. Lactate and carbacholine when added simultaneously, neutralize their action. The inhibitory action of intracellular cAMP on the transport is supposed to be a result of the diminition of a pool of endogenous weak organic acids which may take part in the exchange of diffusion with the marker anion across basal plasma membrane.


Carcinoma of colon after ureterocolic anastomosis: implantation on calyceal mucosa. Two cases are reported of the development of mucoid adenocarcinoma of the colon in young patients, nineteen and thirty-four years after ureterocolic anastomosis for benign conditions. One patient showed implantation of the colonic neoplasm on the mucosa of an upper calyx in the obstructed kidney. Patients who have undergone ureterocolic anastomosis have a greatly increased risk of the development of large-bowel neoplasms. When suspected, radiologic examination of the colon using a water-soluble contrast material, together with rectosigmoidoscopy or colonoscopy, is essential. Because of the serious nature of this complication, it is suggested that the recent trend to return to the use of large bowel in urinary diversion may be hazardous, especially in the young patient with a benign disease.


Prostatic mucinous carcinoma.

Prostatic mucinous carcinoma. Four criteria are proposed for establishing the pathologic diagnosis of prostatic mucinous carcinoma. Twenty-one reported cases of this rare tumor are reviewed, and a new case is presented. The clinical and pathologic features of 16 authentic features of 16 authentic cases are analyzed.


[Purification and properties of two forms of soluble 3',5'-AMP-dependent protein kinase from rabbit myocardium]. Two forms of 3' : 5'-AMP-dependent protein kinase were purified from the rabbit myocardium. The concentrations of 3' : 5'-AMP-necessary for maximum stimulation of form I and II were the same but the second form of the enzyme was activated by this concentration to a greater extent. The seeming Km by ATP for the both forms in the presence of 3' : 5'-AMP is found to be 8.3.10(-6)M. For enzyme form I the seeming Km by histone H1 was 0.43 mg/ml and for form II--0.67 mg/ml.


[Aminotransferase and dehydrogenase activity in human brain tumours]. Asparate and alanine aminotransferase activity is approximately the same in different lobes of cerebral hemispheres of people with an uninjured central nervous system. The maximal activity of lactate, malate and succinate dehydrogenase is in the temporal lobes and thalami, the minimal one is in the corpus callosum. The activity of aminotransferases in the brain tumour lowers: in the dedifferentiated tumour the asparate aminotransferase shows a 23-24% decrease; in the case of the meningeal sarcoma it is 2.5 times as low: the activity of alaine aminogransferase is almost 10 times as low. The activity of malate dehydrogenase decreases in the neuroectodermal tumours and sharply (almost twice) in multiform glioblastoma. In the dedifferentiated meningiomas the activity of all the dehydrogenases is increased.


[Effect of potassium orotate and guanine on calcium uptake in small intestine of chickens with different amounts of vitamin D3]. Potassium orotate and guanine are established to accelerate the duodenum physiological response of chickens with experimental rachitis to administration of vitamin D3 in the in vivo experiments. They stumulate the uptake and transport of calcium, increase the content of calcium-binding protein and affect the activity of alkaline phosphatase. Guanine is a more effective stimulator as compared to orotate. A rise in the calcium uptake in the duodenum of the chicken which were given guanine started considerably earlier than the intensification of the calcium-binding protein synthesis in it. This suggests a possibility of the calcium uptake initiation by vitamin D3 through the mechanisims independent of the calcium-binding protein biosynthesis.


Ovine pulmonary cytomegalovirus.

Ovine pulmonary cytomegalovirus. Cytomegalic cells with intranuclear inclusions were identified in lung tissue from one of two weanling Western lambs with pneumonia and Mycoplasma ovipneumoniae infection. On the basis of light and electron microscopy, cytomegalovirus infection was diagnosed. Arrays of viral particles whose morphology was consistent with that of viruses of the herpes group were in the intranuclear inclusions of cytomegalic cells.


Quantitative observations on experimental reo-like virus (rotavirus) infection in colostrum-deprived calves. Ten calves were challenged with one of two strains of reo-like virus (rotavirus). Changes in the daily faecal and urinary outputs were monitored and packed cell volume, plasma sodium, potassium and urea levels were measured. Faeces were examined for the presence of rotavirus by direct electron microscopy and immunofluorescence in cultures of PK(15) cells. All calves excreted rotavirus in the faeces for several days. Two calves remained clinically normal throughout the experiment, but in the remaining calves, faeces became mucoid in consistency and yellow-white in colour. In only two calves did the daily faecal output exceed 500 g with a fall in the dry matter content to less than 10 per cent. Slightly elevated blood urea levels and hyperkalaemia were the only changes observed in blood chemistry and these quickly returned to normal. Virus antigen was observed in the epithelial cells by immunofluorescence in the proximal and middle small intestine of calves. Pathological lesions occurred predominantly in the proximal small intestine of nine calves examined.


[Biochemical changes in the adrenals and their function in mechanical trauma]. Concentration of corticosterene, activities of succinate dehydrogenase and cytochrome oxidase, contents of ascorbic acid, reduced glutathione, free amino acids, RNA and DNA were studied in rat and rabbit adrenal glands within 10 min, 5, 10 and 24 hrs after crushing of the soft tissues of posterior extremities under conditions of unaltered and stimulated by ACTH functioning of adrenal glands. Stable increase in the biochemical parameters studied, caused by the ACTH effect, occurred in adrenal glands under this pathology.


[Seasonal fluctuations in the kallikrein-kinin system indices]. State of kallikrein-kinine system was studied in 100 persons of young and mature age during various seasons of year. Season variations in content of kininogen, kallikreinogen as well as in BAEE-esterase activity of blood serum were observed in young persons. In mature persons the season variations of antitryptic and kininase activities were also observed in blood serum. The kinine system of young persons was apparently less subjected to season variations as compared with the persons of mature age.


[Effect of hemodialysis on erythrocyte acetylcholinesterase and adenosine triphosphatase activity in chronic renal insufficiency]. Erythrocytes of patients with chronic kidney insufficiency exhibited high hexokinase activity as well as low activity of acetylcholinesterase and K+, Na+-dependent ATPase. The Km value of acetylcholinesterase for acetyl thiocholine was not altered in the reaction and the enzyme proved to be more resistant to heat denaturation. Therapy with permanent hemodialysis [8-10 hrs per day within some months] normalized K+, Na+-dependent ATPase activity and activated acetylcholinesterase. These effects may be considered as evidence for detoxication and normalization of metabolism. At the same time, high hexokinase activity and increased resistance of acetylcholinesterase to heat inactivation were maintained.


[Molecular mechanisms of hypothalamic hexapeptide regulation of the links in glycogen metabolism]. Alterations in content of glycogen as well as in activity of phosphorylase and phosphoprotein phosphatase were studied in various rat tissues after intravenous administration of a new hypothalamic hexapeptide Tyr-Gly-Leu-Pro-Gly-NH2. An increase in phosphoprotein phosphatase activity was observed in heart muscle, which correlated with transformation of phosphorylase A to the B form and with accumulation of glycogen. The opposite effect was found in liver tissue and sceletal muscle.


[Complexes of apo-B-containing lipoproteins and glycosaminoglycans with a density greater than 1.063 gML in the human aorta]. Interaction of lipoproteins of very low and low density with glycosaminoglycans was studied in vitro. Using analytical and preparative ultracentrifugation the complexes formed were shown to possess a density above 1.063 g/ml. Similar complexes were identified in extracts of human aorta. The formation of the complexes was stimulated in atherosclerotic impairments of aorta.


[Isolation of the plasma membranes of fat cells without using collagenase]. A method is described for isolation of plasmatic membranes of rat fatty cells immediately from fatty tissue without the treatment with collagenase. Homogenization of fatty tissue was carried out in large volumes of buffered sucrose and EDTA at room temperature followed by sucrose density gradient centrifugation. The preparations obtained exhibited high specific activity of the marker enzyme of plasmatic membranes [5'-nucleotidase and K+, Na+-ATPase], as well as high ability for specific binding of insulin.


Effect of prostaglandins on hepatic cyclic nucleotide concentration, carbohydrate and lipid metabolism. The effects of exogenous prostaglandin E(1) (PGE(1)) or prostaglandin E(2) (PGE(2)) were studied in the isolated perfused rat liver and in the intact canine liver in order to determine the possible physiological role of prostaglandins on hepatic carbohydrate and lipid metabolism. The data indicate that PGE(1) and PGE(2) did not stimulate cyclic AMP (cAMP) and cyclic GMP (cGMP) concentrations in intact dog liver and PGE(1) failed to stimulate cAMP or cGMP in fed or fasted perfused rat liver. PGE(1) did not promote hyperglycemia, glycogenolysis, lipolysis, or prevent epinephrine-induced hyperglycemia in the isolated perfused rat liver. Other known glycogenolytic agents including glucagon and epinephrine increased cAMP and glycogenolysis in the same perfusion system. This study does not support a physiologic role for PGE(1) on hepatic glycogenolysis or lipolysis. If PGE(1) subsequently is found to influence other metabolic parameters such as lipogenesis, gluconeogenesis, ureogenesis or amino acid transport in isolated perfused liver, such alterations would probably occur independent of changes in cyclic nucleotide activity.


The Berkson bias in action.

The Berkson bias in action. Thirty years ago Berkson recognized that differences in selection rates of different diseases for admission to the hospital will systematically change the frequency with which those diseases co-exist in hospitalized patients from the frequency rate in the general population. Mainland subsequently demonstrated that postmortem studies systematically show a lower co-morbidity rate for any two individually lethal diseases than would be expected from the individual prevalence of these diseases. In studying the concurrence of bacterial endocarditis and cirrhosis, we examined the relationship of these diseases at autopsy where, according to this concept, we would expect a negative association. We found the frequency of bacterial endocarditis to be three times greater in cirrhotic than in non-cirrhotic patients, a statistically significant difference that was even more convincing, since a negative correlation was anticipated. In accord with the Berkson-Mainland hypothesis, however, no such association was seen between bacterial endocarditis and either emphysema or myocardial infarction, two other chronic diseases of different lethality. Similarly, glioblastoma multiforme, a brain tumor with a high mortality rate, showed a negative correlation with cirrhosis, emphysema, and myocardial infarction. A corollary of this bias-that the mean age at death should be lower in patients dying with two lethal diseases than in patients dying of either disease alone-was supported by our study. This investigation provides evidence to validate the Berkson-Mainland hypothesis, and suggests that rather than being always an adverse bias, it may be used beneficially to document the validity of the increased co-existence of diseases at autopsy.


Hepatic heme metabolism and its control. This review summarizes heme metabolism and focuses especially upon the control of hepatic heme biosynthesis. Activity of δ-aminolevulinic acid synthetase, the first enzyme of heme biosynthesis, is of primary importance in controlling the overall activity of this biosynthetic pathway. Δ-aminolevulinic acid synthetase is subject to inhibition and repression by heme, and numerous basic and clinical studies support the concept that there exists within hepatocytes a "regulatory" heme pool which controls activity of δ-aminolevulinic acid synthetase. In addition, activity of this enzyme is repressed by feeding, especially by ingestion of carbohydrates (the so-called "glucose effect"). Studies pertaining to the mechanisms underlying this effect are also reviewed. The "glucose effect" appears to be mediated by glucose or perhaps by glucose-6-phosphate or uridine diphosphate glucose, rather than by metabolites further removed from glucose itself. Unlike the situation in E. coli, the "glucose effect" in liver of higher organisms is not mediated by alterations in intracellular concentrations of cyclic AMP. Effects of heavy metals, especially iron, on hepatic heme metabolism are also considered. Iron has been found to inhibit formation and utilization of uroporphyrinogen III and to lead to decreased concentrations of microsomal heme and cytochrome P-450. Administration of large amounts of iron is also associated with an increase in activity of heme oxygenase, a property shared by several other metal ions, most notably cobalt. This effect of iron or cobalt administration is similar to the effect of heme administration in increasing heme oxygenase activity; however, we believe it is unlikely that iron, rather than heme itself, is a physiologic regulator of hepatic heme metabolism, although this hypothesis has lately been proposed.


Effects of hormones on changes in cytochrome P-450, prolyl hydroxylase, and glycerol phosphate acyltransferase in primary monolayer cultures of parenchymal cells from adult rat liver. Previous studies have shown that isolation and primary culture of rat hepatocytes in a standard, chemically defined medium is associated with selective changes in microsomal function. These changes were found to be selectively sensitive to addition of hormones to the culture medium. The concentration of cytochrome P-450 declined dramatically during the first 24 hours of incubation. However, cytochrome P(1)-450, a form of the hemoprotein induced by polycyclic aromatic hydrocarbons, was resistant to this change. Cytochrome P(1)-450 levels selectively rose during the first ten hours in culture and, thereafter, declined at a less rapid rate than did the cytochrome P-450 in normal hepatocytes or in cells prepared from phenobarbital pretreated animals. Addition of dexamethasone to the medium at the time of cell plating partially prevented the fall of cytochrome P-450 and of (14)C-heme in microsomes prepared from hepatocytes derived from rats given 5(14)[C]-δ-aminolevulinic acid. This suggests that the steroid decreases degradation of the hemoprotein. As compared to the loss of cytochrome P-450 in cultures of normal hepatocytes, the hemoprotein fell to lower levels in hepatocytes prepared from regenerated liver four days after partial hepatectomy. This result may be related to the accelerated formation of the monolayer in the cultures of regenerated hepatocytes. Both sn-glycerol-3-phosphate acyltransferase activity and glycerol kinase activity declined in the first 24 hours of culture. The fall in the latter enzyme was partially prevented by addition of estradiol. Collagen prolyl hydroxylase, a newly discovered microsomal constituent of the hepatocyte, rose slightly during the first 24 hours in culture. This change was augmented threefold by addition of insulin to the medium. We conclude that the present hepatocyte culture system with its attendant changes in functional phenotype may be useful in better defining the role of hormones in modulating metabolic processes in the liver.


Ectopic ACTH syndrome due to pheochromocytoma: case report and review of the literature. A 51-year-old female was diagnosed preoperatively to have a pheochromocytoma producing ACTH. This diagnosis was based upon her paroxysmal hypertension, hyperpigmentation, and hypokalemia. Elevated levels of serum and urine corticosteroids, plasma ACTH, urinary VMA, and catecholamines fell after a right adrenal pheochromocytoma was removed. Subsequently this tumor was found to have a high content of ACTH. Review of the literature indicates a mortality rate of 57% for this syndrome. Proper preoperative recognition and management can result in total cure.


Sequences homologous to BAV component of HL23V in baboon tissues. The BAV component of HL23V virus (HL23V-BAB) hybridized to DNA from different Baboon tissues and appears to be an endogenous Baboon virus. Competition hybridization studies show that HL23V-BAB is closely related to viruses isolated from various Baboon species: P. hamadrys, P. papio, and P. cynocephalus. Competition hybridization studies also show that normal Baboon tissues contain more copies of proviral DNA than cells infected in vitro.


Density-dependent growth inhibiting interactions between 3T3 and SV40-3T3 cells in mixed cultures. 3T3 cells are shown to reduce SV40-3T3 cell population growth in a denisty-dependent manner in co-cultures of 3T3 and SV40-3T3 cells. The development of this inhibitory activity roughly parallels the development of density-dependent inhibition of growth in homogeneous 3T3 control cultures. The extent of reduction of SV40-3T3 growth can be manipulated by pretreatment of 3T3 cells with a high serum concentration. SV40-3T3 growth rates are reduced by factors between 10 and 20 under optimum inhibitory conditions as compared to SV40-3T3 growth in control cultures.


Density-dependent growth adaptation kinetics in 3T3 cell populations following sudden [Ca2+] and temperature changes. A comparison with SV40-3T3 cells. Lowered extracellular [Ca2+] cause low growth rates and low stationary cell densities in 3T3 cell cultures as compared to physiological [Ca2%]. Under otherwise constant conditions the extracellular [Ca2+] determines a stable stationary cell density, which can be reached by increase of net cell number or decrease of net cell number, depending on cell density at the time of [Ca2+] adjustment. SV40-3T3 cells do not show this [Ca2+] dependency. At 39 degrees C 3T3 and SV40-3T3 cell populations show an increased growth rate at low cell densities as compared to cell populations at 35 degrees C. Approaching the stationary density the growth rate of both cell sorts is reduced faster at 39 degrees C than at 35 degrees C, leading to lower stationary cell densities at 39 degrees C than at 35 degrees C. A temperature change from 39 degrees C to 35 degrees C or in the opposite direction can affect the stationary cell density of 3T3 cell populations only if applied before reduction of growth rate by density-dependent growth-inhibiting principles has taken place.


[Dynamics of visual cortex and hippocampal electrical activity during prolonged immobilization]. As the result of chronic immobilization of rats, their EEG of the visual cortex and hippocampus showed an increased energetic capacity predominantly in the theta-frequency range, a lowered level of synchronization in response to light, reduced sleep duration due to the late falling asleep and waking at different stages. Their sleep became more superficial, the duration of its deeper stages (especially of the paradoxical sleep) decreased, the correlation between the sleep depth and muscular tone and heart-rate was disturbed. The rate of these disorders depended on individual characteristics of the animals nervous system.


Detection of enterotoxigenicity and attachment factors in Escherichia coli strains of human, porcine and bovine origin; a comparative study. Porcine and bovine strains of E. coli suspected to be enterotoxigenic, were tested for heat-labile enterotoxin (LT) production by means of a test measuring the stimulation of the synthesis of 3151 cyclic adenosin monophosphate (cAMP test) and rounding mouse adrenal tumor Y1 cells (Y1 test), and for heat-stable enterotoxin (ST) production by means of the baby mouse test (BM test). The test results were compared with those of the ligated gut test (LG test) using pig and calf intestine. One hundred and eleven strains of human origin were tested in the cAMP test, the Y1 test and the BM test. All strains were tested for the presence of the attachment factors K88, K99, P987 and CF10407. Seventy-four of 117 bovine strains produced only ST and all 74 ST-producing strains possessed K99 antigen. None of the 43 nonenterotoxigenic strains possessed K99. The presence of K99 antigen is therefore a reliable indicator of enterotoxigenicity in bovine strains. Porcine strains produced LT, ST or LT + ST. The K88 antigen was found in 52 out of 101 enterotoxigenic strains, K99 and P987 in 7 and 6 strains respectively and the latter 13 strains produced only ST. P987 was only detected after subculturing in liquid medium to enhance pilus formation. Eleven out of 111 strains of human origin stimulated cAMP synthesis but failed to round Y1 cells, whereas 4 known LT producers were positive in both tests. Attachment factors were found only in 2 of the latter 4 strains.


[Effect of cholin- and serotoninergic substances on self stimulation in rats]. The influence of choline- and serotoninergic agents on the pedal self-stimulation (SS) was studied in male rats of Wistar line. Physostigmine decreased the frequency of pressing on the pedal whereas fluoxetine didn't influence SS. Scopolamine activated SS and lowered the threshold of the SS-reaction. P-chloroamphetamine effect depended on the action phase of the drug and was manifested both in depression and activation of SS. Preliminary administration of fluoxetine decreased the activating effect of scopolamine and enhanced the depressing effect of physostigmine. A combination of p-chloroamphetamine and cholinergic agents was accompanied by a tendency toward weakening of depressing effect of physostigmine and toward enhancing of activating effect of scopolamine. It is suggested that serotoninergic mechanisms in case of changes in activity of cholinergic processes, depress the system of positive reinforcement. A functional interaction of choline- and serotoninergic neurotransmitter systems seems probable.


[Neurological disorders in endometriosis]. A long-term study of 324 females with endometriosis aged 20--52 years permitted to systematize some syndromes of neurological disorders, depending upon the localization and stage in the progress of endometriosis. In an active infiltrating extension of endometrioid heterotopy there prevail syndromes of peripheral nervous structure lesions. In the late period pseudoneurotic disorders are encountered. The main principles of treatment are discussed.


[Excitatory neuronal responses developing shortly after application of an electrical stimulus to the cerebral cortex]. The responses of neurones in the sensorimotor area of the intact cortex and in the neuronally isolated cortical slab to direct electrical stimulation was investigated in unanaesthetized rabbits. By a number of parameters the excitatory response of the units may be divided into several individual reactions which set in at different time periods and are apparently of different nature. It is assumed that the short-latency responses are to a considerable degree due to excitatory input to the units along intracortical pathways. Excitatory responses with a 20 to 40 ms latency, appearing at a period of the so-called inhibitory pause, and postinhibitory excitatory responses reveal a considerable dependence on the input from the subcortical formations, activated in a secondary way by the stimulus applied to the cortex.


[Antidromal action potentials as a manifestation of trace excitation]. The possibility of occurance of action potentials (AP) in neuronal terminals after preliminary excitation of a cortical area was studied in unanaesthetized, non-immobilized rabbits. It was found that a low-frequency subconvulsive stimulation of the sensorimotor cortex may lead to a spontaneous appearance of AP groups that spread antidromically toward the soma of callosal neurones in the opposite hemisphere. Groups of spontaneous antidromic AP were recorded in the cortex after the disappearance of convulsive activity caused by application of penicillin. It is assumed that the observed phenomena reflect a prolonged retention of increased excitability in the terminals of cortical neurones after the end of electrical stimulation or penicillin action.


Comparison of two tests for heterozygosity in congenital adrenal hyperplasia (CAH). The increase of plasma cortisol (F), androstenedione (A), 17 alpha-hydroxy-progesterone (17-OH-P) and testosterone (T) was measured after iv administration of ACTH in heterozygotes for CAH and in controls under two different conditions: Test 1: ACTH stimulation was performed without any particular preparation. Test 2: 1.5 mg of dexamethasone (dex.) was given the evening before the ACTH stimulation. Plasma F, A, 17-OH-P and T were measured by specific radioimmunoassays (RIA). Following ACTH stimulation, the increase of 17-OH-P was significantly higher in CAH-heterozygotes than in controls in both tests (P less than 0.0005). Heterozygotes were characterized by a 17-OH-P increase after ACTH stimulation exceeding the + 2 SD limit of the 17-OH-P increase found in controls. The detection of female heterozygotes was considerably improved by the administration of dex. before testing (test 2). In males, however, a better identification of heterozygotes was obtained without previous administration of dex. (test 1). By these tests, 100% of female (test 2) and 79% of male (test 1) CAH heterozygotes could be correctly identified. There were no significant differences in the levels of F, A and T between heterozygotes and controls except for decreased T levels in test 1 (2P less than 0.01) in most male heterozygotes after ACTH stimulation.


[Mechanisms of habituation of the electroexcitable membranes of cortical neurons]. Habituation of the cortical neurone response is attended with change in the membrane excitability generating peak potentials. Excitability of spontaneous AP trigger zones increases non-specifically. This is due to a non-specific depolarization shift of the membrane potential during habituation. Excitability of the trigger zones of AP evoked by a monotonous stimulus, decreases: the depolarization critical level shifts in the positive direction and the threshold potential increases. Excitability of the trigger zones of AP elicited by an extrastimulus, enhances: the depolarization critical level shifts in the negative direction and the threshold potential decreases. Excitability changes of trigger zones of evoked AP during habituation are specific, local, reversible and resulting from changed electrogenic properties of the zones: they are underlying the change in the response of the neurone electrically excitable membrane in the process of habituation.


The effect of short-term testosterone treatment in boys with delayed puberty. Eight boys with severely delayed puberty without pathological cause were treated for 6 months with testosterone. This resulted in acceleration of skeletal maturation and a marked increase in height and weight. No adverse effects were found on hypothalamic-pituitary and gonadal maturation. Basal LH, FSH and testosterone levels rose to nearly adult values at follow-up within a year and pituitary responsiveness to LH-RH increased markedly.


Restoration of the gonadotrophin response to LH-RH and oestrogen administration in patients after molar abortion. The relation of the hypothalamic-pituitary effect on gonadotrophin secretion and the concentration of serum hCG after molar abortion was investigated. Gonadotrophin release after a bolus injection of LH-RH or conjugated oestrogens was observed in 17 women until 5 months after molar abortion. Little if any response of gonadotrophin was observed at a hCG level of 100 mIU/ml or more, but the response of LH and FSH to LH-RH were restored to normal when the serum hCG level decreased to below 100 mIU/ml. A normal response of LH to conjugated oestrogens was observed at a serum hCG level of 20 mIU/ml or less. These findings suggest that a high level of hCG interferes with pituitary gonadotrophin secretion, that the threshold hCG levels for normal responses of gonadotrophins to LH-RH and oestrogen are 100 and 20 mIU/ml, respectively, and that secretion of gonadotrophins is restored even in the presence of a low hCG level.


[Morphological liver diagnosis in radiology]. Based on the experiences incurred in the years 1970 to 1977, this thesis deals with the efficiency of sonography, scintigraphy and angiography as well as such supplementary diagnostic procedures as ERCP, hepatography and computed tomography in circumscribed hepatic processes. Based on the typical clinical findings obtained, recommendations are made on further diagnostic procedures according to the given hospital structure in Austria: 80% of liver metastases and circumscribed space-occupying primary lesions may be diagnosed by sonography in Basic Hospitals (Standardkrankenanstalten) while cystic processes may be excluded. Solitary space-occupying lesions will have to be examined further by scintigraphy and angiography on the next highest level, the General Hospital (Schwerpunktkrankenanstalt). In combined application, diagnostic accuracy increases to 90%. ERCP, hepatography and percutaneous transhepatic cholangiography are used in special clinical cases only. Computed tomography, available in Central Hospitals (University Hospitals), will not replace the other morphological, diagnostic procedures.


[Pseudohypoparathyroidism type I and vitamin D therapy]. In pseudohypoparathyroidism type I pharmacologic dosis of vitamin-D can correct hypocalcemia. Several authors who had investigated vitamin-D-metabolism in these patients, found impaired renal conversion of 25-hydroxyvitamin-D to 1,25-dihydroxy-vitamin-D. Treatment of 2 patients with pseudohypoparathyroidism type I with vitamin-D-3 and 1 alpha-Hydroxycholecalciferol consecutively resulted in a nonuniform response with regard to the normalisation of serum-calcium. This led us to the conclusion that the disturbances of vitamin-D-metabolism in pseudohypoparathyroidism type I is heterogenous.


[Microtransplantation of hormone receptors by cell fusion]. Defective hormone receptors are cultivated in cell cultures and subsequently reconstituted by, in-vitro cell fusion technique.


Paths and ways of epilepsy.

Paths and ways of epilepsy. The importance assigned to different brain sites for the initiation and conduction of epileptic activity has changed with times, the significant zones being somehow alternatively the cerebral cortex and various centrencephalic structures. Rather than renew this controversy, the available experimental evidence indicating that for the production of epilepsy, the entire brain, or at least several structures and not only discrete cortical or subcortical focal areas must participate, is critically reviewed.


Analysis of unit pairs in the hippocampus. Unit pairs were recorded from dorsal hippocampus in curarized rats injected with physostigmine, during spontaneous activity and stimulation of hippocampal afferents. Interactions between neurons and with the theta (theta) rhythm were investigated with statistical procedures which included: autocorrelations, crossocorrelations, peristimulus-time-histograms (PSTHs) and joint-peristimulus-scatter-diagrams (JPSs). Three types of pairs were found: (1) theta pairs, with rhythmical bursting units phaselocked with theta; (2) non-theta pairs, having non-rhythmical cells; and (3) mixed pairs. Theta pairs showed periodical crossrelation between units which fired in phase or out of phase. Non-theta pairs could interact or not. Many interacting non-theta pairs showed a degree of phaselocking with theta. Mixed pairs were rare, but when interacting they always revealed positive periodical crosscorrelations. Stimulus-elicited phase relationships (reset) and rhythmical interactions within the theta pairs suggest a common source for their rhythmicity and reset. In related non-theta pairs the stimulus usually modified their interactions suggesting loose functional connections.


F response and H reflex analysis of physiological unity of gravity and antigravity muscles in man. Observational differences between reflex (H reflex) and antidromic (F response) activation of segmental motoneurons by a peripheral electrical stimulus are described. In contrast to H reflexes, the percentage of F responses found after a series of stimuli is directly related to the pick-up field of the recording electrode consistent with this response being due to the variable activation of a small fraction of the available motoneuron pool. Despite the differing physiological mechanisms, both F responses and H reflexes can be used to demonstrate similar relative "central excitatory states" for antigravity muscles (i.e. extensors in the lower extremity and flexors in the upper extremity) and their antagonist gravity muscles. H reflexes were elicited not only in their usual location in certain antigravity muscles but also in unusual locations by length/tension changes in agonist and antagonist groups as well as by passive stretch. The data argue for the physiological unity of similarly acting gravity and antigravity muscles as well as supporting a meaningful role of group II afferents in normal segmental motoneuron pool excitability.


An ultrastructural study of cultured human meningioma cells. Ultrastructural alterations in human meningioma cells growth in vitro are reported. In early passages the cells retain some of the characteristic features of the original tumors. These include interdigitations associated with intercellular junctional devices (e.g., desmosomes, gap junctions). However, with repeated subculture these features tend to be less frequent. Typical whorl formations are observed only in primary cultures. The number of cytoplasmic filaments, lipid inclusions and other dense bodies increases with time in culture. Cytoplasmic invaginations into nuclei and the appearance of very large cells become more frequent in repeatedly transferred cultures.


Neuritis of the cauda equina, a chronic idiopathic polyradiculoneuritis in the horse. Four cases of neuritis of the cauda equina (NCE) were studied by light and electron microscopy. Examination of sacral intradural rootlets revealed inflammatory cell infiltrates and an array of myelinated fiber changes which included myelin stripping by invading mononuclear cells and macrophages, as well as splitting and vesiculation of myelin lamellae without obvious participation by leukocytes. More distally in the extradural roots, there was marked granulomatous inflammation, and demyelinative changes were overshadowed by widespread evidence of irreversible axon damage. In all cases, unusual crystalline inclusions appeared in the endoneurium and sheaths of the rootlets and fascicles. The changes in NCE were compared and contrasted with those observed in acute and chronic inflammatory demyelinative neuropathies.


Flow cytometric analysis of the DNA distribution in human brain tumors. Flow cytofluorometric analysis was used to determine the distribution of the DNA content in cells from selected areas of normal human brain and in benign and malignant brain tumors. Propidium iodide was employed as DNA fluorochrome and the analysis was carried out on a suspension of single cells. Normal, nonstimulated human lymphocytes were used as diploid controls. With nonneoplastic tissue an average of 91% of the cells were diploid (presumably in G0 or G1 stage of the cell cycle). The cells of most benign tumors were mainly diploid (77-98%), nine specimens of pituitary adenomas had large numbers of aneuploid cells. In glioblastoma multiforme the proportion of diploid cells was significantly diminished and polyploid cells were frequently seen. Similar results were obtained in other malignant tumors, with metastatic tumors showing the greatest ploidy variation, which included triploid, tetraploid, and hypertetraploid cells. The analytical method used provides valuable information of significant clinical importance on the DNA distribution in brain tumor cells.


Establishment of a human oligodendroglial cell line. A human oligodendroglial cell line has been established from a mixed glioma. Over a period of 22 months, the cell consisted of cells with the morphologic features of such a strong perinuclear halo, dichotomous branching, and a tendency to aggregate and float in the medium. In small aggregates, most cells are bipolar. The cell line also continues to synthetize the S-100 protein specific to neural tissue. The response of this cell line to dibutyryl-cyclic AMP is striking, resulting in a remarkable narrowing and elongation of the cell processes. This cell line could be used for studies on glial differentiation and neuron-glia interaction.


Sequence of motor nerve terminal involvement in acrylamide neuropathy. Acrylamide neuropathy is characterized by distal multifocal axonal degeneration. In this condition long and large myelinated fibers are affected more than sort and thin fibers. The purpose of the present study was to investigate the sequence of nerve terminal involvement. The study was limited to axons that belonged to one type of neuron, of approximately equal diameter but differing in length. Axon terminals from alpha motor neurons were investigated in five muscles from rats. The results show that the initial motor nerve terminal degeneration is widespread and not restricted to terminals of the longest axons with the largest volumes. It is suggested that the variation in degree of involvement of the motor nerve terminals is determined both by differences between endplates and the regenerative capacity of neurons.


Pathological alterations of ependyma and choroid plexus after experimental cerebral infection of mice with Sendai virus. The effects of intracerebral inoculation of Sendai virus into young adult mice were investigated by immunofluorescence, light, and electron microscopy. Immunofluorescence of virus-specific antigens was maximal on the third day after inoculation, revealing infection of leptomeninges, ependyma, and choroid plexus. Histologically, meningitis, ependymitis, and choroiditis occurred between the second and third days. The choroiditis was associated with formation of vacuoles within the cytoplasm of epithelial cells. The vacuoles reached diameters up to 50 micrometer. The ubiquitous vacuolization of plexus epithelia resulted in a honeycomb-like pattern. Opaque viral inclusions were visible within the cytoplasm of choroidal and ependymal epithelium as well as in mononuclear inflammatory cells. On electron microscopy, they were composed of intracytoplasmic nucleocapsid accumulations. Viria lay free between microvilli of plexus epithelial cells, and budding virus structures were observed at cellular surfaces. Occasionally, complete viria occurred in the cytoplasm of plexus epithelial cells and were surrounded by a unit membrane from which they appeared to arise by budding. The formation of this small cavity can be interpreted as the first stage of vacuole formation.


A clinicopathological study on soft tissue tumors of the head and neck. The present study consists of 651 cases of soft tissue tumors originating in the head and neck area. Among these tumors 628 were benign (96%), while there were only 23 malignant cases (4%). In the benign group hemangiomas showed the highest incidence (47%) followed by tumors of adipose tissue (19%) and those of peripheral nerves (12%). Rare tumors consisted of nodular fascitis, hibernoma, lipoblastomatosis, glomus tumor, granular cell tumor, and chondroma. The majority of cases in the malignant group were either those of muscle origin or blood vessel origin. Excepting for two cases of rhabdomyosarcoma of the embryonal type and two cases of angiosarcoma, all showed recurrence and/or metastasis and terminated in death. Three cases of liposarcoma of either well-differentiated or myxoid type had a good prognosis with all three living for 3 or more years without any recurrence. Other malignant tumors consisted of malignant schwannoma, fibrosarcoma, malignant fibrous histiocytoma, alveolar soft part sarcoma, and chordoma. The age, sex, anatomical location, and differential diagnosis have also been described.


Cystic partially differentiated nephroblastoma and multilocular cyst of the kidney. Report of two cases of so-called multilocular cyst of the kidney. Two cases of so-called multilocular cyst of the kidney are presented. Although both cases satisfied all of the criteria which characterize the multilocular cyst of the kidney, one had cystic lesions and neoplastic lesions (nephroblastoma-like lesions) and the other had only cystic lesions and was complicated with hamartoma. We prefer the term "cystic partially differentiated nephroblastoma" as the diagnostic term for the former and "multilocular cyst of the kidney" for the latter. A study of 40 reported cases of multilocular cystic lesions of the kidney revealed that cases having only cystic lesions were distributed in all ages from 4.5 months to 71 years and that cases having neoplastic lesions were seen in infants from 4 months to 2 years.


Phosphorylation of endogenous proteins by endogenous protein kinase of density gradient--purified plasma membrane vesicles of Ehrlich cells. A phosphorylation of endogenous acceptor protein(s) has been demonstrated to occur in membraneous vesicles prepared from Ehrlich ascites tumour cells. The reaction was catalyzed by endogenous protein kinase in the presence of exogenous (gamma32P)ATP. A considerable increase of the specific protein kinase activity took place when the plasma membrane preparation was subjected to a further gradient centrifugation in Dextran T 150. This was done in the presence of a slightly alkaline phosphate buffer containing Mg-ions which resulted in the formation of a well defined vesicular preparation at density 1.035 in the gradient. The apparent Km and Vmax for the reaction with vesicles and exogenous (gamma32P)ATP were determined and found to be 0.022 mM and 0.23 nmol x mg-1 x 10 min-1, respectively. Neither cyclic AMP nor cyclic GMP did stimulate the protein kinase-catalyzed reaction. Instead, a clear inhibition of the reaction by the cyclic nucleotides was unexpectedly registered. Adenosine at 0.5 mM also inhibited the reaction. Calcium ions were inhibitory at all concentrations tested in the presence of a fixed (gamma32P)ATP/Mg2+ ratio. When Mg-ions were stoichiometrically replaced by Ca-ions practically no activity was observed.


Plasma catecholamines, cyclic AMP and metabolic substrates in hemorrhagic shock of the rat. The effect of adrenal demedullation and 6-OH-dopamine treatment. Plasma catecholamines, cyclic AMP and metabolic substrates in hemorrhagic shock of rats was studied in 4 groups of animals: 1) Control rats, 2) rats with adrenal demedullation, 3) rats with 6-OH-dopamine induced chemical sympathectomy, and 4) rats with combined demedullation and sympathectomy. The rats were bled to a systemic blood pressure of 35 mmHg. The basal plasma level of noradrenaline (NA), adrenaline (A) and dopamine (DA) in control animals was each about 1 nmol/1. After hemorrhage for 1 h the A levels had reached 50 nmol/l and there was little further rise after 4 h. The rise was eliminated by demedullation but unaffected by sympathectomy. NA levels rose continuously in the control and in the sympathectomized rats. At 1 h the level was about 4 nmol/l and at 4 h about 20 nmol/l. The demedullated rats showed a 3-fold increase in circulating NA, while little or no change was seen in the combined demedullated and sympathectomized rats. DA levels did not change in any of the groups during the first hour, but were markedly elevated after 4 h of hypotension. Cyclic AMP and glucose levels in plasma showed a rapid increase 1 h after hemorrhage and thereafter returned to or below basal values. Demedullation largely prevented the increase, while sympathectomy had no effect. The increase in lactate and pyruvate levels were diminished but not eliminated by either sympathectomy or demedullation. Glycerol levels were unchanged and FFA decreased in all groups of rats. The results show that the adrenal medulla is the dominating source of plasma catecholamines in hemorrhagic shock in rats. The initial increase in plasma glucose and cyclic AMP appear to be largely mediated by adrenal A. The subsequent fall in these parameters and derangement of circulatory homeostasis are not, in the present shock model, primarily due to a failure of catecholamine secretion, but rather to a decreased responsiveness of peripheral tissues to catecholamine stimulation.


Reacting ultrastructure of the human oligodendrocyte (a study of cerebral cortex distant to brain tumours). Electron microscopical examination of adjacent human cerebral cortex from patients with brain tumour revealed the following morphological distinctive features of the oligodendrocyte: the presence of a diffuse electron dense material, large quantities of free ribosomes or ribosomal rosettes, eccentric nucleus with irregular clumps of chromatin, swollen perinuclear cisterna, extensive cytoplasmic microtubules, well-developed Golgi apparatus opposite the eccentric nuclei, dilated endoplasmic reticulum and mitochondria. The majority of oligodendrocytes contain large indefinable heterogeneous electron-dense structures within their perikaryon or processes. Oligodendrocytes with similar inclusion bodies are seen in the vicinity of capillaries. For these reasons a possible phagocytic activity of the human oligodendrocyte seems likely.


Improvement in regional ventilation and perfusion after radiotherapy for unresectable carcinoma of the bronchus. Ventilation/perfusion scans were obtained in 45 patients with unresectable carcinoma of the bronchus. Of these 45 patients, 35 were reinvestigated shortly after radiotherapy and 17 of them had additional later follow-up studies. Both ventilation and perfusion were always abnormal in the lung affected by the tumor; perfusion was usually more impaired than ventilation. These abnormalities were difficult to detect or to evaluate from the standard chest radiograph. After radiotherapy, ventilation improved in 83% and perfusion in 86% of the patients. This improvement was associated with amelioration of breathlessness, which improved in 74% of the patients. Slow but progressive deterioration of regional ventilation and perfusion were subsequently observed. This was often associated with the development of radiation fibrosis. Spirometric measurements (VC, FEV1) were moderately imparied at the initial assessment (83% and 66% of predicted, respectively), probably due to coexisting chronic airway obstruction, and did not show significant changes after radiotherapy or during the follow-up. Radionuclide studies of regional perfusion and ventilation proved more sensitive and more specific than tests of overall lung function for the functional assessment and follow-up of patients with unresectable carcinoma of the bronchus.


Doughnut pattern of technetium-99m pyrophosphate myocardial uptake in patients with acute myocardial infarction: a sign of poor long-term prognosis. Thirty survivors of acute myocardial infarction with 3+ or 4+ positive technetium-99m pyrophosphate myocardial scintigrams were followed up for 28 +/- 3.1 months (mean +/- standard deviation). Three patient groups were identified from the pattern of radioactive uptake in the scintigram: Group I, 16 patients with focal uptake (anterior in 7, lateral in 2, posterior in 3 and inferior in 4); Group II, 6 patients with anterior myocardial infarction and a doughnut pattern of uptake; Group III, 8 patients with nontransmural myocardial infarction and a diffuse pattern of uptake. Late complications developed in all patients with the doughnut pattern of uptake compared with 43 percent of patients with the focal pattern and 12 percent of patients with the diffuse pattern. After discharge from the hospital, five of six patients with a doughnut pattern of uptake died (mean survival time 9.8 months after the initial myocardial infarction). This mortality rate (83 percent) was significantly greater than that of patients with a focal (mortality rate 6 percent) or diffuse (no mortality) pattern of uptake. The doughnut pattern of technetium-99m pyrophosphate myocardial uptake in patients with acute myocardial infarction appears to identify a subgroup of patients with a very poor long-term prognosis.


Correlation of estrogen receptor levels with histology and cytomorphology in human mammary cancer. Histologic and cytomorphologic features of mammary carcinoma have been correlated with estrogen receptor (ER) levels determined by the dextran-coated charcoal (Scatchard) analysis in 51 primary mammary carcinomas. The results were expressed as follows: ER-positive above and ER-negative below 10 fmol/mg protein and ER-rich above and ER-poor below 250 fmol/g tissue for premenopausal patients (750 fmol for postmenopausal patients). Most lobular carcinomas were ER-positive and ER-rich (84.6%). A similarly high percentage (88.9%) of ER-positive and ER-rich determinations was seen in ductal carcinomas with tubular features, whereas only about half of the remaining ductal tumors were ER-positive or ER-rich. The highest ER values were obtained in the lobular carcinomas and in ductal carcinomas with tubular features. Three cytomorphologic indices independent of variation in tumor histology showed a strong correlation with ER values: maximal epithelial cellularity of the tumor (P less than 0.001); cellular size (P less than 0.05); nuclear size (P less than 0.05).


High-density lipoprotein cholesterol. Significant bias between methods. Cholesterol content of the high-density lipoproteins has become of interest in evaluating the risk of development of coronary heart disease. There is an inverse relationship between high-density lipoprotein cholesterol and risk. The authors found a significant bias (11.1 mg/dl; 0.289 mmol/l) in a comparison of a rapid cholesterol oxidase method and the Abell--Kendall method for quantitating high-density lipoprotein cholesterol. The two methods did not differ in the usual range of total serum cholesterol. Since methodology may vary, each laboratory's performance should be assessed prior to use of published risk factor data. The authors then studied normal male and female volunteers aged 20 to 35 years. They conclude that high-density lipoprotein cholesterol is of value as a risk factor indicator in this age group. The relationship of total serum cholesterol to high-density lipoprotein cholesterol was studied. The authors conclude that they are independent indicators. Further, there is a range of efficiency of the high-density lipoprotein lipid-clearing function. Finally, the authors attempted unsuccessfully to predict high-density lipoprotein cholesterol from lipoprotein electrophoresis patterns.


Immune-complex glomerulonephritis associated with cytomegalovirus infection. Histologic and immunopathologic studies were performed at autopsy on the kidneys of a patient in whom hematuria and proteinuria developed in association with cytomegalovirus (CMV) pneumonitis. Light microscopic examination of the kidneys revealed focal mesangial proliferative glomerulonephritis. Immunofluorescent microscopy revealed a granular deposition of IgG, IgA, C3, and C4, mainly in the mesangium. CMV antigens were also demonstrated in a similar immunofluorescent pattern. Glomerulus-bound immunoglobulins were eluted and demonstrated to contain antibodies to CMV antigens. These findings suggest that in some patients who have CMV infection immune-complex glomerulonephritis is induced by glomerular deposition of CMV antigen-antibody complexes.


Granular cell tumor of the common bile duct. Case report and review of literature. A case of granular cell tumor is reported and the main features of the previously reported cases are summarized. This lesion usually presents in a black woman as a small tumor obstructing the common bile duct and resulting in cholecystitis and/or obstructive jaundice. The cell of origin is still disputed. Local resection with cholecystectomy and choledochoduodenostomy appears to be the treatment of choice.


Hepatic bruits in malignant liver tumors. There have been few reports concerning hepatic bruits in malignant liver tumors, especially in those other than hepatocellular carcinoma. Lately we noticed hepatic bruits in several cases of malignant liver tumors. The murmurs were confirmed by sound recordings. In cases of hepatocellular carcinoma the murmurs were continuous or continuous with late systolic accentuation. In a case of cholangiocarcinoma of the liver the murmur was continuous with late systolic accentuation and in a case of metastatic liver carcinoma it was systolic. These murmurs were considered to be caused by various mechanisms and some of them are discussed in this paper. Hepatic bruits would be a useful aid in diagnosing hepatic tumors.


The association of low levels of HDL cholesterol and arteriographically defined coronary artery disease. Epidemiologic studies have found associations between low levels of high density lipoprotein (HDL) cholesterol and increased risk of coronary artery disease, using myocardial infarction or angina pectoris as endpoints. However, since most studies have not correlated HDL cholesterol with the presence, severity, or location of anatomically proven coronary disease, the present study measured HDL cholesterol levels in 483 men and women undergoing coronary arteriography. Consistent and statistically significant trends of decreasing mean HDL cholesterol levels with increasing numbers of diseased coronary arteries were observed in both men and women and in younger and older age groups. Although women without coronary disease had much higher levels of HDL cholesterol than men without coronary disease, the differences between men and women with similar degrees of coronary disease were small. Low levels of HDL cholesterol were associated with left main coronary disease; patients with both triple vessel disease and left main disease had lower levels of HDL cholesterol than did patients with triple vessel disease without left main disease. These results were not explained by the possible associations of low density lipoprotein cholesterol or triglycerides with HDL cholesterol. These findings suggest that low levels of HDL cholesterol are important risk factors for the development of atherosclerosis and that they may be useful for identifying patients at high risk of certain anatomic patterns of coronary artery disease.


High density lipoprotein cholesterol and incidence of coronary heart disease--the Israeli Ischemic Heart Disease Study. Using univariate and multivariate analyses, the association between high density lipoprotein (HDL) cholesterol and coronary heart disease (CHD) incidence was investigated. Over 150 cases of myocardial infarction (MI) occurred among 6500 Israeli adult males in a five-year prospective study. At age 50 years and over, there is a significant inverse association between MI incidence and HDL cholesterol. This relationship persists when controlling for risk factors such as age, other cholesterol components, smoking, blood pressure, weight, and diabetes mellitus. Unlike hypercholesterolemia and smoking, the relative risk with HDL cholesterol increases with age above 50. Similar patterns of association occur between HDL cholesterol and angina pectoris incidence, sudden unexpected death and deaths from MI. It is suggested that HDL cholesterol is an independent risk factor for CHD, especially in males over 50, and the implication of this study is that increased HDL cholesterol might play a protective role in the pathogenesis of CHD.


Non-polio enterovirus activity in Wisconsin based on a 20-year experience in a diagnostic virology laboratory. Laboratory test results, demographic information, and clinical data on 1364 patients who had specimens submitted to the Wisconsin State Laboratory of Hygiene and from whom non-polio enteroviruses were isolated during 1957--1976 were examined. Echoviruses (echo) and Coxsackievirus group B (CB) and group A (CA) were isolated from 719, 389, and 256 of the patients, respectively. Thirty-five different serotypes were identified in the 20-year period. The six most frequently occurring serotypes (echo 9, CB 5, echo 18, CB 2, CB 4, and echo 6) were associated with 57 per cent of all illnesses. The first three serotypes occurred in an epidemic-like manner whereas the next three appeared to be endemic. Eighty-eight per cent of all isolations were from patients whose illnesses began in July through October. The percentage of CA isolates obtained from adults was much smaller than the corresponding percentages seen with CB or echo. A majority of the non-polio enteroviruses were obtained from males. Central nervous system and gastrointestinal tract involvement was greatest with echo and CB 5 tract and lowest with CA and CB 1--4 illnesses. The highest frequency of respiratory tract involvement was with CA and echo 9 illnesses and rash was most frequent with CA illnesses. The highest frequency of hospitalization was with CB 5 patients.


Risk factors in lip cancer: a questionnaire survey. An analysis was made of potential risk factors of cancer of the lip in Finland. The series comprised 290 lip cancer patients, and the controls were 254 patients with squamous cell carcinoma of the skin of the head and neck, all reported to the Finnish Cancer Registry in 1972-1973. The results obtained in a questionnaire survey (response rate, 75%; 54% of the total series) indicated that the male lip cancer patients had engaged in outdoor work and smoking with significantly greater frequency than had the male controls. Together, these two risk factors posed a markedly increased risk (RR = 15.4). However, when the factors were analyzed separately, each excluding the effect of the other, no significant risk could be noted. The male lip cancer patients had recurrent herpetic infections with significantly greater frequency than did the male controls. No significant differences were apparent with respect to urban or rural residence. It is concluded that tobacco smoking and outdoor work probably act together to induce lip cancer. The mode of interaction between these factors and the etiologic role of herpesvirus are discussed.


Misclassification and the design of environmental studies. Many authors have documented the existence of effects due to misclassification. This paper examines the size of these effects in the context of environmental studies. Misclassification occurs because of the use of surrogate measures of exposure. Misclassification causes relative risks to appear smaller than they are, with larger relative risks being seriously affected. The power of statistical tests is reduced, but not as seriously.


Patterns and determinants of conjugated estrogen use. In view of the carcinogenic potential and widespread use of conjugated estrogens (CEs), this study evaluated patterns and determinants of oral ambulatory CE use. Among 1273 women 30 to 69 years of age interviewed in Greater-Boston hospitals, there were 161 (13%) ever-users of CEs; 88 (7%) had used the drug within the preceding year. The median duration of use was three years. Prominent determinants of use were age, menopause and history of menopausal symptoms. Physician prescription survey data from an independent source suggest that CE use has been common throughout the United States, and may have declined after the reports linking CEs to endometrial cancer were published in 1975. If CE use indeed increases the risk of endometrial cancer some fivefold, an important public health problem exists.


Epidemic viral gastroenteritis.

Epidemic viral gastroenteritis. Epidemic viral gastroenteritis is a significant world wide problem. In developed countries, gastroenteritis accounts for significant morbidity and loss of time from work; in the Third World it is the leading cause of mortality among infants and children. Recent technologic advances have been associated with an explosion of research activity. Two virus groups, the Norwalk-like agents and the rotaviruses, are currently accepted as causative agents of viral gastroenteritis in man. The problem of viral gastroenteritis is reviewed both from a current and a historic perspective.


Pituitary adrenal recovery following short-term suppression with corticosteroids. To provide clinical guidelines for the use of high-dose short-term glucocorticoid therapy, we studied recovery of the hypothalamic-pituitary-adrenal axis in 10 normal men following the administration of suppressive doses of prednisone (25 mg twice daily for five days). Cortisol responses to insulin-induced hypoglycemia and synthetic ACTH before treatment were compared with responses two and five days after concluding the prednisone course when adrenal function was not influenced by the presence of exogenous steroid. Two days after prednisone therapy, peak cortisol responses to both hypoglycemia (11.0 +/- 0.9 microgram/dl mean +/- SEM) and synthetic ACTH (13.3 +/- 1.4 microgram/dl) were significantly reduced compared to pretreatment (20.6 +/- 1.6 and 27.3 +/- 2.5 microgram/dl, respectively, p less than 0.001). Five days after concluding the prednisone therapy, peak cortisol response to hypoglycemia had returned to near pretreatment levels although peak cortisol response in the adrenal gland to synthetic ACTH (22.3 +/- 1.1 microgram/dl) remained reduced (p less than 0.05). These data suggest that brief courses of high-dose prednisone therapy may limit the adrenal component of the hypothalamic-pituitary-adrenal response to stress for up to five days.


Do endorphin residues of beta lipotropin in hormone reinforce reproductive functions? The beta-endorphin residue of pituitary beta-lipotropin hormone, which regulates utilization and storage of body fat, is several times more potent than morphine in raising pain tolerance. It also produces habituation and dependency behavior. Recently it was found to be present in amniotic fluid and to be a releaser of prolactin. It now appears that the placenta is a rich source of endorphins. These findings may open a new chapter in understanding molecular determinants of behavior patterns responsible for natural selection and survival of vertebrate species. Clinical application of basic information and new concepts relating endorphins to maternal behavior patterns and neonatal physiology is the purpose of this communication. A brief review of the literature, some data from [3H]opiate-binding assays, observation of maternal performance, and reports of maternity patients' feelings and motivations suggesting that these hormone molecules mediate formation of affectional attitude, appetitive systems, and maternal behavior will be presented.


Prolactin-secreting pituitary adenomas in women. II. Menstrual function, pituitary reserves, and prolactin production following microsurgical removal. A prospective study of 46 women with prolactin-secreting pituitary adenomas and amenorrhea and/or galactorrhea was performed to determine the influence of the selective transsphenoidal removal of these tumors on pituitary and reproductive function. This procedure was effective in restoring menstrual function in 34 of 41 women and in eliminating lactation in 30 of 40 women. Tumor size and preoperative serum prolactin concentrations were the most important factors in predicting the postoperative disappearance of symptoms. Normal menstrual function returned in 33 of 34 women with tumors less than 2 cm in diameter but in only one of seven women with tumors greater than 2 cm. Similarly, galactorrhea disappeared in 29 of 34 women with tumors less than 2 cm but in only one of six women with larger tumors. Menses returned in 31 of 32 women and galactorrhea disappeared in 25 of 31 women with preoperative serum prolactin levels below 200 ng/ml; conversely, menses returned in only three of nine women and lactation ceased in one of six women with preoperative serum prolactin concentrations above 200 ng/ml. Prolactin concentrations decreased in 42 of 43 patients following the removal of pituitary adenomas and returned to normal in 30. Postoperative pituitary reserves of adrenocorticotropic hormone, growth hormone, luteinizing hormone, and follicle-stimulating hormone were normal in most patients. These data indicate that the removal of prolactin-secreting pituitary adenomas by a neurosurgeon accomplished in this surgical technique is effective in restoring menstrual function and eliminating lactation in most women, especially if the tumor is less than 2 cm in diameter and the preoperative serum prolactin concentration is less than 200 ng/ml.


Rhegmatogenous retinal detachment complicating cytomegalovirus retinitis. Six eyes in four patients with cytomegalovirus retinitis developed retinal holes and retinal detachment. Holes appeared in areas of necrosis and were typically large and round with shaggy edges. Differentiation from exudative detachment was sometimes difficult because of obscuration of the fundus by vitreous haze. Cryotherapy was successful in closing open breaks without detachment; cryotherapy and exoplant surgery were used effectively to treat the initial detachments. The occurrence of massive periretinal proliferation and late development of new areas of hole formation or retinitis complicated therapy for these detachments.


A comparative trial of clofibrate and nicotinyl alcohol tartrate in hyperlipoproteinemic patients. The effects of nicotinyl alcohol tartrate (Roniacol) and clofibrate (Atromid-S) on plasma cholesterol, triglycerides and lipoprotein cholesterol concentrations were compared in 19 patients with hyperlipoproteinemia in a 32-week, double-blind, crossover trial. Determination of serum clofibric acid concentrations, used to check compliance, allowed us to detect an error in the order in which the drugs were dispensed. Both drugs decreased (p less than 0.01) plasma cholesterol approximately 17% in patients with type II hyperlipoproteinemia. Nicotinyl alcohol reduced plasma triglycerides by 20% in six and clofibrate in eight of the nine patients with type IV hyperlipoproteinemia, although the mean effect was not statistically significant due to the large variance. Both drugs decreased (p less than 0.02) very low density lipoprotein (VLDL) cholesterol in the type IV patients; however, clofibrate increased (p less than 0.05) low density lipoprotein (LDL) cholesterol, whereas nicotinyl alcohol did not. Neither drug altered high density lipoprotein (HDL) levels significantly. In future studies, the effect of hypolipidemic drugs on the major classes of plasma lipoproteins should be determined in addition to the response of plasma lipids.


The sensitivity and heterogeneity of histochemical markers for altered foci involved in liver carcinogenesis. Subcutaneous injection of iron dextran resulted in a hepatic siderosis within 2 weeks in rats, as previously reported for mice. Hepatic carcinomas as well as neoplastic nodules in rats were entirely or mainly free of stainable iron and, thus, could be readily identified histologically. In addition, early carcinogen-induced altered foci were resistant to iron accumulation. In rats fed 0.02% N-2-fluorenylacetamide (FAA) for 13 weeks, the number of iron-resistant foci identified following iron injection was the same as that observed with dietary iron overload. Histochemical investigation of enzymatic markers that have been used to identify foci in rats revealed that foci characterized by enzymatic reactions of positive gamma-glutamyl transpeptidase and decreased adenosine triphosphatase and glucose-6-phosphatase corresponded to those characterized by resistance to iron accumulation. However, in quantitative analysis of the early carcinogen-induced foci in rats given iron dextran following a diet containing 0.02% 2-FAA for 13 weeks, more lesions were detected by resistance to iron accumulation than by any of these other properties. There was considerable phenotypic heterogeneity among foci for the enzyme markers. It is concluded that resistance to iron accumulation is a more sensitive and reliable marker for early carcinogen-induced altered hepatocellular foci than is any other histochemical property.


Rabbit cardiomyopathy associated with a virus antigenically related to human coronavirus strain 229E. A new disease of rabbits is described. Following an acute febrile course, animals die or recover by the 11th day postinoculation. The characteristic pathologic finding is multifocal myocardial degeneration and necrosis. The disease can be transmitted by various routes with tissue filtrates or with infectious sera diluted to 10(-6) and passed through 0.1 micron filters. Virus particles with morphologic features characteristic of a coronavirus are present in infectious but not in normal rabbit serums. The antigen(s) in the infectious serums cross-reacts with the 229E and the OC43 strains of human coronavirus. Antigen cross-reacting with the 229E virus is detectable by immunofluorescent staining in frozen sections of heart tissue from sick but not from healthy animals. Animals surviving infection seroconvert to coronavirus specificity, as demonstrated by the presence in convalescent serums of antibody capable of reacting with the 339E virus. Susceptibility to infection has not been demonstrated in mice, hamsters, or guinea pigs, and the virus was not adapted for growth in tissue culture. It is uncertain whether the agent is a natural pathogen of rabbits or a coronavirus contaminant from another species, possibly human. The name rabbit infectious cardiomyopathy is suggested for this disease.


Mental status, functioning, and stress in chronic schizophrenic patients in communicity care. The author studied the interactions between functioning, stress, and psychological deficit, variables considered essential to the schizophrenic patient's adjustment in the community. The results indicate that comprehensive measurement of functioning and stress correlates significantly with mental status. A breakdown by the components of functioning and stress revealed further areas of interaction between these variables. An important finding was that anxiety contributed maximally to the prediction of stress and depression to that of functioning. These data seem relevant to the schizophrenic patient's degree of social adjustment in the community.


Riboflavin requirement for the cultivation of axenic Entamoeba histolytica. Riboflavin was found to be essential for the cultivation of axenic Entamoeba histolytica. This is the first demonstration of a flavin requirement by the organism. Panmede, the principal source of flavins in the axenic medium, was treated with activated carbon to remove flavins. Medium made with this flavin-deficient Panmede, and supplemented with ribonucleic acid failed to support the multiplication of amebae in serial subculture, but did so when riboflavin was added. The concentration of riboflavin required to achieve maximal growth was about 1.3 microgram per ml medium. Studies on riboflavin uptake revealed that amebae lack a high-affinity transport system for this vitamin. The rate of riboflavin uptake was equivalent to the rate of pinocytotic uptake of fluid as previously determined.


The serologic response of hamsters to experimental liver inoculations with Entamoeba histolytica as measured by indirect hemagglutination test and enzyme linked immunosorbent assay. Results of testing 298 sera from hamsters inoculated in the liver with Entamoeba histolytica and from 25 uninoculated controls by indirect hemagglutination (IHA) and enzyme linked immunosorbent assay (ELISA) showed that measurable amounts of antibody appeared as early as 5 days after inoculation, generally increased to a high level within 20 days, and persisted for the duration of the experiments (58 days). There was fair correlation between size of liver lesion and titers. Strain differences in amebae used for antigen and for inoculation could not be detected by either test. The IHA test appeared to be very sensitive, and titers of 1:16 and above were specific. With the ELISA technique, it was tentatively concluded that titers of 1:32 were specific for anti-amebic antibodies but only those of 1:128 and above were indicative of liver infections in the experimentally infected hamsters.


Diarrhea associated with rotavirus in rural Guatemala: a longitudinal study of 24 infants and young children. A population of 24 infants and young children followed prospectively during the first 3 years of life was studied for the occurrence of rotavirus infection by using enzyme-linked immunosorbent assay to detect virus in stools. Infection with rotavirus was associated with 26 (14.2%) of 183 selected diarrheal episodes. Twenty of the 24 infants and young children had diarrhea associated with rotavirus on at least one occasion and six had two such episodes. Rotavirus infection was documented in over 50% of the dehydrating episodes studied, thus further indicating the importance of rotavirus in this population.


Ten clinical cases of human infection with venezuelan equine encephalomyelitis virus, subtype I-D. The clinical and laboratory findings in ten humans infected with Venezuelan equine encephalitis virus, subtype I-D, are described in this report. Clinical and laboratory data indicate that, in contrast to equine infections, human infection with these enzootic virus strains (I-D) is similar to human infection with epizootic strains (I-ABC). In most cases there was an abrupt onset of fever, muscle pain, and vomiting. Virus was recovered from sera obtained during the first 3 days of illness. Lymphopenia occurred in all patients, and neutropenia occurred in three. No sequelae of these infections were apparent.


Cutaneous leishmaniasis--a case with persistent organisms after treatment in presence of normal immune response. A Peace Corps volunteer in Senegal, West Africa contracted cutaneous leishmaniasis which had several noteworthy features. One of the three presenting cutaneous ulcers was associated with subcutaneous nodules and viable organisms were recovered from healing lesions after multiple courses of treatment, including amphotericin B. Yet, the patient was found to exhibit both humoral and cell mediated features of normal immunologic responsiveness. Ultimately, clinical and parasitological cure occurred. The patient's organism was found to produce lesions in the foot pads of mice.


Arboviruses in New York State: an attempt to determine the role of arboviruses in patients with viral encephalitis and meningitis. In a reveiw of 2,963 patients with signs of infections of the central nervous system in New York State in 1966--1977, arboviruses were found to be the confirmed or presumptive etiologic agents in 60 patients. California encephalitis (CE) virus was the most common (44 patients), followed by Powassan (POW) virus (8), St. Louis encephalitis virus (7), and eastern equine encephalitis (EEE) virus (1). Most patients (47) were children. The incidence of encephalitis was higher in patients with arbovirus findings than in infections with any other of the common neurotropic viruses. The disease was fatal in two patients, one infected with POW virus, the other with EEE virus. Most patients with CE virus infections resided in suburban areas. All POW infections were contracted in six rural counties known for their recreational facilities.


Diagnosis of a carotid body chemodectoma with dynamic radionuclide perfusion scanning. The first case of a carotid body chemodectoma that was diagnosed using dynamic radionuclide perfusion angiography and subsequently excised is presented. The value of this technic in the investigation of pulsatile tumors is emphasized.


Granular cell myoblastoma involving the common bile duct. Three cases of granular cell myoblastoma involving the large bile ducts are reported. Two of the patients were proved to have multifocal tumors. These tumors may clinically simulate sclerosing adenocarcinomas. Technical difficulties with these tumors for the consulting pathologist are discussed.


Gastrinoma associated with common bile duct obstruction and the ectopic production of ACTH. A case of adrenocortical hyperfunction due to ectopic production of ACTH by a gastrin-producing tumor of the pancreas is described. Cushing's syndrome preceded the appearance of the overt Zollinger-Ellison syndrome by 2 years and was treated by bilateral adrenalectomy. The Zollinger-Ellison syndrome was initially treated with cimetidine, which successfully reduced the secretion of gastric acid. Because the pancreatic gastrinoma continued to grow, causing obstruction of the common bile duct, biliary diversion and total gastrectomy were performed. There is evidence that the pancreatic gastrinoma was the source of the ectopic production of ACTH and possibly secretion. The role of Histamine-2 blocking agents as therapy in the Zollinger-Ellison syndrome is discussed.


Long-term treatment with beclomethasone dipropionate aerosol in asthmatic children with special reference to growth. Thirty-one children, 19 boys and 12 girls, aged 3.4--10.8 years, with severe perennial bronchial asthma were treated with beclomethasone dipropionate aerosol (BDA) for 16-40 months. The dose was initially 400 micrograms a day and was gradually reduced to the lowest level giving control of symptoms. Earlier steroid or ACTH-treatment in six children was stopped during the BDA-treatment. At the start of the treatment the mean deviation of height compared with normal values for Swedish children was -0.10 s.d. for the boys and -0.51 s.d. for the girls. At the end of the observation period the deviation was -0.22 s.d. and -0.58 s.d., respectively. The increase in deviation was not significant. Bone age was also slightly retarded before beclomethasone treatment but this deviation was not accentuated during the observation period. It is concluded that treatment with BDA does not retard growth or skeletal maturation in children. The number of acute admissions to hospital was reduced by more than 50% during the first year of treatment.


Changes in the metrial gland of the rat uterus following ovariectomy on day 10 of pregnancy. Rats were subjected to ovariectomy or a control operation on day 10 of pregnancy and light and electron microscope studies carried out to examine the cells of the decidua basalis and the mesometrial triangle. Degeneration of the decidua basalis was rapid but proliferation in the mesometrial triangle and differentiation of the typical granulated cells continued for some time, and resulted in the formation of a metrial gland. The earliest effect noted in the metrial gland was the appearance of inclusions in the fibroblast-like stromal cells one day after ovariectomy. During the next four days many stromal cells became packed with a variety of inclusions and it is suggested that some of these may represent phagocytosed cellular debris. Some debris appeared to be in intercellular spaces and was probably derived from granulated cells. Some granulated cells appeared to develop apparently empty vacuoles and this may be a preliminary stage in degeneration. Although granulated cells decreased to become very few in number five days after ovariectomy, the precise mechanism of their loss and the relationship of this to the hormonal environment could not be established.


Carcinogenicity of halothane in Swiss/ICR mice. A simplified in-vivo bioassay system was used to test the carcinogenic potential of halothane in Swiss/ICR mice. Halothane was tested only at its maximum tolerated dose, and histologic examination was performed only on tumor masses and other grossly abnormal tissues found at necropsy. Two groups, each of 15 timed pregnant mice, were exposed to either halothane, 500 ppm (0.05 per cent), or compressed air for two hours on days 10--19 of pregnancy. Five days after birth the offspring were similarly exposed, three times weekly, for 78 weeks. After a ten-week, no-treatment, observation period, all remaining mice were examined by necropsy. Mice dying or killed in extremis before final sacrifice at 88 weeks of age also underwent complete gross necropsy unless extensive cannibalism or autolysis precluded examination. The incidences of malignant tumors, hepatomas or modular hyperplasias, and benign tumors in halothane-treated mice were 7, 6, and 20 per cent, respectively; there were similar incidences of these lesions in control animals. It is concluded that under the conditions of this experiment, lifetime administration of halothane at its maximum tolerated dose is not associated with an increased incidence of neoplasia in Swiss/ICR mice.


An analgesic action of intranvenously administered lidocaine on dorsal-horn neurons responding to noxious thermal stimulation. Using extracellular single-unit recording techniques, effects of intravenously administered lidocaine on dorsal-horn nociceptive neurons were studied in cats made decerebrate whose spinal cords had been transected. Thirty-seven neurons in Rexed lamina V responding to high-threshold mechanical and noxious thermal stimuli (radiant heat, using Hardy-Wolff-Goodell dolorimeter) were studied. Lidocaine hydrochloride, 2.5, 5, and 10 mg/kg, iv, produced dose-related suppression of both spontaneous activity and responses of these neurons to noxious thermal stimulation. Spontaneous discharge frequencies at maximum suppression, observed 3--7 min after administration of each of the three doses of lidocaine were 64 +/- 14 (mean +/- 1 SE), 32 +/- 8, and 25 +/- 9 per cent of control values, respectively; responses to noxious thermal stimuli were 83 +/- 5, 52 +/- 8, and 39 +/- 7 per cent of the control values, respectively. Threshold skin temperature to noxious thermal stimulation increased from 44.7 +/- 0.4 C (control) to 46.3 +/- 0.7 C with lidocaine, 5 mg/kg (P less than 0.05), to 47.8 +/- 0.8 C with lidocaine, 10 mg/kg (P less than 0.01). The times necessary for recovery varied in a dose-related fashion. Plasma lidocaine concentrations 5 min after lidocaine, 5 mg/kg, averaged 3.6 +/- 0.7 microgram/ml. These data support the clinical impression that intravenously administered lidocaine produces analgesia at plasma concentrations of 3--10 microgram/ml. It is suggested that lidocaine may block conduction of nociceptive impulses, at least in part, by suppression of spinal-cord nociceptive neurons.


The facial reflex of allergy.

The facial reflex of allergy. The facial reflex, originally described by Franz Chvostek, is shown to be of value in allergy by assessing the relative irritability of muscle tissue (cardic, smooth, skeletal) and the effect of certain drugs frequently used by allergists upon them.


[Fibroadenoma and phyllode tumors. Cytopathological aspect]. Fibro-adenomas and phyllode tumors of the breast are a classical cause of errors in cyto-diagnosis. On the basis of six personal cases, the authors show that the cytological diagnosis of fibro-adenoma is possible and that there are certain minimal factors which favourise the presence of a phyllode tumour. They emphasize the differential characteristics between fibro-adenomas and carcinomas on the one hand, and between fibro-adenomas and mastitis on the other hand.


Humoral and cellular responses in swine exposed to transmissible gastroenteritis virus. Swine exposed to attenuated transmissible gastroenteritis virus had higher virus-neutralizing antibody titers than did swine exposed to virulent virus. The cellular response, measured by the direct leukocyte migration-inhibition (LMI) procedure, was greater in swine exposed to virulent virus than in swine exposed to the attenuated virus. Leukocytes from exposed swine were inhibited more in the LMI procedure in the presence of the homologeous sensitizing antigen than in the presence of the heterologous viral antigen. The humoral response measured by virus neutralizing reached a peak 21 days after exposure, and the cellular response measured by LMI reached a peak 28 days after exposure.


Cellular immunity shown in pseudorabies virus-infected pigs by leukocyte migration-inhibition procedure. Cellular immunity in pigs inoculated with pseudorabies virus (PRV) was studied by the agarose plate technique of direct leukocyte migration-inhibition procedure. Migration of leukocytes from PRV-infected pigs was inhibited in the presence of PRV antigen, whereas migration of leukocytes from nonexposed pigs was not inhibited in the presence of the same antigen. The migration of leukocytes collected 4 days after intranasal exposure to PRV was inhibited; humoral antibodies could not be detected until 7 days after exposure. Cellular immunity was present in pigs 14 days after inoculation with inactivated PRV antigens; low concentrations of neutralizing and precipitating antibodies were present at this time. The leukocyte migration-inhibiton procedure was found to be a useful tool in studying the role of cellular immunity in PRV infections.


Isolation and culture of endothelial cells from the lungs of small animals. Techniques are descirbed for the isolation and culture of endothelial cells from the lungs of small animals. The cells are collected by retrograde perfusion of blood-free lungs with buffered saline containing collagenase. The cells are characterized by light microscopy, electron microscopy of thin sections and surface replicas, and by the presence of angiotensin-converting enzyme (ACE). ACE was assayed using 3H-benzoyl-Phe-Ala-Pro as substrate and was localized by indirect immunofluorescence using guinea pig endothelial cells incubated with rabbit antibodies to guinea pig lung ACE followed by goat anti-rabbit globulins conjugated to fluorescein. Thus, endothelial cultures can be established using small animals commonly employed in studies of pulmonary processing of vasoactive substances.


The structure-activity relationships of halogenated biphenyls as enzyme inducers. Polyhalogenated biphenyls induce microsomal mixed-function oxygenases in many species including man. They can be divided into two classes of inducers. 3,4,5,3',4', 5'-Hexa- and 3,4,3',4'-tetrachlorobiphenyls appear to interact with the TCDD receptor, albeit at 100 to 1,000 times the dose. The structure required for 3-MC (TCDD)-type induction seems to be the presence of at least two adjacent halogens in the lateral positions (meta and para) of the benzene rings, and an absence of halogens in the ortho positions adjacent to the biphenyl bridge. It is likely that halogenation of the ortho positions prevents binding by blocking planar configuration. These isomers, although less toxic than TCDD, are much more toxic than other PCB isomers. Most halogenated biphenyl isomers are phenobarbital type inducers or are inactive. The structure-activity relationship for this type of induction is less clear, but active isomers include 2,4,2',4'-tetra-; 2,4,5,2',4',5'-; 2,3,4,2',3',4'-; 2,3,5,2',3'.5'-and 2,4,6,2',4',6'-hexachlorobiphenyls and 2,4,5,2',4',5'-hexabromobiphenyl. The inactivity of many of the lower chlorinated isomers as inducers (mono-through tetrachloro-) may be related to their rapid metabolism. The cytochrome which is induced by commercial PCB and PBB mixtures appears to be identical to a mixture of cytochromes from phenobarbital- and 3-MC-treated rats. These structure-activity relationships suggest that the "mixed inductive" effects and much of the toxicity of PCB and PBB mixtures are due to the presence of compounds related structurally to the active chlorinated dibenzofurans or 3,4,3',4'-tetrachlorobiphenyl.


Cohort study of Michigan residents exposed to polybrominated biphenyls: epidemiologic and immunologic findings. Polybrominated biphenyls (PBB) were dispersed widely in Michigan by a 1973 shipping accident in which PBB was introduced into cattle feed. Human exposure resulted principally from ingestion of contaminated dairy food products. To determine whether PBB exposure has or will cause acute or chronic illness, a prospective cohort study of 4545 persons has been undertaken. Three exposure groups were sought; all persons living on PBB-quarantined farms; persons who had received food directly from such farms; workers (and their families) engaged in PBB manufacture. Enrollment rates were 95.6, 95.1 and 78.0%. Also enrolled were 725 persons with low-level PBB exposure. All were queried concerning 17 symptoms and conditions related possibly to PBB. Venous blood was drawn on 3639 and analyzed for PBB by gas chromatography. Mean serum PBB levels were 26.9 ppb in quarantined farm families, 17.1 in recipients, 43.0 ppb in workers, and 3.4 ppb in the low exposure groups. No associations were found between serum PBB levels and symptom prevalence rates. To evaluate peripheral lymphocyte function, T and B cell quantitation and in vitro responses to 3 nonspecific mitogens were studied in 34 persons with highest PBB levels (mean, 787 ppb), and in 56 with low values (mean, 2.8 ppb). No statistically significant differences in lymphocyte number or function were noted.


The neurotoxicity of polybrominated biphenyls: results of a medical field survey. Neurologic symptoms were the earliest and most prominent symptoms recorded in Michigan farm residents exposed to PBB as compared to a non-PBB exposed control farm population in Wisconsin. In Michigan (particularly among males) those who exhibited the most marked symptoms tended to show diminished performance as assessed by special tests, although population differences in performance were not as marked. Low indices of performance were also significantly correlated with intake of home-produced foodstuffs, particularly during the years 1972--1974 and store-bought products during the years 1975--1976. Between 1972 and 1976 the Michigan farm residents studied made significant changes in their consumption patterns of products suspected to be contaminated with PBB, as compared to those of Wisconsin farm residents. Serum PBB levels were not found to be significantly higher in Michigan males and females exhibiting the most prominent neurologic symptoms. Serum PBB levels were negatively correlated with performance test scores, particularly in males in older age groups.