An improved method for computed tomography of the base of the skull in head scanners that utilize a water bag. The original EMI Mark I head scanner as well as the Artronix Neuro CAT scanner utilize a water bag surrounding the patient's head. One of the disadvantages of this system is that the patient's head may be displaced out of the scanning beam by the pressure of the water bag, thus making it difficult to obtain good scans of the base of the skull or the posterior fossa. A device that utilizes an adjustable footboard and restraining straps around the legs to hold the patient in position is described. Although designed specifically for the Artronix Neuro CAT scanner, it can readily be adapted to other scanners that utilize a water bag. In our experience it has worked well in restraining caudal movement of patients, thus enabling us to obtain good images of the posterior fossa and base of the skull.


Steroids and apparent cerebral atrophy on computed tomography scans. Computed tomography scans of 15 long-term steroid users showed varying degrees of apparent cerebral atrophy, not expected at their ages (8 to 40 years). Most were suffering from autoimmune diseases. There appeared to be some correlation between dosage and degree of apparent atrophy. There was surprisingly little clinical evidence of cerebral dysfunction associated with this apparent atrophy. In two of the cases, the appearance of the brain improved following decrease or cessation of steroid use. Speculations are made on possible causes.


Computed tomography of the orbit with special emphasis on coronal sections: Part I. Normal anatomy. Computed tomography (CT) of the orbit is capable of demonstrating soft tissue structures not visualized yet by any other radiological modality. The possibility of obtaining direct coronal slices has added a new dimension to the study. Direct enlargement viewing on the display console reveals many anatomical details. For better evaluation of pathological findings, an accurate anatomical knowledge is required. The purpose of this study is to report on the normal anatomy of the orbital soft tissues made visible by CT, with emphasis on the coronal views.


Computed tomography of the orbit with special emphasis on coronal sections: Part II. Pathological anatomy. Visualization of orbital soft tissue structures by computed tomography in direct coronal and axial studies is extremely useful in diagnosis. Direct enlargement viewing of scans has disclosed minute anatomical details. This study reviews some of our experiences in the investigation of a variety of lesions within the orbit and attempts, in particular, to illustrate the value of direct coronal studies.


Computer assisted tomography of orbital lesions in Wegener's granulomatosis. The orbital lesions in six patients with Wegener's granulomatosis were studied by computer assisted tomography (CAT). Four patients had active orbital disease and proptosis, and each was found to have orbital masses accompanied by varying degrees of bone and sinus destruction. Two additional patients with histories of proptosis had no orbital lesions at the time of CAT study.


Tissue characterization by an analysis of the distribution of attenuation values in computed tomography scans: a preliminary report. Attenuation values as measured by a computed tomography scanner are distributed in both magnitude and space. The distribution in magnitude can be described by the mean, standard deviation, and skewness of histograms of attenuation values. The distribution in space can be characterized by auto-correlation functions or histograms of gradients. Using these measures of scan structure, it has been shown that the spatial distribution of attenuation values can be influenced by tissue. Also, there are some indications that changes in tissue structure corresponding to disease can be detected.


Computed tomography of solitary pulmonary nodules: experience with scanning times longer than breath-holding. Thirty-one patients with solitary pulmonary nodules--18 benign and 13 malignant--proven by either tissue diagnosis or prolonged follow-up were evaluated by computed tomography (CT). A device (ACTA scanner 0100) with scanning times greater than breath-holding was used with full understanding of its related limitations. A retrospective study of the CT features of these nodules led us to establish several criteria for benign nodules. CT evidence of calcium is felt to be the most important feature of benignancy. In the absence of calcium, irregular nodule margins, perinodular fibrosis, satellite nodules, and pleural thickening opposite a peripherally situated nodule are helpful to suggest its benign nature.


Relative detectability of intracranial calcifications on computed tomography and skull radiography. Phantom studies comparing skull radiography and cranial computed tomography (CT) show that CT is 5 to 15 times more sensitive than skull radiography in the detection of intracranial calcifications. The difference in detectability varies with object size. The relative sensitivity of CT increases with increased object size within the constraints of the section thickness. The relationship of these findings to the detectability of pineal and choroid calcifications is discussed.


The apical artifact: elevated attenuation values toward the apex of the skull. An artifact that can cause an elevation in CT numbers of as much as 20 Hounsfield units toward the apex of the head is described. This artifact was first noted on the EMI CT1010 scanner but has been observed in other scanners as well. Phantom studies of this artifact have revealed that its primary origin is the beam hardening distortion due to the large amount of bone present in apical cuts. This has been verified by computer simulations. An intuitive explanation of the origin of the artifact is also presented.


Radiation necrosis of the brain: correlation between computed tomography, pathology, and dose distribution. Delayed necrosis of the brain following exposure to high doses of radiation is a recognized hazard. It is important to predict the nature of these postradiation changes, since surgical removal of radiation necrosis may reverse neurological deterioration of patients so affected. The present report stresses the importance of correlating the findings on computed tomography (CT) scans and zones of high radiation dose on dose reconstruction plans in order to differentiate between delayed radiation necrosis and tumors of the brain. This differentiation is not possible using the criteria of CT alone.


Computed tomography in the evaluation of encephaloceles in infants and children. Computed tomography (CT) is an accurate diagnostic modality in the evaluation of encephaloceles. The axial and coronal planes, contrast enhancement attenuation measurement of the contents of the encephalocele, and the use of the standard and reverse modes for viewing the CT images are all valuable in this evaluation.


Abdominal CSF pseudocyst secondary to ventriculoperitoneal shunt: diagnosis by computed tomography in two cases. Two cases are presented in which the preoperative diagnosis of abdominal cerebrospinal fluid pseudocyst was made by computed tomography (CT). The collection can be well outlined by this method, and measurement of density values characterizes the contents as a water density; the relationship of portions of the shunt catheter to the pseudocyst can be demonstrated as well. It is suggested that, in a patient with a ventriculoperitoneal shunt who develops abdominal signs or symptoms, CT can provide the definitive diagnosis of this entity.


Choice of the plane of incidence for computed tomography of the cerebral cortex. A study has been carried out to determine how different planes of incidence may influence the computed tomographic projection of the different parts of the cerebral cortex. Knowledge of the patterns displayed with the different incidences should help in the identification of the various cortical (as well as high ventricular) structures.


Computed tomography after psychosurgery. The computed tomography scans of patients who had frontal leukotomy show bilateral cysts in the frontal lobes that have attenuation values similar to cerebrospinal fluid, and are not contrast enhanced.


Preparation and fractionation of goat kappa-casein: analysis of the glycan and peptide components. Whole goat kappa-casein was prepared by chromatography of whole casein on hydroxyapatite. Chromatography of whole kappa-casein on DEAE-cellulose separated 5 fractions. All of them were sensitive to chymosin. Their amino acid and carbohydrate composition, phosphate content and molecular weight were determined. Galactose, N-acetylgalactosamine, N-acetyl and N-glycolyl neuraminic acids were identified in whole kappa-casein. It appears that goat kappa-casein, like cow, buffalo and ewe kappa-caseins, is composed of several fractions having identical peptide chains and differing in their carbohydrate contents. The main fraction, devoid of carbohydrate, was treated with chymosin. The para-kappa-casein and caseinomacropeptide were isolated. Their amino acid composition and phosphate content were determined.


Glucocorticoids in mammary secretions and blood serum during reproduction and lactation and distributions of glucocorticoids, progesterone, and estrogens in fractions of milk. Concentrations of glucocorticoids were measured in milk and blood serum during the estrous cycle, prepartum, parturition, postpartum, and early and late lactation. Glucocorticoids in milk did not change during the estrous cycle, averaging .35 ng/ml whereas they averaged .50 ng/ml prepartum, 3.08 ng/ml at parturition, and .50 ng/ml 1 wk postpartum. Glucocorticoids in milk declined from .59 ng/ml to .25 ng/ml as lactation advanced from 1 to 10 mo. Concentrations of glucocorticoids in blood serum were approximately 8 to 10 ng/ml during all reproductive states. There was no positive relationship between percentage of milk fat and concentrations of glucocorticoids in milk. Cortisol was the predominant glucocorticoid in serum; in milk corticosterone concentrations exceeded those of cortisol. Glucocorticoids, being more polar, had higher affinity for the nonlipid portion of milk; in contrast, progesterone, estradiol 17beta, and estrone were located predominantly in the lipid fraction of milk.


Symposium: wise use of chemicals, drugs, and additives by dairy producers. Clearance procedures for new animal drugs and feed additives. We have attempted to provide an overview of the Food, Drug, and Cosmetic Act as it pertains to animal drugs and feed additives. The Act requires that each new animal drug application or food additive petition contain sufficient data to prove that the drug or feed additive is safe and effective before the drug or feed additive can be marketed. It also gives the Secretary of Health, Education, and Welfare the power to remove from the market a previously accepted drug if it is shown to be unsafe or lacks effectiveness. The Bureau of Veterinary Medicine has prepared guidelines to aid applicants in compiling ans submitting the necessary information for approval of drugs to be used in dairy cattle. A copy of these guidelines and a Drug Use Guide, which aids the dairymen to correctly use approved drugs, can be obtained from the Bureau.


Development, manufacture, and distribution of animal drugs. Much effort goes into the research, development, and manufacture of quality drugs to be used by the dairy producers. Food and Drug Administration aids in the process by establishing minimal requirements, reviewing data, and approving products conforming to their regulations. To misuse products or drugs is an invitation to trouble since little is known about the safety or efficacy of drugs other than for the manner in which they are labeled. Thus, the key to wise use of drugs is to read the label instructions.


Postsurgical, chronic, nonprogressive, cutaneous ulcers: a possible variant of pyoderma gangrenosum associated with diabetes mellitus. Two patients developed persistent ulcers on the trunk after cutaneous surgery. Both had "chemical" diabetes mellitus. Bacteriologic and histopathologic studies of the ulcers were not revealing of cause. The characteristics of the ulcers are described, and are contrasted with typical lesions of pyoderma gangrenosum and Meleney's postoperative progressive synergistic bacterial gangrene. We believe these patients had variant lesions of pyoderma gangrenosum.


Keratoacanthoma recurrent after surgical excision. A 62-year-old man developed a recurrent keratoacanthoma within two and a half weeks after grossly and microscopically complete removal of the primary tumor. X-irradiation of the recurrent lesion caused partial regression, and then intralesional injections of a suspension of triamicinolone caused final resolution of it. Although dermatologists generally practice partial destruction and surgeons almost always do total excision, neither method invariably cures this benign tumor, and repeated treatment may be necessary.


Hamartomatous basal-cell carcinoma.

Hamartomatous basal-cell carcinoma. A 25-year-old woman developed a basal-cell carcinoma in the skin over the right scapula. The histopathology of the lesion revealed elements of typical basal-cell carcinoma as well as adenoid, trichoepitheliomatous, and ductal differentiation. Hamartomatous basal-cell carcimoma is a rare variant of ordinary basal-cell carcinoma as well as adenoid, trichoepitheliomatous, and viduals. It is a less aggressive neoplasm and may remain stationary for years. Its recognition as an entity brings awareness that basal-cell carcinomas sometimes occur in young persons.


Punch biopsies of nails: a simple, valuable procedure. A simple technique for punch biopsies of nails is described. Local anesthesia with a solution of lidocaine, without epinephrine, is used. Digital block and tourniquet hemostasis are not required. The simplicity of the method ought to encourage more nail biopsies, increase the accuracy of diagnosis and improve treatment of diseases of the nails.


Malignant melanoma and subsequent other malignancies. This report describes two young men who suffered from cutaneous malignant melanomas and subsequently other malignancies, namely, adrenal in one and testicular in the other.


Two methods of assessing the type A coronary-prone behavior pattern in Belgium. Two methods developed in U.S.A. for measuring the Type A coronary-prone behavior pattern--the Structured Interview and the self-administered Activity Survey, were translated into French and Flemish and utilized in a large preventive cardiology study in Belgium. The distribution of behavior-type judgments made by trained interviewers were compared to similar data from North America and found to be similarly symmetrical but clustering more toward central categories in Belgium. The Activity Survey, when scored by the scoring key developed in California, yielded averages for this Belgian group which appeared to be more in the Type B direction than the California sample, particularly in terms of Job-Involvement and tendencies toward haste and impatience. The Activity Survey scales and Structured Interview judgments showed a strong correspondence, with a 70% agreement observed between the Interview and Type A scores. This comparability between findings in Belgium and U.S.A. suggests that the concept of the Type A behavior pattern has sufficient cross-cultural validity to permit the derivation of reliable measurements and to make feasible the determination of whether Type A behavior is a risk factor for coronary disease internationally.


Hypertension and myocardial infarction.

Hypertension and myocardial infarction. In a representative series of male patients (n = 504) surviving the hospital stay of a first myocardial infarction the prevalence of hypertension and the influence of hypertension on the prognosis during 2 yr follow-up were studied. According to the definitions used hypertension had been detected before or was detected after myocardial infarction in 36% of the patients. Two thirds had a history of hypertension known before infarction. The systolic and diastolic blood pressures measured at 3 months and 1 yr after infarction increased with age. There was no difference between patients with and without hypertension with respect to a number of different variables recorded during the hospital period, nor in multiple risk according to a logistic function. There was no difference in death rate between the two groups. However, the rate of non-fatal reinfarction was significantly higher among the hypertensive patients. Hypertension remained as a risk factor for after myocardial infarction when the possible confounding influences of serum lipid levels and tobacco smoking were analysed.


Sampling behavior of cohort rates for recurrent events. Large sample properties of cohort rates of recurrent events based on denominators computed from follow-up table quantities are derived and illustrated using health services utilization data. Ignoring the variation in the denominator may result in an inaccurate estimate of the precision of a cohort rate when the loss rate is high and the duration of follow-up long.


Comparison of osteitis condensans ilii and ankylosing spondylitis in female patients: clinical, radiological and HLA typing characteristics. A study comparing 12 patients with ankylosing spondylitis (AS) to 25 with osteitis condensans ilii (OCI), referred to a rheumatic disease center, was carried out to determine whether OCI represents a varient of AS in women. In the group with OCI, chronic lumbodorsal pain was present in 9, 36%, a 'fibrositis' syndrome in 6, 24%, and 16, 64% had recurrent episodes of polyarthralgia. A definite arthritis with effusion developed in 10 patients, 40%. No patient with OCI had iritis or colitis, whereas 4 patients with AS had iritis and four had colitis. Radiographs of the spine showed no evidence of spondylitis in the OCI group. Of the 25 patients with OCI, only 2, 8% were HLA B27 positive compared with 11 of 12 patients with AS, 92%. These results suggest that OCI is not a variant of AS in women.


Evaluation of multiple causes of death in occupational mortality studies. An exploratory examination of the possibility of using multiple causes of death information from death certificates in mortality studies has been undertaken. The formation of a matrix of primary by contributory causes has been suggested. The matrix gives an overall picture of mortality patterns, serves as a scheme to identify disease combinations, and can be utilized as a data-editing device. From the matrix, several conventional, as well as several new statistics can be computed. The methodology has been illustrated with data from a cohort of steelworkers. The gain in information as a result of routinely recording multiple causes of death has also been discussed.


Hyporeninemic hypoaldosteronism--case report and observation of dissociated renin and erythropoietin activity. A case is reported of hyporeninemic hypoaldosteronism, diagnosed during an evaluation of hyperkalemia. Urine and plasma aldosterone concentrations were depressed despite hyperkalemia and were not responsive to ACTH, cosyntropin, and angiotensin 2. Adrenal glucocorticoid function was normal. Plasma renin activity also was low, and was hyporesponsive to stimulation, including intravascular volume contraction and potassium depletion. Autonomic nervous function was intact. Of the 32 previously reported cases of selective hypoaldosteronism, plasma renin activity was low in the majority of cases in which it was measured. A classification of the types of selective hypoaldosteronism is presented. It is of interest that the serum erythropoietin activity in this case was increased while plasma renin activity was markedly depressed.


Tympanic membrane perforations in cats: configurations of losses with and without ear canal extensions. In cat, a small tympanic membrane (TM) perforation produces a low-frequency loss--in terms of sound pressure changes (deltaSP) in front of the TM re a 10-micronV round window cochlear microphonic (RW CM)--that varies inversely with frequency at a rate of 12dB/octave with a surgically shortened external auditory meatus (EAM). Losses were determined at the outer opening (deltaSP00) and at the TM (deltaSPTM) of four artificial EAM's of various lengths, volumes, and leakiness. In the low-frequency region, a leaky EAM produced a flat loss. In the midfrequency region, the flatness of losses was attributable to (1) the length of the EAM and (2) the location at which the loss was determined. EAM volume was not related to the configuration of the loss. Losses, under all conditions, were always identical in shape and magnitude for the open and closed systems. Clinically, hearing losses due to TM perforations are essentially frequency independent, especially in the low frequencies. The relation between voltage changes (deltaV) across the transducer and losses with different EAM's suggests that the discrepency between audiometric results and CM losses--at least in the high and midfrequencies--may be due to the use of precalibrated SPL's in clinical audiometry.


Auditory-nerve response from cats raised in a low-noise chamber. A litter of four cats, born and raised in a soundproofed chamber, was studied in an attempt to determine which, if any, features of the auditory-nerve response from routinely available cats might be due to the chronic effects of noise exposure. Two features of routine-normal response were especially suspect in this regard: (1) a "notch" in the distribution of single-unit thresholds centered at characteristic frequencies (CF's) near 3 kHz and (2) a compression of the distribution of rates of spontaneous discharge for units with CF above 10 kHz. A third feature of response in routine animals was the presence of a small number (roughly 10%) of units with virtually no spontaneous discharge and very high thresholds, sometimes 80 dB less sensitive than high-spontaneous units of similar CF. In the data from chamber-raised animals, the high-spontaneous units showed exceptionally low thresholds at all CF regions, however, there were signs of the midfrequency notch in the threshold distribution of at least two of these animals. The compression of the spontaneous rate distribution was not seen in any of the three most sensitive animals. The data suggest that there is a significant amount of "normal pathology" in the high-CF units from routine animals. Low-spontaneous, high-threshold units were present in all four chamber-raised ears with the same characteristics as in routine animals (exceptionally narrow tuning curves and exceptionally low maximum discharge rates) and at roughly the same percentage of the unit sample. A class of units with medium spontaneous rates and intermediate thresholds could also be identified. The possible significance of a classification of auditory-nerve units according to spontaneous rate is discussed.


Categorical perception--phenomenon or epiphenomenon: evidence from experiments in the perception of melodic musical intervals. Categorical perception was investigated in a series of experiments on the perception of melodic musical intervals (sequential frequency ratios). When procedures equivalent to those typically used in speech-perception experiments were employed, i.e., determination of identification and discrimination functions for stimuli separated by equal physical increments), musical intervals were perceived categorically by trained musicians. When a variable-step-size (adaptive) discrimination procedure was used, evidence of categorical perception (in the form of smaller interval-width DL's for ratios at identification category boundaries than for ratios within categories), although present initially, largely disappeared after subjects had reached asymptotic performance. However, equal-step-size discrimination functions obtained after observers had reached asymptotic performance in the adaptive paradigm were not substantially different from those initially obtained. The results of other experiments imply that this dependence of categorical perception on procedure may be related to differences in stimulus uncertainty between the procedures. An experiment on the perception of melodic intervals by musically untrained observers showed no evidence for the existence of "natural" categories for musical intervals.


Temporal integration of tone glides.

Temporal integration of tone glides. Temporal integration of rising and falling tone glides against a 50-2800-Hz background of noise at a sound pressure level of 60 dB re 20 micronPa was studied in two experiments. Glides were in the frequency ranges 200-700 Hz and 1200-1700 Hz for durations of 5-120 ms. Results indicate an asymmetry in the detectability of rising and falling glides of short duration, with rising glides detected at lower signal intensities in both frequency ranges. These effects are discussed in terms of differences in pattern of frequency analysis of identical, but temporally reversed, waveforms.


Compatibility between psychophysical and physiological measurements of aural combination tones. Neural studies of combination-tone (CT) responses in the eighth nerve and antroventral cochlear nucleus of anesthetized cats give evidence of stimuluslike intracochlear CT's with a similar amplitude spectrum as inferred from human psychophysics. An unsolved problem raised in these studies is the gross discrepency between the phase of CT's measured psychophysically and neurally. It is unknown whether incompatibility lies in the cochleas or the criteria for measuring CT's in the different experiments. New psychophysical experiments were developed to clarify this issue. Secondary CT's (SCT) were generated by the interaction between a primary cubic CT (CTT) and a third tone in the stimulus. The SCT measured by cancellation exhibits similar properties to those of a CT generated by the comparable two-tone stimulus. The SCT is eliminated when the CCT is cancelled. These findings support the view that CT's exist in the cochlea as spatially distinct, stimuluslike excitations, and that CT excitations are eliminated by psychophysical cancellation. The SCT phase provides a measure of the CCT phase without requiring direct cancellation of the CCT. Phase measurements by the new indirect and older direct methods imply that the CT phase may be constant with changing sound level of the primary stimulus as found in the neural studies; these measurements also reveal nonlinear phase effects not found in neural studies. The new data suggest that the CT phase discrepancy may be caused by a real difference between the nonlinear mechanisms in the alert humans and anesthetized cats, and provide new constraints for clarifying this issue through further study.


Verification of the optimal probabilistic basis of aural processing in pitch of complex tones. Periodicity pitch for complex tones has been quantitatively accounted for by a two-stage process of Fourier-frequency analysis subject to random errors and significant nonlinearities, followed by an harmonic pattern recognizer that makes an optimum probabilistic estimate of the fundamental period of musical and speech sounds. The theory predicts that periodicity pitch is a multimodal probabilistic function of a given stimulus. A clear and empirically supported distinction is made between limitations on the pitch mechanism caused by the stochastic nature of aural frequency representation and by the deterministic resolution bandwidths of aural frequency analysis. This model was developed earlier [J. L. Goldstein, J. Acoust. Soc. Am 54, 1496-1516 (1973)] to account for probabilistic data on pitch errors [A. J. M. Houtsma and J. L. Goldstein, J. Acoust. Soc. Am. 51, 520 (1972)] measured with periodic stimuli comprising two successive harmonics. This paper presents new predictions by the theory that were calculated, with computer simulation where needed, for known probabilistic pitch data from stimuli comprising three to six successive harmonics. Predicted pitch errors increase with increasing errors in estimating the frequencies of stimulus harmonics and decrease as more harmonics are added to the stimulus. Optimum processor theory fully accounts for the multicomponent pitch data on the basis of similar errors in estimating component stimulus frequencies as reported earlier, thus providing further evidence for the optimum probabilistic basis of aural signal processing in pitch of complex tones.


Evidence for a general template in central optimal processing for pitch of complex tones. Optimum processor theory successfully accounts for earlier pitch data by including the constraint that component tones in a complex stimulus are estimated as successive harmonics. This constraint gives the paradoxical prediction that a periodic complex tone comprising nonsuccessive harmonics cannot evoke periodicity pitch corresponding to its period. Most published data from pitch-shift experiments imply the necessity for this constraint. New periodicity pitch experiments on pitch shift and musical interval recognition were performed which prove that the theoretical constraint is not generally true. New and old data are reconciled by replacing the maximum likelihood estimation of the theory with maximum posterior probability estimation and removing the successive harmonic constraint. Periodicity pitch is estimated by optimizing the match between the aurally measured frequencies of stimulus components and a general harmonic template over some a priori expected pitch range. The new, more general, formulation reduces in many experimental situations to the successive harmonic constraint as a special case.


Detectability of varying interaural temporal differences. Detectability and salience of time-varying interaural temporal differences (IATD's) were measured in three experiments by determining observers' ability to follow the temporal fluctuations of a "moving stimulus"--a 3000-Hz low-pass computer-generated noise presented binaurally with a sinusoidally varying IATD. In the first two experiments the peak IATD (deltat the "extent of movement") was manipulated to determine, for different rates of interaural variation (fm), threshold discriminability of the "moving" stimulus from a reference (two-interval forced-choice paradigm). The nonmoving reference was either a dichotic noise stimulus (experiment 1) or a dichotic noise stimulus whose "image width" matched that of the excursions traced by the "moving stimulus" (experiment 2). Threshold deltat's in the two experiments were similar, increasing from 30 microns at fm = 0 Hz to 90 microns at fm = 20 Hz, indicating a "low-pass characteristic" for the binaural system. Thresholds decreased again for fm = 50 Hz, apparently because at these high rates of "movement" observers used other cues than the varying IATD's to perform the task. The third experiment measured the threshold of a binaural click in the presence of a "moving noise" masker as a function of fm and of the instantaneous IATD of the masker when the click was presented. As fm increased, click threshold gradually became independent of the masker's instantaneous IATD, again suggesting a "low-pass" characteristic for the binaural system; additionally, there was some evidence for a lag in the system's response for fm greater than 5 Hz. The data from the three experiments are discussed in terms of results from other studies which have investigated temporal aspects of the binaural system. The possible existence of movement detectors in the auditory system is discussed.


Psychophysical tuning curves measured in simultaneous and forward masking. The level of a masker necessary to mask a probe fixed in frequency and level was determined as a function of masker frequency using a two-interval forced-choice technique. Both simultaneous- and forward- masking techniques were used. Parameters investigated include the level of the probe tone and the frequency of the probe tone. The general form of the psychophysical tuning curves obtained in this way is quite similar to that of single-neurone tuning curves, when low-level probe tones are used. However, the curves obtained to forward masking generally show sharper tips and steeper slopes than those found in simultaneous masking, and they are also generally sharper than neurophysiological tuning curves. For frequencies of the masker close to that of the probe a simultaneous masker was sometimes less effective than a forward masker. The results are discussed in relation to possible lateral suppression effects in simultaneous masking, and in relation to the observer's use of pitch cues in forward masking. It is concluded that neither the simultaneous-masking curves nor the forward-masking curves are likely to give an accurate representation of human neural tuning curves.


Auditory handicap of hearing impairment and the limited benefit of hearing aids. The aim of this article is to promote a better understanding of hearing impairment as a communicative handicap, primarily in noisy environments, and to explain by means of a quantitative model the essentially limited applicability of hearing aids. After data on the prevalence of hearing impairment and of auditory handicap have been reviewed, it is explained that every hearing loss for speech can be interpreted as the sum of a loss class A (attenuation), characterized by a reduction of the levels of both speech signal and noise, and a loss D (distortion), comparable with a decrease in speech-to-noise ratio. On the average, the hearing loss of class D (hearing loss in noise) appears to be about one-third (in decibels) of the total hearing loss (A + D, hearing loss in quiet). A hearing aid can compensate for class-A-hearing losses, giving difficulties primarily in quiet, but not for class-D hearing losses, giving difficulties primarily in noise. The latter class represents the first stage of auditory handicap, beginning at an average hearing loss of about 24 dB.


Temporal switching between binaural information sources. An estimate of the rate of perceptual switching between two binaural information sources was sought by a procedure which employed an emergent perceptual property--the shape of the binaural sound image. Random polarity-modulated pulse trains were delivered to the two ears with controlled periods of interaural phase agreement and of phase disagreement. As the rate of alternation between the two interaural states is increased, discrimination suffers. With equal periods of phase agreement and disagreement, threshold periods of 2.2-3.4 ms, or about 300-450 alternations per second, are obtained. Such rates far exceed estimates of the rate of interaural switching obtained by other experimental paradigms. With unequal periods of agreements and disagreements, a minimum threshold period of 1.5 ms is the limiting factor. Large individual differences were noted. Other procedures for coding binary information yielded similar results. Rapid switching rate thresholds are obtained for narrow-band signals over a wide frequency range. A "central integration time" is identified with the threshold interaural switching period, and appears to be identical with the minimum integration time for monaural tasks.


Auditory thresholds and kanamycin-induced hearing loss in the guinea pig assessed by a positive reinforcement procedure. Absolute thresholds from 125 Hz to 52 kHz are determined for six guinea pigs trained by a positive reinforcement method. Four to five hundred trials were conducted during daily testing sessions and little between- or within-subject variability was found. Two of the six animals were subsequently treated with kanamycin and the development of a hearing loss for the high frequencies was followed. Loss of outer and to a lesser extent inner hair cells was well correlated with the threshold shift observed. Contrary to the experience of previous investigators, this operant training procedure has proved as efficient as that for other species of experimental animals, such as the monkey and the chinchilla. It holds excellent promise for future auditory behavioral work with the guinea pig.


Fundamental frequency in the speech of infants and children. Fundamental frequency ranges of six normal infants and children from 33 to 169 weeks were determined by narrow-band spectrographic analysis. Fundamental frequency values ranged from 30 to 2500 Hz, well outside the values reported in previous studies of noncry utterances. The use of fry, modal, and high registers is also discussed.


Asymptotic threshold shift in chinchillas exposed to impulse noise. Five monaural chinchillas were exposed to a repetitive, reverberant, impulse noise for ten days. The impulse-noise source was a mechanized hammer hitting a steel plate at a rate of 1/s. The average, peak over pressure within the holding cage was 113 dB SPL. Auditory thresholds were determined before and after exposure at 0.5, 1, 1.4 2, 2.8, 4, 8, and 16 kHz  utilizing shock-avoidance conditioning. During  exposure thresholds were monitored on a daily basis at 0.5 and 8 kHz. Within one hour from the start of the exposure, threshold shift at 8 kHz had reached an asymptotic level, while threshold shift at 0.5 kHz leveled off after 24 h of exposure. Asymptotic threshold shift (ATS) levels of both  frequencies varied between 30 and 50 dB across animals. Median threshold shift for both frequencies recovered to within 10 dB of normal after 40 days of recovery. Maximum permanent threshold shift (PTS) was at 2 and 2.8 KHZ with median PTS of 17 and 13 dB, respectively. After final thresholds were obtained (50-70 days), the cochleas were examined histologically using the surface preparation technique. A comparison is made between impulse-noise-induced ATS and ATS produced by continuous-noise sources.


Adaptation of residue pitch.

Adaptation of residue pitch. Residue pitch was examined by means of adaptation. The monaural perceptibility of a residue pitch was measured before and after exposure to ipsilateral or contralateral adapatation stimuli of variable spectral composition. Several aspects of adaptation were investigated: pitch channel specificity, number of stimulus components necessary to adapt a residue channel, importance of temporal and spectral factors for adaptation, and the relation between pure-tone and residue pitch. It was found that there are residue-pitch channels specifically sensitive to the spectral region and ear of presentation of the stimulus. At least two harmonics were necessary to adapt a residue channel, and pitch channels were found to be insensitive to temporal factors. Residue and pure-tone pitch seemed to be extracted by different mechanisms, having independent channels. The data presented augment the understanding of pitch perception and suggest refinements for pitch-perception models.


Ultrasonic velocity and attenuation in mammalian tissues. A compilation, from the original papers, is presented of the data on the acoustic properties (i.e., velocity and attenuation) of mammalian tissues in the megahertz range of frequencies used in medical ultrasonics. The actual values reported have been quoted to present a clear picture of the current state of knowledge in order to enable it to be assessed and to enable future workers to compare their own results directly. In the 20 years since the last such compilation, the progress in estimating the relative contributions of the animal species, the condition of the tissues, the temperature and frequency at which measurements were made, and the method of measurement to the observed variation has been small. It is hoped that this compilation together with summarizing tables will both be of practical use to the worker in the field and also encourage the establishment of a stronger body of fundamental information for the application of ultrasonics in biology and medicine.


The distributed response of complex branching duct networks. We describe an efficient method for stimulating the distributed response of complex asymmetrically branching networks which satisfy requirements of network self-consistency. Individual tree links may be dispersive and lossy. As a case in point we simulate the response of the human lung, and characterize the variations in pressure with frequency, path, and position. The effects of tree asymmetry are found to be significant above 100 Hz in the air-filled lung.


A modal perspective of lung response.

A modal perspective of lung response. The qualitative modal structure of lung response is investigated. Asymmetry of the branching airway network of the lung leads to clumping of system eigenvalues into distinct and well-separated clusters at low frequency. The breadth of the eigenvalue clusters increases with the degree of asymmetry and frequency. At high frequency the breadth of the clusters exceeds the cluster spacing so that distinct eigenvalue clusters are no longer observed. Symmetric airway networks lead to degenerate mode clusters with large eigenvalue redundancy. The average density of eigenvalues of the undamped system is estimated to be higher than 0.5 per Hz. All modes appear to be in modal overlap.


Infrasound and sound: differentiation of their psychophysiological effects through use of genetically deaf animals. The effects of steady-state acoustic stimulation on resistance of fatigue, as shown by reduction of swimming time, was studied on three sublines of mice, one of which is genetically deaf. High frequency (500-10000 Hz) reduce swimming time from 25% to 50% in mice with normal hearing at a 60-80-dB threshold, but have no effect on deaf mice. Low frequencies and infrasounds (6-50 Hz) reduce swimming time in all mice similarly, even deaf animals, but the threshold is higher (160-115 dB). The use of genetically deaf animals therefore permits elimination of the auditory component; differentiation of the effects of air-borne from those of mechanical vibrations are thus possible.


Activity level: a comparison between actometer scores and observer ratings. Activity level of 13 boys (aged 9-13) from a day hospital program was measured using actometers in classroom, gym, woodshop, and group therapy settings. Ratings of Ss' activity were obtained from mothers using the Werry scale, and from six clinical staff familiar with the Ss using the Davids scale. It was predicted that activity ratings would have situationally specific relationships with actometer-measured activity level according to the rater's opportunities for observation. Comparisons between measures indicated that all clinical staff ratings correlated significantly with actometer activity in the classroom (r = .49 to r = .73), while mothers' ratings correlated significantly with actometer activity in gym (r = .67), and woodshop (r = .77), and with overall activity (r = .65), a combined measure derived from actometer scores in the four conditions tested. Five of six clinical staff raters showed significant interrater reliability (r = .58 to r = .83). Results are discussed in terms of their implications for solution of current problems in assessment of activity level and hyperactivity.


The Peer Preference Test as a measure of reward value: item analysis, cross-validation, concurrent validation, and replication. Thirty-six preschoolers were administered and retested on a 15-item Peer Preference Test designed to measure the reward value of peers for each child. Test-retest reliability was .88, and after item analyses, 12 items were maintained in the test. The revised test was then administered to 29 other preschoolers. Test-retest reliability was .77, and item analyses indicated that each item made a significant contribution to the overall test. Concurrent validation of the test was demonstrated using both a picture sociometric and a behavioral measure. In addition, the Evers-Pasquale and Sherman (1975) study was replicated, using 10 preschool social isolates.


A comparison of human and automated instruction of autistic children. While it appears reasonable to assume that the autistic child might benefit from the development of programmed instruction and teaching machines to teach imitation, concepts, and receptive vocabulary skills, no systematic research to date has seriously investigated such possibilities. The purpose of this study was to compare the effects of automated versus teacher-controlled instruction in the education of autistic children. Four autistic children, each with extreme deficits in language, social, and self-care behaviors, were trained on a matching-to-sample task under three different instructional situations within an intrasubject replication design and multiple baseline procedure. Analysis of the data showed the following results: (1) The teacher, manually operating the teaching machine, was able to teach and maintain the matching-to-sample task; (2) the same autistic children did not acquire or maintain the task when taught by the machine alone; and (3) the teacher alone (without the machine) was able to teach and maintain the task. The results suggest that automated instruction may, at least, serve as a valuable aid to teachers of autistic children. However, before machines can be used without the participation of a trained teacher, further research appears necessary. Several areas, including the role of motivation in automated instructional settings, the saliency and effectiveness of reinforcers, and the importance of controlling antecedent stimulus conditions and off-task behavior are discussed as areas of primary concern in the development of automated instruction for autistic children.


Peer facilitation of generalization in a preschool classroom. Two 5-year-old deviant preschoolers taught each other, as peer-tutors, to identify pictorial figures describing prepositional relationships. During training sessions monitored by the experimenter, the child in the peer-tutor role presented stimulus materials and provided consequences for the responses of the child in the tutee role. An assessment of generalization by each child to an academic classroom setting occurred each day. The data showed that the peer-tutor could facilitate generalization, when the tutee was probed in the peer-tutor's presence. However, it was found that the salience of the peer-tutor's presence was critical to this effect. In particular, when the peer presented the stimuli or offered occasional consequences for some correct responses, generalization was greatly enhanced.


Response cost and impulsive word recognition errors in reading-disabled children. Subjects were 30 fourth grade children with average intellectual ability but reading achievement at least 1.5 years below grade level. Each child was given two word-recognition lists, the first one as a pretest and the second list under one of three different experimental conditions: control, positive reinforcement (1 nickel for each word read correctly), and response cost (1 of 40 nickels taken back for each word read incorrectly). Relative to the control condition, positive reinforcement led to a significant increase in response latency but no change in errors, while response cost led to both a significant increase in latency and a significant decrease in reading errors. The entire group was found to be impulsive on the Matching Familiar Figures test. The successful reduction in impulsive reading errors was interpreted as support for Kagan's hypothesis that the impulsive child evidences low concern about errors on such academic tasks.


Normative data on revised Conners Parent and Teacher Rating Scales. Normative data are presented for 570 children on newly revised versions of the Conners Parent and Teacher Rating Scales. Symptom ratings were factor analyzed and structures compared favorably with those obtained using earlier versions of the questionnaires. Interrater correlations (mother-father, parent-teacher) were also reported. Age and sex effects were found to be significant determinants of children's scores, while social class effects were nonsignificant.


Cognitive slippage in children vulnerable to schizophrenia. Psychological deficit research with adult schizophrenics has been hindered by numerous methodological problems that may be avoided by the prospective study of children vulnerable to the disorder. An object sorting task was administered to 156 children of schizophrenic patients, 102 children of depressed patients, and 139 children of normal parents. The children were between 6 and 15 years old. The children of schizophrenic parents made fewer "superordinate" sorting responses than those of normal parents, and more "complex" sorts (a category of inadequate responses) than children of either normal and depressed parents. Our analyses showed that these deficits could not be explained by differences in intelligence. These deficits in conceptual performance may reflect the genotypic predisposition to schizophrenic and/or represent an early precursor of later maladjustment.


Judged school problems and competencies of referred children with varying family background characteristics. The school adjustment problems and competencies of referred children with varying family background histories were compared. Children from homes characterized by low parent interest in education had more severe learning problems and fewer competencies than either matched referred controls without such a history or matched referred children under family pressure to succeed. The relationship of these findings to other studies of school adjustment and family background was considered.


What I think and feel: a revised measure of children's manifest anxiety. The 1956 adaptation for children of Taylor's Manifest Anxiety Scale, the Children's Manifest Anxiety Scale, was revised to meet current psychometric standards. A 73-item revision draft was administered to 329 school children from grades 1 to 12. Based on item-analysis criteria for rbis greater than or equal to .4 and .30 less than or equal to p less than or equal to .70, 28 anxiety items were retained along with 9 of the original 11 Lie scale items. A cross-validation sample of 167 children from grades 2, 5, 9, 10, and 11 produced a KR20 reliability estimate of .85. Anxiety scores did not differ across grade or race. Females scored significantly higher than males. For the Lie scale, significant differences appeared by grade and race. No sex differences were obtained on the Lie scale. The resulting scale appears useful for children in grades 1 to 12 and may aid in future studies of anxiety as well as assisting the clinician in the understanding of individual children.


Note on locus of control and academic achievement in institutionalized juvenile delinquents. The previously reported relationship between internal locus of control and academic achievement was explored with the Nowicki-Strickland Locus of Control Scale for Children (Nowicki & Strickland, 1973) and seven measures of academic achievement in a random sample of 45 male residents of seven state learning centers for juvenile delinquents. Correlations between overall locus of control scores and all seven measures were significant, but with intelligence controlled in a partial correlation, locus of control scores were found to add little to the prediction of academic achievement from IQ scores alone. Discussion addressed possible explanations for the current findings in terms of the meaning of the scale for a nonnormal group and the effects of situations on responses of subjects.


Stevens-Johnson syndrome (erythema multiforme) following ingestion of trimethoprim-sulfamethoxazole on two separate occasions in the same person: a case report. Despite its content of a long-acting sulfa, the manufacturers claim that the literature shows no case reports of Stevens-Johnson syndrome reaction to trimethoprin-sulfamethoxazole. A case report in an enlightened Nigerian who inadvertently took the drug a second time and had second and more severe reactions is reported.


Long-term effects of beclomethasone dipropionate on prednisone dosage in the corticosteroid-dependent asthmatic. The average prednisone dosage of 54 corticosteroid-dependent asthmatics was computed for one year prior to initiation of beclomethasone dipropionate. This was compared to the average prednisone dosage after nine months on the beclomethasone with progressive tapering of prednisone to either dose compatible with control of asthma or discontinuation. Beclomethasone was found clinically useful in the great majority of these patients because it permitted a significant decrease in dosage of prednisone, a change from daily to alternate-day prednisone, or discontinuation of prednisone after cautious tapering. The first two advantages were most evident in those asthmatics who initially required higher doses of oral steroids while the latter was evident in those requiring lower doses. Those patients whose prednisone dosage does not appear to be beneficially affected by the use of beclomethasone should be suspect as to adherence to proper medical dosage schedule.


Treatment of asthma in children with triamcinolone acetonide aerosol. Triamcinolone acetonide aerosol, 100 microgram qid, was administered for 8 wk to 5 steroid-dependent asthmatic children and 10 who had not previously required continual corticosteroid treatment. Symptomatic control and pulmonary function improved in all 15 children despite discontinuation of oral corticosteroids in 3 of the steroid-dependent children. Determination of morning plasma cortisol concentrations disclosed no evidence of substantial adrenal suppression. Satisfactory symptomatic control has subsequently been maintained for 6 to 32 mo with doses of 100 microgram bid to 300 microgram qid without more extreme changes in plasma cortisol concentrations than were observed during the first 8 wk.


Quantitation of IgE antibody specific for ragweed and grass allergens: binding of radiolabeled allergens by solid-phase bound IgE. IgE antibody specific for multiple allergens extracted from grass and ragweed pollens was measured by radioimmunoassay. The assay depends on the interaction between IgE antibody bound to a polystyrene solid phase, , 125I-labeled grass allergens (GA), and ragweed allergens (RW). The binding of 125I RW by serum IgE antibody from 37 allergic patients ranged from 0.2 ng to 75 ng RW protein (P) bound per ml. This binding of 125I RW by patient's IgE was paralleled by their IgE binding of 125I antigen E (AgE), a purified allergen from ragweed pollen (r = 0.90, p less than 0.001). Inhibition of patient's IgE binding of 125I RW by highly purified AgE ranged from 25% to 85% indicating individual differences in patient's IgE response to inhaled ragweed pollen. The binding of 125I GA by serum IgE antibody from 7 grass-sensitive patients ranged from 0.6 ng GA P bound per ml to 15 ng. This assay should be useful in the study of IgE responses to environmental agents containing multiple allergens and has the advantage that other antibody classes cannot interfere with the interaction between IgE antibody and labeled allergens.


Relationships between prednisone therapy, disease activity, and the total serum IgE level in allergic bronchopulmonary aspergillosis. Allergic bronchopulmonary aspergillosis (ABPA) is an unusual syndrome caused by hypersensitivity to Aspergillus spores growing in the bronchii. Previous investigators have suggested that the IgE levels and precipitating antibodies may vary according to disease activity. We have been able to closely follow 12 out of a group of 40 ABPA patients with IgE and serum precipitating antibody measurements. Our results confirm that both the total serum IgE and the precipitin response vary according to ABPA disease activity. In particular the IgE trend appears to mirror the disease activity in that a rising level may portend a flare, while a stable or declining value implies disease remission.


Environmental factors associated with preschool obesity. III. Dietary intakes, eating patterns, and anthropometric measurements. This longitudinal study of children from six months to six years of age showed differences by age, sex, and race in dietary intakes, eating patterns, and anthropometric measurements. Except for calories and iron at all ages and calcium between two and four years, most children consumed at least two-thirds of the Recommended Dietary Allowances. Dietary protein was consistently high at all ages. There was no apparent relationship between the use and need for vitamin or mineral supplements. At six years of age, most children ate five meals or snacks per day. Television commercials, children accompanying mothers to grocery stores, and the publicized relationships of dietary fat and cholesterol to coronary disease influenced food practices of families. Anthropometric measurements revealed that boys were consistently taller and heavier than girls. However, at all ages, even at six months, girls had higher skinfold values than boys. These data on dietary intakes, eating practices, and anthropometric measurements will be correlated with obesity indexes at each age in subsequent papers.


Quality characteristics of wheat-bran chiffon cakes. Wheat bran was substituted for cake flour in chiffon cakes at 10, 20, and 30 per cent levels. Bran incorporation significantly affected (P less than 0.05) the appearance, height, and grain of chiffon cakes. Cake height decreased and cell size and cell wall thickness increased with higher levels of bran. Tenderness decreased with higher levels of bran. Compressimeter readings were higher with bran substitution at the 10 and 20 per cent levels. Sensory evaluation indicated no significant differences (P less than 0.05) between the control and 10 per cent bran cakes for moistness, flavor, and overall acceptability. Panelists did note a significant (P less than 0.05) decrease in tenderness and softness and an increase in crumbliness with higher bran levels. All chiffon cakes, regardless of bran level, were termed acceptable.


Mineral content of dairy products. II. Cheeses. Twenty-one kinds of commercial cheese were analyzed for fat, solids, protein, and five major and four trace minerals. Calcium, magnesium, sodium, and potassium were determined by atomic absorption; phosphorus was determined colorimetrically. Flameless atomic absorption was used to determine iron, zinc, copper, and manganese. The data agreed in general with published values, although there were instances of wide variation. The data represent a comprehensive compilation of the mineral contents of popular cheeses that should be helpful to dietitians and nutritionists.


Food production relationships between entrée combinations and forecasted demand. Macro elements and values for associated Time Measurement Units were applied to three classifications of entrées to synthesize production time for 100, 300, and 500 portions. Average handling and process time for each classification and time per portion were calculated. Data revealed that roast and single-item entrées required greater average handling time than combination entrées, because more individual handling of portions was required as forecasted demand increased. Process time for combination and single-item entrées increased as forecasted demand increased. The time for the single-item classification doubled for 300 and 500 portions, because oven capacity was exceeded. Production time data were applied to six combinations (menu mixes) and quantity levels of entrée classifications to determine production feasibility in a simulated foodservice system. Production problems were encountered in five of the six menu mixes because of system constraints. This study indicated that total production time estimates would be useful to foodservice managers when planning a menu mix, scheduling production personnel, and forecasting labor costs.


Treatment of hypertension in the elderly with pindolol and clopamide. After a 2-week washout period, 30 elderly hypertensive patients were treated with pindolol (a beta-adrenergic blocker) for 3 weeks. In 13 patients the reduction in blood pressure was satisfactory and treatment with pindolol was continued for another 4 weeks. In 17 patients the subsequent treatment was supplemented with clopamide (a diuretic) for 4 weeks; in 6 the results were satisfactory. Side effects were few and mild.


Werner's syndrome: analysis of 15 cases with a review of the Japanese literature. Fifteen patients with Werner's syndrome were studied--12 males and 3 females, whose ages ranged from 17 to 59 years. Most of the previously reported clinical characteristics were confirmed, and an additional finding was the frequent occurrence of flat feet and hyperreflexia of the patellar and Achilles tendons. Also noted were an excessive urinary excretion of hyaluronic acid and a decrease in the T-cell subpopulation. The significance of these findings is discussed.


Clinical value of the London Psychogeriatric Rating Scale. The London Psychogeriatric Rating Scale (LPRS) was developed in answer to the demand for a reliable psychometric rating scale suited to a psychogeriatric population. All inpatients on a Psychogeriatric Unit (approximately 140 at any specific time) were rated with the LPRS every third month for an 18-month period. The 4 components of the total score include a measure of mental status originally derived by factor analysis. Predictive validity has been established in terms of various clinically relevant areas including the following: a) ward placement; b) outcome (continued hospitalization, discharge, or death); c) diagnosis (by scoring levels and progress patterns across time); and d) ability of the patient to function in, or benefit from, a particular treatment program. The scale has been used successfully to assess a given patient's progress quantitatively and globally over a long period.


Geriatrics program for medical students. II. Impact of two educational experiences on student attitudes. In an innovative program in geriatrics for undergraduate medical students, the preliminary report concerned attitudes toward the aged among health care personnel. This follow-up report concerns the stability of, and changes in medical students' attitudes toward the aged after participation in one of the following types of geriatric educational experience: 1) a Family Practice clerkship, or 2) a selective course in Medical Humanities. Although both experiences resulted in positive changes in general attitudes, the one that emphasized empathy toward the elderly along with observation of healthy aged persons produced more positive feelings about rehabilitation potential. Implications for the geriatric training of physicians are discussed in the light of these findings.


Abdominoperineal resection in the octogenarian. Traditionally, abdominoperineal resection has been the accepted surgical therapy for anorectal carcinoma. A review is presented of the experience with this procedure at the University of Iowa Hospitals, involving 52 patients (33 men, 19 women) over the age of 80 (median, 81 years). The most common symptoms were: rectal bleeding in 35 patients, change in character of stool in 35, weight loss in 13, and abdominal pain in 7. A rectal mass was palpable in 45 patients and visible by sigmoidoscopy in 3 others. Of the 52 patients, 23 percent (12/52) died before postoperative discharge from the hospital, and 32 percent of the survivors had significant postoperative complications. The most lethal complications were related to problems of surgical technique. The median survival time for patients discharged from the hospital was 22 months, with causes of death being equally distributed between recurrent carcinoma and other disorders. Abdominoperineal resection remains an acceptable method for treatment of anorectal carcinoma in the aged (80 or older) provided it is carried out with meticulous technique and careful selection of the patients.


Second heart sound: a phono-echocardiographic correlation in 20 cardiac patients. In 20 cardiac patients, a study was made of the relationship between the second heart sound (S2) recorded by phonocardiography and the motion of the aortic valve recorded by simultaneous echocardiography. Since the first component of S2 coincided with closure of the aortic valve in all 20 patients, it is concluded that the origin of the first component of S2 may be related to aortic valve closure.


"Silent" thyroiditis with symptomatic hyperthyroidism in an elderly patient. A 93-year-old woman who presented with cardiac and gastrointestinal symptoms was found to have transient hyperthyroidism due to "silent" thyroiditis. The diagnosis was supported by the appropriate correlation between serum thyroid hormone levels and the thyroidal I-131 uptake and scan.


Serum digoxin levels in elderly nursing home patients: appraisal of routine periodic measurements. An assessment was made of the clinical value of routine periodic measurement of serum digoxin levels in 51 elderly nursing home patients with cardiac disease. The findings showed that the serum digoxin level was not correlated with the dosage of digoxin nor the patient's clinical state of digitalization. All patients were effectively digitalized, as judged clinically, and no digitalis toxicity occurred despite a wide range of serum digoxin levels. When adequate medical supervision, electrocardiograms, roentgenograms, serum electrolyte determinations and renal function tests are available, the routine periodic measurement of serum digoxin concentration does not offer any additional benefit in the management of nursing home patients with cardiac disease.


Senile confusion: limitations of assessment by the face-hand test, mental status questionnaire, and staff ratings. Three of the most common and convenient measures of senile confusion are informal staff ratings, the Face-Hand Test (FHT) and the Mental Status Questionnaire (MSQ). A group of 112 geriatric patients in two extended care facilities, and a volunteer sample of 40 community aged were examined by means of the FHT and MSQ. These instruments proved valuable in differentiating patients rated as confused from those rated as lucid and alert, and from the community subjects. However, each of these measures, as well as the staff ratings, produced false negative findings. Staff ratings incorrectly identified a hypochondriacal and paranoid patient as confused. The FHT scores of lucid and alert patients with some brain damage were low. MSQ scores of some poorly educated immigrants were very low, even though these patients were rated as lucid and alert by the staff and passed the FHT. One normally lucid and alert patient with a fever and an irregular rapid pulse failed both the FHT and the MSQ. Guidelines for further use of these instruments are presented.


Consumer attitudes toward health policy and knowledge about health legislation. Consumer attitudes toward key issues affecting health policy decisions in the local community have been ignored both by local health policy makers and by medical sociologists. The authors report an empirical analysis of: (1) consumer attitudes towards federal intervention in health care; (2) consumer perceptions of the free market philosophy of health providers; (3) consumer perceptions of their involvement in health policy making; (4) consumer confidence in present systems of health services delivery; and (5) consumer awareness of recent major health legislation. It was found that consumers are poorly informed about recent health care legislation. The authors compared the attitudes of consumers with those held by local hospital board members toward health policy issues. The differences for all comparisons were statistically significant. The authors argue that hospital board members attribute problems in health services delivery to demand dysfunctions while consumers perceive the problems to be a result of supply dysfunctions. Thus, failure to include consumers on health policy boards guarantees the absence of a solution-oriented dialogue and promotes the continuing predominance of a provider-biased ideology.


Regulatory policy and abortion clinics: implications for planning. The practicalities of formulating regulatory policy associated with elective abortion often place public health officials at the center of political controversy. Resulting conflicts can inhibit a rational consideration of long-term objectives in implementing a national policy which assures legal accessibility to all who would select abortion as an alternative to term birth. Regulation which uses primarily structural criteria for monitoring and evaluating services tends to de-emphasize the importanc of contraceptive counseling as a component of abortion services. Our process/outcome evaluation of abortion clinics located in Chicago suggests that contraceptive counseling provided at the time of the abortion procedure has a potential long-term impact in terms of reducing the need for elective abortion. We suggest that regulation policy should include process and outcome criteria which support the eventual reduction in need for abortion as a long-range policy goal and suggest key issues for consideration when such a policy is formulated.


Federal influence on state health policy. This paper reports on research that was intended to demonstrate the impact of federal programs on state health policy goals. The sample included four Public Health Service programs (Health Planning and Resources Development, Nurse Training, Cooperative Health Statistics and the Community Mental Health Centers program) in six states (Colorado, Maryland, Michigan, Oregon, South Carolina, and Texas). The authors conclude that, in general, states' political environments tailor program implementation to suit state preferences.


Politics and economics of hospital cost containment. Voluntary and regulatory efforts toward hospital cost-containment have accelerated with rapid increases in those costs and under pressures of national health insurance. Possible causes of hospital cost inflation are examined in the context of market analysis and with reference to the nature of hospitals as institutions facing special combinations of economic and political conditions and pressures. Some details of voluntary experiments and state regulatory efforts are examined in order to assess the elements of experience to date and their relationships to causes of hospital cost inflation. Federal proposals for a regulatory cap on costs are also discussed along with a view of how such proposals are related to probable causes of hospital cost inflation and of the relevance of other experience.


The distribution of Ancylostoma caninum larvae in the central nervous system of the mouse infected with single or repeated doses. The distribution of Ancylostoma caninum larvae in the various regions of the central nervous system of mice of previously uninfected or reinfected groups was studied. Although a dose of 4000 larvae was lethal, the distribution of larvae was not appreciable in the CNS. Many larvae were recovered from the cerebral hemispheres and cerebellum of infected mice whereas no incidence of eye involvement was observed in any mouse. In the reinfected mice groups there was a much lower recovery than in the previously uninfected groups in the latent period of study.


The influence of physical factors on the behaviour and infectivity of miracidia of Schistosoma mansoni and S. haematobium. II. Effect of light and depth. A striking difference was found in the responses of Schistosoma mansoni and S. haematobium miracidia to the intensity and direction of light and to gravity. S. mansoni miracidia were found to be positively phototactic and sensitive to small changes in light intensities. They were indifferent to gravity. S. haematobium miracidia however were negatively phototactic and unable to distinguish low light intensities from darkness. They showed a strong positive geotaxis. Both S. mansoni and S. haematobium miracidia could successfully find and infect snails to a depth of 2 metres of water: the significance of these findings in relation to transmission of schistosomiasis in the field is discussed.


Studies with Brugia pahangi. 15. Cobalt 60 irradiation of the worm. Infective larvae of Brugia pahangi were irradiated at 10, 25 or 45 krads by means of a Cobalt 60 source. In cats, 10 krads caused the worms to be stunted and sterile but allowed them to become 5th stage, migrate posteriorly into the afferent lymphatic, and produce pathology. 25 krads prevented the worms from developing beyond the early fourth stage and from migrating away from the popliteal lymph node. No gross pathological reacions were evident. 45 krads produced the same effects as 25 krads but the longevity of the worms was much reduced.


Studies with Brugia pahangi. 16. Precipitation antibody in infected cats detected by counterimmunoelectrophoresis. In cats infected with normal, or irradiated, infective (L3) larvae of Brugia pahangi counterimmunoelectrophoresis revealed the presence of antibody to soluble antigens derived from microfilariae, adults and infective larvae of the same parasite. Infected cats with a persistently high to moderate microfilaraemia gave positive precipitin reactions to L3, microfilarial and adult worm antigens. Cats which had become amicrofilaraemic had antibody to L3 and microfilarial antigens but not to adult worm antigen. Serum from cats inoculated with irradiated L3 larvae produced a precipitin reaction only to the L3 antigen.


Two new species of Enenterum Linton, 1910 (Digenea) in the marine fish Neoscorpis lithophilus (Kyphosidae) from the south-western Indian Ocean. Enenterum elsti sp. nov. and E. prudhoei sp. nov. are described from the intestine of Neoscorpis lithophilus off Mapelane, Natal, South Africa. These species differ from others of the genus Enenterum in the ratio of oral sucker to body-length and in the length of the prepharynx. E. elsti differs from E. prudhoei in size, in sucker-ratio and in the number and configuration of the oral lobes. A key to the species of Enenterum is presented and the status of the genus briefly discussed.


Dioctowittus spp. Chabaud and Le Van Hoa 1960 (Nematoda: Adenophorea) from Australian snakes. Dioctowittus denisoniae n. sp. from Denisonia punctata differs from D. wittei and D. chabaudi in the smaller size, lack of vestigeal male precloacal sucker, short egg-filaments, the presence of lateral expansions at the posterior end in the male, and in the expansions of the oesophageal tissue between the stichocytes. Dioctowittus sp. from Liasis amethystimus differs from the three described species in the posession of lateral lobes at both extremities.


Polyonchobothrium scleropagis n. sp. (Cestoda: Pseudophyllidea) from the Australian osteoglossid fish Scleropages leichardti Günther. Polyonchobothrium scleropagis (Cestoda: Pseudophyllidea) is described as a new species from the Australian osteoglossid fish Sclerophages leichardti Günther.


Studies on humoral immunity against Taenia taeniaeformis infection in rats. Rats were infected with doses of 100, 1000, 5000 and 10 000 eggs of Taenia taeniaeformis. Haemagglutinating antibody to cysticerus antigen was detected at the 4th week of infection. The appearance and levels of antibody titre did not vary greatly with the infective dose. An IgM peak appeared at the 6th week, with IgG appearing slightly later and continuing to rise. Transfer of serum from the 1st week onwards from infections with 1000 eggs however could confer significant protection. Dilutions of hyperimmune serum (1 ml volumes) of up to 1/32 conferred significant protection on normal recipients. Hyperimmune serum transferred up to 4 days before challenge could confer 80% protection whereas serum transferred 4 days after challenge was totally non-protective. The significance of this finding is discussed in the light of current knowledge of metacestode immunity.


Evidence for glycogen particles in the peroxisome of riboflavin deficient mouse kidney. In the proximal tubular cells of the kidney in riboflavin deficient mice, electron dense particulate materials of about 30 nm in diameter were observed in the matrix of the peroxisome-like cytoplasmic bodies. The cytochemical study showed that these cytoplasmic bodies were negative for acid phosphatase activity and positive for DAB reaction, thus indicating that these organelles were peroxisomes. The particulate materials in peroxisomes were well stained with aqueous uranyl acetate, lead tartrate, alkaline bismuth and periodate acid bismuth. These particles were also digested by amylase. These results indicated that the particulate materials in peroxisomes were native glycogen particles. From the present study it was apparent that the peroxisome contained glycogen particles, and suggested the possibility that in some conditions glycogen might be synthesized in the peroxisome.


Localization of carbohydrate components in rat colon with fluoresceinated lectins. Cryostat sections of rat descending colon were studied by fluorescence microscopy after exposure to conjugates of fluorescein isothicoyanate with lectins from Glycine max (soybean), Triticum vulgaris (wheat germ), Ricinus communis (castor bean), Ulex europaeus, (gorse), Dolichos biflorus (horse gram) and Canavalia ensiformis (concanavalin A) (Jack bean). No two lectins showed identical patterns of fluorescence. FITC-conjugates of soybean and D. biflorus lectins reacted strongly with the mucus present in the crypt lumens and with the surface (as well as cytoplasm) of the epithelial cells suggesting that these sites are rich in terminal, non-reducing, N-acetylgalactosamine residues. Wheat germ, R. communis, U. europaeus and concanavalin A-FITC conjugates did not stain mucus but showed fluorescence in the cytoplasm of absorptive cells as well as in the lamina propria and submucosa. The FITC-R. communis conjugate also reacted with structures in the apical portion of epithelial cells that may correspond to the Golgi apparatus.


Effect of rabbit strain on activity level and cytotoxicity of serum complement. Serum samples from about 10 males and 10 females from each of 16 genetically defined strains of rabbits and from one hybrid were tested as sources of complement for the microtiter lymphocytotoxicity test. Lymph nodes from mice of strain B10.A/Sn were used as the target cells with a strong H-2 alloantiserum. Results indicate marked strain differences. Rabbit serum from a hybrid between the two best strains IIIC/J and IIIVO/J was almost as satisfactory as the parental strains and better than all other strains tested in this system, indicating a genetic basis for the response. The results of testing aliquots of these serum samples against other test systems including human cell lines will have to be in hand before a general statement can be made, but preliminary unpublished data against lymph nodes from A/HeJ and C3H/HeJ strain mice and tumor cells from an ascites form of a sarcoma Sal-A are encouraging and suggest a consistent superiority of the two strains and the hybrid between them referred to above.


Cytophotometric analyses of myocardial RNA in rats exposed to altitude hypoxia. Analytical cytophotometry of azure B-stained heart sections was employed to investigate the pattern of myocardial ribonucleic acid (RNA) alterations in rats exposed to acute (1-2 days) and prolonged periods (1-8 weeks) of hypoxia exposure (380 torr). Data support the existence of a slight transient drop in myocardial RNA on day one of exposure followed by a restoration to levels slightly elevated over controls during a 1- to 8-week exposure interval. Because of the high variability in RNA levels among myocytes (coefficient of variation, ca 40%), a shift in the proportion of low and high RNA containing segments of the myocyte population proved to be a more sensitive indicator of suppression or augmentation of RNA synthesis than the use of average RNA levels of the cell population analyzed. Microscopic analyses revealed the presence of compensatory vascular responses which could be effective in ameliorating the extent of tissue hypoxemia, i.e., capillary vasodilation on day 1 with a progressive increase in vascularization with prolonged exposure.


Polymorphism at the glucosephosphate isomerase locus in the dog. A polymorphism of the enzyme glucosephosphate isomerase (GPI) in canine red blood cells is reported. This polymorphism was detected by horizontal starch gel electrophoresis utilizing a tris-EDTA-borate buffer system of pH 8.0. Four out of 92 dogs examined appeared to be heterozygous at this locus.


Relative mobility of con A and anionic receptor sites on the cell surface of lymphocytes. A quantitative-cytochemical study. Events following the binding of Concanavalin A and cationized ferritin to the surface of normal human peripheral blood lymphocytes were followed using ultracytochemical methods. In this paper, we described a technique involving microdensitometry, which was employed in order to make a comparative cytochemical quantitation of the dense horseradish peroxidase-diaminobenzidine reaction products representing the states of Concanavalin A receptors under various conditions of distribution and redistribution. The technique presents a direct approach to the analysis of various probes that are currently being employed for studying the nature and distribution of various cell surface components. An attempt was also made to analyze the distribution of anionic sites, and their lateral redistribution is compared with the mobility of Concanavalin A receptors. The data presented suggests an independent mobility of receptors for Concanavalin A and cationized ferritin.


The genetics of blind--a lethal factor in mice. The linkage relationships of the lethal gene blind (Bld) in the mouse were investigated. The gene is located on chromosome 15, between uw and bt. The distance uw--Bld is 28.2 +/- 5.1 cM: Bld--bt is 14.9 +/- 2.7 cM: and Bld--Ca is 24.6 +/- 2.6 cM. Incomplete penetrance and/or reduced viability of Bld/+ animals was found when blind animals were crossed to several strains, but the cross female DBA/2J X male blind yielded complete penetrance and specificity. Evidence is presented for the presence of X-linked modifiers affecting the penetrance and possible increased viability of Bld in strain DBA.


Stigma, sex and society: a new look at gender differentiation and sexual variation. This paper takes a critical look at the hormonal basis of sexual behavior and concludes that it plays no part in determination of sexual activity or sexual preference in any of its forms including homosexuality and transsexualism. The empirical evidence of psychosexual functioning does not support Money's schema which suggest that sexual variation (homosexuality), transsexualism, and transvestism are incongruities of gender identity. At alternative approach which places gender differentiation and sexual variation in a social context is presented.


Couples: the hidden segment of the gay world. This study explores the relationships of 15 homosexual couples--5 female and 10 male couples. In duration the relationships ranged from 7 months to 13 years. In age the partners ranged from 19 to 50. Findings indicate that the partners met in social as compared with sexual settings, that relationships are more common for females than for males, that female more than male couples require sexual fidelity between partners, that male more than female couples desire children, and that there was no "butch-femme" role playing in the relationships. Social incompatibility of partners and social pressure are seen as causes for the breakup of relationships.


Toward a new model of treatment of homosexuality: a review. A review of the literature of outcome studies in the psychoanalytic or behavioral treatment of homosexuality reveals limited results when "heterosexual shift" is the goal. Recently, however, a growing body of empirical knowledge has accumulated that challenges the illness or maladaptive model of homosexuality. Consequently, a new model has been emerging that is designed to assist homosexuals to recognize, accept, and value their sexual identity and to help them adjust to this identity in a predominantly heterosexual society. Unfortunatley, only a few studies exist that examine the result of this new approach.


The effects of social sex-role stereotypes and sexual orientation on psychotherapeutic outcomes. This paper examines the relationship of biological sex, social sex-role stereotypes, and sexual orientation of client and the therapist to psychotherapeutic outcomes. It was hypothesized that analogus biological sex, departures in social sex-role, and sexual orientation of client and therapist would have positive effects on psychotherapeutic outcomes. Twenty-four clients and 16 therapist, including five client-therapist pairs, were interviewed on how issues of social sex-role stereotyping and sexual orientation arose and were dealt with in therapy. The results indicated (a) a trend toward more positive outcomes when client and therapist were of the same sex, and (b) that similarity of sexual orientation of client and therapist is related to positive psychotherapeutic outcomes. The results for deparature from social sex-role stereotypes were inconclusive.


The male adolescent involved with a pederast becomes and adult. A longitudinal study of nine cases in reported where the adolescent male was engaged after puberty in sexual activity with an adult male. Observations are reported in the 2nd, 3rd, and 4th  decades after the teenage years in these cases. The subjects were drawn from a pool of 200 similar cases and are the cases where the most data are available. Implications for professionals dealing with adolescent sexuality are made. Gaps between what is legally permitted and what is actual practice are pointed out. Need for further research and the areas for that research are implied. A case against premature labeling is made.


Physician participation in health insurance plans: evidence on Blue Shield. Various health insurance programs, including Blue Shield, have developed arrangements whereby the physician agrees to accept the insurer's reimbursement as payment in full. Incentives facing the physician to accept an arrangement of this type are reviewed in this study. The empirical work uses data on individual physicians from a 1973 survey. The results indicate that physician willingness to accept insurer reimbursement as payment in full is sensitive to the amount the insurer pays for specific procedures and to other insurance program characteristics. Physicians located in high patient income areas and/or with relatively prestigious credentials are less likely to accept insurer payments as payment in full. The empirical findings are used to generate policy implications pertaining to the Medicare and Medicaid programs, to medical care quality-access tradeoffs, and to national health insurance.


Molecular heterogeneity of secretory IgA anti-DNP antibodies. Evidence is presented that demonstrates that the microscale sucrose isoelectric focusing technique can be used to assess the molecular heterogeneity of secretory IgA anti-DNP antibodies. The data indicate that substitution of the DNP group on the bacterial carrier, pneumococcus, can limit the structural complexity of secretory IgA anti-DNP antibodies. The data support the concept that factors governing secretory IgA antibody heterogeneity are analogous to those influencing the heterogeneity of serum IgG antibodies.


Polymorphism of tissue and serum amyloid A (AA and SAA) proteins in the mouse. Amino acid sequence studies of the amino terminal 25 residues of amyloid A (AA) protein and the serum precursor (SAA) induced with casein or LPS indicate differences in the sequence at position 6 and significant heterogeneity at several other positions in SAA. These findings suggest that SAA is a polymorphic serum protein and raise the possibility that only certain forms of SAA are processed to the tissue amyloid fibril.


A quantitative fluorometric assay for detection and characterization of Fc receptors. A new quantitative fluorometric binding assay that uses fluoresceinated aggregated IgG is proposed for the study of Fc receptors. The method was compared with a radiolabeling binding assay on three well characterized murine cell lines (38C-13, EL4, and BW). The apparent association constant of the binding and the amount of aggregated IgG bound per cell at saturation were calculated. The fluorometric assay enables the detection of 5 X 10(-10) M bound aggregated IgG. Inhibition studies with monomeric IgG, reduced and alkylated aggregated IgG, and aggregated F(ab')2 fragments of IgG confirmed the specificity of the assay. Staphylococcal protein A inhibited the binding of the aggregated IgG to Fc receptors.


A specific indicator for mouse lymphocyte C3b receptors. IgM-sensitized sheep E bearing guinea pig C4 and C3b (EAC43bgp) react as strongly with mouse spleen cell C3b receptors as do optimally prepared EACmo. Yet, when the C3b is converted to C3d by incubation with heated serum at low ionic strength, reactivity with mouse spleen cells is completely lost whereas binding to guinea pig spleen cells remains high. It is concluded on the basis of this and other evidence that EAC43bgp are a sensitive and specific indicator for mouse lymphocyte C3b receptors. Degradation of the C3b on these cells will not cause misleading binding to C3d receptors, as could occur with cells bearing mouse C3b.


Immunologic tolerance in the chicken. I. Isolation of two suppressive fractions from serum of chickens tolerant to bovine serum albumin. Serum from 14-day-old chickens rendered tolerant at hatching with 1250 mg bovine serum albumin (BSA)/KBW was found to suppress an adoptive secondary response to BSA and an in vitro response to sheep red blood cells (SRBC). Chromatographic separation resulted in three fractions: I, II, and III. The suppressive activity was found to be contained in fraction I (m.w. greater than 1 X 10(6)) and fraction III (m.w. less than 2.5 X 10(4)). Analysis of fraction I by affinity chromatographic techniques revealed that it was composed of soluble BSA-antibody complexes and their removal removed the suppressive activity. Analysis of peak III revealed that the suppressive activity could only be removed by BSA and anti-Line 3 antiserum columns.


Trinitrophenylated red cells (E-TNP) as a model for antibody-independent activation of the complement system via the classical pathway. Recently, it was shown that DNP-substituted human serum albumin (DNP-HSA) bound directly C1q, a subcomponent of C1. Evidence is presented that TNP-conjugated erythrocyte (E-TNP) were lysed by autologous sera as source of complement (C). The lysis was strongly dependent on the TNP substitution rate so that the TNP-carrying erythrocytes can be used directly as an indicator for the TNP-C interaction. The TNP-induced lysis of erythrocytes required the presence of C1q, C4, and Ca++, indicating a dependency on the classical pathway of C. Purified C1 is directly bound to E-TNP; C1 bound to E-TNP could be transferred to EAC4. From E-TNP-C1 the intermediates E-TNP-C14 and E-TNP-C142 can be formed by successive addition of C4 and C2 similarly to EAC14 and EAC142. Native C1 can be activated to C1 by E-TNP in the same fashion as by EA. The E-TNP model provides evidence that the "activated" Fc part of the antibody molecule is not unique in its ability to trigger the internal activation of C1. Molecules with negatively charged groups, like polyanions, or molecules with high electron dense groups, like DNP or TNP, can activate the C system via the classical pathway by binding directly to C1q.


Corticosteroids block newly induced but not constitutive functions of macrophage cell lines: myeloid colony-stimulating activity production, latex phagocytosis, and antibody-dependent lysis of RBC and tumor targets. Hydrocortisone at 10(-4) M added to macrophage cell lines had no effect on the following activities: J774.1 antibody-dependent phagocytosis and lysis of sheep RBC, RAW 264 antibody-dependent lysis of tumor targets, latex bead phagocytosis by PU5-1.8 cells, and constitutive production of myeloid colony-stimulating activity (CSA) by WEHI-3 cells. In contrast, 10(-4) M hydrocortisone completely inhibited LPS or PPD activation of the following functions: induced production of myeloid CSA, stimulation of latex phagocytosis and stimulation of antibody-dependent lysis of tumor targets by PU5-1.8 cell line, and stimulation of antibody-dependent lysis of RBC targets by RAW 264 cell line. Lower concentrations of hydrocortisone or dexamethasone at 10(-6) M inhibited the LPS induction of CSA from 55 to 90%. Growth inhibition of PU5-1.8 cells caused by 1 microgram/ml LPS was also partially reversed by corticosteroids. Thus, steroids block these newly induced but not constitutive functions of these macrophage cells in culture.


Oxygen immunosuppression: modification of experimental allergic encephalomyelitis in rodents. Using protocols that incorporated double blind examination of animals sensitized to CNS antigen, we confirmed and amplified earlier findings of the complete suppression of EAE in rodents by hyperbaric oxygen. The effects of O2 were related to the gas pressure and duration of treatment. The development of paralytic disease was prevented for 34 days after sensitization (the longest interval studied). Compressed air or normobaric O2 administered under similar conditions did not modify the course of illness. Within 7 to 10 days after the discontinuance of oxygen therapy the majority of treated guinea pigs developed typical signs of EAE with characteristic lesions in the CNS. The relapses occurred  sooner in the Lewis rat. The development of the delayed hypersensitivity reaction to myelin basic protein and to tuberculin is also suppressed by O2 therapy indicating that its effects upon autoimmune encephalomyelitis involves fundamental alterations of the cellular components of the immune response, some or all of which are reversible.


Kinetic assessment of alternative complement pathway activity in a hemolytic system. II. Influence of antibody on alternative pathway activation. By using a kinetic assay, we have examined the role of antibody in the lysis of rabbit erythrocytes (RaRBC) through the alternative complement (C) pathway. Sera from some hypogammaglobulinemic (Hgamma) humans and all agammaglobulinemic chickens tested had subnormal activity in the assay. Heated normal human or chicken sera, but not heated Hgamma sera, restored activity to deficient Hgamma serum and initiated hemolysis in the presence of rabbit serum as C source. Absorption of heated normal human serum with RaRBC, but not with sheep erythrocytes or zymosan, removed its ability to reconstitute deficient Hgamma serum. Normal hemolytic activity could be resotred to Hgamma serum with human IgM, IgG, or colostral IgA, with goat anti-RaRBC IgG, or with an eluate from serum-sensitized RaRBC, but not with myeloma IgA. Restoration of hemolytic activity to Hgamma serum could be achieved in a dose-dependent fashion with the F(ab')2 fragment of IgG. These results suggest that antibody exerts a significant rate-limiting effect on alternative pathway activity in the RaRBC lytic system. This raises the possibility that antibody may be required for efficient alternative pathway activity in vivo and that the pyogenic infections that occur in Hgamma individuals are due to inefficient activation and fixation of C3 through either the classical or alternative pathway.


Nonspecific suppressive and cytostatic activities mediated by human colonic carcinoma tissue or cultured cell extract. We have previously shown that soluble extracts from human colonic carcinoma (SCE) were potent inhibitors of the PHA-induced DNA synthesis of normal allogeneic peripheral lymphocytes. From the present study, SCE appeared to have a broad and nonspecific range of activity. The SCE-suppressive effect was observed whatever the lymphoid organ or the animal species used as a source of stimulated lymphocytes. Moreover, we always obtained a complete inhibition of the lymphoproliferative response to all tested mitogens including PHA, Con A, PWM, and, for animal lymphocytes, LPS. In addition to the suppressive activity on lymphocytes, SCE also inhibited proliferation of cultured human CCL6 embryonic intestine cells and HT29 colonic carcinoma cells, and of cultured rat fibrosarcoma cells. Soluble extracts from HT29 cells (SCCE) were able to mimic the nonspecific suppressive and cytostatic activities of SCE. The suppressive activity was also found in extracts from hepatic metastases (SHME) of a primary colonic tumor. In contrast, soluble extracts from normal liver or nonmalignant colonic mucosa did not interfere with cell proliferation. These data suggest that both SCE and SCCE contain molecular components(s) that can inhibit a wide variety of proliferating cells, including stimulated lymphocytes.


In vitro sensitization of human lymphocytes against histiocytic lymphoma cell lines. II. Characterization of two different effector activities and of suppressor cells. Peripheral blood lymphocytes (PBL) from normal human donors were tested for natural killing (NK) activity and for two types of in vitro induced cytotoxicity against allogeneic diffuse histiocytic lymphoma (DHL) cell lines. Culture-induced cytotoxic (CIC) activity developed in cultures of unseparated PBL incubated in the presence of fetal bovine serum (FBS) but not in the presence of human serum (HS). The CIC mediating effector cells were removed by nylon wool adherence, whereas the NK cells were not. A second type of in vitro induced cytotoxicity was obtained by specific sensitization against DHL cells (SIC). The SIC effector cells were not retained by nylon wool. SIC was manifested after sensitization in medium containing HS but not in FBS-containing medium unless nylon wool adherent cells were removed before sensitization. The lack of SIC in the presence of FBS appeared to be due to nylon wool-adherent suppressor cells. Such suppressor activity was also removed by plastic adherence or elimination of phagocytic cells. CIC and suppressive activity were found to be mediated by different cell populations.