Permeability of retinal capillaries in rats with inherited retinal degeneration.

The permeability of retinal capillaries in RCS rats with inherited retinal degeneration was investigated with horseradish peroxidase used as a tracer. Five-week-old rats showed typical degeneration of photoreceptor cells and accumulation of outer segment debris, but retinal capillaries were not permeable to peroxidase. At 10 weeks of age, capillaries in the inner retina appeared normal, but many in the outer retina were leaky. Peroxidase activity in these latter vessels was demonstrable in the basal laminae of endothelial cells and pericytes and in vesicles on the luminal and abluminal sides of the endothelium. Tracer also permeated the intercellular spaces in the surrounding area. The number of leaky capillaries in the outer retina increased during the course of the dystrophy. The site of the leak in permeable capillaries has not yet been established; it may be due to an alteration of the endothelial cell junctions or of transcellular vesicular transport. In the choriocapillaris, peroxidase permeated Bruch's membrane and the basal infoldings between adjacent pigment epithelial cells; tracer progression along the intercellular spaces was blocked at the zonulae occludens at the apicolateral border. The RCS rat may be a useful model for studying the morphological basis of changes in capillary permeability associated with retinal degeneration.


Mass cells in ocular tissues of normal rats and rats infected with Nippostrongylus brasiliensis.

In orbital exenteration specimens from 14 rats, 93% of the mast cells were found in the lids, the limbus, and the conjunctiva, 5% in the orbital tissues, and less than 1% in the globe. The density of mast cells was highest in lid (2843/mm3), limbus (2822/mm3), and orbit (2184/mm3) and lowest in bulbar conjunctiva (794/mm3), ciliary body (512/mm3), and sclera (176/mm3). There was no significant difference in the distribution or density of mast cells in orbital exenteration specimens from normal rats compared with rats infected with the worm Nippostrongylus brasiliensis. We concluded that certain ocular structures are rich in mast cells, which suggests that these structures might be susceptible to injury mediated by mast cell products.


An estimate of image quality in the rat eye.

The point spread function on the optic axis of the rat eye is indirectly estimated to increase from a half-height width no greater than 12.5' to not less than 36' after dilation of a 0.33 mm pupil diameter to 3.0 mm.


Studies on the structure of the two infectious types of densonucleosis virus.

No electrophoretic differences were detected between the nucleic acids of the two types of densonucleosis virus, DNV-I and DNV-II. Both virus types had similar isoelectric points. Although the viral proteins found in each type were identical, their stoichiometry differed. The localization of the structural protein, by labeling with periodate-oxidized glycoprotein, supported the hypothesis that 60 molecules of p49 aggregated into a dodecahedron (12 pentamers), whereas the two other proteins (p59 and p69) might have a stabilizing function and were localized on the outer surface of the p49 dodecahedron.


Classification of peste des petits ruminants virus as the fourth member of the genus Morbillivirus.

Peste des petits ruminants (PPR) is a virus disease of sheep and goats in West Africa. When first described, the virus was considered a variant of rinderpest virus. The biological and physicochemical characteristics of the virus indicate that it is closely related to measles, rinderpest and canine distemper viruses. These three viruses form the genus Morbillivirus of the Paramyxoviridae. PPR virus is sufficiently distinct from these 3 viruses to justify considering it as the fourth member of the Morbillivirus genus.


A study of the measles virus-induced proteins incorporated into the cell membrane.

The polypeptide composition of a measles virus isolate from a case of subacute sclerosing panencephalitis, the Halle strain, and the distribution of these polypeptides in the cell membrane have been investigated. In purified virus preparations, four major polypeptides were identified with molecular weights corresponding to 80K, 62K, 42K and 37K daltons. A minor band was found at 69K and several others with molecular weights +/- 100K. By specifically labeling the proteins exposed at the surface of BGM cells either persistently or lytically infected with the Halle virus, it was shown that only the 80K and 42K viral polypeptides were present in the cell membrane. Furthermore, it was observed that PAGE profiles of cellular polypeptides differed between infected and noninfected cells.


A rapid method for detection of Bhanja virus in infected ticks.

A rapid method has been developed to detect Bhanja virus in experimentally infected Hyalomma asiaticum ticks by an indirect hemagglutination test. The titer of viral antigen is suspensions prepared from infected ticks ranged from 1:640 to 1:2,560; the antigen was demonstrated in both unfed and engorged ticks during an observation period from 2 weeks to 5 months after infection. The test is simple, easily reproduced, highly sensitive and specific, and may be useful for field studies with Bhanja virus.


Phage Mu mutants with increased transduction abilities.

Mutants of the Escherichia coli phage Mu with increased transduction frequencies are describe. These mutants can be subdivided as (i) mutants in which only the marker used for detection is affected and (ii) mutants in which all other markers tested are also effected, but not to the same extent. The possible mechanisms of the altered transducing properties are discussed.


A multicomponent, multipoint infrared ambient air monitor.

With the tremendous advances in electronics today, it is now possible to take existing analytical instruments and give then a "brain" so that many analytical procedures which were impossible or costly a few years ago can now be done with relative ease, at a fraction of the costs. This paper deals with a microcomputer-controlled air monitor which allows us to identify many different components at a multitude of different locations. System operation is explained as well as data accuracy as they relate to application in a plastics research pilot plant.


Ultrasonic transesophageal measurement of hemodynamic parameters in humans.

A noninvasive method has been developed to monitor centerline blood velocity waveforms and vessel diameter in the descending aorta and pulmonary artery of conscious humans. An esophageal endoscope fitted with miniature ultrasound transducers is swallowed and positioned in the esophagus near vessels of interest. The transducers are connected to ultrasound Doppler velocimeters and echotrack instrumentation to obtain the pertinent hemodynamic parameters. This paper describes the design and fabrication of the esophageal ultrasound transducers and the techniques involved in human applications. In addition, blood velocity and wall motion measurements obtained in conscious men at rest and during exercise are described.


Feedback control in the management of cardiac arrhythmias.

We have devised a computer technique for the control of drug therapy in the management of cardiac arrhythmias. In our system the computer monitors the electrocardiogram in real time, determines the percent of premature ventricular beats (PVBs) using a correlation coefficient technique, and compares it to a desired rhythm. If the measured rhythm departs from the setpoint, an antiarrhythmic drug is infused by the computer. Based upon the pharmacokinetics of the drug, the infusion is delivered so as to attain an immediate change in the blood drug concentration utilizing an exponential infusion technique. The control algorithm is a modified proportional controller. Closed-loop control experiments have been performed in canines with an induced myocardial infarction. The antiarrhythmic agent disopyramide phosphate was used to correct the resulting arrhythmias. Our results suggest that computer control of drug therapy can profitably be applied to the management of cardiac arrhythmias in the coronary care unit.


The emergence of cardiac nondisease among children in Iran.

In a prospective study over a one-year period, 476 new patients, aged three days to 21 years, were seen in a pediatric cardiology clinic held three times a week in two hospitals. Of these patients, 290 (61%) were normal; in 238 (82%) of these a physician had made a definite diagnosis of heart disease. The usual bases for a diagnosis of heart disease in these cases of "cardiac nondisease" were an "elevated" antistreptolysin O titer, growing pains, hyperventilation and functional murmurs, or a combination of these. Of these 238 cardiac nondisease patients, 188 (79%) were under active treatment for up to seven years (mean, 1.23 years). This treatment included monthy penicillin injections for 104 patients for up to seven years; restriction of physical activity in 98 patients; up to six months of aspirin therapy for 25; up to three months of bed rest for 23; steroids for 17; and 'prophylactic" tonsillectomies for 11 patients. Some patients with comfirmed heart disease (35 of 97) were receiving grossly inappropriate treatment. All this represents a significant change in the pattern of pediatric care from that which existed 10 years ago, when cardiac nondisease was nonexistent and many cases of heart disease went unrecognized and untreated. In this report, possible reasons for the emergence of cardiac nondisease are discussed.


Occupational acroosteolysis in vinyl chloride workers in Israel.

Exposure to vinyl chloride monomer (VCM) may result in a bizarre syndrome, which is characterized by lytic changes in the distal phalanges, cutaneous stigmata of scleroderma, and Raynaud's phenomenon. Detailed case histories of two such patients are presented. Epidemiologic, pathogenetic and radiological aspects of occupational acroosteolysis are briefly reviewed. The possibility is emphasized that the condition may result not only from industrial (i.e., occupational) exposure to VCM but also from exposure in the home or neighborhood (i.e., nonoccupational).


Abnormal excretion of phenolic acids in rheumatic chorea.

Sydenham's chorea can be successfully treated with haloperidol, an agent that is known to interfere with the binding of dopamine to its receptors. This suggests that dopamine and its metabolic end product, homovanillic acid (HVA), might be elevated in Sydenham's chorea. To test this hypothesis, the urine of three patients with the clinical diagnosis of Sydenham's chorea was analyzed for HVA and vanillylmandelic acid (VMA). Urinary HVA and the HVA:VMA ratio were significantly higher in these three patients compared with seven control children. Urinary VMA was not different in these two groups. It is suggested that increased dopamine metabolism is involved in the pathogenesis of Sydenham's chorea and that the determination of urinary HVA and the HVA:VMA ratio may be helpful in establishing this diagnosis. We report a case that demonstrates the use of urinary HVA determination in the diagnosis of Sydenham's chorea.


Legionnaires's disease.

The fist case of legionnaires' disease in Israel is described. In a previously healthy woman, the disease was manifested by a rapidly progressive pneumonia, which was unresponsive to conventional therapy. The diagnosis was confirmed by positive serologic tests and the demonstration of the responsbile microorganism in the patient's lung tissue. Legionnaires' disease should now be suspected in patients with unexplained severe pneumonia, even in countries in which this disease has not been previously recognized.


Carcinogenicity testing for control of environmental tumor development in man.

After briefly reviewing the present status of carcinogenicity testing as an aid to the control of environmental carcinogenesis in man, and discussing in somewhat more detail the relative advantages and limitations of animal testing and the two most widely used short-term assays--the Ames test and in vitro carcinogenesis--special attention is given to two points: 1) the difficulties inherent in extrapolating from the results of experimental tests an index of potential carcinogenic hazards in man; 2) the urgent need for additional testing procedures for the detection of associated factors (such as, cocarcinogenic factors and promoting agents) operating in human carcinogenesis.


Reduction of postoperative infection rate in hip surgery: collaborative effort between orthopedic surgeons and control-of-infection team.

The success of a collaborative program between the ward staff and the control-of-infection team in reducing postoperative infection in patients undergoing hip surgery in a university hospital is described. The program was used to detect infection, to introduce control measures and to evaluate their effectiveness. The infection rate dropped from 25.7 to less than 1.0%, and this low rate was maintained over the 2 1/2 years of follow-up surveillance. The reduction in infection rate was associated with a six-day reduction (22.4%) in the duration of postoperative hospitalization.


Ultrastructural pathology with normal light microscopy of liver in Wilson's disease. A case report.

Light microscopy findings in early Wilson's disease (hepatolenticular degeneration) may be normal even when special cytochemical stains are used. We present a case of Wilson's disease in which light microscopy was negative, while electron microscopy showed the characteristic changes in the hepatocytes. Since low serum ceruloplasmin levels and high urinary copper excretion are not by themselves definite proof of Wilson's disease, and since copper content of the liver is not universally measured, electron microscopy examination of liver tissue appears to be a worthwhile additional tool for the early diagnosis of Wilson's disease.


Value of serum digoxin concentration measurement in the control of digoxin therapy in atrial fibrillation.

The association between steady-state serum digoxin concentrations and control of ventricular response rate (VRR) was studied in 53 consecutive patients with atrial fibrillation. Decreases in VRR were significantly correlated with serum digoxin (rs = -0.22, P less than 0.05). Clinical responses were appropriate to serum digoxin concentrations in 37 patients (69.8%) and were inappropriate in 16 (30.2%) (P less than 0.05). Complicating clinical factors were present in all eight patients with inappropriate responses to therapeutic serum digoxin (0.5 to 2.0 ng/ml) (P = 0.046), but were also found in many patients with appropriate responses and thus could not serve to differentiate between the two categories. Digitalis intoxication occurred in one of the three patients with a concentration of serum digoxin greater than 2 ng/ml (P = 0.056). In 30% of our patients with atrial fibrillation, monitoring of serum digoxin was of value in identifying inappropriate therapeutic responses indistinguishable by clinical means and in defining the subgroup of refractory cases, which allows the prevention of digitalis intoxication.


Cytogenetic investigation of leukemic and preleukemic disorders.

Banding chromosome analysis was performed on 35 bone marrow aspirates from patients with various leukemic and nonleukemic hematologic disorders. Of these, 24 had normal karyotypes, while 11 demonstrated various chromosomal abnormalities. Several of the abnormalities have been previously observed and support the concept of nonrandom involvement of specific chromosomes in aberrations associated with hematologic conditions. In addition, some unique abnormalities were demonstrated in three cases: monosomy 1, trisomy 22, and premature chromosome condensation.


Neurological sequelae of septic meningitis. A follow-up study of 65 children.

Seventy-two children who survived septic meningitis were reevaluated after 3 to 11 years. Thirty-four (52%) of 65 children were found to have neurological sequelae. Of the 34, 15 had major sequelae and 19 showed evidence of only minimal brain dysfunction--namely, hyperkinetic behavior, organic learning disturbances and minor motor disabilities. Acute-phase findings that were significantly associated with the rate of neurological sequelae were age, time between onset and admission, seizures, spinal fluid glucose level and the number of polymorphonuclear cells. In view of the high frequency of late neurological sequelae, it is advisable that children who survive septic meningitis have long-term follow-up in order to detect evidence of minimal brain dysfunction. An early diagnosis will help in proper management.


Growth pattern of boys with isolated gonadotropin deficiency.

The linear growth and skeletal maturation of 19 boys with isolated gonadotropin deficiency, including four with anosmia (Kallmann's syndrome), are presented. With the exception of one prepubertal-age boy (less than or equal to 10 years) and five pubertal-age boys (greater than 10 years), all heights were within normal limits, but below the 50th percentile. With one exception, the bone age was retarded in all boys, even in prepuberty.


Immediate postabortion intrauterine contraception in nulliparous adolescents.

Immediate postabortion insertion of an intrauterine device (IUD) was performed in 162 nulliparous adolescents. No insertion failures occurred. Twelve-month continuation rates were 86.6% for the Copper-7 IUD, 75.4% for the Copper-T device and 48.2% for the Lippes loop. Overall complications were greater for the Lippes loop than for the other two devices. The results suggest that immediate postabortion insertion should be considered for poorly motivated or uneducated adolescent girls who have already failed in contraception and require abortion.


[Unusual mosaicism of chromosome 10 trisomy in a female patient with the Bourneville-Pringle syndrome].

The case history of a patient with tuberous sclerosis with adenoma sebaceum of Pringle, periungual fibromata, epilepsy, retinal phacomata, renal hamartomata and cyst-like lesions of the phalanges is reported. Mosaic trisomy of chromosome 10 was observed in the patient.


["Pigment balance" through oral beta carotene. A new therapeutic principle in cosmetic dermatology].

Report on methods of treatment of unsightly pigment changes in the face with beta-carotene orally given in combination with locally applied sunscreens. This "balance of pigment" results especially in acral vitiligo in good or very good cosmetic effects. The new treatment is described in detail.


[Cullen's postoperative progressive gangrene].

A 23 year old female patient developed postoperative progressive gangrene twice after surgical treatment when she was nine and twenty-three years old.


[The iliac compression syndrome. A cause of recurrent leg ulcers].

The iliac compression syndrome is a congenital vascular anomaly which is presumed to predispose to deep thrombophlebitis. In untreated cases, severe changes with edema of the lower limbs and leg ulcers which is resistent to treatment frequently develop. The diagnosis is established by pelvic phlebography and measurement of venous pressure during weight-bearing. A case is described in which vascular surgery resulted in healing of the ulcerations and considerable improvement of the remaining symptoms.


[Pomade crust].

Exaggerated use of skin care topicals in infants may lead to brownish appositions in the inguinal and gluteal region described as pomade crust. Examination of scraping material by infra-red spectroscopy failed to reveal any residue of emollients but instead was characteristic of human scales. Certain topicals are apparently capable of inducing hyperkeratosis in these body regions.


[Superficial cutaneous nevus lipomatosus (Hoffmann-Zurhelle)].

Neviform hand-sized yellowish or skin colored plaques or linear lesions with flattened papules or folded surface in the gluteal regions, especially in females, point out to nevus lipomatosus superficialis (Hoffmann-Zurhelle). These nevi consisting of mature fat cells among the dermal collagen are rare lesions. The case report of two female patients should remind of this clinical and histological picture.


The separation of human globin chains by ion-exchange chromatography on CM-Sepharose CL-6B.

A chromatographic procedure for the separation of human globin chains is described. This method uses CM-Sepharose CL-6B as ion-exchanger and NaCl gradients formed in sodium phosphate buffers containing urea and 0.05M mercaptoethanol to elute the chains. One advantage of this system is that a column, once packed, may be used repeatedly for several chain separations, thus reducing cost and practical work. The resolution in our hands was also better than that on CM-Cellulose using phosphate buffer gradients.


Immunologic diagnosis of alpha-thalassemia traits.

Frequently it is impossible to diagnose alpha-thalassemia-2 trait from hematologic findings, since the red cell morphology and the MCV are normal. In such cases, after the neonatal period Hb Bart's is not detectable by conventional electrophoreses and chromatography. Antibody against Hb Bart's was produced in rabbits by repeated injections with Hb Bart's from Hb Bart's hydropic fetuses. The antibody was specific for Hb Bart's without crossreaction with Hbs A, A2, E, F and H. By the capillary tube precipitin test Hb Bart's was demonstrable in 82% of 87 obligatory cases for alpha-thalassemia traits, 86% in alpha-thalassemia-1 trait and 79% in alpha-thalassemia-2 trait. The test was positive in 21% of the general subjects, corresponding to the prevalence of alpha-thalassemia in Bangkok. Thus the immunologic demonstration of Hb Bart's appears to offer a diagnostic screening test for alpha-thalassemia traits in the postneonatal period.


Beta 0 thalassemia trait in Sardinia.

The red cell indices and results of globin chain synthesis in peripheral blood of obligate beta 0 thalassemia (beta 0 thal) carriers (parents of homozygous beta 0 thal children) and beta thalassemia (beta thal) carriers identified during mass screening are reported. Red cell indices were similar in obligate beta 0 carriers and in carriers diagnosed during mass screening. However there was a higher incidence of anemia in female obligate beta 0 thal carriers. In Sardinia the beta 0 thal carrier showed the usual hematological characteristics of the high Hb A2 beta thal carrier with microcytosis, hypochromia, reduced osmotic fragility; Hb F greater than 1% was found in 30% of the carriers. With MCV, MCH, osmotic fragility test (OFT) and Shine and Lal discriminant function we found 3.5%, 1.5%, 3.5% and 4.0% respectively false negatives in carrier identification. A part from one subject, all obligate carriers had elevated Hb A2 levels. The alpha/beta ratio in obligate carriers (mean +/- SD) was 1.83 +/- 0.26 (N = 30).


The structure of goat hemoglobins. V. A fourth beta chain variant (beta-D-Malta; 69 Asp is replaced by Gly) with decreased oxygen affinity and occurring at a high frequency in Malta.

During a survey of hemoglobin types in goats in the Republic of Malta a variant (Goat Hb D-Malta) was discovered which differs from normal goat Hb A by the substitution of an aspartyl residue in position beta 69 (E13) by a glycyl residue. The gene frequency of the beta D allele was 0.255; 29 homozygous Hb D goats were present among 327 animals sampled. Homozygous Hb D goats also produce Hb C, whose beta chains are the product of a non-allelic beta C structural gene. Goat Hb D-Malta has a distinctly decreased affinity for molecular oxygen.


Alcohol embryopathy and diabetic fetopathy in the same newborn.

Both alcohol embryopathy and diabetic fetopathy were observed in the same female child. The mother was known to be alcoholic as well as diabetic. At birth the signs of diabetic fetopathy predominated: the child showed edematous subcutaneous fat, birth weight was 3650 g. The heart was enlarged. The patient's blood sugar levels ranged from 0 to 1.4 mMol/1 (0-25 mg/dl). Features of alcohol embryopathy were typical craniofacial dysmorphy, hypotonia of muscles and hyperexcitability. Later on the features of alcohol embryopathy predominated: the child became dystrophic with pronounced microcephaly, and the craniofacial dysmorphy clearly resembled other patients with alcohol embryopathy. This observation is in favour of the hypothesis, that alcohol induces cell hypoplasia in the embryo resulting in postnatal growth retardation. Maternal and consequently embryonic and fetal hyperglycemia induced cell hypertrophy in the embryo and fetus, which compensated the effect of alcohol on birth weight in our patient.


Postaxial polydactyly, hallux duplication, absence of the corpus callosum, macrencephaly and severe mental retardation: a new syndrome?

A male patient presented with a pattern of congenital malformations including macrocephaly, absence of the corpus callosum, hypertelorism, small nose, bilateral inguinal hernias, postaxial polydactyly of all limbs and duplication with syndactyly of the big toes. His development was marked by growth retardation, repeated infections, cyanotic spells, seizures, and gross motor and mental retardation. This case probably represents a newly recognized malformation syndrome of hitherto unknown etiology.


[The mucocutaneous lymph node syndrome or Kawasaki disease].

A case of "mucocutaneous lymph node syndrome" is presented. This syndrome is a nosological entity with clearly defined diagnostic criteria. The disease has mainly been observed in Japan, rarely in other countries. It is named according to its main manifestations on skin, lymph nodes and mucous membranes. We discuss the differential diagnosis and mention the danger of a severe course of this syndrome.


Gynaecomastia in two prepubertal boys with congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency.

Two male children with congenital adrenal hyperplasia due to a 11-beta-hydroxylase defect are described, in whom gynaecomastia developed before institution of therapy, or when the treatment was inadequate. Cortisone in appropriate doses caused the gynaecomastia to disappear.


Steroid synthesizing cellular sites in the ovary of the domestic pigeon Columba livia (Gmelin): a histochemical study.

The ovary of the domestic pigeon, Columba livia, has been assayed histochemically for the localization of delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSDH), 17 beta-hydroxysteroid dehydrogenase (17 beta-HSDA), 11 beta-hydroxysteroid dehydrogenase (11 beta-HSDH), glucose-6-phosphate dehydrogenase (G6P-DH) and NADH-diaphorase activities during different periods of the reproductive cycle. delta 5-3 beta-HSDH, 17 beta-HSDH, 11 beta-HSDH, G6P-DH and NADH-diaphorase activity was found in the theca interna of growing, atretic and postovulatory follicles, the granulosa of ovulatory, atretic and postovulatory follicles, and interstitial gland cells during the pre-incubation and the laying periods. During the incubation and squab feeding periods only delta 5-3 beta-HSDH, G6P-DH and NADH-diaphorase activities were observed in the above mentioned cells. The steroidogenic potential of atretic follicles depends upon the type of atresia a follicle undergoes.


Histochemical characteristics of mucins in the small intestine. A comparative study of normal mucosa, benign epithelial tumours and carcinoma.

The histochemical properties of the mucins in seven benign epithelial tumours and 15 carcinomas distributed along the duodenum, jejunum and ileum were investigated and compared with normal controls. This study reveals that (a) goblet cells in normal small intestine contain neutral and sialomucins but no sulphated material; (b) the proportion of the different types of mucins in the goblet cells vary along the crypts and villi with an increasing amount of sialomucins towards the villus top; (c) mucin composition also changes from duodenum to ileum particularly in the proportions of sialic acid types and in the presence of traces of sulphomucins in the ileal mucosa close to the ileo-caecal valve, suggesting a gradual transition through the small intestine to the colon; (d) benign tumours show the same mucin pattern as normal mucosa; (e) the adjacent to carcinoma shows increasing amounts of sialomucins and sulphomucins; (f) carcinomas present a variety of mucin patterns, and thus the study of mucins seems to be of no value in differentiating tumours of the small intestine from those elsewhere in the gastrointestinal tract. A working hypothesis based on the Unitary Theory of the origin of the intestinal epithelial cells is proposed to explain the variations in glycoprotein synthesis with cell differentiation and carcinogenes.


Protein transmission in the intestine of the newborn lamb: the involvement of acid and alkaline phosphatase activity.

The localization of acid phosphatase activity was differentiated from that of alkaline phosphatase in the foregut of the newborn lamb by light and electron microscopy. The examination of samples from fed and unfed lambs indicated the presence of alkaline phosphatase activity in endocytic vesicles originating from the brush-border. These vesicles, associated with protein absorption, were particularly numerous in fed lambs and occurred throughout the cytoplasm of the enterocytes. Acid phosphatase activity was absent from vesicles in the apical cytoplasm but it was localized in most sub-nuclear vesicles, also in the Golgi apparatus and the lysosomes of macrophages. The sub-nuclear vesicles were often observed in close proximity to the lateral and basement membranes of the enterocytes, also in continuity with the intercellular space. It is suggested that these results indicate the mechanism for transmission of brush-border and lysosomal enzymes, along with the immunoglobulins, into the lymph of the newborn lamb.


Horseradish peroxidase as a label of injured cells.

The present study is concerned with artifacts likely to occur in a horseradish peroxidase exclusion test. Incubation of murine peritoneal macrophages and lymphocytes with the peroxidase showed a close relationship between the number of living cells and the percentage of cells excluding the tracer. The penetration of the cytoplasm by horseradish peroxidase is attributed to an increase in the permeability of the cell membrane during the incubation (ranging from 10 to 120 min). It was not increased by the presence of tracer throughout the incubation period. However, concomitant fixation of the cell in the presence of horseradish peroxidase caused an increase in the influx of the tracer. The horseradish peroxidase exclusing test applied to the guinea-pig organ of Corti has proved to be valid provided that: (a) mechanical lesions prior to the tracer incubation are avoided; (b) incubation is terminated by removal of the extracellular tracer; (c) fixation is carried out as soon as possible; (d) a low concentration of horseradish peroxidase is used; and (e) specimens are incubated in diaminobenzidine-H2O2 medium for the shortest possible period. Although fixation-induced cytoplasmic infiltration by horseradish peroxidase was not detected in cochlear specimens, the findings call attention to possible sources of error and define the level of significance of the test. Horseradish peroxidase does not appear to be a cytotoxic agent under the conditions used.


The routine sectioning of undecalcified bone for cytochemical studies.

A method is described by which serial sections of fresh, undermineralized adult bone can be obtained. Such sections are suitable for cytochemical investigations and can expedite diagnostic histology.


Ultrastructural features of acidic complex carbohydrates in the intercellular matrix of the ovarian follicles in adult mice.

In the intercellular matrix of the granulosa layer of the mouse ovarian follicles, ultrastructural features of acidic complex carbohydrates have been studied by means of dialyzed iron (DI) staining in combination with procedures of digestion with Streptomyces and testicular hyaluronidases. In the intercellular matrix, DI reactive structures containing acidic complex carbohydrates consist of layers of a variable thickness coating the plasma membrane of the granulosa cells and reticular elements distributed in the spaces between the cells. The latter exists in two appearances; one is clumped masses of irregular shapes and different sizes, whereas the other being filamentous figures radiating from the masses. The effects of digestion with Streptomyces and testicular hyaluronidases upon the DI staining of the tissues indicate that the DI reactive structures in the intercellular matrix contain at least three types of acidic complex carbohydrates; hyaluronic acid, isomeric chondroitin sulfates and other acidic glycosaminoglycans. The histophysiological activities played by these particular complex carbohydrates have been briefly discussed.


Short time observations of morphological changes and cholinesterase distribution in lymphatic organs of the mouse after corticosteroid and X-ray treatment.

The changes in thymus, spleen and lymph nodes of the mouse after a single cortisone application or a single whole body x-irradiation were investigated morphologically and histochemically. During 24 h the alterations following the cortisone application are at all stages examined indistinguishable from those following the x-irradiation. The first signs of lymphocyte destruction can be observed already in the first two hours after treatment. Almost at the same time macrophages accumulate at the sites of cell death in the lymphatic organs studied. The eosinophils display a different behaviour. While they accompany the macrophages in the thymus already at the first stages, they appear in the spleen and lymph nodes with a latency of 6 and 8 h, respectively. The highest amount of necrotic cells is found ten hours after both treatments. At the same time the accumulation of macrophages and eosinophils reaches its maximum. The cholinesterase in the lymphatic organs is largely the true cholinesterase. The enzyme-activity increases in the cortex of the thymus gradually 6 h after treatment, showing the highest deposit of reaction product at 10 h. In spleen and lymph nodes the cholinesterase shows only slight variations. The possible role of the cholinesterase-activity in these non-cholinergic tissues is discussed.


DNA content and chromosome number of a heteroploid human tumour cell line.

In this paper investigations concerning the relation between variability of chromosome number and variability of DNA content within the cells of a tumour stemline are reported. A highly heteroploid human tumour cell line was used, which was derived from a chondrosarcoma. Flow cytometrical and scanning cytophotometrical measurements confirmed the heteroploid nature of the original cell line and of several subclones. Measurement of the DNA content per metaphase showed a linear relation between chromosome number and DNA content of heteroploid cells. This finding is discussed with regard to its implications for the mechanism of heteroploidy in tumour cells.


[Peptidases II. Localization of dipeptidylpeptidase IV (DPP IV). Histochemical and biochemical study].

Fresh frozen, unfixed, chloroforme-acetone treated or freeze-dried cryostat sections or sections from aldehyde-fixed blocks of tissue were tried for the histochemical investigation of dipeptidylpeptidase IV (DPP IV) with L-glycyl-L-prolyl(gly-pro)-naphthylamides as substrates and stable or unstable diazonium salts for simultaneous coupling and various buffers, pH 5--7.5 in rats, mice, guinea-pigs, cats, rabbits, hamsters and human enterobiopsies. The best results are obtained with 1.7--3.4 mM gly-pro-4-methoxy-2-naphthylamide and 1 mg Fast Blue B/ml or (with some limitations) 0.025 ml hexazotized new fuchsine/ml in 0.1 M cacodylate or phosphate buffer, pH 7.5 and unfixed sections for the demonstration of the total activity of DPP IV and freeze-dried celloidin-mounted cryostat sections for the precise localization of the enzyme or the detection of lysosomes, Golgi apparatus and secretion granules sections from aldehyde fixed tissue blocks are only suitable to study the lysosomal hydrolysis of gly-pro-naphthylamides between pH 5 and 7 when hexazotized p-rosaniline or new fuchsine are employed. DPP IV is firmly bound to strutures and shows species- and organ-dependent differences. In general, the enzyme occurs in the capillary endothelium, sinusoidal cells, perineurium, epithelial cells of intercalated and striated ducts, microvillous zone of intestinal crypts and villi, uterus, Fallopian tubes, ductus epididymis and proximal renal tubules, hepatocyte and lymphocyte membrane, plasmalemma of pseudostratified and transient epithelia and in the capsules and interstitium of many organs. These sites of activity can be completely inhibited by diisopropyl fluorophosphate and partially by Pb2+; Mg2+, Mn2+, Co2+ EDTA are without any influence. Phenantrolin may activate DPP IV. The biochemical assay works with 10 mM gly-pro-2-naphthylamide in 0.1 M cacodylate buffer, pH 7; the enzyme activity is determined fluorometrically in guinea-pig and rat organs; the data confirm and enlarge the species- and organ-dependent differences revealed by histochemistry. Compared with other dipeptide as well as tripeptide and amino acid naphthylamides the results obtained for DPP IV suggest a peptidylpeptidase which seems to be involved in other metabolic processes beside the degradation of collagen.


Distribution and origin of acetylcholinesterase activity in the capillaries of the brain.

Areas containing AChE-positive capillaries were mapped in the brain of the cat and the guinea pig. Regions with AChE-positive capillaries mostly also contain neuronal elements with AChE activity. Electron-microscopical cytochemistry revealed localization of AChE in basement membranes of endothelial cells and pericytes very often in continuity with activity of the extracellular space. Intraendothelial AChE activity was seen only in pinocytic vesicles. The vascular AChE is thought to be of neuronal origin since no cytochemical evidence has been obtained for a synthesis of this enzyme in endothelial or other non-neuronal cells in the CNS.


Histochemical and cytochemical studies of alkaline phosphatase activity in the synapses of rat brain.

Although a number of studies have been carried out on alkaline phosphatase (A1-P), this enzyme has not definitely been detected in synapses at the electron-microscopic level. Recently, we have successfully demonstrated, by perfusing specimens with 1% glutaraldehyde for fixation for as short a time as 8-10 min, that A1-P activity is localized on the presynaptic and postsynaptic membranes of the rat central nervous system (CNS). There were four types of presynaptic membrane: (1) those with the activity only on the membrane, (2) those with the activity only on the synaptic vesicle membrane, (3) those with the activity on both the presynaptic membrane and the synaptic vesicle membrane, and (4) those entirely free of the activity. The postsynaptic membranes were classified into two varieties: (1) those with the activity in the postsynaptic membrane and the postsynaptic thickening, and (2) those entirely without the activity. Thus, the occurrence of the enzyme activity assumed various combinations of presynaptic and postsynaptic involvement. The incidence of synapses either with presynaptic or postsynaptic activity varied distinctly from site to site.


Elemental analysis of histochemically defined cells in the earthworm Lumbricus terrestris.

A method for preparation of biological specimens for electron probe X-ray microanalysis is described, that aims at retaining the original elemental distribution within the tissue at the cellular level. The tissue is without any chemical fixation, quench-frozen, and 16-micron sections are prepared with a conventional cryomicrotome, transferred to a carbon specimen holder and freeze-dried. Adjacent serial sections, collected on glass slides and stained with various histological procedures, are used to correlate the data obtained by X-ray microanalysis with other histochemical information on the same cell or tissue. To demonstrate the possibilities of the method, sections of the earthworm Lumbricus terrestris were analyzed. In the chloragogenous cells, high concentrations of Ca, Zn and P were found. The inner and outer muscle layer show slightly different properties, both with regard to elemental composition and to myofibrillar ATPase activity.


Mucosubstances of rabbit granulocytes studied by means of electron-microscopic radioautography and X-ray microanalysis.

Rabbit bone marrow cells have been studied by means of light- and electron-microscopic radioautography and X-ray microanalysis. Carrier free sulfuric acid was used as the radioactive precursor in this experiment. Immature granulocytes showed more active incorporation than mature ones. Silver grains were observed in the Golgi apparatus and granules in three kinds of granulocytes. Electron-microscopically, immature granules showed the incorporation of inorganic sulfate, while mature ones did not. Sulfur was detected in all kinds of granules of the three granulocyte types by X-ray microanalysis. It is concluded that incorporated inorganic sulfur may be utilized for the synthesis of acid glycosaminoglycans and the sulfur detected by X-ray microanalysis may be that contained in the acid glycosaminoglycan. The sulfur detected in the specific granules of the heterophil probably derives from proteins or polypeptides incorporating sulfur containing amino acids.


Cytochemical studies on cytoplasmic granular elements in the hamster pineal gland.

The pineal gland of adult golden hamsters (Mesocricetus auratus) was studied by various cytochemical methods at the electron microscopic level: (1) the modified chromaffin reaction specific for 5-hydroxytryptamine (5-HT), (2) argentaffin reaction, (3) zinc-iodide-osmium (ZIO) mixture reaction and (4) acid phosphatase reaction. In the pinealocytes, the dense-cored vesicles (80-160 nm in diameter) show both chromaffinity and argentaffinity, while the population of dense bodies (150-400 nm in diameter) is reactive to ammoniacal silver solution and ZIO mixture but not to the modified chromaffin reaction. After incubation for demonstration of acid phosphatase activity, reaction products are localized in some, but not all, of the dense bodies, in some of the small vesicles in the Golgi region and in one or two inner Golgi saccules. In nerve fibers in the pineal gland, small granulated vesicles are also reactive to the modified chromaffin reaction and ZIO mixture. Based upon these cytochemical results the following conclusions have been reached: (1) dense cored vesicles in the pinealocytes and small granulated vesicles in the nerve fibers of the hamster pineal gland contain 5-HT, and (2) the population of dense bodies in the pinealocytes is heterogeneous, some are lysosomes and the other are possibly the granules responsible for the secretion of pineal peptides.


Ultrastructural distribution of AChE in Catenula leptocephala (Nuttycombe, 1956).

Acetylcholinesterase activity (AChE, E.C. 3.1.1.7) was examined in different tissues of Catenula leptocephala (Nuttycombe, 1956). Eserine and iso-OMPA were used to distinguish AChE from non-specific cholinesterases (ChE, E.C. 3.1.1.8). The enzyme was located mainly in the brain neuropil, the peripheral nervous system, neuromuscular junctions, on the membrane of muscle cells and of cells with rhabdites. The distribution of the enzyme suggests that cholinergic transmission occurs in Catenula leptocephala, while simultaneously the presence of AChE on the membranes of muscle cells points to the receipt of cholinergic stimulation. The role of AChE in differentiation and maturation of cells with rhabdites is also discussed in this paper.


The increase in activity of acid hydrolases in muscles of rats after subcutaneous administration of dimethyl-para-phenylene diamine. A combined histochemical and biochemical investigation. I. The histochemical investigation.

The activity of acid hydrolases in skeletal muscles of normal rats and of rats after subcutaneous administration of dimethyl-para-phenylene diamine (DPPD) was studied with a combined histochemical and biochemical investigation. In this communication the histochemical findings are presented. After 4 days of DPPD treatment, coagulation necrosis, fragmentation and disintegration of fibres were seen in the muscles. An inflammatory infiltrate was seen between the muscle fibres. These pathological changes reached maximum intensity after 7 to 9 days. After 11 days the changes became less, despite continued treatment with DPPD. From the histochemical findings it appeared that the activity of acid phosphatase, beta-glucuronidase and E600 resistant non-specific esterase was increased in both a granular and a diffuse pattern in the skeletal muscles of the DPPD rats. The increase in activity of leucine aminopeptidase was much less pronounced and was mainly granular. The increase in the activity of acid hydrolases ran parallel to the severity of the pathological changes and reached a maximum after 7 to 9 days of DPPD treatment. The statistical calculations of the histochemical findings revealed that the increased activity of one acid hydrolase was significantly paralleled by an increased activity of a second hydrolase. There was a moderate probability that the activity of all other histochemically studied acid hydrolases, with the exception of leucine aminopeptidase, was increased. There was no difference in activity and localization of the acid hydrolases studied in aerobic type I and anaerobic type II fibres. The localization of acid phosphatase and beta-glucuronidase activity in muscle fibres and in inflammatory infiltrate mostly coincided. In cases where these enzymes were localized both centrally and in the subsarcolemnal areas of the muscle fibres, the activity of E600 resistant non-specific esterase was usually, and the activity of leucine aminopeptidase was exclusively located in the subsarcolemnal areas. All of the acid hydrolases examined were found to be present in the inflammatory exudate and in the connective tissue.


[The significance of papillary carcinoma of the thyroid for the ENT specialist (author's transl)].

The otorhinolaryngologist often encounters patients with pathological findings in the thyroid gland which may be overlooked if he is not aware. Alarming symptoms are rarely present in a goiter which is undergoing malignant change. Papillary and follicular carcinomas can exist over long periods of time as nodular goiters with globus symptoms or are discovered after cervical lymph nodes have appeared. The discovery of a goiter is thus of clinical importance regardless of the patient's age. Diagnostic iodine isotope scanning and cytological analysis is to be recommended as a matter of general policy. Excellent results in the treatment of papillary carcinoma can be obtained by subtotal thyroidectomy with modified neck dissection, followed by isotope elimination of remaining thyroid tissue.


[Retention cysts of the vocal cords (author's transl)].

Present day knowledge in laryngology maintains that the free edge of the true cord mucosa is devoid of glands so that retention cysts should not occur in this tissue. When such cysts do occur, it is difficult to define their pathogenesis. Reference is made to the author's earlier study which found a regular occurrence of mucous glands in the squamous epithelial region of the vocal cords. A retention cyst in the true cord is described histologically in the present report. The glands responsible for these cysts are believed to function by moistening the mucous membrane of the vocal cords.


[Treatment of sudden hearing loss as a clinical problem (author's transl)].

From the methods used in treatment of sudden hearing loss, certain measures have been found to be best for the improvement of microcirculation disturbances in the inner ear, as based on antisludge effects. The effectiveness of drugs such as dextran infusion, procaine, xanthinol nicotinate, beta-pyridylcarbinol and heparin cannot be compared, nor can techniques such as stellate block, ATP-infusions, and pure vasodilators (Betaserc). Analysis of oxygen inhalations have thus far been incomplete. In the following analysis, we compared the results of therapy following stellate block in 50 patients with those obtained after dextran-papaverine infusions in 16 hospitalized patients. Prior to treatment, patient parameters (including average hearing loss and time-factor) were made uniform so that further statistical comparison was possible. In the group of patients treated with stellate block, we found an average hearing improvement to be about 23 dB (as based on analysis of single frequencies at 0.5, 1.0, 2.0, 4.0 kHz). In the group of patients treated with dextran infusions, an average hearing improvement of 18 dB was found. Statistical analysis did not indicate any significant effect differences between either treatment method. Taking other information from the literature into consideration, we may establish that the maximum hearing improvement which can be reached with the discussed treatment methods to be about 20--30 dB.


[Computer analysis of electronystagmograms. First report: the normal pendular test ENG (author's transl)].

In an attempt to standardize the interpretation of electronystagmograms the results of computerized analysis of pendular test nystagmograms have been statistically evaluated. All the nystagmus components show marked dependance on age. The range of normal reactions is determined by means of double standard deviation. The cumulogram of the nystagmus slow phase demonstrates the smallest deviation of all the analysed parameters, and this makes it suitable in the pendular test for diagnostic estimation. The cumulogram provides information on nystagmus slow phase duration, amplitude, symmetry or irregularity.


[Antibiotic therapy - a critical review (author's transl)].

The antibiotic management of tonsillitis, acute otitis media, sinusitis and bronchitis is critically reviewed. Tonsillitis due to Group A streptococci must be treated with penicillin for 10 days in order to prevent complications. Antibiotics should not be used locally in pharyngitis or tonsillitis. Tonsillectomy does neither reduce the incidence of streptococcal tonsillitis nor of rheumatic complications. Antibiotic cover for tonsillectomy is not indicated except in patients with rheumatic heart disease or in those with prosthetic heart valves. The indications for the prophylactic use of antibiotics in ear, nose and throat surgery are discussed.


[Immune serum globulin E in patients with leukoplakia (author's transl)].

Significant changes of humoral factors can occur during the development and growth of malignant tumors. Such can be observed by the periodic recording of immune serum globulin E levels if sensitive RIA methods are employed. Observations of normal persons show largely stable immune serum globulin E levels, and are comparable in patients with leukoplakia of the larynx as well as in patients whose malignant conditions were removed by oepration or radiotherapy. In three patients, a statistically significant increase in serum immune globulin E was recorded immediately before malignant degeneration of known leukoplakia occurred, and was also found in 22 control tumor patients who had experienced local relapses of disease.


[Electromyography of the cricoarytenoid muscle in the unsedated patient using the zoom-endoscope (author's transl)].

The EMG enables diagnosis, follow-up and prognosis of vocal cord palsy as well as indications for surgery. Using the zoom-endoscope of von Stuckrad electromyography of the larynx can be performed under topical anaesthesia. With a specially designed instrument the needle electrode can be transorally applied exactly into the posterior cricoarytenoid muscle and into any other muscle of the larynx. As the patient can follow instructions the voluntary muscle activity can be observed on the monitor and stored on tape during inspiration, exspiration and phonation. Replay and electronic summation are possible.


[A comparison of impedance and pure tone audiometry in children (author's transl)].

The results of conventional pure-tone audiometry and impedance audiometry are compared in 386 pre-school children. The children showing abnormal audiograms were subjected to a repeated examination in the ENT Clinic a few weeks later. It was shown, that all children, whose hearing disorders were confirmed, had already had abnormal impedance measurements during the screening examination. On the other hand, pathological changes of the ears were detected in 5.92% of the children only by the impedance measurements and not by the conventional puretone audiometry. Evaluation of the pressure and the acoustic reflex of the middle ear by impedance audiometry is preferred. It is well recommended in the examination of pre-school children, because the procedure takes little time and is easy to perform.


Change in psychoanalytic treatment.

Psychoanalytic treatment aims not simply at removal of symptoms but at basic characterologic improvement. Although change in psychoanalytic treatment is traditionally attributed primarily to insight, the author asserts that insight, although valuable, is not essential to the achievement of such change. Other elements basic to the therapeutic efficacy of all psychoanalytic techniques regardless of their theoretical orientation are discussed. Among additional factors, the implications of warmth and activity on the part of the analyst, and of setting a termination-date, are specifically elaborated on.


Analyzability and capacity for change in middle life.

The stimulus for this paper was the analyst's surprise at the capacity for change in a number of middle-aged patients, some of whom would not have been considered good analytic prospects even if young, especially since they had all had extensive, unsuccessful previous psychiatric and psychoanalytic treatment, in two instances with the author herself. Factors of change in what now constitutes "old age," and of analyzability, rigidity, motivation and readiness for change, countertransference factors, and the significance of a late-appearing corrective emotional experience were all considered, along with a brief re-evaluation of what the analytic process really is, and how change comes about.


Electromyogram pattern of diaphragmatic fatigue.

We studied the effect of breathing at various levels of transdiaphragmatic pressure (Pdi) on the EMG power spectrum of the diaphragm. The diaphragmatic EMG was measured simultaneously with a bipolar esophageal electrode (EE) and surface electrode (SE) placed on the ventral portion of the sixth and seventh intercostal spaces in five normal subjects breathing at functional residual capacity (FRC) against an inspiratory resistance. During each fatigue run the subjects generated a Pdi, with each inspiration, that was 25, 50, or 75% of maximum Pdi (Pdimax) for a period up to 15 min. During runs at 50 and 75% of the Pdimax, which are known to produce fatigue, we found for both EE and SE a progressive increase in the amplitude of the low-frequency (L = 20-46.7 Hz) and a decrease in the high-frequency (H = 150-350 Hz) component of the EMG. These changes were not seen at 25% of Pdimax. The diaphragmatic H/L ratio was independent of Pdi when the diaphragm was not fatigued. H/L fell while the diaphragm performed fatiguing work and this was more rapid at higher Pdi's. It was thus concluded that frequency spectrum analysis of the EMG can detect diaphragmatic fatigue reliably, prior to the time when the diaphragm fails as a pressure generator.


DLO2 in excised lungs perfused with blood containing sodium dithionite (Na2S2O4).

If the excised lung is perfused with blood containing the chemical sodium dithionite (DDT), the PO2 of pulmonary capillary blood is everywhere zero and the membrane diffusing capacity for O2 (DmO2) can be measured by a standard rebreathing technique. The reaction rate of DDT with O2 is not rate limiting in the DmO2. In 15--25 kg dogs anesthetized with pentobarbital sodium (30 mg/kg, iv), left lower lobe was excised, suspended horizontally and perfused with autologous blood at 25--27 degrees C. DDT was added to the blood and the rebreathing alveolar disappearance curves for O2 were measured. The DmO2 ranged from 6 to 43 (ml/min.Torr, STPD) at lung volumes of 240--780 ml (FRC at 6 cmH2O end-expiratory pressure). Lung weight, pulmonary artery pressure, and the DmO2 were stable in the presence of DDT. Histopathology indicates that dithionite in the concentrations used does not harm the lung. Effects of inequalities in the distributions of ventilation, volume, and diffusing capacity were examined in a two-compartment model and compared with the experimental findings.


Interaction between sodium and chloride transport in canine tracheal mucosa.

Canine tracheal mucosae were dissected and mounted as flat sheets in Ussing chambers. Unidirectional isotope fluxes of 22Na and 36Cl were performed across paired mucosae from the same animal. The average spontaneous potential difference was 42 + 1.2 mV (mean +/- SE) lumen negative. The short-circuit current (SCC) 3.09 +/- 0.36 mueq/cm2.h was accounted for by a net Cl secretion of 2.46 +/- 0.26 mueq/cm2.h toward the mucosa and net Na absorption of 0.46 +/- 0.13 mueq/cm2.h toward submucosa. Removal of Cl depressed SCC but had no effect on unidirectional or net Na transport (n = 7). By contrast, removal of Na (n = 6) or the addition of ouabain (n = 7) abolished net Cl secretion and greatly reduced SCC. Theophylline (n = 6) added to the submucosal bath no significant effect on Na transport but stimulated SCC and Cl secretion, suggesting hormonal regulation of Cl transport. The results suggest that the active transport of Na and Cl in this epithelium occur by electrically conductive pathways, i.e., the transport is "electrogenic." Further it appears that Na transport is independent of the presence of Cl but that Cl transport depends on some parameter of active Na transport.


Sensitization of tolerant mice to cold with a serum factor induced by endotoxin.

Endotoxin-tolerant mice are sensitized to cold (5 degrees C) stress by an injection of 0.4 ml serum collected from zymosan-pretreated mice 2 h after an intravenous (iv) injection of 25 microgram endotoxin. Deaths begin after 6 h and most animals die by 10 h, The factor in serum believed to be responsible for this effect is called glucocorticoid antagonizing factor (GAF). Tolerant mice given 10 microgram endotoxin live for 10 h and two-thirds survive for 24 h. Serum from endotoxin-poisoned conventional mice reduces survival time significantly but not as dramatically as that from zymosan-primed mice. The latter serum, but not endotoxin, causes a rapid drop in the core temperature of tolerant mice housed at 5 degrees C and inhibits the endogenous induction of phosphoenolpyruvate carboxykinase (PEPCK) (EC 4.1.1.32) in tolerant mice exposed for 4--5 h to the cold. An injection of 25 microgram endotoxin does not have this effect on the enzyme. Serum that produces these responses also sensitizes mice to endotoxin lethality and blocks the protection normally afforded against endotoxin by adrenocorticoids.


Effect of exercise on postoperative nitrogen balance.

This study was designed to investigate whether exercise, when used as an adjunct to parenteral nutrition, has any influence on postoperative muscle catabolism, amino acid metabolism, and nitrogen balance. Twenty male Sprague-Dawley rats were divided into two groups of exercised and nonexercised animals. All animals underwent laparotomy and jugular vein cannulation, were placed in metabolic cages, and were infused with a dextrose-protein solution at 15 kcal and 0.56 g amino acids/100 g body wt per 24 h for a total of 96 h. The exercised animals were run on a treadmill for 15 min/day for a total of 3 days. There was no difference in nitrogen balance and body weight change between exercised and nonexercised animals, as well as no difference between animals who experienced different degrees of exercise. Total and individual plasma amino acids in the exercised group were 15% lower than in the nonexercised group; the total and individual free amino acids in muscle of the exercised group were 66% higher than in the nonexercised group. This pattern of high levels of amino acids in the muscle, coupled with decreased plasma concentrations, is suggestive of increased amino acid turnover in the muscle of the exercised animals. We suggest that, in the postoperative or postinjury period, exercise has a stimulating effect on amino acid turnover in the skeletal muscle resulting from 1) amino acid (mainly the branched-chain amino acids) consumption for energg metabolism and gluconeogenesis, and 2) protein synthesis. The net balance of both results in nitrogen equilibrium similar to that of a nonexercised control group.


Spectral analysis of human inspiratory diaphragmatic electromyograms.

The inspiratory diaphragmatic EMG was recorded via esophageal electrodes in six normal subjects. The EMG and ECG signals were analyzed by power density spectral analysis, before and after band-pass filtering (20--1,600 Hz). The EMG spectrum was concentrated in the bandwidth 25--250 Hz. Electrode motion introduced a significant artifact only at low frequencies. The ECG spectrum was also concentrated at lower frequencies, but substantial power from the cardiac signal spilled over across most of the EMG spectrum. Band-pass filtering was therefore effective in minimizing the former but not the latter. Of the various power and frequency parameters used to quantitate the EMG spectrum, the most stable was the centroid frequency. This was reproducible within and between subjects, and was not affected by changing tidal volume or inspiratory flow rate.


Pregnancy-induced pulmonary hypertension in cows susceptible to high mountain disease.

Observations in several species suggest that pulmonary vascular reactivity may be reduced during pregnancy. We tested this hypothesis in two groups of unanesthetized cows, one "susceptible" and one "resistant" to high mountain or brisket disease. At the altitude of residence (1,524 m), mean pulmonary arterial pressure was elevated during pregnancy by 18% and total pulmonary vascular resistance by 32% in susceptible but not in resistant cows. During acute exposure to simulated altitudes of 2,120--4,550 m, pulmonary arterial pressure was increased by 16% and total pulmonary resistance by 28% during pregnancy in susceptible cows. The pulmonary pressor response to a 5 microgram/kg bolus of prostaglandin FIalpha was not different during pregnancy in either group. Resistant cows hyperventilated while pregnant, raising arterial partial pressure of oxygen (PaO2) by 6 Torr both at 1,524 m and, on the average, by 7 Torr at altitudes of 2,120--4,550 m. Susceptible cows increased their PaO2 less than did the resistant cows during pregnancy. The results indicated that pregnancy was associated with a greater rise in pulmonary arterial pressure and total pulmonary vascular resistance during acute hypoxia and failed to elicit as great a ventilatory response in susceptible than in resistant cows.


Airway reactivity to nitrates in normal and mild asthmatic subjects.

Epidemiologic studies have reported increased symptoms in young asthmatics when atmospheric pollutants containing nitrates and sulfates are elevated. To determine if inorganic nitrate pollutants cause increased airway reactivity in humans, 10 normal volunteers and 11 mild asthmatics inhaled a sodium nitrate (NaNO3) aerosol with an aerodynamic diameter of 0.46 micron at a concentration of 7,000 microgram/m3, a level 100--1,000 times greater than reported urban levels for nitrates. A sodium chloride (NaCl) aerosol of similar characteristics served as a control. By double-blind randomization, each subject breathed NaCl or NaNO3 for a 16-min period and again 2--4 h later. Deposition studies showed 32--78% retention of the inhaled aerosol. Functional residual capacity, airway resistance, forced vital capacity, 1-s forced expiratory volume, and maximum and partial expiratory flow rates at 60 and 40% of total lung capacity did not significantly change during or after exposure. All subjects remained asymptomatic. To establish if aerosol exposure increased reactivity to a known bronchoconstrictor, subjects inhaled 0.025--1.0% carbachol following the 16-min exposure. Although prior inhalation of NaNO3 or NaCl aerosols did not significantly alter the effect of carbachol on pulmonary function, two asthmatics demonstrated mild potentiation of the carbachol bronchoconstrictor response after nitrate exposure. These results suggest that in normal subjects and mild asthmatics short-term NaNO3 exposure does not alter pulmonary function.


Chronic response of rat brain norepinephrine and serotonin levels to endurance training.

Norepinephrine (NE) and serotonin (5-HT) concentrations were determined in three areas of the rat brain following 8 wk exposure to differing physical activity and dietary regimens. Animals were divided into sedentary and exercise groups, and one-half of each received either a normal or atherogenic diet. The exercise consisted of 30 min of treadmill running, 5 days/wk, for 8 wk. Brains were weighed and sectioned into cerebral cortex, cerebellum, and remainder (midbrain), and fluorometrically analyzed for NE and 5-HT content. In most brain areas, NE and 5-HT levels were significantly greater among exercise-normal diet and exercise-fat diet compared to both sedentary groups. In the cerebral cortex, exercise-normal diet rats possessed higher levels of NE and lower concentrations of 5-HT than sedentary animals. The atherogenic diet did not affect amine levels other than 5-HT in the cortex among exercise rats. The NE results are consistent with prior research indicating its control of sympathetic function. Increased levels of 5-HT in the midbrain may be the neurotransmittal adaptation responsible for decreased appetite and enhanced weight loss following chronic endurance exercise.


A technique for multiple, high-rate blood samplings via an external cannula in rats.

A method for obtaining multiple, high-rate blood sample collections from rats without the use of anesthesia and anticoagulant is described. The surgical procedure consists of a bypass of the carotid via a cannula; this cannula forms a loop above the rat's head and is available for blood sampling. The method permits the investigation of high-frequency oscillations in blood components of rat.


Airway closure and closing volume.

Using boluses of radioactive Xe we compared regional N2O uptake with regional perfusion distribution during open glottis breath hold in five seated men. Measurements were made near residual volume, at closing volume (CV), above CV and when possible, between CV and residual volume (RV). At low lung volumes basal N2O uptake was small whereas basal blood flow was not. This discrepancy was interpreted as evidence of airway closure and was quantitated. All subjects showed extensive basal closure near RV. At closing volume four of five subjects demonstrated closure and some closure was evident in these subjects at volumes in excess of CV. The increase in airway closure with decreasing lung volume was much greater below CV than above it. Conventional CV tracings were obtained using helium boluses; the height of phase IV was positively correlated with the change in airway closure between CV and RV as assessed by the N2O technique. The slope of phase III did not correlate with the amount of airway closure measured at CV. We concluded that the conventionally measured CV is not the volume at which airway closure begins but that the onset of phase IV reflects an increase in basal airway closure and the height of phase IV reflects the amount of basal closure between CV and RV.


Unilateral pulmonary edema in rabbits after reexpansion of collapsed lung.

The effects of the mode of reinflation and of the duration of prior collapse on the development of unilateral pulmonary edema following reexpansion of collapsed lung were studied in a rabbit model simulating the human syndrome of "reexpansion pulmonary edema." The right lungs of rabbits were maintained in an atelectatic state for 0.5 h to 8 days, by injection of air into the pleural space. Reexpansion was achieved in 2 h by application of positive pressure to the airway while a chest tube was connected to underwater seal, or by application of negative pressure (-20 to -100 Torr) to a screened window in the partietal pleura. The lung surface pressures we actually applied by the two methods are not known. Animals were then killed and pulmonary edema was determined by wet-to-dry weight ratios. The incidence of unilateral pulmonary edema increased as the duration of prior collapse was increased (85% after 7--8 days; 17% after 3 days; and 0% after 0,5 h) when reinflated with -100 Torr applied to the pleural window. Although the incidence was less, it also occurred following the use of pleural window pressure less negative than -100 Torr, and after reinflation by positive airway pressure.


Effects of sitting up on pulmonary blood pressure, flow, and volume in man.

Pulmonary vascular pressure, blood flow, and blood volume were measured in the supine and sitting positions in eight subjects with localized lung carcinoma associated with moderate airway obstruction. Supine cardiac output, pulmonary wedge (Ppw) and artery (Ppa) pressure, and pulmonary vascular resistance (PVR) were normal. Circulatory changes in sitting position were also normal: heart rate increased 13 +/- 9% (mean +/- SD); stroke volume fell 21 +/- 15%; cardiac output fell 13 +/- 19%; and arteriovenous O2 difference increased 37 +/- 21%. Neither the difference between mean Ppa and mean Ppw nor the rise of PVR from 92 +/- 25 to 122 +/- 49 dyn.s.cm-5 in sitting position were significant. Pulmonary blood volume (PBV) as measured by a dye-bolus-injection technique fell from 517 +/- 122 ml supine to 360 +/- 43 ml sitting (P less than 0.01). This decrease is best explained by closure of alveolar vessels in the upper part of the lung and by the concomitant cessation of flow in corresponding extra-alveolar vessels, which would prevent distribution of dye in the region. Circumstantial evidence suggests the latter vessels remain open under the large expanding stresses that prevail in the upper lung.


Accentuated hypoxemia at high altitude in subjects susceptible to high-altitude pulmonary edema.

To investigate the hypotheses that activated coagulation, catecholamine release, or arginine vasopressin release are involved in the pathogenesis of high-altitude pulmonary edema (HAPE), we measured these variables in seven subjects susceptible to HAPE and in nine control subjects at an altitude of 1,600 m, and after 6 and 12 h at a simulated altitude of 4,150 m. Each subject was studied twice, once after 3 days of placebo medication and once after 3 days of premedication with aspirin and dipyridamole. At high altitude, HAPE-susceptible subjects showed significantly exaggerated hypoxemia and a slightly higher end-tidal carbon dioxide partial pressure that did not account fully for the hypoxemia. Fibrinolytic activity was significantly accelerated in both groups at high altitude, whereas other coagulation measurements, catecholamines and arginine vasopressin levels, and pulmonary function tests were not significantly changed. Similar findings were obtained after both placebo and platelet-inhibitor premedication. The results indicate that none of the three hypothesized mechanisms, i.e., activated coagulation, excessive catecholamine release, or antidiuresis, would account for HAPE susceptibility. Instead, HAPE-susceptible subjects exhibited exaggerated hypoxemia associated with relative hypoventilation and a widened alveolar-arterial gas pressure difference.


Estimating a distribution's central moments: a specific tidal ventilation application.

A method is presented for extracting central moments of a distribution from data generated by the distribution over a known kernel. It is applied to the problem of the specific tidal ventilation in the lung in the multiple-breath N2-washout setting, and we found that in estimating the mean and variance, the method accurately recovers from test data those values characteristic of a test distribution. Some preliminary results on normal subjects are shown.


Oxygen tensions measured in cat cerebral cortex under hyperbaric conditions.

Pyrenebutyric acid (PBA), the intracellular fluorescent indicator, was used to measure the partial pressure of oxygen (PO2) in the exposed cerebral cortex of anesthetized cats at hyperbaric pressures up to 4 ATA. The validity of the PBA method for determining cortical PO2 was confirmed by demonstrating a precise linear relationship between Pao2 and the reciprocal of the fluorescence of PBA in the brain as the cat was ventilated with sequentially greater oxygen pressures while holding the Paco2 nearly constant. Increments in the Paco2 while the Pao2 was maintained at a high (about 2,000 Torr) level resulted in stepwise greater oxygen tensions in the brain until an oxygenation end point was reached with a Paco2 averaging near 122 Torr. Greater amounts of CO2 did not bring the mean PO2 of the brain, 1,017 Torr, closer to 2,000 Torr. During normocapnia the cortical PO2 was greater than the PO2 of cerebral venous blood collected from the superior sagittal sinus; however, in hypercapnia (PaCO greater than 45 Torr), the PO2 of the sinus blood exceeded the value determined in the cortex. This latter observation is taken as evidence for convective shunting of cerebral arterial blood to venous circulation when hypercapnia is present.


Forced oscillatory respiratory parameters following papain exposure in dogs.

Respiratory mechanics were studied in nine intubated dogs before and after exposure to aerosolized papain under conditions known to produce emphysemalike lesions. Forced oscillatory resistance (RFO), compliance (CFO), and inertance (IFO) were computed from impedance data obtained at transrespiratory pressures of -10, 0 (FRC), +10, and +20 cmHWO. Dynamic compliance during tidal breathing (CTB) was also measured at FRC. After papain exposure CTB and CFO increased by 25% (P less than 0.05) at FRC and at +10 cmH2O. There were no consistent changes in RFO or IFO at FRC. However, RFO showed a greater dependency on transrespiratory pressure, which suggests that the elastic properties of airways may also have been affected by papain. Measurements made in open-chested papain-exposed animals showed that about 17% of total RFO and 20% of total elastance were attributable to the chest wall. Forced oscillatory impedance data are sensitive to experimental changes in lung mechanics and provide useful estimates of standard respiratory parameters.


Effects of lung volume on collateral and airways resistance in man.

The effects of changing lung volume (VL) on collateral resistance (Rcoll) and total airways resistance (Raw) were compared in six young volunteers. At functional residual capacity (FRC) = 55% total lung capacity (TLC), mean Rcoll was 4,664 +/- 1,518 (SE) cmH2O/(l/s) and mean Raw was 1.57 +/- 0.11 (SE) cmH2O/l/s). When VL increased to 80% TLC, Rcoll decreased by 63.3 +/- 7.8%, and Raw decreased by 50.3 +/- 4.2 (SE) %. The decrease in Rcoll with increasing lung volume was not statistically different from that of Raw (P less than 0.05). If the airways obstructed for measurements of Rcoll served between 2 and 5% of the lungs, then Rcoll was approximately 50 times as great as the resistance to flow through airways serving the same volume of lung at FRC. The relationship did not change significantly when VL increased by 25% TLC. If changes in Raw reflect changes in airways supplying sublobar portions of lung, these results indicate that there is no tendency for the redistribution of ventilation through airways and collateral pathways with changes in VL in young subjects.


Vascular and extravascular compartments of the isolated perfused rabbit lung.

The vascular, interstitial, and cellular compartments of 15 isolated, perfused and ventilated rabbit lungs determined by a steady-state indicator-dilution procedure. Five lungs were perfused with constant pulmonary artery flow and zero left atrial pressure for more than 1 h. Edema formation was continuous and pulmonary vascular volume (PVV) decreased initially at a time when pulmonary vascular resistance (PVR) was falling. Increases in PVR were not seen until edema formation had become severe. In 10 other lungs, increases in pulmonary artery or left atrial pressure resulted in elevation of PVV and accelerated edema formation. The initially abrupt increase in PVV was followed by a more gradual increase over a 10-min period. Return of fluid to the vasculature was never observed in these studies. Labeled albumin readily entered the extravascular space but a relatively constant fraction of the interstitium remained inaccessible to albumin. No changes were found in the cellular volume during edema formation.


A new definition of mechanical work done in human movement.

The definition of efficiency of human movement has often been unable to cope with activities such as level gait because the numerator of the efficiency equation includes only external work done by the body on an external load. The major purpose of this paper is to propose a definition that not only accounts for any external work but also the internal work done by the limbs themselves. The internal work involves a new biomechanical analysis that takes into account all potential and kinetic energy components, all exchanges of energy within and between segments, and both positive and negative work done by the muscles. This analysis was applied to a study of over-ground level gait on eight subjects walking at different walking speeds. The internal work/stride as calculated from the sum of segment energies was compared with the same calculation on the body's center of mass energy. The latter was found to be in error (low) by 16.2% and could be low by as much as 40%. The average internal work per body mass per distance walked was 1.09 J/kg.m.


Pulmonary hemodynamic responses to elevated cerebral spinal fluid pressure in the dog.

To investigate the possibility that a pulmonary vasomotor reflex contributes to the pulmonary hemodynamic response to elevated cerebral spinal fluid pressure (PCSF), we studied 10 chloralose-anesthetized dogs in which the left lower lobe (LLL) perfusion was isolated to eliminate the influence of passive factors and of circulating vasoactive agents. Left lower lobe neural integrity was tested by electrically stimulating the stellate ganglion. This resulted in a 35.5% increase in lobar vascular resistance and a 29.1% increase in systemic vascular resistance. Elevating the PCSF to 137 Torr caused the systemic vascular resistance to increase 33.0%, but resulted in no change in LLL vascular resistance. In the intact right lung, this PCSF elevation resulted in increases in pulmonary artery and left atrial pressures, but no change in right lung vascular resistance. Because the neurally intact LLL did not respond to PCSF elevation and the responses of the right lung could be accounted for by passive mechanisms, we conclude that no pulmonary vascular reflex was elicited by PCSF elevation in this preparation.


Responses of pial arterioles after prolonged hypercapnia and hypoxia in the awake rabbit.

The changes in the responsiveness of pial arterioles to CO2 and in the composition of cortical cerebrospinal fluid bathing these vessels were studied in the awake rabbit before and after 6 days exposure to hypercapnia (7% CO2) or hypoxia (10% O2). The vasodilator response of pial arterioles to inhalation of 3--10% CO2 was diminished after prolonged hypercapnia and enhanced after prolonged hypoxia. After both hypoxia and hypercapnia, pial arteriolar responsiveness to CO2 was immediately returned toward control levels by washing the brain surface with normal artificial cerebrospinal fluid. The bicarbonate concentration of cerebrospinal fluid bathing the pial vasculature showed a significant decrease after hypoxia and a significant increase after hypercapnia, whereas CSF pH remained unaltered. We conclude that the alteration in responsiveness of pial arterioles to CO2 is due to a change in the chemical composition of the CSF bathing these vessels, involving an adjustment in the concentration of bicarbonate ions.


Pulmonary arterial distension and activity in phrenic nerve of anesthetized dogs.

In chloralose-anesthetized dogs a constant-flow, right atrium-to-left pulmonary artery, right-heart bypass was created. The right lung root was completely occluded and an isolated pouch of the main pulmonary arteries was perfused with venous blood at controlled nonpulsatile pressures between 10 and 90 Torr. An increase in pulmonary arterial pouch pressure caused an increase in systemic arterial pressure and in respiratory drive. In animals with afferent nerves intact, the increase in respiratory drive was indicated by an increase in the amplitude of the integrated phrenic electroneurogram. In animals with the left vagus nerve cut immediately above the left lung root, the increase in respiratory drive was evident by a shortening of the time of expiration. All responses were abolished by bilateral section of the cervical vagosympathetic trunks. It is concluded that in the preparation described pulmonary arterial distension causes a reflex increase in systemic vascular resistance and in respiratory drive, the afferent path of the reflex being in the vagus nerves.


Effect of work-induced hypertrophy on skeletal muscle of tumor- and nontumor-bearing rats.

Synergistic muscles (soleus and plantaris) from a gastrocnemius-tenotomized hindlimb were compared to the same muscles in a sham-operated hindlimb in both tumor-bearing and non tumor-bearing rats. In nontumor-bearing animals muscle from the tenotomized hindlimb had a significant increase in wet weight (26%), percent-water (5%), and total nitrogen/muscle (10%) consistent with muscular hypertrophy. In tumor-bearing animals, muscle from the tenotomized hindlimb had a significant increase in wet weight and percent water, but there was no significant difference in total nitrogen/muscle. As the tumor burden increased, the final muscle weight, in both the tenotomized and sham-operated hindlimb, was found to decrease proportionately. Only in animals with large (23% body wt) tumor burdens did hypertrophied muscle weigh significantly less than sham-operated muscle from nontumor-bearing animals. This indicated that, in rats with large tumor burdens, work-induced hypertrophy was unable to preserve muscle mass despite the fact that hypertrophied muscle was 24% heavier than contralateral sham-operated muscle.


Demonstration of interlobar collateral ventilation.

In an ongoing series of experiments on mongrel dogs, three dogs were observed to have incomplete lobar fissures (interlobar connection present) between the left upper and left lower lobes. With the interlobar connection unclamped, selective hypoxia of the left lower lobe caused the electromagnetically measured blood flow to the left lower lobe to decrease 41 +/- 4%, whereas with the interlobar connection clamped selective hypoxia of the left lower lobe caused a 52 +/- 4% decrease in left lower lobe flow (P less than 0.05). Following 100% O2 ventilation and with the interlobar connection unclamped, complete occlusion of the left lower lobe bronchus caused no atelectasis or decrease in left lower lobe blood flow, whereas with the interlobar connection clamped complete occlusion of the left lower lobe bronchus caused complete left lower lobe atelectasis and a 58 +/- 3% decrease in left lower lobe blood flow. Histological confirmation of interlobar pulmonary parenchymal connection was obtained in each dog. We conclude that a sufficient amount of interlobar collateral ventilation can occur in dogs with incomplete lobar fissures to prevent absorption atelectasis and alter lobar blood flow reduction usually caused by selective lobar hypoxia.


Catecholamines in dogs during cold adaptation by repeated immersions.

Dogs were immersed in cold water 1 h/day for 30 consecutive days. During the first immersion, oxygen uptake increased approximately sevenfold and colonic temperature decreased; a large increase in plasma epinephrine and norepinephrine concentrations was found; plasma glucose, lactic acid, and free fatty acid (FFA) concentrations were also increased. An adaptative response to cold was evidenced during the 10th immersion by a further increase in oxygen uptake and a reduction in the fall of colonic temperature; plasma epinephrine, glucose, and lactic acid were diminished whereas FFA were higher. Consequently 10 h spent in cold are sufficient to induce an improved capacity for heat production. An enhanced ability to produce nonshivering thermogenesis mediated by epinephrine or norepinephrine is not obvious because after the 30th immersion no enhanced calorigenic response to epinephrine or norepinephrine infusion was found. In dogs mechanisms other than norepinephrine-enhanced sensitivity might be involved in this kind of cold adaptation.


Graded inspiratory inhibition: specific effects of flow rate.

The effect of inspiratory flow rate on graded inspiratory inhibition was examined in barbiturate-anesthetized paralyzed cats normally ventilated by a phrenic-driven servorespirator. Periodically, the animals were inflated, for a single breath, by a constant-flow volume ramp begun at one of several delays following phrenic onset. The phrenic activity during these volume-ramp test inflations was compared with phrenic activity in the absence of volume feedback. The relation between volume and phrenic inhibition was determined for two different flow rates. Inhibition of phrenic activity began when volume above functional residual capacity (FRC) exceeded a time-dependent threshold and, beyond this threshold, continued in a graded fashion. The threshold for the first detectable inhibition declined as inspiratory time progressed both in intact animals and in pneumotaxic-lesioned animals when phrenic activity reached an apneustic plateau. Inspiratory inhibition was associated with similar lung volume above FRC regardless of whether volume resulted from high or low flow rates, suggesting that the processing of the receptor feedback information offsets flow effects on receptor firing.


Intermittent flow in tendon capillary bundles.

The capillary bed has been observed in the Achilles tendon of 40 bullfrogs and 10 guinea pigs for periods of up to 2 h. The opening and closing of adjacent capillaries in a perfused area follows the pattern originally described by Krogh for skeletal muscle but the frequency is slower, as anticipated from the lower metabolic rate of tendon. However, superimposed on this "flickering is a much slower process whereby whole bundles of 20-147 capillaries open and close with little overlap in the tissue areas perfused by each. Periods of no flow averaged 39 min in 70 bundles followed in bullfrogs and 43 min in 34 bundles followed in guinea pigs, although a few failed to open in 100 min. This bundle phenomenon is discussed in relation to the serious implications in mathematically modeling the exchange of gases and nutrients between blood and tissue and the possible errors in assuming time averaging when determining blood perfusion rates. Also mentioned are the likely effects of decompression on closed bundles and the notion is introduced that the bundle phenomenon may be a factor determining which tissues can be injured by decompression.


Fluid shifts during initial phase of immersion diuresis in man.

The object was to study fluid shifts in man during the 1st h of immersion diuresis. Control experiments were done on subjects lying down in air for 4 h with and without vasopressin. During immersion up to the neck, seven of nine subjects had significant diuresis and natriuresis. In the first 20 min of sitting in 33 degress C water, a hemodilution of 2% of blood volume was observed. As diuresis progressed, hemoconcentration began. When vasopressin was given just before immersion to prevent the diuresis, the hemodilution observed was greater and lasted longer. Thus the hematocrit fell by 1.7 U, plasma osmolality by 6.0 mosmol/kg, plasma proteins by 0.33 g/100 ml, and plasma sodium by 5.0 meq/l. We conclude that a hemodilution of about 4% of blood volume occurs during the early plasma of immersion and the degree of hyposmolality observed suggests that the fluid shifted was more hyposmotic than the interstitial fluid alone, possibly because some intracellular water may have shifted into the bloodstream during immersion.


Respiratory mechanics in recumbent dogs anesthetized with thiopental sodium.

Pressure-volume (PV) and conductance-volume (GV) curves were obtained in trained dogs awake and then anesthetized with thiopental sodium, in the prone left lateral decubitus, and supine positions. By paired analyses, induction of anesthesia had no significant effect on lung volumes, static PV curves of the lung or chest wall, or static compliance of the lung or chest wall. In addition, change of posture had little effect on these variables in either the awake or the anesthetized state. Frequently, however, individual dogs showed changes in lung PV curves after induction of anesthesia or change of posture. These PV curve shifts were not accompanied by predictable changes in GV relations. Therefore, we concluded that such changes in the lung PV curve reflect either local artifacts or local deformation of the respiratory system.


Training-induced changes in hormonal and metabolic responses to submaximal exercise.

Plasma glucagon and catecholamines increase during prolonged submaximal exercise, but the magnitude of the increase is less in endurance-trained individuals than in untrained subjects. We have studied the rapidity at which this adaptation occurs. Six initially untrained healthy subjects exercised vigorously (on bicycle ergometers and by running) 30-50 min/day, 6 days/wk, for 9 wk. Prior to the beginning of training and at 3-wk intervals thereafter, participants were subjected to 90-min bicycle ergometer test work loads that elicited 58 +/- 2% of the subjects' initial maximal oxygen consumption. The major proportion of the training-induced decrement in plasma glucagon and catecholamine responses to exercise was seen after 3 wk of training. We conclude that the hormonal component of the training adaptation occurs very early in the course of a vigorous endurance training program.


A neuromuscular mechanism maintaining extrathoracic airway patency.

The ability of the extrathoracic airway (ETA) to remain open when exposed to negative pressure was investigated in rabbits. Postmortem, the ETA collapsed at -6.3 +/- 0.6 cmH2O whereas, during airway occlusion maneuvers in lightly anesthetized animals, it remained patent at pressures as low as -80 cmH2O. This discrepancy suggested that a neuromuscular mechanism maintains ETA patency. Four findings indicated that the genioglossus and geniohyoid muscles, which pull the tongue and hyoid bone anteriorly, help maintain ETA patency: 1) anterior movement of the hyoid bone increased the negative pressure at which the ETA collapsed postmortem, 2) ETA closure during occluded inspirations occurred after 12th nerve section abolished electromyographic activity in these muscles and 3) after deep anesthesia depressed such activity, and 4) closing pressure was linearly related to peak integrated electromyograms of the two muscles. After 12th nerve section, ETA closing pressure became more negative with progressive asphyxia greatly exceeding postmortem closing pressure, which suggests that other muscles also help maintain ETA patency. Blood gas tensions, respiratory system mechanoreceptors, and depth of anesthesia appear to influence genioglossus and geniohyoid activity.


Body carbon dioxide storage capacity in exercise.

Body CO2 storage capacity was measured in nine subjects at two levels of exercise, approximating 30 and 60% VO2max, by measuring the excess CO2 output associated with hyperventilation at constant end-tidal PCO2, and the change in mixed venous PCO2 (PVCO2) measured by rebreathing. CO2 output was measured during 20-s periods and monitored throughout the procedure; hyperventilation was continued until CO2 output had returned to control values. Washout of CO2 was more rapid than previously found at rest, 90% of the change following an increase in ventilation occurring within 4 min. CO2 storage capacity was 1.83 +/- 0.552 (SD) ml-kg--1.Torr--1 at the lower power output and 1.19 +/- 0.490 ml-kg--1.Torr--1 at the higher power output. The CO2 storage capacity was inversely related to PVCO2. It was concluded that the body's capacity to store CO2 decreases with increasing PVCO2; this may be one factor leading to the progressive increase in pulmonary CO2 output at high levels of exercise.


Effects of chronic changes in hemoglobin-O2 affinity in rats.

We have assessed the characteristics of oxygen transport following chronic intraperitoneal administration of sodium cyanate (NaCNO, 90 mg/kg; P50 decreased), o-iodosodium benzoate (OISB, 300 mg/kg; P50 increased), or sodium chloride (NaCl; P50 unchanged) to rats at a rate of 5 times/wk for 16 wk. At the end of this period, the animals were exposed to a low inspired O2 concentration and were subjected to exercise stress. Hill's n50 at pH 6.90-7.60, hematocrit, and the saturation dependency of the Bohr effect (PCO2 constant) were altered by NaCNO only. Cyanate-treated rats gained less weight, probably due to a toxic side effect of the drug. Hypoxemia-induced lactatemia was greatest with a high P50 (OISB). Physical effort (swimming) was tolerated poorly at normal arterial PO2 when P50 was low (NaCNO). Although a left-shifted curve appears beneficial when FIO2 is reduced, reasons for the physiological advantage may be the result of other characteristics of the O2 dissociation curve, not P50 alone.


Acute hypertrophic response of skeletal muscle to removal of synergists.

The purpose of this project was to study the initial rapid enlargement phase of skeletal muscle in response to ablation of synergistic muscles. The first experiment tested the hypothesis that this initial phase is due to inflammation in the enlarging muscle. The wet weight of the plantaris muscle increased significantly (14%) within 1 h after removal of the ipsilateral gastrocnemius muscle. This increase was due to inflammation, as evidenced initially by edema, and within the next few hours, by leukocyte invasion of the interstitium and enhanced hexose monophosphate shunt-reducing capacity. In the second experiment we followed the time course of this inflammatory reaction. The response peaked at 1-5 days following surgery, after which it subsided to control levels by 16 days postsurgery. The final experiments were designed to uncover the factor(s) causing the inflammatory response. Two possible mechanisms were hypothesized: 1) trauma resulting from surgical manipulation of the tissue, and 2) trauma due to elevated stretch and/or tension on the muscle following removal of the synergists. The data indicate that surgical trauma is the causative factor of the inflammatory response in this hypertrophy model.


Fecal fat and trypsin in dogs fed a meat-base or cereal-base diet.

Fat balance studies and quantitative analysis of fecal trypsin were done on 2 groups of Beagles fed either a meat-base (8.8% fat) or a cereal-base (10.5% fat) diet. In the amount fed, the meat-base diet provided 2.5 to 3 times more fat than the cereal-base diet, yet the mean daily fecal fat output of the 2 groups was not significantly different. Thus the percentage assimilation of fat in cereal-base diet (90.0%) was significantly (P less than 0.01) lower than that in the meat-base diet (96.9%). Dietary composition made no significant difference in fecal trypsin output, although the mean output from dogs fed the meat-base diet 4 times higher than that from dogs fed the cereal-base diet.


Determination of fecal fat and trypsin output in the evaluation of chronic canine diarrhea.

Quantitative fat and trypsin analysis was done on the feces of dogs with chronic diarrhea. The results of clinical examination, quantitative fecal analysis, and other laboratory tests permitted assignment of the dogs into one of 4 groups: (1)pancreatic exocrine insufficiency,(2)small intestinal malabsorption,(3)colitis, and(4)other nonspecific or incompletely diagnosed diarrhea. The mean 24-hour fat output was significantly higher (p less than 0.01) in dogs with malabsorption or pancreatic insufficiency than in clinically normal dogs, dogs with colitis, or dogs with nonsteatorrheic diarrheas. The mean 24-hour trypsin output with pancreatic insufficiency was significantly (P less than 0.01) lower, and in dogs with malabsorption, significantly (P less than 0.05) higher than in clinically normal dogs. Normalization of the output data for body weight enhanced the value of fat and trypsin analyses in the differentiation of pancreatic insufficiency and intestinal malabsorption from other causes of chronic canine diarrhea.


Primary hyperparathyroidism in a dog.

A 6-year-old male Standard Poodle had hypercalcemia, hypophosphatemia, and a urinary concentrating defect. A parathyroid adenoma involving the left caudal parathyroid gland was surgically removed. Transient hypocalcemia followed, which resolved without treatment. A renal biopsy did not demonstrate renal parenchymal mineral deposition. Urinary concentrating ability returned after surgery.


Colorectal polyps of the dog: a clinicopathologic study of 17 cases.

Seventeen cases of colorectal polyps in the dog were seen at the Ontario Veterinary College over a 12-year period. The mean age of occurrence was 6.9 years, and males and females were almost equally affected. The Collie was the most frequently affected breed (4/17). The clinical signs were typically dyschezia, periodic intermittent diarrhea and melena, and rectal prolapse of the polyp. The histopatholic classifcation were hyperplastic polyp (1), papillary adenoma (1), tubular adenoma (4), papillotubular adenoma (10), and unclassified (1). Severe epithelial atypia, likely carcinoma in situ, was apparent in 5 of the papillotubular adenomas. Retrospective analysis of survival data after polypectomy suggested a good prognosis, but the results were inconclusive and it is possible that some of the polyps represented premalignant lesions. Large polyps (greater than 1 cm in diameter) frequently had marked epithelial atypia and were considered more likely to recur or to become malignant.