Toxemia of pregnancy in Jerusalem. II. The role of diet. A dietary history was obtained from 180 patients with preeclampsia and eclampsia, representing 92% of all cases occurring in the pregnant population of West Jerusalem over a defined period. The intake of nutrients and 78 items of diet was compared for each patient and two healthy control subjects who were matched for country of origin, parity, month of delivery, age, year of immigration and years of schooling. All diagnoses were made by the same research team and dietary histories were elicited by one of two experienced dieticians. Comparisons between the 180 patients and their respective control pairs showed a significantly reduced intake of calories, proteins and fats and an increase in consumption of sugar and sweets by the patients. The food items involved, including cheese, eggs, olives and nuts, did not appear consistently, however, in population subgroups defined by age, period of immigration and country of origin. Sixty-six patients reported not having changed their diets during pregnancy and these showed no significant differences in consumption of any of the foods or nutrients at the 1% level, when compared with their matched control subjects. All differences observed were confined to the 114 patients who, for one reason or another, had changed their diets. It is concluded that the differences in diet between patients and control subjects are the result, and not the cause, of the toxemia of pregnancy. Supporting and contradictory evidence in the literature is analyzed, and possible sources of the discrepancies are pointed out.


Valyl-transfer RNA formation stimulated by monovalent cations and spermine in rat liver. Valyl-tRNA synthetase from rat liver catalyzes the aminoacylation of tRNA in the presence of a) Mg2+, b) monovalent cations and c) spermine. The degree of aminoacylation with Na+ is equal to that with Mg2+ but the ATP required with Na+ is 25 times lower than that with Mg2+. The aminoacylation becomes almost undetectable in the presence of Na+ when tRNA deprived of Mg2+ is used.


Metabolic aspects of a hypoxia test for placental sufficiency. A hypoxia test for placental sufficiency was performed on 24 healthy pregnant women nearing term and 23 high-risk pregnant women in advanced stages of gestation. Hypoxia was induced by inhalation of a breathing mixture containing 7% oxygen through a semi-open system which permitted partial rebreathing, thus preventing hypocapnia. The changes in fetal heart rate (FHR) resulting from maternal hypoxia were recorded continuously by external or internal monitoring. The changes observed in FHR were more marked in high-risk cases. Maternal blood gases were tested before and after 10 min of hypoxia in 10 normal and 10 high-risk patients. In no case was maternal acidosis observed. All pregnant patients regarded as high-risk because of hypertensive disorders or chronic renal disease manifested metabolic alkalosis. This finding cannot be explained. It is regarded as being responsible for the more severe FHR changes through a negative Bohr effect, which reduces the dynamic exchange of oxygen in the placenta. Metabolic alkalosis does not appear in high-risk pregnant women exposed to milder hypoxia by breathing 12% oxygen. The changes in FHR observed during severe maternal hypoxia, i.e., 7% oxygen, are probably due more to maternal metabolic alkalosis than to placental insufficiency. Consequently, the "severe hypoxia test" cannot be used as a test for placental insufficiency.


Preeclampsia and fetal well-being.

Preeclampsia and fetal well-being. Thirty-three women with preeclamptic toxemia were retrospectively divided into three groups, according to clinical data, urinary estriol excretion, fetal growth, fetal movements and fetal heart recordings. In group 1 (six patients) there was no fetal growth retardation, and fetal motor function and heart rate were normal. In group 2 (17 patients) there was fetal growth retardation, estriol values were usually low, and fetal movements and heart rate were normal. In group 3 (10 patients) fetal movements decreased markedly almost until complete cessation for 12 to 24 h, and pathological changes were present in fetal heart recordings. A classification of preeclamptic toxemia according to these criteria is suggested. Patients who manifest placental metabolic failure, such as the women in group 2, should be hospitalized for observation only, as no immediate danger to the fetus is apparent. If there are signs of severe fetal distress and cardiomotor failure, such as in group 3, prompt delivery is essential to prevent fetal death in utero.


Prognostic parameters in myeloid metaplasia: agnogenic versus postpolycythemic. Thirty-nine patients with myelofibrosis and myeloid metaplasia were diagnosed and followed during the period 1955-74. Twenty-eight suffered from agnogenic myeloid metaplasia and 11 from myeloid metaplasia following polycythemia vera. In an attempt to compare the two groups and to define prognostic guidelines, an analysis of survival with respect to various clinical parameters was made. The median survival time of patients with agnogenic myeloid metaplasia was seven years as opposed to only 28 months for the poltpolycythemic group. Older age at diagnosis, a large spleen, or its rapid enlargement, anemia and leukocytosis, but not thrombocytopenia, had a marked negative effect on survival. The clinical condition of most patients was remarkably stable during the entire course of their disease. If a significant drop in hemoglobin occurred, it was sudden, and caused by gastrointestinal hemorrhage or the development of acute leukemia. No demonstrable effect of therapy on survival was found.


Sickle cell thalassemia in an Israeli family. Sickle cell thalassemia in an Israeli family of Indian extraction is described. The family demonstrates the segregation of the betaS- and beta-thal genes and the interaction phenomenon known to exist in this condition is demonstrated clearly in the propositus.


Acute acoustic trauma - a clinical investigation and prognosis in 433 symptomatic soldiers. An audiological and clinical study was carried out on 433 soldiers suffering from symptomatic acute acoustic trauma (AAT). The severity of AAT was similar following exposure to different types of firearms. The typical subjective complaints were tinnitus and hearing loss and the more severe the objective hearing loss, the more frequent were the typical subjective symptoms. It seems that there are critical sound pressure levels and critical frequencies below which the remnants of infectious processes in the middle ear may have a protective effect on the cochlea in cases of exposure to noise, whereas above these critical levels and frequencies the injurious influence of noise appears to be enhanced. The best known treatment for AAT seems to be removal from further exposure to noise. Further exposure to noise had a significant worsening influence on the average hearing status, while removal from noise significantly improved the audiometric status.


Aplasia of toe phalanges and nails.

Aplasia of toe phalanges and nails. An infant born without toenails and without the middle and distal phalanges of the toes was otherwise normal, on clinical and radiological examination. This is the second case of this entity to be described. It is speculated that an environmental insult at the critical period of fetal toe development may be the cause of the anomaly, but a genetic factor cannot be excluded.


[The polymorphism of collagen. New viewpoints on the structure and function of connective tissue]. Recent studies have established that connective tissue contains several chemically and genetically distinct collagens. Here we discuss the nature of these proteins, their occurrence in different tissues and their involvement in disease processes. Types I, II and II collagens show some similarities indicating a common origin. Morphological studies using antibodies against the various collagens indicate that the different collagens occur in different anatomical structures. Alterations in the distribution of these collagens are seen in tissues in certain disease states and may cause the loss of normal tissue function.


[Animal experiments on the relationship between urinary excretion of hydroxyproline and serum hydroxyproline fractions]. Hydroxyproline excreted withh the urine and the free and peptide-bound hydroxyproline in the serum originate from collagen catabolism in the connective tissue. The relation of protein-bound hydroxyproline in the serum to the collagen metabolism is still contradictory. In normal and lathyritic rats the time dependent changes of specific hydroxyproline activity in the urine and serum after intraperitoneal application of C-14-proline were determined. In normal rats the main part of hydroxyproline excreted in urine and of the protein-bound hydroxyproline in serum have corresponding half-life periods of 0,6-0,7 days and co-ordinate with the neutral salt soluble collagen. Also in lathyritic rats with their increased amount of neutral salt soluble collagen due to an increase collagen synthesis and a retarded transition from soluble to insoluble collagen these two parameters of collagen metabolisms are in agreement.


[Multiple subcutaneous Trichophyton rubrum abscesses. Pathomorphosis of a generalized superficial tinea due to impaired immunological resistance]. A patient with chronic polyarthritis is reported who was treated with corticosteroids over several years and also received azathioprine. The patient developed extensive tinea pedum and corporis which was suddenly complicated by multiple subcutaneous abscesses caused by the same organism, Trichophyton rubrum. This type of dermatophytosis has only rarely been described. It shares some characteristics with the maladie dermatophytique of Hadida and Schousboe. Chronic granulomatous dermatophytoses such as granuloma trichophyticum Majocchi or tinea granulomatosa nodularis cruris or acute suppurative dermatophytoses of the kerion Celsi type present different clinical and histological pictures and develop under different pathogenetic conditions.


[The nodular necrotizing dermatitis].

[The nodular necrotizing dermatitis]. Preferring to the antecedent sparse literature an observation of "dermatitis nodularis necrotica" is described in a 15 year old girl with constipation showing the typical coarse-nodular necrotizing exanthema especially on the extremities. Histologically there was a perivasculitis with prevailing excessive cellular infiltrates (reticulum cells, granulocytes). Immunological tests (immunoelectrophoresis, fluorescence-histology in skin and intestinal biopsy) were negative. On the other hand staphylococcus aureus (as detected in skin scratches and by intracutaneous tests) seemed to play an etiologic role. Thus "dermatitis nodularis necrotica", on clinical grounds somewhat similar to papulo-necrotic tuberculids, seems to be a bacteride with secundary alterations of the skin vessels and not a variant of primary vasculitis.


[Pigmented cysts. Pigmented epidermal cysts and pigmented trichilemmal cyst]. The clinical and histopathological picture of the pigmented epidermal cyst and the pigmented trichilemmcyst is illustrated by three case-reports. The pigment is melanin, which is located in the epithelium of the cyst-wall, the corneocytes of the lumen and in macrophages in the dermis. The clinical appearance of melanin pigmented cysts is blue due to the Tyndall-phenomenon.


[Peticulate acropigmentation, a world-wide disease]. Acropigmentatio reticularis is a peculiar reticulate pigmentation, which consists of small, angular, somewhat depressed, brown macules of uniform color and involves mainly the extenser surfaces of the distal parts of extremities. It occurs sometimes familial and is regarded as an autosomal dominant disease. Acropigmentatio reticularis was published in 1953 by us. Since then, no other reports of Japan appeared until Griffiths recently found the familial occurrence of a reticulate acropigmentation in South Iran and England. It was then confirmed that this acropigmentation is identical with acropigmentatio reticularis and accordingly proves the appearance of the latter outside of Japan.


[Clinical picture of pretibial myxedema and new aspects of diagnosis and pathogenesis]. We have reported on two cases of pretibial myxedema. In one patient, the pretibial myxedema developed symmetrically half a year after the appearance of endocrine exophthalmos. Recently, acropachy developed as well. In the second case, the pretibial myxedema arose unilaterally in an old cicatricial area, six years after the onset of endocrine exophthalmos. In this syndrome, the development of the whole group of symptoms, dermopathy, ophthalmopathy, and osteopathy at the same time is very rare. The clinical picture is seen in thyroid disorders, as a rule occuring in hyperthyroidism, rarely in hypothyroid or euthyroid states. Apparently, the development of the symptoms does not depend on thyroid hormone production. One of our patients showed conspicuous hyperthyroidism, the other, thyroxin deficiency. The thyreohypophyseal feedback mechanism in this syndrome was examined for the first time by means of TRH stimulation tests. In both patients, thyroid auto-antibodies indicative of autoimmune thyroiditis were demonstrated. A high activity of long acting thyroid stimulator was measured in the one patient's serum.


Zinc therapy in acrodermatitis enteropathica. An infant is described with acrodermatitis enteropathica, who initially presented with severe and intractable watery diarrhea. Diagnosis was established at the age of eleven weeks. Serum-zinc concentrations were extremely low and urinary zinc excretion was diminished. Eleven days after oral zinc supplement (100 mg elemental zinc per day), the skin lesions had healed. The high therapeutic doses of zinc required for healing are suggestive that zinc malabsorption is an important pathogenetical factor of this disease.


Treatment of acrodermatitis enteropathica with zinc sulphate. Rerport of 3 cases. The therapeutic effect of orally administered zinc in 3 patients affected with Acrodermatitis enteropathica is reported. Single daily doses of zinc resulted in rapid improvement of the general condition of these patients and in clinical remission within a week. Serum, urine and hair zinc levels as well as alkaline phosphatase, which were very low before treatment, returned to normal after therapy. This brief report confirms the efficacy of oral zinc in the treatment of Acrodermatitis enteropathica.


[Blood pressure in adolescence. Measurements and their relation to body development in 745 healthy school children in Basel]. The average blood pressure measured in a representative sample of 8th grade juveniles (14-16 years) was 120/70 mm Hg. Mean systolic pressure was 5 mm Hg higher in boys. The 90th percentile was 135/80 mm Hg for both sexes. Systolic and diastolic pressure rose with increasing body weight. Correlation with height was less obvious. Difference in weight could not account for all the sex difference in blood pressure. Association of sexual maturation with higher blood pressure values was more pronounced in boys.


[Peak expiratory flow rate among Swiss boys and girls between 4 to 19 1/2 years of age domiciled in the Canton of Geneva in 1972]. Peak expiratory flow rate (PEFR) was measured by means of a Wright peak flow meter on a sample of 2865 boys and 2712 girls selected at random in the Canton of Geneva, Switzerland (resident population of Swiss children and adolescents aged 4-19 1/2 in 1972). Technique of measurements and statistical analysis are described with an aim at standardization. Expected percentiles of PEFR (50, 25, 10 and 2.5) versus standing height are presented in tabular form for boys and girls separately. Nomograms are given allowing graphical determination of expected PEFR percentiles in either sex for any given standing height.


[Reflections on the anorectal pressure profile]. The results of electromanometric studies of the anorectum in 40 children are presented. Owing to a constant flow of rinsing water through the recording tube and owing to a repeated tracing during the same session, there is a more sensitive picture of the anorectal pressure profile than reported hitherto. In addition, the anorectal pressure values are higher. In healthy infants and in most children with constipation and/or encopresis, the anorectal pressure profile can be divided in 2 different parts. These can be differentiated by their amplitude and according to their shape. In a few patients with constipation, there is no difference between the two parts concerning the shape of the anorectal pressure profile, and the values of the anorectal pressures are below normal. But all children with anal sphincter incontinence have a distinctively abnormal anorectal pressure profile, there is not even a numerical difference between the two parts of the anorectal pressure profile, and the anorectal pressures are very low. The relationship between these two parts of the anorectal pressure profile and the muscles of the pelvic floor are discussed and the significance of the mentioned technique evaluated with regard to the diagnosis and treatment of the anorectal disturbances in childhood.


[Coagulation studies from capillary blood in newborn infants]. Coagulation studies from capillary blood, consisting of the determination of fibrinogen, factors II and V and proactivator-plasminogen, were done in 104 newborns. In healthy newborns fibrinogen and factor V was found near the adult level, while factor II and proactivator-plasminogen showed a severe deficit. None of the coagulation factors was dependent of gestational age. Fibrinogen was significantly lower in the group of children with perinatal asphyxia. In ill newborns there was a significant correlation between fibrinogen and factor II and fibrinogen and factor V as was between factors II and V. No correlation could be demonstrated between proactivator-plasminogen and any of the other coagulation factors.


Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in Switzerland. Demonstration of a new variant (G-6-PD Aarau) with chronic nonsphaerocytic haemolytic anaemia. A new variant of erythrocytic glucose-6-phosphate dehydrogenase has been found in a family of Swiss origin. It is associated with chronic nonsphaerocytic haemolytic anaemia. The enzyme from the erythrocytes of a young boy of this family was partially purified 110-fold and characterized. It revealed reduced catalytic activity, increased thermolability and two maxima of the pH activity curve at pH 7.0 and 8.5. The Km value for glucose-6-phosphate was reduced, that for NADP was normal. The enzyme showed an increased inhibitor constant for NADPH with respect to NADP. Electrophoretic mobility was normal (B+). 2-Desoxyglucose-6-phosphate and galactose-6-phosphate were utilized at normal rates, whereas the analogue deamino-NADP gave an increased utilization rate. The mother of the propositus could be identified as heterozygous for this enzyme deficiency. Chronic haemolysis is possibly due to the increased thermolability of the variant enzyme.


[Intestinal mucosa in rats with iron deficiency anemia]. Eighteen albino rats at the age of 15 days were separated in 2 groups of 9 and fed cow's milk exclusively. The milk supplied to the control rats (group I) was supplemented with iron and copper. The months later, the rats were scarificed. The animals of group II were severely anaemic. In each rat, a histological examination of gastric (in group II, only in 2 rats) and jejunal mucosa as well as measurements of total thickness, villous height, epithelial cell height and mitotic index were made. Histology was normal in all the rats. Measurements gave similar results in both groups except for the epithelial cell height which was significantly higher in anaemic rats than in controls. The authors take issue with the methodology followed in previous studies concerning iron-deficient children and suggest that the causal relation between iron deficiency and structural changes of intestinal mucosa in children has not yet been proven.


Familial iminoglycinuria with normal intestinal absorption of glycine and imino acids in association with profound mental retardation, a possible "cerebral phenotype". Spasticity and severe psychomotor retardation in a 2-year-old girl, apparently in expression of chronic progressive encephalopathy, was found in association with prolinuria, hydroxyprolinuria and hyperglycinuria. The pattern and levels of these amino acids in plasma proved to be normal, however, as was their intestinal absorption as well as their concentration in cerebrospinal fluid. The proband appears to be homozygous for iminoglycinuria with an apparent inborn defect of the renal tubular transport system specific to these amino acids. An isolated hyperglycinuria, however, was traced in several obligate heterozygotes in this family. The possibility of a more direct causative link between this anomaly and her clinical manifestations is discussed. Where instances of iminoglycinuria occur in association with cerebral pathology of this type, an analogous impairment of a correspondingly specific cerebral amino acid transport system is postulated.


[Happy-puppet syndrome].

[Happy-puppet syndrome]. Six cases of this syndrome previously reported in Great Britain and in Canada are reviewed in relation to a personal case, a 17-month-old boy. The syndrome's main features are microbrachycephaly and peculiar face, mental deficiency with euphoria and laughter, ataxia and epilepsy consisting in infantile spasms and grand-mal attacks. Though its precise nature and cause still remain unknown, the syndrome seems neither familial nor progressive.


Quantification and identification of particle movement in epidermis after thermal injury. Skin samples from a rabbit hind limb were taken from controls and at 5 min, 2 and 6 hr after a mild thermal injury (60 degrees C for 1 min). Large aggregates of intercellular particles, usually ribosomal in appearance, were seen in 6 hr samples and were accompanied by some peripheral aggregates of particles and by granule-coated vesicles. These structures were present in earlier samples to a lesser extent and were absent from control material. Quantitative assessment showed that intercellular particles apparently increased up to 6 hr whereas peripheral aggregation was maximum at 2 hr. Histochemical analysis confirmed that the particles contained ribonucleoprotein. Other larger particles were seen occasionally and contained carbohydrate. Lymph draining the site showed cellular changes, little change in enzyme activities, and no aggregates of particles.


Further studies on section thickness measurement. A rapid, simple, accurate and reproducible technique for measuring section thickness using an instrument known as a surfometer is described. It has shown that microtome settings cannot be relied upon as a means of monitoring the thickness of sections of quenched or wax-embedded tissue. However, there appeared to be a linear relationship between microtome setting and the thickness of dewaxed sections. Microtome settings seem to provide an accurate indication of the thickness of araldite sections.


The laser in the Lowry technique for microdissection of freeze-dried tissue slices. A new technique for tissue microdissection is described. This procedure, using an u.v.-laser micropreparation instrument, overcomes the extremely time-consuming manual preparation. The u.v.-laser micropreparation design allows fast, precise, reproducible and smear-contamination-free tissue microdissection. The preparation of the tissue sample can be programmed by tracing out the area to be sampled with a non-destructive 0.5 mW He-Ne-laser aiming-beam. The tract is stored in a small electronic unit, which then guides the motor-driven stepping stage on the microscope in the actual dissection run with the u.v.-laser. The laser power is adjustable in the range 4 to 40 kW and controlled by a photo diode displayed on an oscilloscope screen. In the tissue slice, prepared according to Lowry, an unlimited number of cells or tissue compartments can be dissected and afterwards weighed. The procedure described offers a broader use of the quantitative microhistochemical techniques of Lowry and of Neuhoff.


On the histochemistry of neuronal and glial TPPase. Thiamine pyrophosphatase (TPPase) activity in the neuronal Golgi apparatus and in glia cells was investigated using different tissue preparation techniques such as fresh frozen and fixed frozen sections, the effect of ATP as an activator and the fine structural localization of the enzyme activity in glia cell processes and the glio-vascular contact point was observed under the electron microscope. TPPase was demonstrated in the glia cell using only a fixed frozen tissue preparation, activated by ATP with the concentration as low as 0.1 mM. On  the contrary, enzyme activity was detected in the Golgi apparatus of the neuron regardless of tissue preparation, fresh or fixed frozen, or by the addition of ATP to the incubation medium. The identity of the glia cell type showing a positive reaction for TPPase is thought to be part astrocyte and part microglia. The fine structural observation of TPPase localization at the glia cell process ending, particularly at the glio-vascular and glio-fibral (medullated fiber) contact point suggests a functional role of this enzyme for transport of metabolites through glia cell processes to neurons and/or the blood capillary, and also may play a role in regulation of co-carboxylase.


Application of histochemistry to a living organ: polyglucose histochemically synthesized in the paraboloid of the chick accessory cone in vivo by phosphorylase and branching glycosyltransferase. Histochemical application in a living animal was tested on the paraboloid of the accessory cone of the chick retina. After the anterior part of the eye had been cut with a Graefe's knife under ether anesthesia, the posterior part was filled with the medium for phosphorylase under exposure to light. The specimens were embedded for routine electron microscopy and the paraboloid of the accessory cone was observed by electron microscopy. Polyglucose particles were synthesized from glucose-l-phosphate in the paraboloid by the activities of phosphorylase and branching glycosyl transferase and found to be in the cytoplasmic matrices. These particles were larger in size and better stainable with lead citrate than those found in the paraboloid of the retina incubated in the medium in vitro by the conventional histochemical method. Overproduction of polyglucose particles was not found in the paraboloid of the retina incubated in the medium in vivo. These findings suggest that polyglucose particles synthesized in vivo have a close resemblance to native glycogen particles and that glycogen metabolism is regulated by the living cell. Glycolysis may not be related to the membranous structures. Therefore, application of enzyme histochemical techniques to the living organ can demonstrate more accurate morphological aspects of metabolism in the cell.


Histochemical demonstration of cholinesterase activity in the cornea of the rat and the effect of various denervations on the corneal nerves. Cholinesterase (ChE) activities of the rat cornea were demonstrated histochemically by using both light and electron microscopes. Acetylcholinesterase (AChE) reaction was localized in the axolemma of the nerves in the corneal stroma. The epithelial cell membranes and the intraepithelial nerve endings also showed AChE reaction. Non-specific cholinesterase (NsChE) activity was observed only in the endothelial cell membranes. Cervical sympathectomy, ciliary ganglionectomy and stereotactic coagulation of the ophthalmic division of the trigeminal nerve were performed in order to study the routes of the AChE-containing nerves to the cornea. The disappearance of AChE-containing nerves was observed only after ophthalmic neurotomy. It is suggested that the AChE-containing nerves are distributed to the rat cornea exclusively via the ophthalamic nerve. They seem to be sensory nerves.


The localization of thiamine pyrophosphatase activity in the acinar cells of stimulated and non-stimulated sublingual glands of the rat. The distribution of thiamine pyrophosphatase (TPPase) activity in the acinar cells of the rat sublingual gland has been studied at various stages of the secretory cycle following stimulated secretion. The rats were stimulated to secrete by an intraperitoneal injection of isoproterenol and pilocarpine. In non-stimulated glands, TPPase activity is detected mainly in 3--4 cisternae at the inner concave side of the Golgi complex and in some adjacent condensing vacuoles as in other cells. In the acinar cells 1 to 2 h after stimulation, however, reaction product for the same enzyme activity is detected in the cisternae at the outer aspect, as well as the inner aspect, of the Golgi complex and even in the cisternae of the endoplasmic reticulum (ER). About 4 h after stimulation, TPPase activity becomes concentrated in 3--4 cisternae at the inner concave side of the Golgi complex as in the acinar cells under non-stimulated conditions. Morphological observations of the acinar cells 1 to 2 h after the stimulation have indicated that the reorganization of the Golgi complex and ER is a major event which occurs at this stage. It is possible that this cellular event is related to the occurrence of TPPase activity in those sites which normally show negative reaction in non-stimulated state.


The cytochemical localization of cholinesterase activity in the developing chick heart. The electronhistochemical localization of the cholinesterases of developing chick heart muscle cells has been studied with the aid of a substrate which incorporates an enzyme-susceptible thiolester group and a diazonium group into the same molecule. The embryonic chick heart exhibits cholinesterase activity from Hamilton-Hambruger stage 3 through to four days post hatching. Although enzyme activity is not demonstrated in every location at all stages studied, it has been observed on the nuclear envelope, golgi complex, rough and smooth endoplasmic reticulum, mitochondria and myofilaments. A change in the type of activity has been demonstrated, acetylcholinesterase is found during the first fourteen days of development but thereafter, non-specific cholinesterase is seen instead. As nerves have not been found in relation to the working myocardium, further support is given to the concept that an acetylcholine-cholinesterase system of myogenic origin is involved in spontaneous contraction. Consideration of the distribution of enzyme within the myocardial cell, raises the possibility that cholinesterase may be concerned in a regulatory mechanism of protein synthesis, a suggestion made previously in connection with liver cells.


On the vegetative network of guinea pig thoracic spinal cord. A dense AChE-positive network was visualized by light microscopy in the thoracic spinal cord of grown-up guinea pigs of both sexes (bodyweight 250-300 g). This network connects in a horizontal and vertical direction the preganglionic sympathetic nuclei (n. intermediolateralis pars principalis (ILp), n. intermediolateralis pars funicularis (ILf), n intercalatus spinals (IC), n. intercalatus pars paraependymalis (ICpe), (Petras and Cummings, 1972) all along the thoracic spinal cord. In addition to AChE activity, the bundles of fibers of this network also show a strong formaldehyde-induced NA fluorescence. Electron microscopy demonstrated granular vesicles in the cytoplasm of ILp cells. The surface of the ILp and IC neurons is almost entirely covered with synaptic bottons which have clear and granulated synaptic vesicles. The bundles of fibers consists of parallel myelin-free axones and dendrites. On their cource the axones form varicosities. In the varicosities and in the synaptic enlargements there are also clear and granulated (40-100 nm) vesicles. The probable origin of the vegetative network fibers of guinea pig thoracic spinal cord is discussed.


Membrane alteration of trypsin-treated smooth muscle cells and penetration by antibodies to myosin. Smooth muscle cells dispersed by low concentration of trypsin (0.125%) and grown in tissue culture will not bind antibodies against smooth muscle myosin added to the culture medium. These cells will attach, flatten and contract normally. When the trypsin concentration is raised to 0.25%, many of the attached cells will not flatten. Such round cells show uptake of the myosin antibody at the periphery and in the cytoplasm, using the indirect immunofluorescent technique. At a trypsin concentration of 1%, viable cells are no longer observed and all cells show uptake of myosin antibody. It is concluded from these experiments that above a crucial trypsin concentration, the membrane becomes altered sufficiently to permit the penetration of antibodies into the cell interior.


The differentiation of proximal and distal tubules in the male rat kidney: the appearance of aldolase isozymes, aminopeptidase and alkaline phosphatase during ontogeny. 1. The specific activities of aminopeptidase, alkaline phosphatase and aldolase isozymes were measured in homogenates of kidneys taken at different stages of ontogeny. The cellular localization of these enzymes was studied in cryostat tissue sections using substrate linked assays for aminopeptidase and alkaline phosphatase and the mixed aggregation immuno-cytochemical technique for aldolase isozymes; local enzyme concentrations were estimated photometrically. 2. The presence of both aldolase-A and aldolase-B was demonstrated in all metanephrogenic cells (and at still higher concentrations in collecting tubule cells) of the rat fetus 16 days after conception and in the undifferentiated cells of the neogenetic zone of kidney up to 8 days after birth; no aminopeptidase or alkaline phosphatase could be found in these cells. 3. Measurements made on stained tissue sections show that the shift towards aldolase-B, seen in homogenate analyses, is due to a change in the relative amounts of proximal tubules. No evidence was seen for repression in the synthesis of aldolase-A or aldolase-B monomers in the different kidney cells during ontogeny. 4. Two transitions in the mode of nephron differentiation were observed: one was shortly after birth, the other followed weaning. Before the first transition the concentrations of the enzymes increased to different degrees, such that the enzymes reached concentrations comparable with those as in the cells of adult rats by 2 to 4 days post partum. After the second transition proximal tubule size and specific activity of brush border membrane enzymes increased 3 fold. In contrast, the distal tubules did not increase significantly in size, but their aldolase-A concentration increased 3 fold. 5. Evidence based on enzyme quantification and morphometry in kidney sections is presented to demonstrate that the proximal tubule cells show functional adaptation by two independent mechanisms: specific amplification of gene expression and hypertrophy. In contrast, the distal tubule shows functional adaptation only by specific amplification of gene expression.


Reactivity in tissue tryptophyl units in histofluorescence methods using carbonyl compounds. The contribution of tissue tryptophyl residues, with both amino and carboxyl groups linked to the peptide bonds, to visible fluorescence was studied following various histochemical methods. Tryptophan residues of chymotrypsinogen and trypsinogen exhibited visible fluorescence after (1) combined formaldehyde-HCl vapour, (2) combined formaldehyde and acetyl chloride vapour, and (3) glyoxylic acid vapour treatment.


Differentiation of epithelial cells in human jejunum: localization and quantification of aminopeptidase, alkaline phosphatase and aldolase isozymes in tissue sections. Sections from human jejunum were stained histochemically for aminopeptidase and alkaline phosphatase and the aldolase isozymes were detected with the mixed aggregation immuno-cytochemical technique. All enzyme concentrations increased from the bottom to the upper part of the crypt. The concentration of aldolase-A per cell was the same in the upper part of the crypt and the villus, whereas the concentration of the other three enzymes was still higher. Therefore, high amounts of aldolase-B, aminopeptidase and alkaline phosphatase are present in cells highly active in absorption in a fashion similar to that found in the proximal tubule cells of kidney. The relatively undifferentiated cells of the crypts contained both aldolase-A and aldolase-B. Alkaline phosphatase gains its full activity later than aminopeptidase. The synthesis of microvillar membrane enzymes comes to an end earlier than that of the cytosol enzymes.


The presence of aromatic L-amino acid decarboxylase in certain intestinal nerve cells. The presence of aromatic 1-amino acid decarboxylase (AADC) in nerve cell bodies of the intrinsic plexuses of the guinea-pig small intestine was demonstrated by incubating segments of intestine with 1-dopa in the presence of an inhibitor of monoamine oxidase, pargyline. After such incubation, some nerve cell bodies gave a fluorescence histochemical reaction indicative of the presence of a decarboxylated product of 1-dopa, probably dopamine. No fluorescence reaction occurred in the unincubated control or if the inhibitor of AADC, RO 4-4602, was included in the incubation mixture. The AADC-containing cell bodies apparently do not take up and store dopamine, because no fluorescence could be detected after incubation with dopamine and a monoamine oxidase inhibitor. The AADC-containing cells were found in about half of the ganglia of the submucous plexus of the guinea-pig small intestine, but were considerably less frequent in the myenteric plexus. They were also found in the other areas examined in this study, that is, in both enteric plexuses of the guinea-pig distal colon and of the small intestines of rabbits and rats.


Lipids in the skin of a cat-fish Heteropneustes fossilis (Bloch) (Heteropneustidae, Pisces). A histochemical investigation. Localization and characterization of different lipids in the cellular constituents of the skin of Heteropneustes fossilis has been made using several histochemical techniques. High contents of cholesterol, its esters and phospholipids have been correlated with the metabolically active state of the basal cells undergoing cell proliferation and differentiation. The polygonal cells in the outermost layer of the epidermis, though rich in phospholipid contain small amounts of cholesterol and its esters. This has been correlated with the metabolically less active state of theses cells. Neutral lipids and phospholipids in the polygonal cells of the outermost layer may contribute to the contents of surface slime and act as an efficient barrier for the penetration of water through the skin. The deposits of neutral lipids in the subcutis may provide energy during the period of fasting, act as a barrier for water diffusion through the skin and serve as shock absorbing pads protecting the fish from mechanical injury.


Acetylcholinesterase distribution in chick spinal cord cultures. A light and electron microscope study. Explants of 10--12 day chick embryo spinal cord were cultured by coverslip-roller tube method for 3-80 days. The cellular and subcellular localization of acetylcholinesterase activity in cultured neurons was studied by the thiocholine techniques of Karnovsky and Roots and Lewis and Shute. At the light microscopic level, acetylcholinesterase was demonstrated in the neurons of both ventral and dorsal horn regions. Occasionally neurons migrated in the outgrowth zone exhibited strong intracellular activity. At the electron microscopic level, acetylcholinesterase activity was found in the nuclear envelope, granular endoplasmic reticulum and the Golgi apparatus of the neurons. No enzyme reaction was detected in the glial cell cytoplasm.


Ultrastructural identification of monoaminergic synaptosomes from one day old rat brain. Synaptosomes from one day old and adult rat brain were studied. Specific cytochemical methods for demonstrating monoaminergic (MA) nerve endings were used. Permanganate fixation after preincubation with 5-OHDA or alpha-methyl-NA demonstrated MA synaptosomes. Their number was small in the adult (less than 1 %) and still smaller in the one day old rat brain. The MA synaptosomes from developing rats were different from the adult ones. The large amount of endoplasmic reticulum in developing synaptosomes suggests that granular vesicles are formed from endoplasmic reticulum in nerve endings.


[The significance of the CNS for the physiology of hearing (author's transl)]. Some general aspects of auditory perception (funnelling, contrast, pattern recognition, form perception, methodological limitations) are discussed in the first part of this presentation. The modern concept of the hydrodynamics of the inner ear, including electronic modelling of the function of the basilar membrane is their dealth with. For the encoding and decoding processes of the auditory system the different grades of intensity function at the different neuronal levels is compared with that of the envelope of the basilar membranes deflection. The influence of the efferent system is discussed. In a third section of the paper some new results from our department are reported concerning the single unit activity at geniculate level recorded from the awake cat by means of a telemetric system. Neurophysiological correlates to vowel- and consonant detectors and their relations to be the phonem recognition of speech could be demonstrated. Finally, the most recent state of objective audiometry is discussed (DC-potentials, simultaneous records of electrocochleogram and cortically evoked activity, relations to EEG's power spectrum, and brains changes in vigilance) with a view of future approaches to ERA.


[An oesophagotracheal Fistula following prolonged intubation (author's transl)]. Attention is drawn to the case of an oesophagotracheal fistula following prolonged intubation. A combination of physical factors, the use of unsuitable cuffs and a nasogastric feeding tube, are considered to be the cause. Surgical repair of the fistula is advised as soon as possible. While primary closure of the oesophageal defect is always possible, suture of the membraneous trachea may be impossible and a graft may be necessary to cover the defect. For this is recommended oral mucosa, which achieved very good result in this reported case.


[I V. Vocal disturbances in neuro-psychiatric illnesses and in laryngeal paralyses (author's transl)]. In the fourth part of a series on applied phoniatrics, a review of vocal disorders as symptoms of neurological and psychiatric diseases is given. Clinical characteristics, diagnosis, as well as laryngologic and phoniatric aspects of therapy of vocal cord paralysis are also described.


[Prefabricated complex wire replacement of middle ear ossicles (author's transl)]. This article comments on two prefabricated and linked complexes of wire that were used to replace the malleus and incus, and the malleus, incus and stapes.


[Narcosis as anesthesia in middle ear surgery (author's transl)]. Four essential points exist in the use of narcosis for surgery of the middle ear: 1. In addition to local anesthesia, any method of narcosis for anesthesia with endotracheal intubation is suitable for surgery. 2. Surgical procedures utilizing the operating microscope make immobility of the patient mandatory. 3. Establishment of a relatively bloodless surgical field by special techniques (such as use of local vasoconstrictors or controlled hypotension with ganglionic blocking agents or halothane) can be employed. 4. Altered middle ear pressure by nitrous oxide (causing a rise in pressure by 3-4 cm H20) can impede operative procedures.


[Pathology and pathogenesis of chronic secretory otitis media in childhood (author's transl)]. The pathology and pathogenesis of chronic secretory otitis media is described on the bais of quantitative studies of the mucosa, using whole mounts as well as serial sections of normal and biopsy specimens. The pathogenetic is divided into three stages. The initial stage, i.e. the period from the action of the aetiological factor on the middle ear mucosa till the accumulation of mucous secretion, is characterized by inflammatory processes by way of vascular proliferation and dilatation and lymphocytic infiltration. These processes trigger hyperplasia and differentiation of the epithelial cells with subsequent metaplasia of the epithelium into pseudostratified columnar ciliated epithelium with significantly increased goblet cell density and formation of mucous glands. The secretion is predominantly exudative with an admixture of mucus. The secretory stage is dominated by secretion of mucus from active mucous glands and goblet cells, the number of which has been grossly raised. The secretion accumulating in the middle ear is chiefly mucous. During the degenerative stage mucus production abates, and the middle ear returns to normal provided that irreversible adhesive changes have not occurred. The decline in mucus production is due to degeneration and inactivation of the glands combined with decreasing goblet cell density. The epithelium normalizes into cubical epithelium in one or two layers, or through metaplasia changes into secretorily inactive stratified squamous epithelium. The aetiological role of the auditory tube and the importance of tubal function is discussed. The relationship between the ability of the mucosa to produce mucus and the capability of the tube to carry it away is found to be decisive for the clinical course and the severity of the disease.


[Secondary radiogenic cancer of the larynx (author's transl)]. Based on a series of 32 cases of late recurrence of early stage vocal cord cancer, the question of the pathogenesis of these lesions is discussed. Late recurrence, 5 to 18 years after treatment of the first tumour was observed in 3 cases after a laryngofissure procedure only and in 29 cases after laryngofissure combined with postoperative irradiation or after pure irradiation therapy. The clinical and statistical data and the histological picture of the second tumour show with a high degree of certainty that these second tumours are caused by the cancerogenic side-effect of the primary irradation, which destroyed the primary tumour. The danger that a patient, cured from his first cancer by irradiation, develops a second radiogenic cancer rises from year to year that the patient survives and certainly is much higher than had been suspected. Irradiation of a vocal cord cancer in a young patient with a relatively high life expectancy should no longer by used. Irradiated patients must be reviewed until the end of their lifes.


[Reconstruction of the larynx following laryngectomy (author's transl)]. A pedicled flap of chest skin is sutured to a tube and interposed between tracheostome and hypopharynx, similar to Asai's method of laryngeal reconstruction. The technique is described, and the dangers and disadvantages are mentioned.


[Applied phoniatry. V. Laryngeal diagnosis and rehabilitation after laryngeal surgery (author's transl)]. In the last of 5 articles on the benefits of applied phoniatrics hints are given on the differentiation between laryngeal inflammations and tumours. Voice rehabiliation after laryngeal surgery (laryngofissure, partial laryngectomy, total laryngetomy) is demonstrated. Disorders of voice caused by intubation are also described.


[Intensive care in ENT medicine, head and neck surgery (author's transl)]. In intensive medicine we distinguish between intensive care units which have mostly observatory and monitoring functions and intensive therapy units. For the surgical patients of the ear, nose, and throat department the intensive care units are probably of greater significance. The following play an important role: Preoperative work-up including laboratory fluoroscopy and x-rays, pulmonary function tests and blood gas analysis; induction of anesthesia, access to good veins, gastric intubation, urinary bladder catheterization; maintenance of anesthesia and postoperative observation, fluid balance, oral and parenteral feeding, tracheostomy care, bronchial toilet; inhalation therapy. The last receives an extensive discussion.


[Round window membrane pathology in sudden deafness (author's transl)]. Exploration of the middle ear was performed on 15 patients with sudden deafness that had failed to improve after intravenous infusion of Eupaverin and Rheomacrodex. Three patients had abnormalities of the round window membrane, in 2 there was a perilymphatic fistula and in 1 an abnormal bulging of the membrane with no transmission of perilymphatic fluid movement. These 3 patients presented with a history of exertion or stress prior to the onset of symptoms. Surgical closure ofthe 2 fistulae led to improvement of hearing, and perilymphatic decompression in the third patient improved the tinnitus but not the deafness. The possible causes of round window pathology are discussed.


[Epidural haematoma (Hygroma) with a mastoid extension (author's transl)]. A traumatic epidural haematoma, which extended both infra- and supra-tentorially is reported. It also extended into the mastoid antrum and air cell system and was diagnosed by surgical exploration. The radiological findings and treatment are discussed.


[Experiences with polyethylene ventilation tubes in children with recurrent middle ear inflammation (author's transl)]. Middle-ear ventilation tubes (of the Sheehy modification) were placed in 401 ears of 209 children under 16 years of age as treatment for recurrent middle-ear infection. The same procedure was later required in 26% of the cases studied because of further recurrence of middle-ear infection. In four per cent of all patients studied, the ventilating tube failed to cure middle ear disease in spite of controlled concomitant antibacterial therapy. In these cases, an early extrusion of the tube was commonly found. Among all patients, the tube was spontaneously extruded in 76 per cent of the ears, whereas the intubation time was longer than half a year in 53 per cent of the cases. No complications from insertion of the ventilation tubes was seen in the present series of patients. The tympanic membrane was found to be normal in 71 per cent of all cases when follow-up examination was obtained three months after completion in intubation. However, a permanent tympanic membrane perforation was found in five ears (1% of patients). The present study has confirmed the usefulness of middle-ear ventilation tubes, particularly in patients with recurrent middle-ear infections.


[A new pneumatic nasal tamponade (author's transl)]. In order to control severe bleeding in the nose and nasopharynx, a pneumatic nasal tamponade has been devised. The tube is available in three sizes, and can be easily introduced into the nasal cavity to sufficiently block bleeding areas.


[Oral mucosal grafts in laryngeal reconstruction (author's transl)]. In many laryngofissure procedures large mucosal resections are necessary. Free grafts of oral mucosa have been used in over 50 patients over the past 3 years for glottic reconstruction, and these experiences are reported in detail. Its use in the management of papillomata of the adult larynx is stressed.


Evaluation of the effects of presentation rate and speaking rate on children's auditory perception of two levels of linguistic material. Twenty-four first- and second-order sentential approximations of four words each were presented auditorily to two groups of eight normal children. Eight first- and eight second-order approximations were spoken at three rates: 90 (slow); 140 (normal); and 175 (fast) words/min. The 48 approximations were randomized and rates altered as necessary so that one group heard the material at a slow rate (90 words/min) of presentation and the other group at a normal rate (140 words/min) of presentation. The results indicated that although presentation rate did not significantly effect auditory perception, speaking rate did. It was concluded that a slow speaking rate can be expected to enhance the perception of low-level linguistic material regardless of the presentation rate, whereas a normal speaking rate would be best for higher level linguistic material.


Development of absolute auditory thresholds in the house mouse (Mus musculus). The development of hearing in the house mouse (Mus musculus) was behaviorally tested from the first postnatally measurable thresholds to those of young adults. An unconditioned stop reaction on tones was used in 9- to 11-day-old mice, then an unconditioned pinna reflex that can be elicited at low intensities and is not equal to the Preyer reflex. In addition, thresholds from 17- to 19-day-old and adult mice were obtained by a conditioned eyelid reflex. Frequencies between 1 and 80 kHz were tested. First reactions on tones were found at day 10 after birth in the frequency range of greatest sensitivity in the adults (10-20 kHz). The sensitivity optimum at 15 kHz becomes evident at day 14. Up to day 15 a sensitivity increase is noticeable for frequencies below the optimum, whereas high frequency sensitivity increases up to day 18. A second maximum of sensitivity at 50 kHz is measurable in 2- to 3-month-old mice, the threshold curve of which is defined as the standard for Mus musculus. The present behavioral data can well be correlated with existing electrophysiological results in mice and rats.


Idiosyncratic cardiovascular response of human neonates to acoustic stimuli. The heart rate response of acoustic stimuli was assssed for 15 newborns between the ages of 24 and 48 hr. Results of the analyses of covariance demonstrated that although the subjects responded to the stimuli, their responses were idiosyncratic in magnitude, direction, and pattern of rate change. Although spectrum and duration of the stimuli were varied, they were found not to be significant sources of response variation.


The crab louse-review of physiology and study of anatomy as seen by the scanning electron microscope. Effective control of a parasitic infestation is aided by a thorough understanding of the parasite and it interaction with the host. The external anatomy of Phthirus pubis and its egg were studied by scanning electron microscopy and the structures visualized were reviewed to determine their function. The pathophysiology of the insect-host interaction and current treatment recommendations were also reviewed.


Admittance values associated with the acoustic reflex and reflex decay. Acoustic stapedial reflexes were elicited from 10 normal S's in each of three age groups. Susceptance and conductance values were measured for each subject in both the unreflexed and reflexed states and at 10-sec intervals during a continuous, reflex-sustaining stimulation with pure tones. Percentage of reflex decay over time was noted for each group and as a function of stimulus frequency and measurement mode. No significant age group differences were noted. Significant stimulus frequency and measurement mode differences were presented to represent "normal" reflex decay.


Pure tone delayed auditory feedback: development of criteria of performance deterioration. Delayed auditory feedback audiometry, employing pure tones and a keytapping task, was administered at sensation levels from -10 to +50 dB to a sample of the general adult population. Absolute and relative time error as well as pattern error criteria were established on the basis of the -10-dB performances. Ninety percent of the subjects demonstrated tapping errors at sensation levels within 10 dB of auditory threshold.


An artifact in acoustic reflex measurement: some further observations. This study was designed to clarify characteristics of an artifact that has been reported to be a potential source of misleading information when determing acoustic reflex thresholds elicited by low-frequency tones. The study was conducted in two parts. Experiment 1 was concerned with an investigation of acoustic interactions in a sealed cavity between the probe tone from a commercial electroacoustic impedance bridge and interfering tones of various frequencies. Experiment 2 consisted of measurements of sound pressure levels in the sealed external ear canal of the probe ear when the contralateral ear was stimulated by air-conducted pure tones. The results indicated that acoustic reflex thresholds in 250-Hz tones probably cannot be determined for most persons unless special measures are taken to prevent the artifact. The artifact should not occur when the eliciting stimulus is 500 Hz, however.


Minocycline in the treatment of lymphogranuloma venereum. In a study of 80 cases of lymphogranuloma venereum (LGV), minocycline hydrochloride (Minocin) was found to be an effective drug in the treatment of all stages of LGV, including complicated ones. In late cases adjuvant treatment was used in addition to the antibiotic. Healing time in uncomplicated cases was less than 10 days. In complicated cases, both early and late, healing took about 2 to 3 weeks. Reactions to the drug were not significant.


Levamisole resinate as a Dirofilaria immitis microfilaricide in dogs. Dogs infected naturally or experimentally with Dirofilaria immitis were given levamisole resinate at the rate of 5.5 or 11 mg/kg of body weight/day for 10 days. All dogs had been treated with thiacetarsamide sodium approximately 6 weeks earlier. When given at the dosage of 5.5 mg/kg for 10 days, levamisole resinate was not effective as a microfilaricide in either naturally or experimentally infected dogs. Microfilaria counts were reduced in all dogs at this dosage, but never to zero. In all cases where the higher dosage (11 mg/kg) was used, microfilaria counts were reduced to zero within 10 days. Signs of toxicosis were noticed in only 2 experimentally infected dogs, both of which were found to be harboring live adult male D immitis at necropsy.


Lack of reliability of the SISI procedure for determining inner ear threshold. Ten normally hearing subjects were tested using the conductive short increment sensitivity index procedure to evaluate the 60-dB constant as used in the test described by Byers (1974). Also investigated were the effects of frequency and order of presentation on the short increment sensitivity index at high sensation levels. Test frequencies included 1, 2, 4, and 6 kHz in random order. Means of all frequencies exceeded the 60-dB constant implemented by Byers (1974). Intersubject variability was large. Frequency and order of presentation were not statistically significant factors. It was recommended that the conductive short increment sensitivity index be used with caution.


Middle ear muscle activity during speech in stapedectomized and laryngectomized subjects. Middle ear muscle responses associated with speech production were observed in normal-hearing, stapedectomized, and laryngectomized subjects. Impedance changes associated with speech production were monitored by an electroacoustic impedance bridge simultaneously with vocal output. Results from stapedectomized subjects indicate that the tensor tympani muscle contracts prior to vocalization and is part of the neurological pattern of speech production. Data collected from laryngectomized subjects suggest that the presence of sensory fibers from the larynx is not a prerequisite for middle ear muscle activity during speech production.


Northwestern University Auditory Test No. 6: normative and comparative intelligibility functions. A commercially available recording of Northwestern University Auditory Test No. 6 (N.U. No. 6) produced by Auditec of St. Louis was evaluated in a series of four studies. Interlist equivalence of this version was initially investigated, and then normative intelligibility functions were developed using listerners with normal hearing. Intelligibility functions for the original version of N.U. No. 6. prepared by Northwestern University, were then derived, concurrently with functions of the Auditec version, using (1) a group of listeners with normal hearing; and (2) a group with sensorineural hearing loss. The results demonstrated good interlist equivalence for the Auditec version of N.U. No. 6. The comparative intelligibility functions for the Auditec and Northwestern versions of N.U. No 6 furthermore indicated a difference between the two recordings, but it was concluded that for clinical purposes the two versions may be considered equivalent.


Effects of signal processing on intelligibility of speech in noise for persons with sensorineural hearing loss. A person with sensorineural hearing loss accompanied by recruitment has difficulty in understanding amplified speech, especially when speech is in the presence o competition. Two groups of subjects with sensorineural hearing loss with recruitment were tested at +6 and at O dB signal-to-noise (S/N) ratio at preferred levels for unprocessed speech and for speech processed through a two-band compression/equalization of circuit. In addition, unprocessed key word identification scores were compared to those from use of a hearing aid and of a one-band compression/equalization circuit. Processing a two-band compression/equalization circuit improved key word identification scores dramatically for both groups of subjects. The range of improvement for both groups was from 6 to 74%, mean 37.4%, for the S/N ratio of O dB. Subjects who achieved higher scores had high scores for unprocessed tests and had less recruitment present throughout the frequency range. Scores from one-band compression/equalization were compared to those from unprocessed scores; there were no significant differences in key word identification. Design characteristics and an excellent rationale for using two-band compression/equalization are generated by the data of this study.


Basal cell tumors in dogs.

Basal cell tumors in dogs. In a review of neoplasm registry records at Kansas State University (1961 through 1971), 140 basal cell tumors were reported in 32 breeds of dogs, representing 4.3% of 3,230 neoplasms recorded. Mean age of the affected dogs was 6.4 years. The tumors were removed surgically for biopsy in all dogs, 10 of which then had recurrences without metastasis, and required further surgery. The head, neck, and shoulder were a principal site (61%) of basal cell tumors in the dog.


Phenazopyridine toxicosis in the cat.

Phenazopyridine toxicosis in the cat. Severe illness developed after the oral administration of several drugs, including large doses of phenazopyridine (100 mg TID for 4 days) to a cat with dysuria and hematuria. Hemolysis and icterus were evident in blood serum and plasma after day 4 of drug administration, and many hemolyzed red blood cell "ghosts" containing Heinz bodies were observed on a stained blood smear. The cat became anemic and died within 48 hours after the last dose was administered. In an attempt to confirm a cause-and-effect relationship between drug administration and disease, 100 mg of phenazopyridine was given TID (65 mg/kg/day) for 3 days to a clinically normal cat. Nearly 50% of the hemoglobin was oxidized to methemoglobin during the course of phenazopyridine administration. Lower dosages of phenazopyridine (10 and 20 mg/kg/day) for longer periods of administration to 2 other clinically normal cats did not result in illness or anemia; however, the number and size of Heinz bodies and blood methemoglobin content were increased. Evidence of hepatic injury was observed in the clinically affected cat and in 2 of the experimental cats. The relationship between hepatic injury and toxic signs was not determined. Combination products recommeneded for treatment of cystitis in man often contain phenazopyridine. Such products should be avoided in cats unless a safe, effective dosage for phenazopyridine can be established.


Cheyletiella infestation in cats.

Cheyletiella infestation in cats. While routinely examining a fecal specimen of a cat for evidence of intestinal parasitism, large eggs (230 by 110 mu) were observed. tfurther examination of the fecal specimen revealed an adult Cheyletiella sp. mite. Of 42 cats received from the same source, 11 had Cheyletiella mites, found either on the skin or in fecal specimens. Grossly visible skin changes were not observed in any of the cats. The conically shaped sensory organ on genu I of the mite resembled that of Cheyletiella blakei.


Lissencephaly in two Lhasa Apso dogs.

Lissencephaly in two Lhasa Apso dogs. Lissencephaly, a congenital absence of cerebrocortical convolutions, was discovered in 2 Lhasa Apso dogs by clinical and pathologic evaluation. Neurologic abnormalities, which became evident within the 1st year of life, included behavioral, visual, and convulsive disorders. The neurologic abnormalities were mild or delayed in onset after birth, indicating the dog is less dependent on the cerebral cortex for sensorimotor function than is man.


Naturally occurring Tyzzer's disease as a complication of distemper and mycotic pneumonia in a dog. Tyzzer's disease, distemper, and mycotic pneumonia were diagnosed at necropsy of a 6-week-old mixed breed pup. The illness was characterized by lethargy, poor appetite, dysentery, and convulsions, the latter developing just prior to death. The necropsy findings included pale, dilated large intestine and swollen, dark liver. Histologically, multifocal hepatic necrosis, similar to that of Tyzzer's disease in other species of animals, was observed. Bacillus piliformis was found in hepatocytes and necrotic areas of the liver.


Diseases of yearling feedlot cattle in Colorado. During all of 1974 we surveyed, for illnesses and deaths, about 407,000 yearling feedlot cattle. The morbidity was 5.1%, with a case mortality of 18.9% and a population mortality of 1.0%. Both morbidity and mortality were higher during fall and winter than during spring and summer. Of the 3,943 dead cattle, 1,988 were necropsied. The most prevalent diseases were: pneumonia, 48%; diphtheria, 6%; brisket disease, 6%; hemorrhagic colitis, 5%; riding injury, 4%; bloat, 3%; calculosis, 2%; endocarditis, 2%; abomasal ulcers, 2%; bovine viral diarrhea, 2%; embolic pulmonary aneurysm, 1%; and pulmonary edema, 1%.


Atypical interstitial pneumonia in yearling feedlot cattle. During each week of 1974, we surveyed, for illnesses and deaths, a constantly changing population of yearling feedlot cattle that, for the year, totaled 407,000 animals. From 3,943 fatalities, 1,988 necropsies were made; of this number, 106 (5.3%) had atypical interstitial pneumonia. The death rate was higher during summer and fall than during the other seasons and was evenly distributed throughout each of the 4 stages of fattening. Gross pulmonary lesions involved both lungs and were prominent throughout the caudal (diaphragmatic) lobes. Epithelialization, hemorrhage, fibrin, hyaline membranes, emphysema, bronchiolitis, and interstitial edema were common, whereas chromatin strands, bronchiolar edema, interstitial emphysema, and obliterating bronchiolitis were less common histopathologic features.


Brisket disease in yearling feedlot cattle. During all of 1974, we surveyed, for illnesses and deaths, about 407,000 yearling feedlot cattle maintained at 1,600 m altitude. Of 1,988 cattle necropsied, 116 (5.8%) had brisket disease. The malady occurred during all seasons but was most common throughout fall and winter. The gross changes were hypertrophy and dilatation of the right ventricle and generalizaed passive congestion. The postulated causative factors were high genetic susceptibility, rapid growth rate, previous mountain grazing, and hypoventilation with airway hypoxia.


Bulling among yearling feedlot steers.

Bulling among yearling feedlot steers. In a survey to determine the cause of illness and deaths among yearling feedlot cattle, bulling was found to be one of the major problems. During the years 1971-1974, 54,913 (2.88%) steers became bullers and represented an annual loss of around +325,000. Some of the causes of bulling were found to be hormones, either as implants or in the feed. In 1974, from 1,988 necropsies, it was determined that 83 steers died from riding injuries.


Fetal abomasal ulcers in yearling feedlot cattle. During all of 1974, we surveyed, for illnesses and deaths, about 407,000 yearling feedlot cattle. From the 3,943 dead cattle, 1,988 necropsies were made; of this number, 31 (1.6%) had ulcers with fatal perforations or hemorrhages; a similar additional number of necropsied cattle had innocuous ulcers as incidental findings. Ulcers developed during all seasons and all stages of fattening, but were more common during the first 45 days of winter-initiated fattening than during other times. Perforations of the abomasal wall resulted in spillage of abomasal contents into the abdominal cavity and the development of peritonitis.


Sudden deaths in yearling feedlot cattle. A survey of the causes for fatal diseases of yearling feedlot cattle was conducted on more than 407,000 cattle during a 14-month period. Of the 4,260 (1%) cattle that died during this period, 1,358 (32%) were categorized as cases of "sudden death syndrome." Of the 11 most frequent causes of the syndrome, as determined at necropsy, only 4--bloat, pulmonary aneurysms, riding injury, and hemopericardium--were considered as short-course problems and true causes of sudden death. The largest number of cases of sudden death were attributed to pneumonia (113 animals). Consequently, the sudden death syndrome is a misnomer for many long-course diseases and, in some instances, a mask for neglect because, as clinically used, the name frequently includes cattle that have been sick, often with pneumonia, for several days.


Bronchiectasis in yearling feedlot cattle. Thoughout all of 1974, we surveyed, for illnesses and deaths, about 407,000 yearling feedlot cattle. From the 3,943 dead cattle, 1,988 necropsies were made; of the cattle necropsied, 32 (1.6%) had bronchiectasis. In this disease, the permanently dilated small bronchi and bronchioles, located in ventral parts of the lungs, were filled with accumulations of exudate and microorganisms, including Pasteurella hemolytica, Pasteurella multocida, Corynebacterium pyogenes, Escherichia coli, Salmonella anatum, Staphylococcus spp, and Mycoplasma arginini.


A new broad spectrum aminoglycoside antibiotic, G-52, produced by Micromonospora zionensis. G-52 is a new broad spectrum aminoglycoside produced by a species of the genus Micromonospora, Micromonospora zionensis. It has been differentiated from other known related antibiotics by a variety of chemical and biological methods. Its in vitro and in vivo spectrum of activity appears to be quite similar to that of verdamicin and gentamicin but is differentiated from them by its increased activity against 6'-N-acetylating strains.


The structure of antibiotic G-52, a new aminocyclitol-aminoglycoside antibiotic produced by Micromonospora zionensis. Antibiotic G-52, a new aminocyclitol-aminoglycoside antibiotic produced in the fermentation of Micromonospora zionensis, has been shown to be 6'-N-methylsisomicin on the basis of its spectral characteristics. This assignment was confirmed by synthesis of the antibiotic from sisomicin.


Nocardicin A, a new monocyclic beta-lactam antibiotic. I. Discovery, isolation and characterization. Nocardicin A is a new monocyclic beta-lactam antibiotic obtained from the fermentation broth of a strain of actinomycetes. The producing organism, strain WS 1571, was identified as Nocardia uniformis subsp. tsuyamanensis ATCC 21806. The antibiotic, obtained as colorless crystals, exhibits moderate in vitro antibacterial activity against a broad-spectrum of Gram-negative bacteria including Proteus and Pseudomonas. It has low toxicity in laboratory animals.


Gardimycin, a new antibiotic from Actinoplanes. I. Description of the producer strain and fermentation studies. Two strains of Actinoplanes have been isolated that produce a new peptide antibiotic named gardimycin. A detailed taxonomical study of such strains indicates that they differ between themselves and from all the described species of Actinoplanes. For this reason they are considered to be new species; for which the names A. garbadinensis nov. sp. and A. liguriae nov. sp. are proposed. The type strain of A. garbadinensis is A/10889(=ATCC 31049), the type strain of A. liguriae is A/6353 (=ATCC 31048). Studies on the medium and fermentation conditions are reported.


Gardimycin, a new antibiotic from Actinoplanes. II. Isolation and preliminary characterization. The strain Actinoplanes garbadinensis nov. sp. produces a peptide antibiotic, named gardimycin, which is active in vitro and in vivo against Gram-positive bacteria. Isolation and purification of the product have been accomplished by extraction from the broth with butanol and dialysis of the crude extract, followed by counter-current distribution. Gardimycin is an open chain peptide with an approximate minimal formula C84H138N18S3-4O34Na. The following amino acids have been identified by column chromatography of an acid hydrolysate: serine, glutamic acid, alanine, leucine, isoleucine, glycine, valine and two sulphur-containing amino acids whose structure is presently under study. Tryptophan has been identified in an alkaline hydrolysate.


Isolation of a new antibiotic 333-25, related to antibiotic EM 49. (Studies on antibiotics from the genus Bacillus. XI). A new antibiotic, 333-25, active against Gram-positive and Gram-negative bacteria, was isolated from the culture broth of Bacillus circulans 333-25. The antibiotic is a basic acylpeptide containing 2,4-diaminobutyric acid (5), leucine (2), phenylalanine (1) and a fatty acid. It is closely related to antibiotic EM 49, but can be differentiated by chromatographic behaviour.


The constituent amino acids and fatty acid of antibiotic 333-25. (Studies on antibiotics from the genus Bacillus. XII. Measurement of the optical rotational activities of the constituent amino acids of antibiotic 333-25 identified 2,4-diaminobutyric acid (D-form 1, L-form 4), L-leucine (2) and D-phenylalanine (1). The fatty acid constituent was determined to be beta-hydroxy anteisononanoic acid by gas chromatography, nuclear magnetic resonance and mass spectra. Differentiation from the structure of antibiotic EM 49 is discussed.


A butyrylcholinesterase inhibitor produced by Penicillium sp. no. C-81 and its identity with mycelianamide. A screening aimed at obtaining a cholinesterase inhibitor of microbial origin was carried out using Pseudomonas butyrylcholinesterase. A mycelium-extract of a fungus strain, belonging to the genus Penicillium, was found to produce such an enzyme inhibitor. The inhibitor was purified and crystallized as colorless leaflets. From physical and chemical studies, the inhibitor was identified as being identical with an antibiotic, mycelianamide, though this compound was not known to have enzyme inhibitor activity. The kinetics of the inhibition of Pseudomonas butyrylcholinesterase were also studied. Horse serum cholinesterase and hog liver carboxylesterase were also inhibited by the isolated Penicillium C-81 inhibitor, but lipase and acetylcholinesterase were not.


Modifications of a macrolide antibiotic midecamycin (SF-837). I. Synthesis and structure of 9,3''-diacetylmidecamycin. 9,3''-Diacetylmidecamycin (12) was synthesized from 4''-depropionyl-9,2',4''-triacetylmidecamycin (8) by heating the latter with propionic anhydride in pyridine followed by removal of 2'-acetyl group, with or without 18-enolpropionyl group. Direct acetylation of midecamycin (1) led to the formation of the 3'',4''-positional isomer (6). The structure of 12 was determined by mass, NMR and chemical degradation. The location of 3''-acetyl group was shown by the stereospecific 3 leads to 1 acetyl migration catalyzed by a base of 3-O-acetyl-4-O-propionyl-L-mycarose (13), and comparison of NMR and mass fragmentation with the 3,4-positional isomer (15). The latter's structure was independently supported by the nuclear Overhauser effect between methyl and propionyl group at C-3. The intramolecular 4 leads to 3 acyl shift that was taken place in the forced acylation of the mycarose moiety was found to be affected by the anomeric configuration, nature of aglycones and reaction temperature. Reverse 3 leads to 4 acyl migration occurred in acidic hydrolysis.


High resolution mass spectra of malformin and related cyclic peptides. A comparison of the high resolution mass spectra of synthetic and natural preparations of malformin provided new evidence for the revised structure: (see article): The interpretation of the mass spectra was aided by the examination of the spectra of the synthetic peptides, desthiomalformin and enantio-5-valine malformin.


A new semisynthetic 7alpha-methoxycephalosporin, CS-1170: 7beta-((cyanomethyl)thio)acetamido)-7alpha-methoxy-3-((1-methyl-1H-tetrazol-5-yl)thio)methyl)-3-cephem-4-carboxylic acid. The synthesis and antimicrobial activity of a new semisynthetic 7alpha-methoxycephalosporin,7beta [[(cyanomethyl)thiol]acetamidol]-7alpha-methoxy-3-[[(1-methyl-1H-tetrazol-5-yl)thio]-methyl]-3-cephem-4-carboxylic acid (CS-1170), are described. This compound shows interesting antibacterial activity when compared to cefoxitin and cephalothin.


3-Deacetoxy-7-(alpha-amino-1-cyclohexenylacetamido) cephalosporanic acid (SCE-100), a new semisynthetic cephalosporin. I. Comparative in vitro antibacterial activities of SCE-100 and cephalexin (CEX). 3-Deacetoxy-7(alpha-amino)-1-cyclohexenylacetamido) cephalosporanic acid (SCE-100) has a potent antibacterial activity against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration of SCE-100 is 0.2 approximately 12.5 mug/ml against Gram-positive bacteria including penicillin G-resistant Staphylococcus aureus and 6.25 approximately 100 mug/ml against Gram-negative bacteria. SCE-100 inhibits clinically isolated strains of penicillin G-resistant S. aureus and ampicillin-resistant Escherichia coli, as well as the corresponding sensitive strains. The activity of SCE-100 is enhanced by decreasing the inoculum size and is only slightly influenced by medium pH, difference of medium composition and the addition of horse serum. SCE-100 has bactericidal activity against S. aureus and E. coli. There is a stepwise development of in vitro bacterial resistance to SCE-100 by serial transfer of organisms into a liquid medium containing SCE-100. Cross resistance was observed between SCE-100 and other tested cephalosporins.


3-Deacetoxy-7-(alpha-amino-1-cyclohexenylacetamido) cephalosporanic acid (SCE-100), a new semisynthetic cephalosporin. III. Comparative studies on absorption, distribution and excretion of SCE-100 and cephalexin (CEX) in laboratory animals. 3-Deacetoxy-7-(alpha-amino-1-cyclohexenylacetoamido) cephalosporanic acid (SCE-100) was compared to cephalexin with respect to absorption, tissue distribution, and urinary and biliary excretion in mice, rats, rabbits and dogs. The absorption of SCE-100 after oral administration is generally slower than that of cephalexin, but its disappearance from blood and tissues is delayed. The concentration of SCE-100 in the liver is distinctly higher than that of cephalexin. These properties of SCE-100 are most clearly manifested in rats. There is no significant difference in urinary excretion of the two cephalosporins in rabbits and dogs, while in rabbits, biliary excretion of SCE-100 is more intensive than that of cephalexin.


Micromonospora-produced sisomicin components. A sisomicin fermentation carried out in the presence of (methyl-14C)-L-methionine resulted in a crude mixture, composed of methyl-14C-labeled sisomicin as a major component; and two 4''-C-desmethylsisomicin (66-40B and 66-40D) isomer-like components, an unidentified component and a gentamicin A-like antibiotic as minor components. When (methyl-14C)-L-methionine was added in an early stage of the fermentation (24 hours), incorporation of methyl-14C-label into polar components (e.g., gentamicin A-like antibiotic) preceded that into sisomicin. Chromatographic evidence for the bioconversion of (methyl-14C)-gentamicin A to a radioactive sisomicin-like product (possibly (3''-N-methyl-14C)-sisomicin) was seen, when a Micromonospora blocked mutant was incubated in the presence of the former antibiotic.


A new metabolite from Streptomyces hygroscopicus I. Fermentation and isolation. A deoxypentulose has been isolated from the fermentations of a new soil isolate of Streptomyces hygroscopicus (UC-5601). It was found to inhibit weakly and specifically the growth of one strain of Mycobacterium avium (UC-159).


A new metabolite from Streptomyces hygroscopicus II. Identification as 1-deoxy-D-threo-pentulose. Mass spectrometric studies show this metabolite to be a 1-deoxy-pentulose. The sterochemistry was established by reduction to the corresponding 1-deoxy-D-pentitols.


Alborixin, a new antibiotic ionophore: taxonomy, isolation and biological properties. Alborixin is an ionophorous antibiotic of the nigericin group isolated from cultures of a strain of Streptomyces albus. It is active against Gram-postive bacteria and is coccidiostatic, but it is very toxic. The antibacterial principle was extracted with organic solvent from the mycelium, isolated in crystalline form and named alborixin.


Kalafungin. II. Chemical transformations and the absolute configuration. The properties of number of kalafungin derivatives and analogues are consistent with the proposed structure. The absolute stereochemistry of the three active centers was determined to be RRR by optical rotatory dispersion comparisons.


The C-13 NMR spectrum of novobiocin.

The C-13 NMR spectrum of novobiocin. The carbons of novobiocin have been assigned to peaks in the CMR spectrum on the basis of chemical shifts and off-resonance experiments on novobiocin and related compounds.


Social-skills training to modify abusive verbal outbursts in adults. Social-skills training was used to modify abusive verbal outbursts displayed by two adult psychiatric patients. Five target behaviors--looking, irrelevant comments, hostile comments, inappropriate requests, and appropriate requests were monitored during role-played situations. Social-skills training, consisting of behavior rehearsal with modelling, focused instructions, and feedback, was introduced in a multiple-baseline design across individuals. Training improved all target behaviors. The improved behavior generalized to: (1) novel scenes role-played with the original respondent, (2) training and novel scenes role-played with a different respondent, and (3) interpersonal situations on the hospital ward.


Prompts to increase attendance in a community mental-health center. The effect of a brief appointment reminder for mental-health center applicants is reported. A standardized phone message was delivered by an administrative staff member one to three days before the appointment and a sequential experimental design alternating baseline and phone message conditions was used to assess the effects of the procedure. The no-show rate averages were 32%, 11%, 25%, and 14% respectively. The cost of the procedure was $162.00, which was totally recovered when only six appointments were kept. Since over 1000 patients were involved in the study, the return on the investment of +162.00 is considerable. Implications for this procedure are discussed for other community mental-health centers and for other community care-giving agencies.


Classical conditioning of decreases in human systolic blood pressure. Decrease in human systolic blood pressure of 4.35 mm Hg (range: 0 to 12 mm Hg) were classically conditioned in normal and hypertensive subjects using a delayed conditioning paradigm in which a 30-sec auditory stimulus (the conditioned stimulus) was followed immediately by tilting the subject 15degrees head-down to elicit small decreases in blood pressure. Conditioning occurred within five trials. A control group demonstrated that sensitization of the reflex by repeated tilting could not account for the blood-pressure decreases associated with the conditioned stimulus in experimental subjects.


The effects of a self-instructional package on overactive preschool boys. The effects of a self-instructional package on three overactive preschool boys were investigated using a multiple-baseline design across subjects. Behavioral observations of the three target subjects indicated transfer of training effects from the experimental tasks to the classroom. On-task behaviors increased dramatically concomitant with the introduction of the self-instructional package, and treatment gains were maintained 22.5 weeks after baseline was initiated. In addition, the use of an observer-expectancy control condition gave further credibility to the demonstration of a cusal relationship.


The effects of token reinforcement on the behavior of delinquents in cottage settings. A token economy designed to modify the behavior of 125 adolescent males committed to a state correctional institution was implemented in the boys' cottages, focusing on social behavior (peer interaction), rule following, and task completion. The program was sequentially introduced in a multiple-baseline design in three independent cottages; a fourth group served as a comparison cottage. Appropriate behavior increased when the token program was introduced in each cottage. Data were collected for 14 months. Thus, the long-term effects of initial behavior change were assessed.


Sarcomere lengthening and tension drop in the latent period of isolated frog skeletal muscle fibers. A laser diffraction technique has been developed for registering small changes in sarcomere length. The technique is capable of resolving changes as small as 0.2 A in isolated frog skeletal muscle fibers. The small sarcomere lengthening that accompanies the drop in tension in the latent period of contraction was investigated. We suggest this lengthening be named latency elongation (LE). The LE is present in a completely slack fiber and must, therefore, be caused by a forcible lengthening process. Furthermore, the LE is dependent on the existence of an overlap between thin and tick filaments. The rate of elongation and the time interval between stimulation and maximum elongation may vary along the fiber. The maximum elongation was 3-5 A per sarcomere. At any instant the drop in tension is a product of the sum of sarcomere lengthenings along the fiber and the slope stiffness of the series elasticity. The latency relaxation (LR) could be registered in the sarcomere length range from 2.2 mum to 3.6-3.7 mum. The amplitude went through a sharp maximum at 3.0-3.1 mum. In the sarcomere length range from 2.2 to 2.8 mum the delay from onset to maximum LR was nearly proportional to the distance from the Z-line to the overlap zone. A working hypothesis is presented. It is suggested that the LE is caused by a lengthening of the thin filaments.


Intracellular Na+, K+, and C1- activities in Balanus photoreceptors. Ion-sensitive microelectrodes were used to measure intracellular activities (aix) of Na+, K+, and C-1 in Balanus photoreceptors. Average values of aiNa, aiK, and aiCl were 28 mM, 120 mM, and 65 mM, respectively. Equilibrium potentials calculated from these average values were: Na+ +64 mV, K+ - 77 mV, and and Cl- -42 mV; ther average value of the resting potential for all cells examined was -41 mV. Long exposure to intense illumination produced measurable increases in aiNa. Classical Na+ - K+ reciprocal dilution experiments were analyzed with and without observed changes in aiK. As aoK was increased, the membrane depolarized, and aiK increased. Better agreement was found between the membrane potential and the directly determined EK than expected from the standard relation between Em and aoK. The latter produced pNa:pK estimates of the resting photoreceptor membrane that were higher than estimates based on data from the ion electrodes. Generally, Em was more negative than EK as aoK was increased. This is consistent with a significant chloride permeability in the dark-adapted photoreceptor.


The permeability of the sodium channel in Myxicola to the alkali cations. Relative permeabilities to the alkali cations were determined, from the reversal potential (VRev), for the Na channel of internally perfused voltage-clamped Myxicola giant axons. PLi/PNa and PK/PNa are 0.94 and 0.076, respectively. Rb and Cs are not measurably permeant. VRev vs. the internal Na activity was well described by the constant field equation over a 300-fold range of internal Na concentrations. In agreement with findings on squid axons, the PK/PNa was found to increase when the K content of the internal perfusate was reduced (equivalent per equivalent substitution with TMA). Internal Rb and Cs also decreased the PK/PNa. The order of effectiveness of internal K, Rb, and Cs in increasing the Na selectivity of the Na channel was Cs greater than Rb greater than or equal to K. External Li increases the PK/PNa but this may be due to the formation of LiF internally. It may be that substances do not have to traverse the channel in order to affect the selectivity filter. Evidence is presented which suggests that the selectivity of the Na channel may be higher for Na in intact as compared to perfused giant axons. It was concluded that the channel selectivity properities do not reflect only some fixed structural features of the channel, but the selectivity filter has a labile organization.


Neural modification by paired sensory stimuli. With repetitive stimulation of two sensory pathways which are intact within the isolated nervous system of Hermissenda, features of a cellular conditioning paradigm were identified. Type A photoreceptors, unlike type B photoreceptors, produce fewer impulses in response to light following temporally specific pairing of light stimuli with rotation stimuli. Type A photoreceptor impulse wave-forms are also specifically changed by such stimulus regimens. These findings can be explained, at least in part, by increased inhibition of type A cells by type B cells after stimulus pairing.


Age and sex differences in lung elasticity, and in closing capacity in nonsmokers. Static volume-pressure characteristics of the human lung, closing capacity (CC), closing pressure, and subdivisions of lung volumes were measured in 66 adult nonsmokers, aged 24-58 yr. There were systemic differences between the sexes as well as with age. Young females had less elastic recoil at any lung volume than young males. However, males lost elastic recoil with age faster than females so that in the older age groups the recoil was similar. There were no significant changes in compliance over the volume range containing most values of CC in either males or females. By comparing the age regression of CC and of elastic recoil pressures at 40 and 50% TLC we conclude that the increase in CC with age in males was attributable almost entirely to loss of recoil. In females none of the increase in closing capacity with age was attributable to loss of recoil. By exclusion, it is probably attributable to a change in the intrinsic properties of small airways or an increase in the pleural pressure gradient with age.


Energetics of isometric exercise in man. In isometric contractions of the plantar flexors (5-40% of maximal tension, Tmax), VO2 is linearly related to the force exerted, averaging 2 ml/min-kg of tension. At tension levels above 5% Tmax the lactic acid contribution to the overall energy demand is constant at about 20%. Therefore, up to at least 40% Tmax,-muscle blood flow is not totally occluded, though it is impaired even at low force levels. Below 5% Tmax no lactic acid (LA) accumulates in blood. The energy required for the development of the tension is linearly related to the force exerted up to 33% Tmax, thereafter increasing disproportionately. In the transition from rest to static contractions of the plantar and forearm flexors (30 and 40% Tmax, respectively) VO2 increases initially to 200% of the controls, leveling off later at 150%. During recovery, VO2 increases up to 200% of the initial resting level, due to the payment of a large O2 debt, decreasing then with a t 1/2 of about 30 s. The glycolytic component is relatively more important in isometric contractions of the forearm than of the plantar flexors. No LA accumulates in static contractions of the plantar flexors of 5-10 s duration interrupted by equal pauses.


Cold-induced shivering in men with thermoneutral skin temperatures. Twenty-two male Caucasians, aged 20-47 yr, were exposed in a cold room to air temperatures of -33 degrees C while lying in sleeping bags for 2 h. Skin and rectal temperatures as well as electromyographic activity of the chin, forearm, and thigh, were recorded. Shivering occurred in all the subjects, even though skin temperatures were maintained between 31 and 33 degrees C. It is suggested that a counter-current heat exchange occurs whereby the warm blood of the common carotid artery is cooled by cool venous blood in the jugular veins. This cooled arterial blood, in irrigating the hypothalamus, causes shivering.


Effect of adrenergic agents and their mode of action on mucociliary clearance in man. The aerosolized adrenergic (ADR) agent, isoproterenol (ISO), was found markedly to accelerate mucus clearance within the human tracheobronchial tree. Mucus transport was measured by external gamma counting of aerosolized Fe2O3 particles deposited on the mucous membrane during inhalation. Aerosolized epinephrine (EPI), despite its alpha-ADR bronchial vasoconstrictor activity, increased mucus clearance to the same degree as did aerosolized ISO, with its beta-ADR bronchial vasodilator activity. The vehicle used for delivery of the ADR agents, i.e., a H2O aerosol by intermittent positive-pressure breathing (IPPB), itself increased mucus clearance slightly, but did not elicit the enormous increases produced by the ADR agents. Parenteral ISO caused increases in clearances similar to aerosolized ISO and EPI (consistent with different tissue drug levels achieved). Oral atropine delayed clearance, but atropine prior to an ADR aerosol did not alter the mucus transport effect of the ADR agent. ISO and atropine, despite opposite effects on mucus clearance, caused equal bronchodilation. Thus, increased clearance following aerosolized ISO was not dependent on bronchial vasodilation, aqueous aerosol droplets, reflex parasympathetic activation, or bronchodilation, and seems best attributable to increased ciliary beat rate.


Effect of volume history on successive partial expiratory flow-volume maneuvers. In normal subjects, the second of two successive partial expiratory flow-volume (PEFV 2) curves often had higher isovolume maximal expiratory flow rates (Vmax) than the first (PEFV 1) (mean increase 30.2 +/- 13%). The higher Vmax on PEFV 2 was present only when there was a greater lung elastic recoil pressure (Pst(L)). In eight subjects the Pst(L) derived from sequential partial quasi-static pressure-volume curves, from interruption of the flow-volume maneuvers and at the start of the PEFV curves showed that isovolume upstream resistance increased although Vmax also increased after going to residual volume (RV). In four subjects the RV volume history did not change the pressure flow relationship across the upstream airways. If airways dimensions were the sole determinant of Vmax, then Vmax on PEFV 2 would be the same or smaller than on PEFV 1. That the opposite was observed in our study indicates that the increase in Pst(L), which results from parenchymal hysteresis, offsets any dimensional decrease in upstream airways due to airways hysteresis.


Respiratory, circulatory, and ECG changes during acute exposure to high altitude. Quantitative electrocardiographic and accessory circulatory and respiratory mass spectrographic and accessory circulatory and respiratory mass spectrographic studies were carried out on 30 young, healthy subjects at rest during moderately acute, standardized stepwise exposure to simulated altitude up to 7,000 m (PAO2 26.9 mmHg). The ECG (Einthoven and Wilson leads) and the respiratory gases were recorded synchronously during ascent and descent. The extensive data assembled, summarized in six tables and illustrated in seven graphs, represent the basis for future investigations on the single factors which underlie hypoxia-induced ECG changes during exposure to high altitude.


Papain inhibition by serum.

Papain inhibition by serum. Sera from seven animal species (rat, cow, cat, dog, human, rabbit, and hamster) were tested and found to inhibit the papain-catalyzed hydrolysis of alpha-N-benzoyl-L-arginine-p-nitroaniline-HCl (L-BAPA). The relative concentration of inhibitor in each serum sample was expressed in terms of its papain inhibitory capacity (PIC) defined as the number of units of papain inhibited per ml of serum. Rat serum contained the highest concentration of inhibitor while hamster serum contained the lowest concentration. The inhibitor appears to be competitive with respect to L-BAPA and is heat labile and nondialyzable. Antipapain activity can be separated from antitrypsin activity by (NH4)2SO4 fractionation.


PO2 in the carotid body perfused and/or superfused with cell-free media. We measured with a micro-O2 electrode the tissue PO2 (PtO2) in the cat carotid body (CB) to see whether it was adequately oxygenated when perfused or superfused with artificial, cell-free (c-f) solutions (pH = 7.4; temp = 35-38 degrees C). To obtain a relative measure of O2 consumption (VO2), we also measured the rate of disappearance of O2 following stoppage of the blood flow, and compared these disappearance curves with those during stoppage of the c-f perfusion solutions. In 14 cats normal (blood perfusion) PtO2 values ranged from 10 to 104 mmHG; chi = 72 +/- 4 (SE--as used throughout). During 3 h of c-f perfusion with air-equilibrated Locke's solution, PtO2 ranged from 62 to about 160 mmHg; chi = 133 +/- 4. When perfused with Fay's equilibrated with 98% O2-2% CO2 no PtO2 values in the CB were below 300 mmHg (4 cats). In eight additional cats the CB was cleared of blood then superfused with saline equilibrated with 50% O2 underneath and air-equilibrated saline over. Less than 5% of the PtO2 values found were below 5 mmHg. We conclude that most studies on the artificially perfused or superfused CB cannot be invalidated on the basis that the preparations were hypoxic. O2 disappearance curves taken during blood perfusion were significantly faster than during c-f perfusion indicating a marked reduction in VO2 with c-f perfusion.