On the presence of bilirubin in the ocular humors of premature infants. The yellow pigments observed in the ocular humors of premature infants were identified as the plasma pigments bilirubin and oxyhemoglobin. The blood/vitreous humor barrier to bilirubin was estimated to be (1/0.11) for total bilirubin and (1/0.25) for direct-acting bilirubin. Hall method histochemical staining for bilirubin in sections of premature infant eyes was highly positive for the vitreous humor, and suggestive of uptake of bilirubin by the neural-retinal cells.


Mechanism of "hypoglycemic" cataract formation in the rat lens. II. Further studies on the role of hexokinase instability. In Part I1 of this study, the thermolability of lens hexokinase was implicated in the development of an experimental "hypoglycemic" cataract. After eight hours of glucose deprivation, there is a precipitous loss of lens hexokinase. This occurs approximately nine hours prior to the disorganization of the other enzymatic steps in glycolysis. Epithelial hexokinase, as an immediate response to glucose deficiency, shifts from the soluble to the insoluble phase. There is no such shift in the cortex-nucleus where only soluble hexokinase is found. After eight hours of glucose deprivation, both soluble and insoluble hexokinases throughout the lens undergo rapid deactivations. During the first eight hours of glucose deprivation the loss of lenticular ATP and K+ and the gain in wet weight can be reversed by restoring normal glucose levels; beyond eight hours the changes are irreversible. During the period of reversibility, hexokinase activity levels are normal; during the period of irreversibility hexokinase activity is 10 to 20 per cent of normal. Of the substances tested (mannose, galactose, fructose, glutamine, adenosine) only mannose could sustain the lens in the absnece of glucose. Neither endogenous free glucose nor glycogen could sustain the lens in the face of glucose deprivation. There appear to be no alternative exogenous or endogenous energy yielding substrates. The younger the animal, the more susceptible is its lens to glucose deprivation. This most certainly is a reflection of the increased susceptibility of younger lenses to osmotic stress, since lenses in each age group manifested similar changes in hexokinase activity, ATP, Na+, and K+ level.


Identification of A and B forms of monoamine oxidase in the iris-ciliary body, superior cervical ganglion, and pineal gland of albino rabbits. The properties of monoamine oxidase activity in homogenates of the iris-ciliary body, superior cervical ganglion, and pineal gland of albino rabbits have been studied. Inhibition curves using specific inhibitors support the concept of A and B enzyme forms, with the following ratios of A/B activity: iris-ciliary body, 40/60; superior cervical ganglion, 90/10; pineal gland, 13/87. Experiments on enzymes from animals with superior cervical ganglionectomy indicate that both A and B forms in the iris-ciliary body have a predominantly extraneuronal location. No significant differences in activity were observed between iris-ciliary body preparations from normal and denervated animals with substrates specific for A or B forms, or with substrates deaminated by both A and B forms. With tryptamine as substrate the iris enzyme can be inhibited by a variety of common monoamine oxidase inhibitors. Topical application of the inhibitor pargyline lowers intraocular pressure in the normal rabbit eye but not in the sympathetically denervated eye. This observation and in vitro data suggest that the mechanism of action of pargyline is through the adrenergic system and not dependent upon intrinsic activity.


Keratoconjunctivitis associated with sialodacryoadenitis in rats. A high incidence of keratoconjunctivitis was observed in a closed colony of inbred Lewis/Wistar rats. Clinical signs including blinking, ocular discharge, circumcorneal flush, corneal opacity, ulceration, pannus, hypopyon, and hyphema were observed at about three weeks of age. Acute disease subsided by six weeks of age, but some lesions progressed to low-grade chronic keratitis. Six per cent of affected rats developed megaloglobus, which usually appeared by three weeks of age. Lesions included focal or diffuse interstitial keratitis, corneal ulceration, anterior synechia, and inflammatory exudate in the anterior chamber. A high incidence of lenticular and retinal degeneration was associated with megaloglobus. Most affected rats also had harderian dacryoadenitis. Sialodacryoadenitis virus (SDA) was recovered from nasal washes, but not from affected eyes. Serological evidence indicated that SDA virus infection was widespread in the colony.


Corneal glycogen synthesis. I. Evidence for a gluconeogenic pathway in beef cornea. Beef eye anterior chambers were perfused with media containing radiolabeled glycogen precursors. Incorporation of 14C from 1-alanine-U-14C into corneal epithelium glycogen suggested the presence of a gluconeogenic pathway in the eye. Failure to isolate radioactive glucose from 1-alanine-U-14C-containing perfusate after passage through the anterior chamber strongly suggests a corneal site for this pathway.


Hydrostatic pressure effects on deswelling of de-epithelialized and de-endothelialized corneas. The effects of varying hydrostatic pressure on the thinning rate of preswollen de-epithelialized or de-endothelialized corneas has been determined in the specular microscope. The appropriate membrane was removed, the cornea given access to Ringer to swell, and then fluid exchange at that surface blocked with oil. De-epithelialized corneas thin more slowly as hydrostatic pressure on the posterior surface is increased, until fluid movement ceases at 60 to 70 mm. Hg. Fluid movement can occur, therefore, against a considerable hydrostatic pressure. De-endothelialized corneas thin at a higher rate as hydrostatic pressure is increased; this effect is probably a mechanical one with increasing pressure forcing fluid out across the epithelium.


Automatic recording of corneal thickness in vitro. An addition to the specular microscope is described which allows it to record the thickness of the excised cornea automatically as a function of time. The focus of the instrument is scanned mechanically through the tissue, and the position of the reflecting surfaces is detected by a photo-electric system and marked on a chart recorder. The system is able to follow thickness changes over periods of many hours and with an accuracy greater than obtainable by manual operation. This system has been helpful in the evaluation of a new medium which considerably extends the useful lifetime of the corneal endothelial fluid pump.


Etiology of corneal striae accompanying hydrogel lens wear. Vertical striae in the posterior cornea were produced experimentally in ten human subjects by depriving the anterior corneal surface of its normal oxygen supply and inducing corneal edema. These striae were similar in appearance and time of occurrence to those observed in gel lens wearers. Three subjects also wore gel lenses and developed vertical striae while wearing their lenses. These striae were eliminated by increasing the oxygen concentration at the anterior lens surface. The data confirm many clinical observations which have suggested that verical striae are caused by corneal edema accompanying gel lens wear.


Teratogenicity of adenine arabinoside (Ara-A). The potentially teratogenic effect of antiviral drugs, particularly when given systemically, prompted the evaluation of the teratogenic effect of Ara-A when given systemically in doses significantly higher than those used clinically. Under the conditions of this study, neither teratogenic nor embryocidal effects of Ara-A were observed.


Cycloscopy and fluorescein cycloscopy.

Cycloscopy and fluorescein cycloscopy. A biomicroscopic technique for observation of the ciliary process was developed, and cycloscopy and fluorescein cycloscopy have been done as a routine clinical examination. The observations reported here show that a great, previously unimaginable variety of changes in the ciliary process is the usual sequel of congenital or acquired disorders. Fluorescein was seen to leak mainly from the "summit" of the ciliary process in the normal eye. Little or no leakage from the rudimentary ciliary process was seen in cases of aniridia, while vigorous leakage occurring in inflammation or uveal effusion was of particular clinical importance.


The contralateral effect of antidromic stimulation of the trigeminal nerve on the rabbit eye. The effect on contralateral eyes after injuries to one eye has been called the consensual reaction and has been postulated to be either the consequence of a neural reflex or one achieved by circulating substances. Trigeminal stimulation always causes ipsilateral miosis, ocular hyperemia, intraocular hypertension, and a disruption of the blood-aqueous barrier. Disruption of the blood-aqueous barrier in the contralateral eye after stimulation of the trigeminal nerve always occurs and depends on intact sensory innervation to that globe in rabbits. The disruption is not prevneted by pretreatment of the animals with indomethacin. The phenomenon of disruption of the barrier is sometimes accompanied by an elevation of intraocular pressure in the contralateral eye but not by the other irritative responses. Thus, unilateral stimulation of a sensory nerve, the trigeminal, in the rabbit, can produce ipsilateral contralateral disruption of the blood-aqueous barrier.


Analysis of clonidine-induced mydriasis. In addition to its centrally mediated hypotensive action, clonidine causes a decrease in intraocular pressure associated with a long-lasting mydriasis. The present study was conducted to determine to what extent this drug-induced pupillary dilation is of central or peripheral origin. Pupil size was observed in cats anesthetized with pentobarbital. Clonidine (1 to 100 mug per kilogram, intravenously) resulted in a dose-dependent increase in pupillary diameter in intact as well as sympathectomized preparations. These same doses of clonidine produce no effect on the eserinized, parasympathectomized iris. Epinephrine administration (0.1 to 30 mug, intra-arterially) produced an equivalent pupillary dilation in all preparations. In addition, clonidine caused a dramatic decrease in postganglionic ciliary nerve activity and both the decreased nerve activity and pupillary dilation were reversed by intravenous administration of yohimbine hydrochloride. These results suggest that the inhibition of parasympathetic tone by clonidine may involve a central adrenergic inhibitory mechanism.


Sulfated glycolipids in ciliary body epithelium. The sulfated material which locates in the basal membrane of ciliary body epithelium when immature rat eyes are incubated with Na235SO4 was studied. On the basis of its chromatographic behavior compared with standard preparations, we conclude that the material consists of sulfatides.


Rod disc turnover in the dog.

Rod disc turnover in the dog. Tritiated l-leucine was injected intravitreally into normal adult dogs to study rod outer segment renewal. Eyes were removed at various times after injection and the retinas prepared for light microscope autoradiography. Rod outer segment disc turnover was found to be similar to other species, i.e., discs were produced at the base of the outer segments and migrated sclerad with time. The time for turnover averaged 6 days. Cone outer segments never showed banding of the labeled protein but rather a diffuse label such as reported in other species.


Vascularity in the reptilian spectacle.

Vascularity in the reptilian spectacle. Vascularization of the spectacle or brille of the reptile was demonstrated by biomicroscopy, histology, fluorescein (in vivo), and Microfil silicone rubber (in situ) injections. This unusual vascularity provides new evidence for reassessment of the origin and development of this structure, and a useful tool with which to do so.


Regional ventricular dysfunction in coronary artery disease. Percentage asynergy, ejection fraction (EF), left ventricular end diastolic pressure (LVEDP) and the site of coronary artery narrowing or obstruction were measured in 69 patients with significant coronary artery disease. Complete obstruction in the first third of the left anterior descending artery (LAD) produced a mean asynergy of 49% associated with an ejection fraction of 40% and a LVEDP of 19mm Hg. The extent of asynergy was modified by the nature of the underlying coronary artery anatomy and the protective circulation. Complete obstruction in the main right coronary artery produced a mean asynergy of 20% associated with an EF of 67% and LVEDP of 6 mm Hg. Complete obstruction in the first third of the circumflex artery produced a mean asynergy of 15% associated with an EF or 74% and LVEDP  of 14mm Hg. Subtotal obstruction in the first third of the LAD produced a mean asynergy of 25% associated with an EF of 62% and LVEDP  of 7mm Hg. The damage produced by a LAD obstruction was extensive while that of a right or circumflex obstruction was mild. Patients always had a high percentage asynergy after two episodes of myocardial infarction. A negative linear relationship was found between percentage asynergy and EF. There was a rough positive linear relationship between LVEDP and percentage asynergy.


Glucose and insulin responses to an oral glucose load in normal children and adolescents in Israel. Sixty-three normal, healthy children and adolescents (39 males and 24 females) ranging in age from 2 to 20 years, were given a standard oral glucose tolerance test. A tendency to higher blood glucose levels and a statistically significant increase in insulin levels were found in the older age group in response to the glucose load. The older age group showed a significantly higher response of both glucose and insulin when separate percentile curves for prepubertal and pubertal boys and girls were constructed. No statistical differences were found between the sexes. Our findings demonstrate the necessity of applying norms for the oral glucose tolerance test according to age, particularly with respect to insulin values. The possibility of additional differences in response among various populations, as apparent from a comparison with the results of several other investigators, requires further study.


Height and weight of children born to mothers with diabetes mellitus. Height and weight measurements in a group of 55 children born to mothers with juvenile, adult-onset or gestational diabetes mellitus showed that the children born to parents of European or American origin were taller than average. The talles children were those born to mothers with juvenile diabetes mellitus. The distribution of weight-height indexes followed a normal pattern.


Transient neonatal hyperparathyroidism associated with maternal hypoparathyroidism. The newborn infant of a mother with hypoparathyroidism following thyroidectomy showed transient hypercalcemia and hypermagnesemia. Hypophosphatemia, as found in adult hyperparathyroidism, was not noted in this case, or in three of five other reported cases of neonatal hyperparathyroidism secondary to maternal hypoparathyroidism.


Colonic atresia associated with Hirschsprung's disease. A rare case of an infant with both atresia of the colon and Hirschsprung's disease is described. The diagnosis of Hirschsprung's disease was fortuitously made on histological examination of the resected colon. The importance of being aware of the possibility that these two conditions may coexist is stressed.


Human ocular dirofilariasis in Israel.

Human ocular dirofilariasis in Israel. This is the first report of human ocular dirofilariasis in Israel. A single female worm, Dirofilaria (Nochtiella) conjunctivae, was removed from an eye of each of two male patients. In the first case the worm was dead upon removal. It had penetrated into the sclera and was lodged in a subconjunctival abscess. In the second case, the worm was alive and located superficially in a slight swelling near the inner canthus. Surgical removal of the worms under local anesthesia was followed by complete recovery in both patients, with no impairment of vision.


Objective instrumental memory and performance tests for evaluation of patients with brain damage: a search for a behavioral diagnostic tool. Cognition and performance of patients with localized and diffuse brain damage was evaluated through the application of objective perceptual testing. A series of visual perceptual and verbal tests, memory tests, as well as reaction time tasks were administered to the patients by logic programming equipment. In order to avoid a bias due to communicative disorders, all responses were motor, and achievement was scored in terms of correct identification and latencies of response. Previously established norms based on a large sample of non-brain-damaged hospitalized patients served to standardize the performance of the brain-damaged patient since preliminary results showed that age and educational level constitute an important variable affecting performance of the control group. The achievement of brain-damaged patients, corrected for these factors, was impaired significantly in all tests with respect to both recognition and speed of performance. Lateralized effects of brain damage were not significantly demonstrated. However, when the performance was analyzed with respect to the locus of visual input, it was found that patients with right hemispheric lesions showed impairment mainly on perception of figurative material, and that this deficit was more apparent in the left visual field. Conversely, patients with left hemispheric lesions tended to show impairment on perception of visually presented verbal material when the input was delivered to the right visual field.


Incidence and forms of EPH gestosis in twin pregnancy. An increased incidence of EPH gestosis in twin pregnancies is frequently reported. During the past 12 years, 188 women gave birth to twins in our hospital. For these mothers, the incidence of EPH gestosis on admission was 42.5%, in contrast to 31.4% for a control group matched for age, parity and nationality. EPH gestosis occurring in twin pregnancies was more severe than that in single pregnancies.


Midtrimester preeclamptic toxemia in triploid pregnancies. Nineteen advanced triploid pregnancies reported in the literature are reviewed. In 8 of 14 pregnancies for which reliable data were available, severe preeclamptic toxemia (EPH gestosis) developed, most often from the 16th to the 24th week of gestation. In all the toxemic cases, the placenta was large for the stage of pregnancy, the placental coefficient was high (mean 0.83) and extensive areas of molar degeneration were present. Advanced triploid pregnancy is considered a further example of hyperplacentosis causing preeclamptic toxemia. The study of toxemic and nontoxemic advanced triploid pregnancies supports the assumption that hyperplacentosis, rather than being related to excessive placental size, is the expression of trophoblastic hyperactivity.


EPH gestosis in Glasgow, 1970.

EPH gestosis in Glasgow, 1970. Perinatal deaths due to EPH gestosis which occurred in Glasgow during 1970 were studied. There was a high frequency of perinatal deaths among babies born to primigravidae below the age of 20 years and to mothers with proteinuria. The majority of the deaths occurred in babies weighing less than or equal to 2,500 g. It is suggested that some of the deaths were avoidable and that a further reduction in perinatal mortality can still be achieved.


Transplacental effects of thyrocalcitonin on intestinal calcium-binding protein, alkaline phosphatase activity and ossification of long bones in rat fetuses. Pregnant rats were treated with 44, 88 and 176 Medical Research Council munits of thyrocalcitonin (TCT) twice daily during days 10 to 21 of gestation. Nonpregnant rats received the same treatment for 12 days. Administration of TCT to the pregnant rats increased the ash and calcium content of fetal bones and decreased the phosphorus content. The diaphyses were short and contained many persisting enchondral trabeculae and a reduced number of osteoclasts. TCT reduced the fetal intestinal alkaline phosphatase activity but elevated the intestinal calcium-binding protein content. In the pregnant and nonpregnant rats, treatment with TCT resulted in hypocalcemia and hypophosphatemia, and increased the calcium-binding protein content of the duodenal mucosa. In the fetuses, the calcium-binding protein content and alkaline phosphatase activity were higher in the jejunum and ileum than in the duodenum, and were much higher than the values found in adult animals. Our findings indicate that TCT passes through the rat placenta and affects the fetal skeleton and calcium metabolism directly, resulting primarily in decreased bone resorption.


Absorption of ampicillin derivatives from the bovine udder. The rates at which ampicillin, amoxycillin, metampicillin, hetacillin, and pivampicillin are absorbed from the bovine udder were compared, with the absorption rate of (14C)urea as reference. Straight-line semilogarithmic plots of the percentage of unabsorbed drug against time were obtained, suggesting first-order kinetics for the absorption process. Ampicillin, metampicillin and hetacillin were most slowly absorbed. Amoxycillin was absorbed twice as fast as ampicillin. Pivampicillin was absorbed most rapidly-at more than three times the rate of ampicillin.


[Response of collagenous tissue to pigmented tumors]. Using microradiograms (x-rays of histological sections) and polarized light, we examined collagenous tissue surrounding junctional nevi, benign juvenile melanomas, Dubreuilh's melanosis and early malignant melanomas similar to junctional nevi. Wherever there were tumor cells and infiltrates the collagenous tissue was reduced or destroyed, but had not usually been pushed aside as claimed in previous accounts. The absence of a connective tissue membrane, comparable to the border-zone beneath the epidermis, argues against a nevus. Mature collagenous bundles are clearly shown up by microradiograms and by pollarized light. The degree of thier destruction does not make it possible to distinguish between nevi and malignant melanomas.


[Allergic delayed reactions of the skin: the role of the antigen histotopy]. Delayed skin reaction to tuberculin were elicited in 10 healthy persons by patch testing and intracutaneous application of the antigen (Tine-Test). Biopsies revealed basically identical tissue reactions. After intracutaneous injection of the antigen as well as after Tine-testing the changes were solely found in the dermis, while after patch testing dermal and epidermal alterations were prominent. The type of response elicited by the same allergen in man-the so called tuberculin type of the eczematous type-therefore are due to a differential localization of the antigen.


Demonstration of agglutinating antibodies against Vibrio parahaemolyticus in the yellow tail flounder (Limanda ferruginea). Sera from the salt water fish (Yellow tail flounder) and the fresh water fish (rainbow trout) were tested for the presence of circulating antibodies against nine strains of Vibrio parahaemolyticus and one of V. alginolyticus. Thirteen out of 26 flounder sera tested gave agglutinating reactions against one specific strain of V. parahaemolyticus; strain No. 3525. Seven rainbow trout sera tested failed to agglutinate any of the strains tested. All agglutinating activity was lost upon boiling the antigen, therefore, the fish antibodies are due to surface antigens (K-antigens) and not to somatic antigens. The specific V. parahaemolyticus strain No. 3525 belongs to the serological type 03:K30, which might be common to the sea waters of the Eastern United States. The possibility that fish serve as a reservoir to Vibrio parahaemolyticus and its possible implication in the transmission of human disease are discussed.


Field evaluation of the Becton-Dickinson SST. The Becton-Dickinson VACUTAINER BRAND SERUM SEPARATOR TUBE (SST) was evaluated in a field test in five hospitals. The SST evacuated blood drawing tube contains a semi-solid silicon polymer which migrates to the serum-clot interface during centrifugation causing a barrier to form which separates serum from red cells. Eighteen clinical chemistry determinations were studied. No clinically significant SST induced changes were observed when compared to conventional blood drawing tubes. Statistically significant changes (t-test, p=0.05) were observed for bicarbonate, calcium, chloride, cholesterol, glucose (Beckman Analyzer), and sodium. For each test (glucose, uric acid, etc.) data were analyzed twice; once as a complete set, and once as a subset consisting of abnormal data only. The small, statistically significant LDH bias observed in the earlier (2,3) clinical trials was not present.


Internal circuit noise of hearing aids and speech intelligibility. The circuit noise generated internally by various components of a hearing aid is influenced mostly by circuit gain and frequency response. The measurement of this variable and its effect, if any, on the listener's ability to unders-and monosyllabic words through a hearing-aid system was investigated. The overall circuit noise of 10 behind-the-ear hearing aids of different brands with comparable gain and frequency response was measured. Based on these measurements, a low-noise and a high-noise hearing aid were selected as the test aids. The internal circuit noise of each test aid was then measured automatically by utilizing a 1/3-octave-band tracking filter. Monosyllabic words were recorded through the test aids at two gain settings. The prerecorded test tapes were presented to 32 normal-hearing listeners. Findings indicate that different amounts of circuit noise generated internally by a hearing aid do exist among various aids. However, the noise generated by the hearing aids used in this study does not affect significantly the intelligibility of monosyllabic words.


Relation between lateralization and loudness in asymmetrical hearing losses. The purpose of these experiments was to study the role of interaural intensity and loudness differences in median-plane lateralization. Observers who either wore an earplug in one ear or had an asymmetrical hearing loss varied the intensity of simultaneous tone bursts at the two ears to center a sound image inside their heads. Hard-of-hearing Ss with conductive and cochlear losses centered the tone bursts by setting them somewhere between equal intensity and equal loudness at the two ears. Although Ss with the simulated loss first centered the tones on the basis of equal loudness, after several days of wearing the ear plug, they centered in the same manner as observers with long-term hearing losses.


Relative efficiency of warbled-tone and conventional pure-tone testing with children. Thirty-four normal-hearing 4-year-old children were tested with conventional steady-state pure tones and with warbled tones to compare efficiency of the stimuli. Three measures of efficiency were used: (1) amount of time to train a child to perform the experimental task; (2) amount of time required to obtain thresholds; and (3) number of ascents used for obtaining thresholds. The strong implication by the literature that warbled tones would result in greater clinical efficiency was not supported by the comparisons of the experimental measures. It was concluded that convincing evidence to persuade the audiologist to select warbled over conventional steady-state pure tones for testing children was lacking.


Aided and unaided narrow band noise thresholds in listeners with sensorineural hearing impairment. This study explored the relationship between narrow band noise thresholds obtained under aided and unaided conditions with normal listeners and with subjects demonstrating sensorineural hearing impairment. Pure-tone and narrow band noise thresholds obtained under earphone conditions were found to approximate each other within 3 dB. Mean noise thresholds obtained in sound field required less sound pressure than thresholds obtained under earphone conditions. In comparing the predicted aided noise thresholds with the observed thresholds, a 4-dB mean difference was found. The close relationship between hearing aid acoustic gain and changes in aided narrow band noise thresholds suggests the use of narrow band noise audiometry in hearing-aid selection when traditional measures cannot be used.


Linguistic background and test material considerations in assessing sentence identification ability in English- and Spanish-English-speaking adolescents. This study investigated the influence of linguistic background differences on sentence identification by groups of English- and Spanish-English-speaking adolescents. Subjects were required to identify recorded meaningful and nonmeaningful (synthetic) sentences presented in a white noise background using a closed message set-response format. The results indicate that linguistic background variables significantly influence sentence identification ability and that these variables are not adequately controlled for by a closed message set. A significant difference in the ability to identify meaningful and nonmeaningful sentences was revealed. Contrary to previous indications, synthetic sentence identification appeared to be contingent upon key work or phrase recognition.


Megakaryocytic myelosis in a cat.

Megakaryocytic myelosis in a cat. A myeloproliferative disorder in a cat was characterized by abnormal proliferation of megakaryocytes in the bone marrow and by severe, nonregenerative anemia. The number of circulating thrombocytes was increased markedly, with many giant and morphologically bizarre forms. Terminally, the circulating blood contained large numbers of undifferentiated blast cells. The spleen and liver were infiltrated by megakaryocytes and mononuclear mesenchymal cells of uncertain identity.


Perception of periodicity pitch by hearing-impaired listeners. The perception of periodicity pitch was examined in normal and hearing-impaired listeners. Hearing-impaired listeners exhibited varying degrees of damage to the basal (steep and gradual high frequency hearing losses) and apical (low-frequency hearing losses) portions of the cochlea. The four groups of listeners matched the pitch of the sinusoids to the pitch of air conduction pulse trains with pulse repetition frequencies of 150 and 250 located at center frequencies of 2000 and 4000 Hz. Normal-hearing listeners had no difficulty in perceiving the periodicity pitch. Hearing-loss subjects presented complex response patterns that seemed related to damage to high-frequency (basal) portions of the cochlea, but in general, did not make pitch matches corresponding to the wave-form periodicity. The data support experiments suggesting that the basal portion of the cochlea is responsible for the detection of periodicity pitch. It is also suggested that place information may influence pitch recognition for hearing-imparied listeners.


Evaluation of automatic screening tympanometry in the identification of middle ear pathology. This study was designed to evaluate the diagnostic sensitivity of a prototype tympanometric screening instrument. Results from automatic tympanometry and complete electroacoustic impedance measurements (tympanometry, static compliance, and acoustic reflex thresholds) were compared to otologic diagnosis in 53 ears with middle ear pathology. Results suggested a high percentage of agreement between screening tympanometry, results from a complete impedance test battery and pneumatic otoscopy. These findings lend support for theuse of screening tympanometry in school hearing-screening programs and in pediatric practice.


Aggressive pharmacologic and surgical treatment of spinal cord injuries in dogs and cats. Aggressive pharmacologic and surgical treatment of spinal cord injuries in 22 dogs and 3 cats resulted in a recovery rate of 44% of all 25 animals. Excluding 5 animals that were euthanatized at surgery because of visualized cord transection and 5 that died during surgery because of secondary lesions, the recovery rate was 73%. This is compared with a recovery rate of 39% (7/18) for animals treated with more conservative methods at the same institution during an earlier period. Of the 7 animals without spinal cord transection and treated within 4 hours of injury, all recovered, pointing to the merits of early surgical intervention.


Further study of existence regions for the "ventriloquism effect". The "ventriloquism effect" refers to the perception of speech sounds as coming from a direction other than their true direction, due to the influence of visual stimuli from an apparent speaker. In these experiments, the ventriloquism effect was observed for conditions in which the subject turned his eyes 30 degrees to watch a speaker on a TV monitor. It was found that (1) the ventriloquism effect could be obtained for (hidden) auditory sources 20-30 degrees from the position of the TV speaker; (2) a strong ventriloquism effect could be obtained for an auditory stimulus at an angel of 150 degrees right of the subject's straight ahead when the TV source (toward which the subject's gaze was directed) was at 30 degrees right of straight ahead. Lesser effects were obtained for sound sources at 130 and 170 degrees right of the subject's straight ahead.


Observations on the intraarticular use of corticosteroids in the racing thoroughbred. A project to determine if intraarticular corticosteroid therapy was deleterious to the racing Thoroughbred was carried out in the 1971, 1972, and 1973 racing seasons. Of 22 horses available for follow-up examination, 6 had radiographic evidence of deterioration; 1 of these was destroyed because of probable corticosteroid-induced arthropathy. The remaining 16 horses did not have any evidence of deterioration. One of the 16, a stakes winner, had been given 12 injections into the left front fetlock during the 3-year period. It was concluded that if proper and careful aftercare is adhered to, intraarticular injections of corticosteroids can be carried out with relative impunity.


Mitral valve prosthesis for correction of mitral regurgitation in a dog. Mitral regurgiation with atrial fibrillation in a 3-year-old St. Bernard dog was corrected by digitalization, placement of a mitral valve prosthesis, and direct current cardioversion. The atrial fibrillation eventually returned and became refractory to cardioversion.


Hereditary cerebellar cortical and extrapyramidal nuclear abiotrophy in Kerry Blue Terriers. Ten Kerry Blue terriers from a kennel in New York and 3 from a kennel in California developed clinical signs of a progressive cerebellar disorder, with its onset between 9 and 16 weeks of age. In 9 sequential necropsies, progressive cerebellar cortical degeneration, with loss of Purkinje's cells, was demonstrated. As the disease progressed, there was bilateral symmetric degeneration of the olivary nuclei followed by degeneration of the substantia nigra and caudate nucleus, bilaterally. The California and New York dogs were related, and an autosomal recessive inheritance was proposed for the disease.


The musculature of the proximal pelvic limb of the Eastern Grey Kangaroo Macropus major (Shaw) Macropus giganteus (Zimm). The proximal pelvic limb musculature of the Eastern Grey Kangaroo, Macropus giganteus (Zimm) is described with nine illustrations. The text is based on dissections of 44 Grey Kangaroos ranging in empty body weight from 791 g to 58 kg.


The ultrastructural relationships between Sertoli cells and spermatogenic cells in the rat. The cell-to-cell junctions between Sertoli cells and between Sertoli cells and spermatogenic cells have been described and illustrated in the rat seminiferous tubule. The most important junction is a zonula (or macula) adherens which exists between Sertoli cells on the one hand and spermatogonia on the other. No such junctions are observable between Sertoli cells and late spermatids in the Golgi, acrosomal or cap phases. Mitochondria in these spermatids are the 'energized' type and are lined up close to the inner aspect of the cell membrane; whereas in all other spermatogenic cells they are 'non-energized' and randomly orientated. Almost all the ultrastructural characteristics of steroid hormone-secreting cells have been observed in Sertoli cells. The functional significance of these findings is discussed.


Ingestion of colloid in a keratinized epithelium and its localization in membrane-coating granules. An electron-dense tracer (Thorotrast) was injected into the lamina propria of the keratinized epithelium of the buccal mucosa of rats. Electron microscopy showed that it crossed the basal lamina and penetrated the intercellular spaces of the epithelium up to the proximal layers of the stratum granulosum. Thorotrast was ingested by the epithelial cells in the stratum basale and stratum spinosum and localized in large vesicles and eventually in the membrane-coating granules. The latter, already known to contain lysosomal enzymes, are therefore to be regarded as secondary lysosomes formed in part as a sequel of endocytosis in deeper cell layers. The postulated origin of MCGs directly from the Golgi apparatus is rendered less likely by this observation. Thorotrast remaining in the cells when keratinization is completed is either dispersed into the cytoplasm or else incorporated into keratohyalin granules.


A parametric analysis of the growing CFHB (Wistar) rat. Measurements of body weight and body, tail and hindlimb lengths were made at various times during the postnatal development of the CFHB-Wistar rat using simple techniques which avoided unnecessary stress being applied to the animal. All the graphical relationships studied using these measurements indicated that growth was divided into two phases which meet at 16 days. This was particularly noticeable when either body length or hindlimb length was plotted against either age or body weight. Body weight appeared to be a better indication of maturity than time; and linear relationships were found when measurements of body lengths were plotted against the square root of body weight. Curvilinear graphs were obtained when body weight was plotted on alternative scales. Results suggest that prior to 16 days metabolism is probably directed more towards attaining sufficient maturity to enable the animal to survive independently, than to increasing its stature; but after 16 days this situation is reversed.


A new antifungal antibiotic, trichostatin. A new antibiotic, trichostatin, was isolated from the metabolites of strains of Streptomyces hygroscopicus. It is active against trichophytons and some fungi. The structure was determined to be a derivative of a primary hydroxamic acid by chemical and spectroscopic evidences.


Two new antibiotics, A-218 and K-41. Isolation and characterization. Two new antibiotics, A-218 and K-41, were isolated from strains identified as Streptomyces hygroscopicus. The antibiotics are characterized as polycyclic polyether compounds and are active against gram-positive bacteria.


Isolation of a new polyether antibiotic, lonomycin. A new polyether antibiotic, lonomycin, was isolated from the culture of Streptomyces ribosidifcus strain TM-481. The antibiotic obtained as a sodium salt is a colorless prism having a molecular formula of C44H75O14Na(M.W. 850), m.p. 188 approximately 189 degrees C, and has no absorption maxima in the ultraviolet region. The infrared and NMR spectra of the antibiotic suggest the presence of a carboxyl and four methoxyl groups. Lonomycin shows antimicrobial activity against gram-positive bacteria.


Studies on a new polyether antibiotic, Ro 21-6150. A new polyether antibiotic, Ro 21-6150, has been isolated from culture broths of Streptomyces hygroscopicus, strain X-14563. Ro 21-6150 has ionophore properties and is active in vitro against gram-positive bacteria.


Cefuroxime - a new cephalosporin antibiotic. Cefuroxime is a new broad spectrum cephalosporin antibiotic for administration by injection. It is stable to most beta-lactamases. It is active against gram-positive organisms, including penicillinase-producing staphylococci, and has wide activity against gram-negative bacilli including Enterobacter and many strains of indole-positive Proteus spp. The substance is also highly active against Haemophilus influenzae and Neisseria gonorrhoeae. Studies on human volunteers showed that it produced high, long-lasting blood levels with virtually complete recovery of unchanged antibiotic in the urine. No evidence of toxicity due to cefuroxime was found. Slight, short-lived pain followed intramuscular injection, and the compound was well tolerated intravenously.


Antimetabolites produced by microorganisms. XIII. The synthesis and microbiological production of a novel amino acid, L-2-amino-4-(2-aminoethoxy) butanoic acid. A novel amino acid, L-2-amino-4-(2-aminoethoxy-)-butanoic acid, was isolated from a fermentation broth of Streptomyces sp. X-11,085. It was shown to be identical with the chemical reduction product of an antimetabolite antibiotic, L-2-amino-4-(2-aminoethoxy)-trans-3-butenoic acid, a co-product in the fermentation. Addition of the title compound to the fermentation led to an enhanced yield of the antimetabolite suggesting that the saturated amino acid serves as a precursor for the antimetabolite.


In vitro and in vivo evaluation of versicolin, an antifungal antibiotic. Versicolin is mainly active against Trichophyton rubrum. It is inactivated by serum. However, attainable blood level can be fifteen to twenty times higher than the fungicidal concentration for as long as 4 hours after a single intravenous administration of the maximum tolerable dose of 25 mg/kg body weight of mouse. It has no haemolytic activity like other polypeptide antibiotics. Skin does not show the presence of any measurable amount of the antibiotic. It is excreted through urine to the extent of 65% of the maximum tolerable dose of the antibiotic administered intravenously. Versicolin is effective against experimental infection by T. rubrum in guinea pigs at dose as low as 2.5 mg/kg body weight. The antibiotic shows no sign of subacute toxicity at these curative doses.


Metabolic fate of cephacetrile after parenteral administration in rats and rabbits. 1. The metabolic fate of 14C-cephacetrile was studied in rats and rabbits. The plasma level of intravenously injected cephacetrile decreased with half-lives of 17 and 22 minutes in rats and rabbits respectively, this decline being associated with a rapid appearance of the active metabolite, desacetylcephacetrile. Intramuscularly injected cephacetrile was rapidly absorbed by rats with a maximum plasma level at 20 minutes and a half-life of 16 minutes. Cephacetrile and desacetylcephacetrile did not enter erythrocytes. Cephacetrile was weakly bound to the plasma protein in the rat, rabbit and man. 2. Both in rats and rabbits, almost all of the injected radioactivity was excreted in the urine within 72 hours as the intact antibiotic and desacetylcephacetrile, only small amounts appearing in feces via bile. Neither the gamma-lactone of desacetyl-7-cyanacetamidocephalosporanic acid nor the violet-reddish pigment (CGP-695) produced from cephacetrile were detectable in the plasma or urine of the animals. 3. In rats given the labeled antibiotic intravenously, the radioactivity was widely distributed with concentrations being high in the kidney, plasma and liver, and lowest in the brain. The radioactivity crossed the rat placenta and appeared in the fetus. Radioactivity in these tissues disappeared as the plasma level declined. 4. During daily intramuscular injection of 14C-cephacetrile to rat, no significant changes were observed in the peak level of the plasma radioactivity or in the half-lives. In addition, dosing of the labeled antibiotic for 7 days caused no increase in tissue levels of radioactivity.


Studies on pleuromutilin and some of its derivatives. A number of derivatives of pleuromutilin (I) and of its degradation product, mutilin (II1, was prepared. The new monotosylation product of pleuromutilin (IIIc) served as the key substance for modification of the glycolic acid side chain. From the pleuromutilin monosuccinate (IIIk) water-soluble salts were obtained, among them the crystallized diethylaminoethanol salt that was investigated more closely. Some of the pleuromutilin derivatives showed antimicrobial activity.


Biotransformation, a new approach to aminoglycoside biosynthesis: II. Gentamicin. Utilizing a paromamine-producing mutant of Micromonospora purpurea blocked in the production of gentamicin, bioconversion of various minor gentamicin components into the gentamicin C complex was demonstrated. The compounds tested were structurally related to the gentamicin C's and are found as minor components in the gentamicin fermentation. Based upon the bioconversions detected, a branched pathway for the biosynthesis of the gentamicin C components is proposed.


Effect of D-Glucarates on basic antibiotic-induced renal damage in rats. Dehydrated rats regularly develop acute renal failure following single injection of aminoglycoside antibiotics combined with dextran or of antibiotics only. Oral administration of 2,5-di-O-acetyl-D-glucaro-1,4-6,3-dilactone protected rats against renal failure induced by kanamycin-dextran. The protective effect was prevalent among D-glucarates, and also to other saccharic acid, hexauronic acids and hexaaldonic acids, although to a lesser degree, but not to a hexaaldose, sugar alcohols, substances inthe TCA cycle and other acidic compounds. D-Glucarates were effective against renal damage induced by peptide antibiotics as well as various aminoglycoside antibitocis. Dose-responses were observed in the protective effect of D-Glucarates. With a D-glucarate of a fixed size of dose, approximately the same degree of protection was obtained against renal damages induced by different basic antibiotics despite large disparities in administration doses of different antibiotics. D-Glucarates had the ability to prevent renal damage but not to cure it. Rats excreted acidic urine when they were spared from renal lesions by monosaccharides. The reduction effect of D-glucarates against nephrotoxicity of basic antibiotics was discussed.


Antibiotic DE-3936, a polyether antibiotic identical with lonomycin. Taxonomy, fermentation, isolation and characterization. Antibiotic DE-3936 was isolated from the fermentation broth of a streptomycete No. 9735-1, which is identified as a strain of Streptomyces hygroscopicus. The antibiotic is a hydrophobic compound having the molecular formula of of C44H75O14Na and is  active against Gram-positive bacteria, mycobacteria, mycoplasma and protozoa, especially coccidia. Its chemical and biological properties indicate that antibiotic DE-3936 belongs to the group of polyether antibiotics and is identical with lonomycin.


Isolation of brevistin, a new peptide antibiotic. Studies on antibiotics from the genus Bacillus. IX. A new peptide antibiotic, brevistin, was isolated from the culture broth of Bacillus brevis 342-14. Brevistin is an acylpeptide with an approximate empirical formula of C63H91N15O18 containing aspartic acid, threonine, glycine, valine, isoleucine, phenylalanine, tryptophan and 2,4-diaminobutyric acid. The antibiotic is soluble in acid and alkaline water. Its hydrochloride is soluble in methanol. Brevistin is active against Ggam-positive bacteria in vitro and in vivo, and is of low toxicity to mice.


The structure of brevistin. Studies on antibiotics from the genus Bacillus. X. Acid hydrolysis revealed the constituent amino acids by brevistin as follows: aspartic acid (D-form 2, L-form 1), L-threonine (1), glycine (1), sum of L-valine and L-isoleucine (1), L-phenylalanine (1), L-trytophan (1), and 2,4-diaminobutyric acid (D-form 1, L-form 1). The constituent fatty acid was elucidated to be anteisononanoic acid by gas chromatography-mass spectrometry. A lactone linkage was proved between phenylalanine and the hydroxy group of threonine. Opening the lactone ring with dilute alkali afforded brevistinic acid. Deacylation with an enzyme preparation, Polymyxin Acylase, gave deacyl brevistinic acid. Cleavage reaction with N-bromosuccinimide, sequential analysis by EDMAN degradation and some additional evidences clarified the total structure of brevistin.


Isolation of a new antibiotic, laterosporamine. Studies on antibiotics from the genus Bacillus. XIII. A new antibiotic, named laterosporamine, was isolated from the culture broth of Bacillus laterosporus 340-19. The antibiotic is active against Gram-positive and Gram-negative bacteria in vitro and in vivo. It is a water-soluble basic substance, positive to ninhydrin, SAKAGUCHI'S and DRAGENDORFF'S reagents. A non-peptidic structure with an approximate empirical formula C17H35N7O4 was suggested.


A30641, a new epidithiodiketopiperazine with antifungal activity. A new antibiotic, designated A30641, having in vitro activity against Gram-positive bacteria and fungi has been isolated from a strain of Aspergillus tamarii. Chemical and physical characterization indicate that it is a member of the class of antibiotics containing the epidithiodiketopiperazine moiety.


Isolation and characterization of satellite antibiotics, mimosamycin and chlorocarcins from Streptomyces lavendulae, streptothricin source. Under novel conditions of culture, Streptomyces lavendulae No. 314 was found to produce new antibiotics, chlorocarcins and mimosamycin in addition to streptothricin. The antibiotics are extracted from culture filtrate with organic solvents and further purified by silica gel chromatography. Chlorocarcins A, B and C are closely related basic antibiotics which are active against gram-positive bacteria, EHRLICH carcinoma and L 1210 leukemia of mice. Mimosamycin is a neutral antibiotic which is mainly active against mycobacteria. Production, isolation and physicochemical properties of the antibiotics are described.


Identification of producer and biological activities of new antibiotics, mimosamycin and chlorocarcins. A strain of Streptomyces, No. 314 identified as a Streptomyces lavendulae produced under a novel condition of culture, four new antibiotics, mimosamycin and chlorocarcins A, B, and C. Among the components of chlorocarcin complex, chlorocarcin A was found to be most biologically active. This antibiotic inhibited the growth of Staphylococcus aureus FDA 209P and Corynebacterium diphtheriae at the concentrations of 0.1 and 0.003 mcg/ml, respectively. Chlorocarcin A also exhibited antitumor activity on EHRLICH carcinoma, ascitic and solid forms, and mouse leukemia L1210. Mimosamycin proved to be mainly active on Mycobacterium tuberculosis and inactive on the experimental murine tumors.


Further purification and characterization of macromomycin. The antitumor polypeptide, macromomycin (MCR) produced by Streptomyces macromomyceticus, was purified by ammonium sulfate precipitation, ultrafiltration and chromatographic techniques using Amberlite IRA-410, DEAE Sephadex A-25 (CI- and OH-type) and Sephadex G-50. Purified MCR was obtained as a white powder by lyophilization. MCR, thus purified, exhibited a single peak on Sephadex G-50 chromatography with no detectable contaminant by ultracentrifugation and polyacrylamide gel electrophoresis. MCR is an acidic polypeptide having an isoelectric point of pH 5.4. It contains no arginine and methionine. The molecular weight was 11,700, 12,500 and 11,400 by amino acid composition, gel filtration and analytical ultracentrifugation, respectively. MCR is labile as a lyophilized powder but is successfully stabilized by the addition of maltose.


The chemistry of actinocarcin. I. Further characterization and C-terminal structure of actinocarcin. The amino-acid composition and molecular weight of actinocarcin, and C-terminal structure of actinocarcin are reported in this paper. By STEIN-MOORE'S and ultraviolet-absorption methods, the molar ratio of amino acids in actinocarcin was determined. The N-terminal amino acids are alanine and valine. The C-terminal amino acid, determined by hydrazinolysis, is tryptophan. The molecular weight is about 11,000 as estimated by ARCHIBALD'S method and amino acid analysis. Three fragments, named BrCN-I, BrCN-II and BrCN-III, were obtained by cyanogen bromide cleavage. The structure of BrCN-III, namely the C-terminal structure of actinocarcin was determined by EDMAN degradation.


Microbial production of amphotericin B-3H and the synthesis of its sodium desoxycholate (carboxyl-14C) complex and methyl-14C-ester. Amphotericin B-3H with a specific radioactivity in excess of 4 muCi/mg was produced by fermentation of Streptomyces nodosus IMRU 3694 in a complex medium, using acetate-3H as a precursor. The medium employed gave a production yield of 2.5 approximately 3.5 mg/ml of amphotericin B. The most efficient incorporation of acetate-3H occurred when the precursor was added at 24 hours after inoculation. It was observed, that the amount of amphotericin A co-produced in the fermentation broth with amphotericin B was significantly reduced by the addition of ethanol to the production medium. Complete inhibition of amphotericin A production was achieved at a level of 2% ethanol in the fermentation medium without an appreciable effect on the yield of amphotericin B. Methanol, 1-propanol, 2-propanol and 1-butanol lowered the yield of both antibiotics indiscriminately. The syntheses of amphotericin B-3H-Na desoxycholate (carboxyl-14C) complex and amphotericin B-3H methyl-14C-ester are also described.


Nafcillin and oxacillin: comparative antistaphylococcal activity in mice. The therapeutic properties of nafcillin, oxacillin and erythromycin were determined in mice infected with a strain (Evans) of Staphylococcus aureus shown to be tolerant to the bactericidal action of penicillinase-resistant derivatives of penicillin. The therapeutic activity of these agents was also correlated with the extent of colonization of kidneys by resistant clones of S. aureus Evans. The CD50 values or potency ratios proved that nafcillin was highly active against this organism, whereas oxacillin and erythromycin were capable of protecting the animals to a lesser degree. Of the agents studied, only nafcillin was capable of preventing or interfering with the colonization of the kidneys by S. aureus Evans. Although the exact interpretation and application of these data in the management of clinical problems remains to be determined, the observations suggest important differences between nafcillin and oxacillin in vivo and that it is difficult to predict the antibacterial efficacy of these drugs solely from MIC and MBC data.


Effect of ether on control of rate and depth of breathing in newborn rabbits. The effect of ether anesthesia on Hering-Breuer inflation reflexes of newborn rabbit pups was investigated. Studies were done at a level of anesthesia at which an apneustic pattern of respiration is seen in vagotomized animals. The hypothesis that increase in vagal influence on respiratory frequency is accompanied by increase in influence on contractile force of the inspiratory muscles was tested. Two aspects of the Hering-Breuer reflex, breath duration and airway pressure developed with an elastic load, were evaluated simultaneously. This was done by performing airway occlusions at FRC--the results expressed as percent slowing on occlusion and as effective elastance (E'rs). The animals were studied with and without anesthesia, before and after vagotomy. Anesthesia resulted in a marked increase in vagal influence on inspiratory duration (34% increase) and on total breath duration (36% increase). In contrast E'rs was decreased (20%) after anesthesia whereas passive elastance was slightly increased. The vagal contribution to E'rs was essentially the same before and after anesthesia (36-38%). Thus ether anesthesia increases one aspect of the Hering-Breuer reflex without changing the other. These findings are likely due to depression of the central nervous system rather than due to peripheral effects of ether.


Fibrinolytic and hemostatic changes during and after maximal exercise in males. To evaluate changes in fibrinolytic activity, factor VIII and other hematological variables during and after a progressive step increment in work load, 10 healthy male subjects (22-27 yr of age) were exercised to exhaustion on an electromagnetic bicycle ergometer. Blood samples were drawn serially throughout the experiment. Little change in fibrinolytic activity was observed before 70-80% maximum heart rate (MHR) was achieved. Major changes occurred after 80% MHR. Peak values coincided with maximum exercise. In contrast major changes in factor VIII were observed between 95 and 100% MHR with peak values occurring 5-10 min postexercise. An increase in white blood cell count, platelet count, and retention was observed at maximum exercise. One individual failed to demonstrate an increase in either fibrinolytic or factor VIII activity. Relating the data to either the percent maximal oxygen uptake or percent maximal heart rate demonstrates the importance of the exercise protocol and exerting all subjects to the same relative level of physiological work.


Effects of water immersion to the neck on pulmonary circulation and tissue volume in man. Utilizing the rebreathing of a gas mixture containing C2H2, C180, He O2, and N2, we obtained serial measurements of the pulmonary capillary blood flow (Qc), diffusing capacity per unit of alveolar volume (DL/VA), functional residual capacity (FRC), pulmonary tissue plus capillary blood volume (VTPC), and O2 comsumption (VO2) in five normal subjects under the following conditions: 1) 6 h of sitting, 2) 4 h of sitting while immersed in thermoneutral water to the neck, and 3) 4 h of lying in thermoneutral water to the neck. Water immersion (NI) was preceded and followed by 1-h prestudy and 1-h recovery periods. The measurements were made at 30-min intervals. Seated NI produced a fourfold increase in sodium excretion (UNaV), a 25-36% increase in Qc, a 45-59% increase in DL/VA, and a 30-36% decrease in FRC. This occurred as early as the 1st h of NI and persisted throughout the 4-h period of study. Throughout the seated control and NI periods, VO2, heart rate, and VTPC remained constant. During supine NI, Qc, HR, DL/VA, FRC, and VO2 did not differ significantly from supine prestudy. These date demonstrate that seated NI causes a significant increase of Qc and DL/VA which persists throughout the immersion period. Furthermore, the lack of change of VTPC suggests that the central vascular engorgement induced by seated NI is not accompanied by extravasation of fluid into the pulmonary interstitial space.


Prediction of body density in young and middle-aged men. The purpose of this investigation was to predict body density of young (18-22 yr) and middle-aged (40-55 yr) men and to determine if generalized equations were appropriate to both populations. The dependent variable, body density, was determined by the hydrostatic technique. Independent variables included 7 skinfold fat, 11 girth, and 7 diameter measures; age; height; and weight. Mean body density for young men was 1.068 g/ml (SD +/- 0.014) and percent fat, 13.4 (SD +/- 6.0); the values for middle-aged subjects were 1.043 g/ml (SD +/- 0.0130) and 24.7% (SD +/- 5.9). Incomplete principal components analysis was used to examine the dimensions measured by the independent variables, and these analyses revealed differences between samples. Using multiple regression analysis, with the exception of girth measurements, the slopes of the regression lines were equal. For all analyses, however, the intercepts were different. These results confirmed the need for different regression equations for these populations. The most accurate prediction for young men was with two skinfold, four girth, and two diameter measures (R = 0.88; SE = 0.0069 g/ml); two skinfold and three girth measures accurately predicted body density for middle-aged men (R = 0.84; SE = 0.0074 g/ml).


Single-breath oxygen tests for individual lungs in awake man. Single-breath oxygen (SBO2) tests for individual lungs were performed in five healthy awake volunteers. In the supine position, all subjects consistently showed a closing volume (CV) for both lungs. In the lateral position, CV was demonstrated in all analyzable SBO2 tests for the dependent and in 20 of 28 for the nondependent lung. CV consistently occurred in the dependent before it occurred in the nondependent lung (asynchronous onset of CV). After CV had been reached in the nondependent lung, a mean of 77 ml of gas was still expired from the dependent lung. No changes in CV for individual lungs were demonstrated with changes in body position. Expiratory flow limitation consistently occurred first in the dependent lung (asynchronous onset of flow limitation). In the lateral position, at high lung volumes, the dependent lung achieved higher flow rates; later in expiration, the nondependent lung contributed progressively more gas to the total expirate (asynchronous emptying). In general, our findings are consistent with both the "asynchronous flow limitation" and the "airway closure" interpretations of CV. However, some of the results are not consistent with either theory.


Lactate metabolism in resting and exercising dogs. The effect of treadmill run on the turnover rates of glucose ([2-3H]glucose) and lactate ([U-14C]lactate), on the rates of oxidation (ROX) of lactate, and its conversion to glucose (L LEADS TO G) were measured with the primed constant-infusion technique. Comparable lactate turnover rates were obtained at rest by infusing epinephrine, or Na-L(+)-lactate with or without norepinephrine. With increasing lactate levels (L) the rate of disappearance (RdL), ROX, and L leads to G increase in a linear manner. At the same lactate level, RdL, ROX, and L leads to G are significantly higher in the running dog. Exercise increased the metabolic clearance rate of lactate threefold. At rest ROX and L leads to G represented about 50% and 18-19% of RdL, respectively. The corresponding values in the running dogs were 55% and 25%, respectively. At rest about 9% of the hepatic glucose output arose from lactate while during exercise this varied from 7 to 26% depending on RdL. It is concluded that a) the working muscle produces and utilizes lactate at the same time, and b) "in vivo" the major factor which controls both ROX and gluconeogenesis is the substrate supply.


Human lung mechanics during water immersion. We measured lung volumes, static deflation pressure-volume curves of the lung, maximum expiratory flow-volume curves, and closing capacities in five men standing immersed to the neck in water. FRC was decreased 27%, while other lung volumes did not change significantly. At high lung volumes immersion tended to increase lung elastic recoil while recoil was decreased at low lung volumes, changes compatible with vascular congestion. Maximum expiratory flow was increased at high lung volumes, probably because of hydrostatic pressure. At low lung volumes maximum expiratory flow was decreased. This was probably due to decreased recoil since the relationship between elastic recoil and maximum flow was unchanged. Closing capacities by the N2 technique were unchanged but the slope of the alveolar plateau and the amplitude of cardiogenic oscillations were decreased in some individuals. Static and dynamic lung properties were unchanged by 5 min of immersion with tidal volume restricted to 0.5 liter. Though immersion produced volume restriction comparable with that reported with chest strapping, it did not produce similar changes in lung mechanics.


Chronic carbon monoxide poisoning: effects on performance of the isolated right ventricle. Rats were exposed continuously for 21-35 days to 500 ppm carbon monoxide (37.4-39.2% HbCO). Aerobic resting force (RF)-active isometric twitch force (AF) curves of isolated right ventricle preparations were constructed at 27 degrees C. CO and control groups are nearly identical when expressed as percent of maximal AF over the range of RF used. There are no significant differences in AF either at the peak of the curve or at RF = 1 g. During 15 min of anoxia AF declines at both RF's used. Increased anoxic tolerance is apparent in all CO preparations when anoxic AF is plotted as percent of preanoxic AF. The effect is most marked at RF = 1 g, where time to one-half preanoxic AF is 12.6 +/- 0.9 vs.9.3 +/- 0.8 min for CO-exposed and controls, respectively. However, no significant differences in "absolute" AF are seen between the groups at either level of RF at any minute during anoxia. Aerobic recovery of CO preparations is markedly enhanced at 1 g RF. Anoxic tolerance and aerobic recovery differences, however, are smaller at the peak of the RF-AF curve. Effects on time to peak AF and maximal rate of rise of AF are not marked at either level of RF in CO preparations.


Transit time analysis of the forced expiratory spirogram in growth. In the search for more sensitive indicators of airway obstruction Fish et al. (Am. Rev. Respirat. Diseases 109: 700, 1974) have proposed a transit time analysis of the forced expiratory spirogram. In this method the forced vital capacity (FVC) is divided into volumes of air and each volume is assigned a transit time; the nature of the FVC can be described by the transit times' mean, standard deviation, and index of skewness. In a group of 48 healthy nonsmoking subjects between the ages of 9 and 22 yr we found that all three quantities decreased with increasing age. This demonstrates an improvement in the function of the peripheral airways with lung growth. In contrast to the increase in flow rates with lung growth, none of this improved function can be attributed to increased lung volume.


Effects of hypocapnia and hypocapnic alkalosis on cardiovascular function. Cardiovascular effects of hypocapnia and hypocapnic alkalosis with and without a fluid load were studied in four groups of dogs (group I: fluid load control; group II: fluid load-isolated hypocapnia; group III: fluid load-hypocapnic alkalosis; group IV: no fluid load-hypocapnic alkalosis). Hypocapnic alkalosis was induced by mechanical hyperventilation, and isolated hypocapnia by the simultaneous administration of 0.1 N HCl. Respiratory alkalosis was also studied during administration of a saline fluid load. Cardiac output and stroke volume increased in all groups receiving a fluid load (including isolated hypocapnia and hypocapnic alkalosis groups), but both fell significantly during hypocapnic alkalosis without fluid load. Pulmonary artery wedge pressure rose in groups with hypocapnic alkalosis with fluid load and isolated hypocapnia with fluid load, but did not change significantly with hypocapnic alkalosis without fluid load or in the normocapnic group with fluid load. It is concluded that cardiac output and stroke volume fall in response to hypocapnic alkalosis but both are maintained with a fluid load at the expense of an increased left ventricular preload.


Effects of hypercapnia on mouth pressure during airway occlusion in conscious man. The effects of hypercapnia and inspiratory flow-resistive loading on mouth pressure during periods of arrested airflow were studied in conscious human subjects to determine the usefulness of inspiratory muscle force in the assessment of respiratory neural efferent activity. Hypercapnia increased the peak end-inspiratory mouth pressure (Ppeak) during complete airway occlusion and the pressures at 100, 200, and 300 ms after the onset of inspiration (P100, P200, P300). During rebreathing without added mechanical loads, P100 and Ppeak increased linearly with the electrical activity of the diaphragm and changes in P100 and Ppeak during hypercapnia correlated well with ventilatory responses to PCO2 (DELTA V/DELTA PCO2) suggesting that occluded mouth pressures are reliable measures of respiratory activity. In individuals with the greatest reduction in delta V/DELTA PCO2 during inspiratory flow-resistive loading, changes in P100 and Ppeak with PCO2 increased only minimally. In contrast, there was a much greater increase in occluded mouth pressures with hypercapnia in the presence of mechanical loading when inspiratory flow-resistive loading failed to depress delta V/DELTA PCO2. In all subjects, occluded mouth pressures were greater at any given PCO2 during mechanical loading than during free breathing. Mechanical loading resulted in augmented respiratory neural efferent activity unexplained by alterations in chemical stimulation.


Effects of hypercapnia and flow-resistive loading on tracheal pressure during airway occlusion. To determine whether the isometric force of concentration of the inspiratory muscles could be used to assess respiratory efferent neural activity, the tracheal pressure generated by the inspiratory muscles during airway occlusion (occluded tracheal pressure) was measured during progressive hypercapnia in anesthetized dogs breathing normally and breathing against added flow-resistive loads. Hypercapnia increased the peak end-inspiratory tracheal pressure and the occluded tracheal pressures generated 100, 200, and 300 ms after the onset of inspiration. The duration of the occluded inspiratory effort generally remained unchanged and the configuration of the pressure tracing was not affected. During normal breathing occluded tracheal pressures increased linearly with tidal volume and with the electrical activity of the diaphragm and the external intercostal muscles both before and after vagotomy. Inspiratory flow-resistive loading reduced the ventilatory response to CO2 but did not affect occluded tracheal pressures at any given PCO2 or the change in pressures with hypercapnia both before and after vagotomy. Similarly, expiratory flow-resistive loading failed to affect occluded tracheal pressures. These results suggest that occluded tracheal pressures measure respiratory efferent neural activity and can be used as indices of CO2 responsivity even during mechanical loading in anesthetized animals.


An intercostal-phrenic inhibitory reflex in human newborn infants. An effect of phasic distortion of the rib cage on inspiratory time was studied in thirty sleeping newborn infants. Distortion was produced by both manual compression of various rib cage diameters, and by occluding the airway at functional residual capacity, allowing diaphragmatic contraction to alter rib cage shape. With rapid distortion produced by these maneuvers, inspiration was often terminated prematurely. The effect was dependent upon there being a rapid rate of distortion, and was most readily elicited when inward motion involved the lower lateral rib cage. The results indicate a potent inspiratory inhibitory reflex, originating most probably from the spindles of intercostal muscles. This reflex acts to decrease tidal volume and ventilation when rates of rib cage retraction are high during spontaneous breathing.


Convective and diffusive gas mixing in human lungs: experiments and model analysis. Equilibration of inspired with lung residual gas was studied by a single-breath technique for varying breath-holding time with He, Ar, and SF6 as test gases. The ratio of end-expired (FE') to mean lung concentration after expiration (FL) was always below unity, indicating imperfect mixing of gas in the lung. The ratio of FL/FE' for all gases increased with tB, for any tB the ratio was smallest for SF6 and greatest for He. Similarly, Bohr dead space (VD) at any given tB was greatest for SF6 and smallest for He, with VD decreasing toward an asymptotic value common for all gases as tB increased. The results were analyzed quantitatively on a serial three-compartment model of the lung. Model analysis suggests that both diffusion and convection are effective in equilibrating test gases in the lung during breath holding. Further, stratified inhomogeneities in the absence of convective gas mixing in the alveolar space would seriously limit alveolar respiratory gas exchange; with convection, however, stratification is likely to impose only moderate constraints on resting gas exchange.


Effect of hypoxia on the pressure developed by inspiratory muscles during airway occlusion. The effect of progressive isocapnic hypoxia on the pressure generated by the inspiratory muscle during airway occlusion was studied in 10 awake subjects during normal and obstructed breathing. Isocapnic hypoxia was produced by rebreathing a gas mixture of 6% CO2 in air while the expired gas was passed through a CO2 scrubber so as to maintain PACO2 constant (42.6 mmHg +/- 2.2 SE). Occlusion of the airway was performed randomly for a single breath at FRC. In all 10 subjects maximal pressure (Ppeak) and the pressures measured 100, 200, 300, and 400 ms after the onset of inspiration increased during hypoxia. Furthermore, good correlation was noted between the occlusion pressure response to hypoxia (delta P/DELTA[1/PO2-32]) and simultaneous changes in ventilatory response to hypoxia (delta VI/DELTA[1/PO2-32]). The occlusion pressure response to hypoxia therefore seems to be a reliable measure of respiratory center output. When rebreathing was repeated during inspiratory resistive loading, the occlusion pressure at any given PO2 and delta P/DELTA(1PO2-32) measured in the first 400 ms of inspiration increased in 9 of 10 subjects. Since PACO2 and PAO2 during both control and loaded experiments were the same, the increase in occlusion pressure in the presence of flow-resistive loading appeared to represent a neurally mediated increase in inspiratory motoneuron activity.


Central circulation during exercise after venesection and reinfusion of red blood cells. To study central circulation at different levels of hemoglobin (Hb) concentration, five subjects performed submaximal and maximal exercise in three different situations: 1) control, 2) after venesection of 800 ml of whole blood, and 3) after reinfusion of the red blood cells about 30-35 days after venesection. Maximal oxygen uptake (VO2 max) decreased from 4.27 l-min-1) at control to 4.03 l-min-1 after venesection (P less than 0.05) and increased to 4.61 l-min-1 after reinfusion (P less than 0.05). Maximal values on cardiac output (Q), heart rate (HR), and stroke volume (SV) were the same in the three situations. Thus, there was no compensatory increase in Qmax due to the lowered arterial oxygen content (Cao2) after venesection. An increase of the Cao2 (Hb concentration) and a lowering of the Cvo2 contributed equally to the increased VO2 max after reinfusion. At a given submaximal VO2, HR and blood lactates were increased at lowered Hb concentration and decreased at increased Hb concentration over control levels. Correlation coefficient for the change in Q in relation to the acute change in Hb concentration at a given submaximal VO2 was -0.49 (P less than 0.05).


Heat storage regulation in exercise during thermal transients. Rate of heat storage (S) was measured by using direct and indirect calorimetry simultaneously in 11 subjects during rest and exercise at three ambient temperatures (Ta of 20, 25, and 30 degrees C), and at two work intensities (40 and 90 W). At rest, the mean value of S was -64.9 W at 20 degrees C, -26.1 W at 25 degrees C, and +9.9 W at 30 degrees C. After 50 min of exercise at 40 or 90 W, S tended toward zero at the three ambient temperatures. This indicates that thermal equilibrium was reached. In addition, at the end of the exercise periods total heat losses (R + C + E) measured at a Ta of 20, 25, and 30 degrees C were similar, i.e., independent of Ta. During the thermal transients and the steady state of exercise, the calorimetric method allows immediate measurement of S to be made, since all the physical terms of the body heat balance equation are determined. The changes in mean body temperature (delta Tb) measured by thermometry showed a delay of 5-10 min when compared with delta Tb measured by calorimetry. Thus, determination of delta Tb by thermometry is not directly applicable during thermal transients, unless the observed delay is taken into account. Our results also support the concept that Tb may be the regulated variable of the thermoregulatory system, since we obtained a very significant and uniform correlation between Esk and delta Tb at the three Ta and the two work intensities which were studied.


Oxygenation and deoxygenation velocity factors of chorioallantoic capillary blood. The oxygenation and deoxygenation rates of capillary blood of chicken embryo were measured precisely with a microphotometric reaction apparatus. The velocity factors expressed as Fcox and Fcdeox in ml O2-ml RBC-1-S-1-mmHg-1 were calculated as functions of oxygen saturation. They were similar to results previously obtained in human blood using the rapid flow apparatus. The continuous registration of the reaction with oxygen enables us to estimate the equilibrium time of blood when passing through the chorioallantoic capillary. The value obtained was almost identical to the contact time indirectly assessed from the CO reaction. The diffusing capacity of the chorioallantoic capillary plexus of the 16-day-old embryos was estimated as 7.3 x 10(-3) ml-min-1mmHg-1 by using the values of the Fcox and the equilibrium time determined here together with the values of the blood flow and hematocrit which had been obtained in the previous experiments.


Adaptive modifications in the thermoregulatory system of long-distance runners. In seven long-distance runners (42 km or more) the thermoregulatory responses to acute external cooling and heating, under resting conditions, were recorded and compared with those in physically untrained controls. Sweating as well as shivering thresholds were significantly decreased in the runners when compared either in terms of mean body temperature (Tb) or esophageal temperature (Tes); Tb and Tes were reduced in the runners at rest under thermoneutral conditions. Moreover, cold sensation in the runners occurred at lower Tb. The runners thus behaved as if the "set point" of their thermoregulatory system had been reset to a lower level. As for the sweating threshold, the shift is quantitatively comparable to that found in heat adaptation. The described modifications in long-distance runners would prolong the time period until a dangerous body temperature-one of the important limiting factors in physical endurance-is reached during heavy exercise.


Influence of bronchomotor tone on regional ventilation distribution at residual volume. We studied the topographical distribution of 133Xe boluses inhaled slowly from RV, as well as the distribution of regional volumes at RV (RVr) in seven seated normal subjects before and after aerosolized isoprenaline (ISO) and after aerosolized methacholine hydrochloride (Mech). After Mech the ratio of inhaled 133Xe in the upper lung regions to that in lower lung regions (U/L) decreased from 3.21 +/- .33 (mean +/- 1 SE) to 1.27 +/- 0.12 (P less than 0.001) and returned to 3.89 +/- 0.55 after Iso. Iso alone increased U/L from 3.23 +/- 0.47 to 5.49 +/- 0.85 (P less than 0.025). The height of phase IV in expired 133Xe vs. volume plots correlated with U/L, being greater after Iso and smaller after Mech in each subject. The difference in RVr between upper and lower lung regions decreased after Mech in four out of five subjects from 0.22 TLC to 0.11 TLC. Iso alone did not change the gradient of RVr. The results are consistent with the concept that increased bronchomotor tone widens the range of critical opening and closing pressures with a more patchy and extensive distribution of airway closure.


Influence of diaphragmatic contraction on ventilation distribution in horizontal man. The washout of a bolus of helium (inhaled from residual volume) during relaxed expiration (RE) through a resistance was compared with that during expiration with voluntary diaphragmatic contraction (VDCE) achieved by tensing the abdominal muscles while maintaining constant expiratory flow (less than 0.4 l/s). In six subjects in the lateral decubitus position, phase IV during RE started at 58 +/- 1.6% vital capacity (VC) (mean +/- 1 SE). During VDCE, when the transdiaphragmatic pressure (Pdi) exceeded 30 cmH2O, phase IV commenced at 8.2 +/- 0.8% VC. The expired He concentration (FEHe) at lung volumes greater than 70% VC was 1.3 +/- 0.05 times that during RE. In supine subjects VDCE flattened the slope of the alveolar plateau and decreased closing volume by 3.7 +/- 0.4% VC. Our results suggest that when the diaphragm is relaxed in the horizontal subject, the hydrostatic gradient of pressure within the abdomen enhances early emptying of dependent lung zones. Diaphragmatic contraction results in more homogeneous emptying. We conclude that diaphragmatic tone influences the vertical gradient of regional volume, and hence of pleural pressure. The latter is not constant, being less during inspiration than during expiration. Therefore, differences in the changes of applied pressure between dependent and nondependent lung regions influence ventilation distribution in subjects in the horizontal posture.


A square-pulse flow method for measuring characteristics of the arterial bed. A device was designed to provide a "square" pulse of blood flow into the arterial system. Pulses were injected into the carotid artery of the rabbit during transient cardiac arrest. Analysis of pressure response curves generated by the flow provides information as to the state of the arterial tree. With certain assumptions it is possible to estimate from these curves lumped values of peripheral resistance, critical closing pressure, and arterial compliance. In a series of 12 rabbits the mean value of peripheral resistance was found to be 0.21 +/- 0.7 mmHg-ml-1-min and critical closing pressure was estimated to be 23.6 +/- 3.8 mmHg. This method gives two possible values for arterial compliance 0.036 +/- 0.010 and 0.055 +/- 0.010 ml-mm-1 based, respectively, on the rise and decay curves of the pressure response. The theory and limitations of the method are discussed. The use of the method is illustrated in following the response to increased PCO2 and hemorrhage.


Reflex and mechanical circulatory effects of graded Valsalva maneuvers in normal man. In 17 normal subjects we studied the changes evoked by five levels of expiratory pressure (EP) ranging from 2.5 to 30 mmHg in a number of circulatory variables during the last 10 s of a 30-s Valsalva maneuver. Variables studied included mean arterial (MAP) and pulse (PP) pressures; right atrial (RAP) and peripheral vein (PVP) pressures; cardiac output (CO); total peripheral resistance (TPR) and heart rate (HR). EP-circulatory response curves were obtained in each subject a) before autonomic block; b) after cardiac effector block (atropine + propranolol); c) after "total" autonomic block (atropine + propranolol; guanethidine + phentolamine). Mechanical effects were determined from results during "total" autonomic block. They included EP-related rises in RAP and PVP each to about 0.7 mmHg/mmHg applied EP, and falls in CO, MAP, and PP to levels of approximately 50%, 70%, and 80% of resting respectively at EP 30 mmHg, but no changes in TPR and HR. Reflex effects included EP-related rises in HR and in TPR and in MAP, to levels of 160%, 160%, and 115% of resting respectively at EP 30 mmHg. The afferent input profile is probably complex, and the role of the different receptor groups may vary at the different levels of EP.


Oxygen electrode syringe as an instrument for determining oxygen-hemoglobin dissociation curves. A new instrument is described which simplifies the measurement of the oxygen-hemoglobin dissociation curve, using small volumes of blood. An oxygen electrode, as the plunger of a syringe accommodating increasing volumes of blood at predetermined levels of saturation with oxygen, measures the amount of dissolved oxygen in the plasma, which is proportional to the gas tension.


A clinical catheter for continuous blood gas measurement by mass spectrometry. A new Teflon catheter for continuous in vivo measurement of blood gases by mass spectrometry has an outer diameter of 0.032 in. and can be inserted through percutaneous puncture with an 18-gauge needle. Response time (63% of a total change) is 40 s for oxygen and 65 s for carbon dioxide. When calibrated in analyzed gas at 37 degrees C, the catheter-mass spectrometer system has been shown to analyze tonometered blood with an error of 1.6% for oxygen and 1.9% for carbon dioxide. Temperature dependence is 2.0% per degrees C for oxygen and 1.6% per degrees C for carbon dioxide. The catheter was thrombo-resistant during in vivo use in seven dogs and measurements compared favorably with results of blood sample analyses by standard hospital methods. Compared with previous devices, the new catheter provides size and convenience, advantages that make it more applicable for routine clinical use.


Transthoracic admittance plethysmograph for measuring cardiac output. A plethysmograph for measuring ventricular stroke volume (SV) from the transthoracic admittance variation was developed. A correlation study between the SV values determined by this method (SVy) and those measured by Kubicek's transthoracic impedance method (SVz) was carried out on 24 healthy subjects; the correlation coefficient was r = 0.99 and the regression line of SVY on SVz was y = 1.03x - 0.47. Based on the results obtained through the study, it was concluded that the admittance method was more advantageous than the impedance method for measuring SV.


Changes in cold-induced vasodilation during Arctic exercises. The effect of exposure to cold on cold-induced vasodilation (CIVD) was examined in military personnel who had experienced a 2-wk stay in the Artic. During this time, the daily regimen consisted of long marches over difficult terrain and sleep in unheated tents with diurnal temperatures ranging from -10 to -40 degrees C. In tests conducted before and after the 2-wk period, CIVD was measured in the left middle finger of each subject by its immersion in ice water. After the 2-wk period, the value of mean finger temperature during the test had decreased relative to that observed before the test, the time required before the first vasodilative temperature increase occurred had become greater, and the finger temperature value at which the vasodilative increase was initiated has been lowered. These changes manifest a deleterious effect of cold exposure on the CIVD, contrary to expectations, and suggest that the effect of short-term cold exposure is to produce a general rather than peripheral acclimation in these subjects.


A sensitive five-breath N2 washout test of distribution of ventilation. The amount of nitrogen eliminated in the first five breaths after start of oxygen breathing was compared with the amount that would be removed in these breaths, if alveolar mixing were uniform. The ratio of these two amounts is a measure of the degree of unevenness of ventilation; it was determined in 41 nonsmokers, 22 heavy smokers, and 6 patients with chronic obstructive pulmonary disease. The "five-breath index" (ratio x 100) in the nonsmokers ranged between 90 and 100. In 16 of the smokers, it was less than 87.5 (95% confidence limit of normals), although in only 5 of these, spirometric tests (MMEF) were considered abnormal. The index in the 6 patients ranged between 51 and 83. The test is highly reproducible, simple to perform, and might be of value in the detection of early lung disease.


Aerosol penetrance: a sensitive index of peripheral airways obstruction. Early injury of the small airways has been demonstrated in asymptomatic smokers. Ventilatory tests including the maximum midexpiratory flow rate and closing volume have been useful in clinical detection of small airways disease in symptomatic subjects. In the present study, airway "obstruction" was assessed aerodynamically by gamma camera measurements of chest radioactivity following the inhalation of 131I-labeled aerosol (aerodynamic mass median diameter 3 mum). Studies were performed in normal subjects, asymptomatic smokers, and patients with chronic obstructive lung disease. An aerosol penetrance index (AeP) was devised from determinations which involved 1) an analysis of central (inner zone) and peripheral (outer zone) deposition of aerosol in the lung and 2) a ratio of initial counts to 24-h counts in the periphery (outer zone) of the lung. AeP values were 41.5 +/- 11.5 for the normal group, 20.9 +/- 7.6 for the smoker group, and 10.6 +/- 5.2 for the subjects with chronic obstructive airway disease. AeP was significantly reduced in the smokers indicating that the AeP is a sensitive index of early peripheral airways obstruction.


Reference sample method for cardiac output and regional blood flow determinations in the rat. The reference sample method was used for simultaneous determinations of cardiac output and regional blood flows in conscious rats. Microspheres (15 +/- 5 mum in diam) labeled with strontium-85 were injected into the left ventricle and known volumes of reference sample were withdrawn from peripheral arteries. The calculated cardiac output measurements agreed with the previously reported values in rats. The percent distribution of the cardiac output to the brain, intestinal bed, and lungs were different from the reported values obtained in the rats using larger spheres. These differences may be related to the use of smaller spheres and to differences in the preparation. The absolute regional flows to various organs expressed in terms of milliliters per minute per gram tissue weight were also determined. The results indicate that the reference sample method can be applied to smaller mammals for determinations of regional flows and cardiac output.


Reusable tubular membrane oxygenator for isolated organ hemoperfusion. A reusable tubular membrane oxygenator is described for hypotraumatic hemoperfusion of isolated organs in physiological studies. The constructed oxygenator was of approximately 0.24-m2 effective surface area and contained 450 silicone rubber capillaries of 0.51-mm nominal ID, 34.9 cm long, fixed by conical-shaped, plastic blood headers at manifolds made from Dow-Corning MDX-4-4210 silicone elastomer. During ex vivo hemoperfusions in dogs at inlet hemoglobin saturations near 67%, oxygen transfer rates of the oxygenator increased serially, from 16.6 +/- 1.7 ml/min per m2 (mean +/- SD) at blood flows of 100 ml/min to 34.1 +/- 3.8 ml/min per m2 at flows of 500 ml/min. The oxygenator was thromboresistant and of much loss priming blood volume and wall compliance than the nonresuable Travenol membrane oxygenator of 0.26-m2 effective surface area. The tubular oxygenator was easily cleaned and reassembled, with reproducible oxygen transfer rates. It should prove useful for hemoperfusion studies in organs of moderate size, such as the isolated canine kidney, stomach, and pancreas.


Oxygen affinity of human blood in presence of carbon monoxide. If carbon monoxide is present in the blood, it is necessary to quantitate its effect on apparent O2 affinity in order to properly compute venous PO2 and P50. Ways of doing this are analyzed theoretically. The classical principles of Haldane and of Roughton and Darling are reviewed and simplified. The method of computation of PO2 in the presence of CO as introduced by Forster is shown to be in considerable error. The source of this error is determined. The error produced if the presence of CO is ignored during the computation of P50 is analyzed.


Gas exchange in man during combined +Gz acceleration and exercise. Gravity and acceleration from head to foot (+Gz) handicap gas exchange by shifting blood from thorax to dependent veins and creating a ventilation/perfusion (V/Q) mismatch in the lung. At 1 G leg exercise improves V/Q matching. Gas exchange was measured in six subjects +1, +2, and +3 Gz during rest and two levels of exercise, either unloaded pedaling or 600 kpm/min. The VO2 for pedaling was clearly related to G level, but work efficiency was unaffected. Acceleration lowered resting Pao2 while raising VE/VO2, HR, AaDo2, VD, and VD/VT. Unloaded pedaling returned VE/VO2 and HR toward their 1-G values. In contrast, at 3 G each increase in VO2 caused a fall in Pao2 and a rise in AaDo2. The VD showed no further change with exercise, while VD/VT decreased at all G levels. It thus appears that only some of the effects of acceleration are counteracted by exercise, probably by the peripheral muscle pump. Any accompanying rise in VO2 adds to the stress of acceleration, due to limitations on gas transport.


Total and regional cerebral blood flow measurement with 7-10-, 15-, 25-, and 50-mum microspheres. Cerebral arteriovenous shunting of 7-10-, 15-, 25-, and 50-mum labeled microspheres was studied in 12 anesthetized dogs. Approximately 8% of the 7-10-mum spheres were shunted to cerebral venous blood, whereas less than 2% of the 15-, 25-, and 50-mum spheres were shunted. Cerebral vascular dilatation induced by hypoxia or hypercapnia did not alter the shunting. The calculated total cerebral flow was 10-15% lower with 7-10-mum microspheres as compared with simultaneous flows measured with the larger microspheres which also suggests that 7-10-mu spheres were shunted through the brain. The calculated distribution of cerebral flow was similar with 7-10- and 15-mum spheres but markedly altered when 50-mum spheres were used. Repeated injections of 15-mum spheres were used. Repeated injections of 15-mum microspheres given under stable conditions yielded total cerebral blood flows which averaged +/- 6% of their respective mean and the regional distribution of flow was highly reproducible. These data suggest that, in dogs, 15-mum spheres are an appropriate size to use to measure cerebral blood flows, since shunting is minimal, the distribution is not artifactually distorted, and the measurements are reproducible.


Elastic constants of inflated lobes of dog lungs. The elastic constants of dog lungs were determined at various degrees of inflation. In one set of experiments, the lobes were subjected to deformations that approximated the conditions of uniaxial loading. These data, together with the bulk modulus data obtained from the local slope of the pressure-volume curve, were used to determine the two elastic moduli that are needed to describe small nonuniform deformations about an initial state of uniform inflation. The bulk modulus was approximately 4 times the inflation pressure, and Young's modulus was approximately 1.5 times the inflation pressure. In a second set of experiments, lobes were subjected to indentation tests using cylindric punches 1-3 cm in diameter. The value for Young's modulus obtained from these data was slightly higher, approximately twice the inflation pressure. These experiments indicate that the lung is much more easily deformable in shear than in dilatation and that the Poisson ratio for the lung is high, approximately 0.43.


Two-dimensional determination of thermosensitive sites within the goat's hypothalamus. In two conscious goats with chronically implanted multithermodes the distribution of thermosensitive sites within the anterior hypothalamus was determined. Changes in heat production at Ta=+5 degrees C and changes in respiratory evaporative heat loss at Ta=+33 degrees C in response to discrete temperature stimuli were measured and the magnitude of the responses was correlated with the histologically assessed position of the probes transmitting the stimuli. In both animals the array of probes was centered close to the center of the thermosensitive area. The density of thermosensitive structures increased toward the center of the area covered by the probes. The most sensitive points were situated close to either side of the midline in those frontal planes which contained the nuclei supraoptici and paraventriculares. No difference was found between cold- and warm-sensitive sites.


Contribution of gular flutter to evaporative cooling in Japanese quail. Oxygen consumption, body temperature (Tb), and evaporative water loss (mwe) were determined in intact Japanese quail (Coturnix coturnix), and in quail in which the hyoid musculature responsible for gular flutter had been surgically transected several days prior to study. Abolishing gular flutter reduced total mwe by an average of 20% at air temperatures (Ta) above 40 degrees C. Treated birds developed a significantly greater degree of hyperthermia during acute heat stress than the controls and, unlike the controls, were unable to maintain Tb less than Ta above 40 degrees C. These data demonstrate that gular flutter represents a significant cooling mechanism in heat-stressed quail.


Effect of aerosolized isoproterenol on resting myogenic tone in normals. The effects of aerosolized isoproterenol on expiratory (exp) and inspiratory (insp) conductance (Gaw), maximal exp and insp flow (VEmax and VImax), and static elastic recoil pressure (Pst) were measured in 12 normals. Both exp and insp Gaw increased throughout the vital capacity (37% at 50% VC; P less than 0.01). VEmax increased only at 50% VC (9%; P less than 0.01). VImax and Pst did not change. Accordingly, a dichotomy existed between the Gaw and Vmax changes during both exp and insp. We do not attribute this dichotomy to loss of driving pressure or to volume-time-dependent behavior of airway tone. We interpret the increased exp and insp Gaw to indicate isoproterenol deposition within and bronchodilatation of larger central airways (trachea, main stem, lobar, segmental). Since insp Gaw increased and VImax did not, we conclude that the caliber of these central airways is not the exclusive deteminant of VImax, that the caliber of some more distal airways (subsegmental and beyond) did not change, and that these airways are important determinants of VImax. We conclude that non-uniform distribution of isoproterenol could account for the Gaw-Vmax dichotomy during inspiration, and that such non-uniform distribution coupled with resultant increased compliance and compressibility of the downstream segment could account for the Faw-Vmax dichotomy during expiration.